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pipeline_output.txt
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pipeline_output.txt
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Text:
We have developed a unique male-sterility and fertility-restoration system in rice by combining Brassica napus cysteine-protease gene (BnCysP1) with anther-specific P12 promoter of rice for facilitating production of hybrid varieties. In diverse crop plants, male-sterility has been exploited as a useful approach for production of hybrid varieties to harness the benefits of hybrid vigour. The promoter region of Os12bglu38 gene of rice has been isolated from the developing panicles and was designated as P12. The promoter was fused with gusA reporter gene and was expressed in Arabidopsis and rice systems. Transgenic plants exhibited GUS activity in tapetal cells and pollen of the developing anthers indicating anther/pollen-specific expression of the promoter. For engineering nuclear male sterility, the coding region of Brassica napus cysteine protease1 (BnCysP1) was isolated from developing seeds and fused to P12 promoter. Transgenic rice plants obtained with P12-BnCysP1 failed to produce functional pollen grains. The F
Targets:
['Cysteine Proteases']
Preds:
b'["Bacterial Proteins", "Recombinant Fusion Proteins", "RNA, Viral", "Recombinant Proteins", "Proteins", "DNA", "DNA-Binding Proteins", "Carrier Proteins"]'
Text:
Opioid misuse in the context of chronic opioid therapy (COT) is a growing concern. Depression may be a risk factor for opioid misuse, but it has been difficult to tease out the contribution of co-occurring substance abuse. This study aims to examine whether there is an association between depression and opioid misuse in patients receiving COT who have no history of substance abuse.
Targets:
['Analgesics, Opioid']
Preds:
b'["Anti-Bacterial Agents", "Antineoplastic Agents", "Cytokines", "Biomarkers", "Antipsychotic Agents", "Anti-Inflammatory Agents, Non-Steroidal", "Anti-Inflammatory Agents", "Immunosuppressive Agents"]'
Text:
Compared to in situ vascular physiology where pro and anti-hemostatic processes are in balance to maintain hemostasis, the use of ECMO in a critically ill child increases the risk of hemorrhagic or thromboembolic events due to a perturbation in the balance inherent of this complex system. The ECMO circuit has pro-hemostatic effects due to contact activation of hemostasis and inflammatory pathways. In addition, the critical illness of the child can cause dysregulation of hemostasis that may shift between hyper and hypocoagulable states over time.
Targets:
['Anticoagulants', 'Hemostatics']
Preds:
b'["Biomarkers", "Antineoplastic Agents", "Antipsychotic Agents", "Biomarkers, Tumor", "Anti-Inflammatory Agents, Non-Steroidal", "Insulin", "Anti-Inflammatory Agents", "Anti-Bacterial Agents"]'
Text:
Coincidence cloning allows the isolation of sequences held in common by two genomic DNA populations. Human DNA from two human-hamster hybrid cell lines was amplified by Alu-repeat primers (Alu PCR) and the products originating from the shared human chromosomal region were cloned. To achieve this, human sequences were amplified with very similar Alu primers from the two different human-hamster hybrid cell lines. The products were then digested with an appropriate restriction enzyme (either BamHI or Sal I), combined, denatured, and reannealed. The derived heteroduplex molecules (originating from the human regions common to both cell lines) had single BamHI and Sal I cohesive ends due to the primers used, so that they could be cloned in a double-digested plasmid vector. We used this method to enrich about 10-fold for Alu PCR products from the human chromosome 19q13.2 region, resulting in a region-specific clone collection. About 90% of the recombinants with BamHI-Sal I inserts are derived from the common region. This approach allows the boundaries for the regional probe isolation to be defined by combinations of hybrids rather than single hybrid cell lines, thus permitting greater flexibility in the selection of regions for probe isolation.
Targets:
['Oligonucleotide Probes', 'DNA']
Preds:
b'["DNA", "RNA, Messenger", "DNA-Binding Proteins", "Bacterial Proteins", "DNA, Viral", "Genetic Markers", "Proteins", "DNA Primers"]'
Text:
The lipophilic fluorescent probe diphenylhexatriene (DPH) has been shown previously to behave as a marker of plasma membrane in living cell systems, and it is therefore been widely used in membrane fluidity studies via fluorescence anisotropy measurements. The anisotropic coefficient, which is inversely related to the rotational motion of the probe in membrane phospholipids, was significantly higher at 37 degrees C than at 23 degrees C for 9 series of red blood cells ghosts obtained from three healthy subjects. We also have studied the importance of the nature of two different polaroid films which permits the observation of fluorescence polarization.
Targets:
['Fluorescent Dyes', 'Diphenylhexatriene']
Preds:
b'["DNA", "Polymers", "Collagen", "Proteins", "Biomarkers, Tumor", "Antineoplastic Agents", "Biomarkers", "Contrast Media"]'
Text:
An efficient method for the N-heterocyclic carbene (NHC)-catalyzed conjugate addition of acetyl anions to various α,β-unsaturated acceptors (Stetter reaction) has been optimized by using 2,3-butandione (biacetyl) as an alternative surrogate of acetaldehyde. The disclosed procedure proved to be compatible with microwave dielectric heating for reaction time reduction and with the use of different linear α-diketones as acyl anion donors (e.g. 3,4-hexanedione for propionyl anion additions). Moreover, the unprecedented umpolung reactivity of cyclic α-diketones in the atom economic nucleophilic acylation of chalcones is herein presented. Mechanistic aspects of the thiazolium-based catalysis involving linear and cyclic α-diketone substrates are also discussed.
Targets:
['Ketones', 'Thiazoles']
Preds:
b'["Antineoplastic Agents", "Anti-Bacterial Agents", "Proteins", "Polymers", "Peptides", "Water", "Recombinant Proteins", "Amino Acids"]'
Text:
Detection, diagnosis and identification of Leishmaniasis may be difficult owing to low numbers of parasites present in clinical samples. The PCR has improved the sensitivity and specificity of diagnosis of several infectious diseases. A leishmania specific PCR assay was developed based on the SSUrRNA genes which amplifies DNA of all Leishmania species. Point mutations occurring within the rRNA genes allow differentiation of the Leishmania complexes using primers constructed with the 3/ ends complementary to the specific point mutations present in the SSU rRNA genes of the Leishmania species. Biopsy material, blood, lesion impressions and blood spots on filter paper can be used in the assay. In a longitudinal study on the incidence rates of VL, subclinical cases and PKDL in an endemic region of Sudan, filter paper blood spots from proven and suspected VL patients, PKDL and control samples from an endemic region in Sudan are being taken. The blood spots were analyzed in the DAT and by PCR and results compared with clinical and parasitological data. The first results indicate that the PCR on blood spots is a simple and sensitive means of detecting active VL; in PKDL patients parasites are detectable in the skin.
Targets:
['DNA, Kinetoplast', 'RNA, Protozoan', 'RNA, Ribosomal']
Preds:
b'["Biomarkers, Tumor", "RNA, Messenger", "Antibodies, Monoclonal", "Antineoplastic Agents", "DNA, Viral", "DNA", "Biomarkers", "Genetic Markers"]'
Text:
Extended-spectrum β-lactamases (ESBLs) are enzymes capable of hydrolyzing oxyimino-β-lactams and inducing resistance to third generation cephalosporins. The genes encoding ESBLs are widespread and generally located on highly transmissible resistance plasmids. We aimed to investigate the complement of ESBL genes in E. coli and Klebsiella pneumoniae causing nosocomial infections in hospitals in Ho Chi Minh City, Vietnam.
Targets:
['Anti-Bacterial Agents', 'DNA, Bacterial', 'beta-Lactamases']
Preds:
b'["Bacterial Proteins", "Recombinant Proteins", "Transcription Factors", "Anti-Bacterial Agents", "RNA, Messenger", "DNA Primers", "DNA-Binding Proteins", "DNA, Bacterial"]'
Text:
In the early 1990s, breakthrough discoveries on the genetics of Alzheimer's disease led to the identification of missense mutations in the amyloid-beta precursor protein gene. Research findings quickly followed, giving insights into molecular pathogenesis and possibilities for the development of new types of animal models. The complete toolbox of transgenic techniques, including pronuclear oocyte injection and homologous recombination, has been applied in the Alzheimer's disease field, to produce overexpressors, knockouts, knockins and regulatable transgenics. Transgenic models have dramatically advanced our understanding of pathogenic mechanisms and allowed therapeutic approaches to be tested. Following a brief introduction to Alzheimer's disease, various nontransgenic and transgenic animal models are described in terms of their values and limitations with respect to pathogenic, therapeutic and functional understandings of the human disease.
Targets:
['Amyloid beta-Peptides']
Preds:
b'["RNA, Messenger", "Proteins", "MicroRNAs", "Transcription Factors", "DNA", "Antineoplastic Agents", "DNA-Binding Proteins", "Biomarkers"]'
Text:
Inbred mice with the mutation diabetes C57BL/KsJ db+/db+ and the mutation obese C57BL/6J ob/ob displayed a total liver mitochondrial capacity to oxidize glutamate or succinate which was approximately eight times greater than the capacity of the C57BL/6J +/+ control mice. This increase in oxidation capacity was estimated by multiplying the observed twofold increase in each of the following components: total liver weight, the mitochondrial protein content per gram of liver, and glutamate or succinate respiration activity per milligram of liver mitochondrial protein. No significant difference in liver mitochondrial function and capacity for oxidation was observed between db+/db+ and ob/ob mutants, which indicated that these results may be primarily mediated by the genetic factors responsible for obesity and hyperphagia in these mutants, and not by the genetic traits associated with diabetes. These findings may provide a biochemical foundation in support of the thrifty gene hypothesis.
Targets:
['Glutamates', 'Proteins', 'Succinates', 'Glutamic Acid', 'Succinic Acid']
Preds:
b'["RNA, Messenger", "Recombinant Proteins", "Antineoplastic Agents", "Anti-Bacterial Agents", "Biomarkers", "Transcription Factors", "Insulin", "Blood Glucose"]'
Text:
Human alveolar echinococcosis (AE) is caused by the fox tapeworm Echinococcus multilocularis and is usually lethal if left untreated. The current strategy for treating human AE is surgical resection of the parasite mass complemented by chemotherapy with benzimidazole compounds. However, reliable chemotherapeutic alternatives have not yet been developed stimulating the research of new treatment strategies such as the use of medicinal plants. The aim of the current study was to investigate the efficacy of the combination albendazole (ABZ)+thymol on mice infected with E. multilocularis metacestodes. For this purpose, mice infected with parasite material were treated daily for 20 days with ABZ (5 mg/kg), thymol (40 mg/kg) or ABZ (5 mg/kg)+thymol (40 mg/kg) or left untreated as controls. After mice were euthanized, cysts were removed from the peritoneal cavity and the treatment efficacy was evaluated by the mean cysts weight, viability of protoscoleces and ultrastructural changes of cysts and protoscoleces. The application of thymol or the combination of ABZ+thymol resulted in a significant reduction of the cysts weight compared to untreated mice. We also found that although ABZ and thymol had a scolicidal effect, the combination of the two compounds had a considerably stronger effect showing a reduction in the protoscoleces viability of 62%. These results were also corroborated by optical microscopy, SEM and TEM. Protoscoleces recovered from ABZ or thymol treated mice showed alterations as contraction of the soma region, rostellar disorganization and presence of blebs in the tegument. However both drugs when combined lead to a total loss of the typical morphology of protoscoleces. All cysts removed from control mice appeared intact and no change in ultrastructure was detected. In contrast, cysts developed in mice treated with ABZ revealed changes in the germinal layer as reduction in cell number, while the treatment with thymol or the ABZ+thymol combination predominantly showed presence of cell debris. On the other hand, no differences were found in alkaline phosphatase (AP), glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) activities between control and treated mice, indicating the lack of toxicity of the different drug treatments during the experiment. Because combined ABZ+thymol treatment exhibited higher treatment efficiency compared with the drugs applied separately against murine experimental alveolar echinococcosis, we propose it would be a useful option for the treatment of human AE.
Targets:
['Anthelmintics', 'Thymol', 'Albendazole']
Preds:
b'["Anti-Bacterial Agents", "Antineoplastic Agents", "Biomarkers", "Antibodies, Monoclonal", "RNA, Messenger", "Recombinant Proteins", "Biomarkers, Tumor", "Immunoglobulin G"]'
Text:
The anti-inflammatory and antibacterial mechanisms of bone marrow mesenchymal stem cells (MSCs) ameliorating lung injury in chronic obstructive pulmonary disease (COPD) mice induced by cigarette smoke and Haemophilus Parainfluenza (HPi) were studied. The experiment was divided into four groups in vivo: control group, COPD group, COPD+HPi group, and COPD+HPi+MSCs group. The indexes of emphysematous changes, inflammatory reaction and lung injury score, and antibacterial effects were evaluated in all groups. As compared with control group, emphysematous changes were significantly aggravated in COPD group, COPD+HPi group and COPD+HPi+MSCs group (P<0.01), the expression of necrosis factor-kappaB (NF-κB) signal pathway and proinflammatory cytokines in bronchoalveolar lavage fluid (BALF) were increased (P<0.01), and the phagocytic activity of alveolar macrophages was downregulated (P<0.01). As compared with COPD group, lung injury score, inflammatory cells and proinflammatory cytokines were significantly increased in the BALF of COPD+HPi group and COPD+HPi+MSCs group (P<0.01). As compared with COPD+HPi group, the expression of tumor necrosis factor-α stimulated protein/gene 6 (TSG-6) was increased, the NF-κB signal pathway was depressed, proinflammatory cytokine was significantly reduced, the anti-inflammatory cytokine IL-10 was increased, and lung injury score was significantly reduced in COPD+HPi+MSCs group. Meanwhile, the phagocytic activity of alveolar macrophages was significantly enhanced and bacterial counts in the lung were decreased. The results indicated cigarette smoke caused emphysematous changes in mice and the phagocytic activity of alveolar macrophages was decreased. The lung injury of acute exacerbation of COPD mice induced by cigarette smoke and HPi was alleviated through MSCs transplantation, which may be attributed to the fact that MSCs could promote macrophages into anti-inflammatory phenotype through secreting TSG-6, inhibit NF-кB signaling pathway, and reduce inflammatory response through reducing proinflammatory cytokines and promoting the expression of the anti-inflammatory cytokine. Simultaneously, MSCs could enhance phagocytic activity of macrophages and bacterial clearance. Meanwhile, we detected anti-inflammatory and antibacterial activity of macrophages regulated by MSCs in vitro. As compared with RAW264.7+HPi+CSE group, the expression of NF-кB p65, IL-1β, IL-6 and TNF-α was significantly reduced, and the phagocytic activity of macrophages was significantly increased in RAW264.7+HPi+CSE+MSCs group (P<0.01). The result indicated the macrophages co-cultured with MSCs may inhibit NF-кB signaling pathway and promote phagocytosis by paracrine mechanism.
Targets:
['Anti-Bacterial Agents', 'Anti-Inflammatory Agents']
Preds:
b'["RNA, Messenger", "Cytokines", "Tumor Necrosis Factor-alpha", "Biomarkers", "NF-kappa B", "Reactive Oxygen Species", "Antioxidants", "Recombinant Proteins"]'
Text:
Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammatory airway disease punctuated by exacerbations (AECOPD). Subjects with frequent AECOPD, defined by having at least two exacerbations per year, experience accelerated loss of lung function, deterioration in quality of life and increase in mortality. Fibroblast growth factor (FGF)23, a hormone associated with systemic inflammation and altered metabolism is elevated in COPD. However, associations between FGF23 and AECOPD are unknown. In this cross-sectional study, individuals with COPD were enrolled between June 2016 and December 2016. Plasma samples were analyzed for intact FGF23 levels. Logistic regression analyses were used to measure associations between clinical variables, FGF23, and the frequent exacerbator phenotype. Our results showed that FGF23 levels were higher in frequent exacerbators as compared to patients without frequent exacerbations. FGF23 was also independently associated with frequent exacerbations (OR 1.02; 95%CI 1.004-1.04;
Targets:
['Fibroblast Growth Factors', 'fibroblast growth factor 23']
Preds:
b'["Anti-Bacterial Agents", "Antineoplastic Agents", "Biomarkers", "Biomarkers, Tumor", "Immunosuppressive Agents", "Antiviral Agents", "Antibodies, Monoclonal", "C-Reactive Protein"]'
Text:
Fatty acid synthase (FAS), a biosynthetic enzyme, normally functions in the liver to convert dietary carbohydrate to fat, but it is minimally expressed in most other normal adult tissues. FAS is expressed at markedly elevated levels in subsets of human breast, ovarian, and prostate carcinomas that are associated with poor prognoses. During the menstrual cycle, the expression of FAS in the human endometrium is closely linked to the expression of the proliferation antigen Ki-67, estrogen receptor (ER), and progesterone receptor (PR).
Targets:
['Ki-67 Antigen', 'Receptors, Estrogen', 'Receptors, Progesterone', 'Fatty Acid Synthases']
Preds:
b'["RNA, Messenger", "Biomarkers", "Recombinant Proteins", "Transcription Factors", "Insulin", "Cytokines", "DNA-Binding Proteins", "Blood Glucose"]'
Text:
Numerous biochemical experiments have invoked a model in which B-cell antigen receptor (BCR)-Fc receptor for immunoglobulin (Ig) G (FcgammaRII) coclustering provides a dominant negative signal that blocks B-cell activation. Here, we tested this model using quantitative confocal microscopic techniques applied to ex vivo splenic B cells. We found that FcgammaRII and BCR colocalized with intact anti-Ig and that the SH2 domain-containing inositol 5'-phosphatase (SHIP) was recruited to the same site. Colocalization of BCR and SHIP was inefficient in FcgammaRII-/- but not gamma chain-/- splenic B cells. We also examined the subcellular location of a variety of enzymes and adapter proteins involved in signal transduction. Several proteins (CD19, CD22, SHP-1, and Dok) and a lipid raft marker were co-recruited to the BCR, regardless of the presence or absence of FcgammaRII and SHIP. Other proteins (Btk, Vav, Rac, and F-actin) displayed reduced colocalization with BCR in the presence of FcgammaRII and SHIP. Colocalization of BCR and F-actin required phosphatidylinositol (PtdIns) 3-kinase and was inhibited by SHIP, because the block in BCR/F-actin colocalization was not seen in B cells of SHIP-/- animals. Furthermore, BCR internalization was inhibited with intact anti-Ig stimulation or by expression of a dominant-negative mutant form of Rac. From these results, we propose that SHIP recruitment to BCR/FcgammaRII and the resulting hydrolysis of PtdIns-3,4,5-trisphosphate prevents the appropriate spatial redistribution and activation of enzymes distal to PtdIns 3-kinase, including those that promote Rac activation, actin polymerization, and receptor internalization.
Targets:
['Actins', 'Receptors, IgG', 'ShPI proteinase inhibitor', 'Trypsin Inhibitor, Kunitz Soybean', 'Phosphatidylinositol 3-Kinases']
Preds:
b'["RNA, Messenger", "DNA-Binding Proteins", "Transcription Factors", "Membrane Proteins", "Recombinant Proteins", "Recombinant Fusion Proteins", "Carrier Proteins", "Proteins"]'
Text:
Rain gardens have been recommended as a best management practice to treat stormwater runoff. Replicate rain gardens were constructed in Haddam, CT, to treat roof runoff. The objective of this study was to assess whether the creation of a saturated zone in a rain garden improved retention of pollutants. The gardens were sized to store 2.54 cm (1 in) of runoff. Results show high retention of flow; only 0.8% overflowed. Overall, concentrations of nitrite+ nitrate-N, ammonia-N, and total-N (TN) in roof runoff were reduced significantly by the rain gardens. Total-P concentrations were significantly increased by both rain gardens. ANCOVA results show significant reductions in TN (18%) due to saturation. Redox potential also decreased in the saturated garden. Rain garden mulch was found to be a sink for metals, nitrogen, and phosphorus, but rain garden soils were a source for these pollutants. The design used for these rain gardens was effective for flow retention, but did not reduce concentrations of all pollutants even when modified. These findings suggest that high flow and pollutant retention could be achieved with the 2.54 cm design method, but the use of an underdrain could reduce overall pollutant retention.
Targets:
['Environmental Pollutants', 'Nitrates', 'Phosphorus', 'Lead', 'Copper', 'Zinc', 'Nitrogen']
Preds:
b'["Water Pollutants, Chemical", "Anti-Bacterial Agents", "Soil", "Soil Pollutants", "Water", "Culture Media", "Oxygen", "Nitrogen"]'
Text:
In some populations, complete shifts in the genotype of the strain of measles circulating in the population have been observed, with given genotypes being replaced by new genotypes. Studies have postulated that such shifts may be attributable to differences between the fitness of the new and the old genotypes.
Targets:
['Measles Vaccine']
Preds:
b'["Biomarkers", "RNA, Messenger", "DNA", "Transcription Factors", "Insulin", "Anti-Bacterial Agents", "Genetic Markers", "DNA-Binding Proteins"]'
Text:
Following experimental partial hepatectomy of 70% in the rat, there is a semisynchronized surge of hepatocyte proliferation that ceases after 48 to 72 hours. Little is known about the determinants governing the termination of the proliferative phase, although transforming growth factor (TGF) beta has been implicated as an important inhibitor of hepatocyte replication in this model. We previously reported an additional non-TGF-beta inhibitor in medium conditioned by nonparenchymal cells isolated from regenerating liver (CM-NPC-Reg) between 24 and 48 hours after partial hepatectomy, but it was not found in medium conditioned by nonparenchymal cells from unoperated control liver. CM-NPC-Reg suppressed replicative DNA synthesis of primary rat hepatocytes in response to hepatocyte growth factor (HGF), epidermal growth factor (EGF), or TGF-alpha as assessed by 3H-thymidine incorporation. We now present evidence that interleukin (IL)-1 is the major inhibitor of hepatocyte DNA synthesis present in CM-NPC-Reg. IL-1 receptor antagonist abrogated the inhibition, as did antibodies to rat IL-1alpha and -beta; a combination of both antibodies was required, implicating both IL-1alpha and IL-1beta as active constituents in CM-NPC-Reg. To investigate in vivo changes in IL-1 expression, we assessed expression of IL-1alpha messenger RNA (mRNA) in whole rat liver following partial hepatectomy; mRNA was down-regulated at 10 hours in the pre-replicative phase of liver regeneration and up-regulated at 24 hours and 48 hours when proliferation is waning. Rat hepatocytes isolated from liver 24 hours after partial hepatectomy showed increased sensitivity to the inhibitory action of IL-1. Exogenous IL-1beta, administered parenterally to a group of rats at 0 and 12 hours after partial hepatectomy significantly reduced the incorporation of the thymidine analogue, bromodeoxyuridine (BrdU), into hepatocytes at 18 hours. These data indicate that nonparenchymal cells isolated from regenerating rat liver elaborate IL-1, and support the hypothesis that IL-1 plays a role suppressing hepatocyte proliferation and terminating the surge of DNA synthesis induced after partial hepatectomy.
Targets:
['Culture Media, Conditioned', 'Insulin', 'Interleukin-1', 'RNA, Messenger', 'Receptors, Interleukin-1', 'Recombinant Proteins', 'Epidermal Growth Factor', 'DNA']
Preds:
b'["RNA, Messenger", "Transcription Factors", "Cytokines", "DNA-Binding Proteins", "Tumor Necrosis Factor-alpha", "NF-kappa B", "Calcium", "Membrane Proteins"]'
Text:
The glycosylation of alpha-dystroglycan (α-DG) is crucial in maintaining muscle cell membrane integrity. Dystroglycanopathies are identified by the loss of this glycosylation leading to a breakdown of muscle cell membrane integrity and eventual degeneration. However, a small portion of fibers expressing functionally glycosylated α-DG (F-α-DG) (revertant fibers, RF) have been identified. These fibers are generally small in size, centrally nucleated and linked to regenerating fibers. Examination of different muscles have shown various levels of RFs but it is unclear the extent of which they are present. Here we do a body-wide examination of muscles from the FKRP-P448L mutant mouse for the prevalence of RFs. We have identified great variation in the distribution of RF in different muscles and tissues. Triceps shows a large increase in RFs and together with centrally nucleated fibers whereas the pectoralis shows a reduction in revertant but increase in centrally nucleated fibers from 6 weeks to 6 months of age. We have also identified that the sciatic nerve with near normal levels of F-α-DG in the P448Lneo- mouse with reduced levels in the P448Lneo+ and absent in LARGEmyd. The salivary gland of LARGEmyd mice expresses high levels of F-α-DG. Interestingly the same glands in the P448Lneo-and to a lesser degree in P448Lneo+ also maintain considerable amount of F-α-DG, indicating the non-proliferating epithelial cells have a molecular setting permitting glycosylation.
Targets:
['Dag1 protein, mouse', 'Proteins', 'Dystroglycans', 'Fkrp protein, mouse', 'Transferases', 'Large1 protein, mouse', 'N-Acetylglucosaminyltransferases']
Preds:
b'["RNA, Messenger", "DNA", "Recombinant Proteins", "Bacterial Proteins", "Peptides", "DNA Primers", "Membrane Proteins", "Proteins"]'
Text:
The transition states and activation barriers of the 1,3-dipolar cycloadditions of azides with cycloalkynes and cycloalkenes were explored using B3LYP density functional theory (DFT) and spin component scaled SCS-MP2 methods. A survey of benzyl azide cycloadditions to substituted cyclooctynes (OMe, Cl, F, CN) showed that fluorine substitution has the most dramatic effect on reactivity. Azide cycloadditions to 3-substituted cyclooctynes prefer 1,5-addition regiochemistry in the gas phase, but CPCM solvation abolishes the regioselectivity preference, in accord with experiments in solution. The activation energies for phenyl azide addition to cycloalkynes decrease considerably as the ring size is decreased (cyclononyne DeltaG(double dagger) = 29.2 kcal/mol, cyclohexyne DeltaG(double dagger) = 14.1 kcal/mol). The origin of this trend is explained by the distortion/interaction model. Cycloalkynes are predicted to be significantly more reactive dipolarophiles than cycloalkenes. The activation barriers for the cycloadditions of phenyl azide and picryl azide (2,4,6-trinitrophenyl azide) to five- through nine-membered cycloalkenes were also studied and compared to experiment. Picryl azide has considerably lower activation barriers than phenyl azide. Dissection of the transition state energies into distortion and interaction energies revealed that "strain-promoted" cycloalkyne and cycloalkene cycloaddition transition states must still pay an energetic penalty to achieve their transition state geometries, and the differences in reactivity are more closely related to differences in distortion energies than the amount of strain released in the product. Trans-cycloalkene dipolarophiles have much lower barriers than cis-cycloalkenes.
Targets:
['Alkenes', 'Alkynes', 'Azides']
Preds:
b'["Peptides", "Ligands", "Amino Acids", "Polymers", "Proteins", "Peptide Fragments", "DNA", "Water"]'
Text:
Diffusion coefficients of sodium in barium borosilicate glasses having varying concentration of barium were determined by heterogeneous isotopic exchange method using (24)Na as the radiotracer for sodium. The measurements were carried out at various temperatures (748-798 K) to obtain the activation energy (E(a)) of diffusion. The E(a) values were found to increase with increasing barium content of the glass, indicating that introduction of barium in the borosilicate glass hinders the diffusion of alkali metal ions from the glass matrix. The results have been explained in terms of the electrostatic and structural factors, with the increasing barium concentration resulting in population of low energy sites by Na(+) ions and, plausibly, formation of more tight glass network. The leach rate measurements on the glass samples show similar trend.
Targets:
['Barium', 'Sodium']
Preds:
b'["Polymers", "Water", "Biocompatible Materials", "Solutions", "Titanium", "Gels", "Membranes, Artificial", "Solvents"]'
Text:
To study the possible implication of endogenous serotonin in the control of glucagon secretion in man, normal volunteers were subjected to alpha-cell stimulation before and after oral treatment with serotonin antagonists (cyproheptadine and methysergide) and with an inhibitor of serotonin synthesis (para-chlorophenylalanine, PCPA). After administration of cyproheptadine (16 mg daily, for two days) the glucagon responses to arginine (N=12) and to insulin-induced hypoglycemia (N=9) were more marked than in the control experiments (differences between maximal elevations: +165 pg/ml, P less than 0.0001, and +197 pg/ml, P less than 0.02, respectively). After methysergide treatment (9 mg daily, for two days), a potentiation of arginine-provoked glucagon secretion was also observed (+260 pg/ml, P less than 0.002; N=7). Similarly, after PCPA administration (2 g daily, for four days) the alpha-cell responsiveness to both aminogenic (N=12) and hypoglycemic (N=7) stimuli was enhanced (+108 pg/ml, P less than 0.05, and +164 pg/ml, P less than 0.05, respectively). Since glucagon secretion is potentiated by treatment with drugs which either antagonize serotonin action or inhibit its synthesis, the suggestion can be made that endogenous serotonin modulates alpha-cell function in man by acting as an inhibitor.
Targets:
['Insulin', 'Serotonin Antagonists', 'Cyproheptadine', 'Serotonin', 'Glucagon', 'Arginine', 'Fenclonine', 'Methysergide']
Preds:
b'["Insulin", "Blood Glucose", "Norepinephrine", "Calcium", "Cyclic AMP", "Dopamine", "RNA, Messenger", "Acetylcholine"]'
Text:
The multitubulin hypothesis holds that each tubulin isotype serves a unique role with respect to microtubule function. Here we investigate the role of the α-tubulin subunit Tuba1a in adult hippocampal neurogenesis and the formation of the dentate gyrus. Employing birth date labelling and immunohistological markers, we show that mice harbouring an S140G mutation in Tuba1a present with normal neurogenic potential, but that this neurogenesis is often ectopic. Morphological analysis of the dentate gyrus in adulthood revealed a disorganised subgranular zone and a dispersed granule cell layer. We have shown that these anatomical abnormalities are due to defective migration of prospero-homeobox-1-positive neurons and T-box-brain-2-positive progenitors during development. Such migratory defects may also be responsible for the cytoarchitectural defects observed in the dentate gyrus of patients with mutations in TUBA1A.
Targets:
['TUBA1A protein, human', 'Tubulin']
Preds:
b'["RNA, Messenger", "Transcription Factors", "DNA-Binding Proteins", "Membrane Proteins", "Drosophila Proteins", "Nuclear Proteins", "Carrier Proteins", "Nerve Tissue Proteins"]'
Text:
Hepatocellular carcinoma (HCC) is a leading cause of death worldwide. Among the surgical and nonsurgical treatments available, radiofrequency ablation (RFA) and sorafenib have been shown to have efficacy. There is little evidence whether combination of these therapies would have additional benefits.
Targets:
['Phenylurea Compounds', 'Niacinamide', 'Sorafenib']
Preds:
b'["Biomarkers, Tumor", "Antineoplastic Agents", "Immunosuppressive Agents", "Biomarkers", "Adrenal Cortex Hormones", "Antibodies, Monoclonal, Humanized", "Angiogenesis Inhibitors", "Antibodies, Monoclonal"]'
Text:
Postoperative analgesia using propacetamol was studied in 50 patients, 42 +/- 16 years old, after little or moderate surgery. Two grams of propacetamol in intravenous perfusion were administered every six hours. Three scales were utilized to note the intensity of the pain (simple verbal, behavioral and visual analogue scales), before the first injection and, one, four, six hours after. From this study, satisfactory analgesic efficiency and good tolerance of propacetamol were established.
Targets:
['Analgesics', 'Acetaminophen', 'propacetamol']
Preds:
b'["Blood Glucose", "Insulin", "Oxygen", "Anti-Inflammatory Agents, Non-Steroidal", "Calcium", "Analgesics, Opioid", "Hydrocortisone", "Anticoagulants"]'
Text:
The common channel theory suggests that bile reflux, through a common biliopancreatic channel, triggers acute pancreatitis. In the present study, this controversial issue was evaluated using an experimental model of hemorrhagic necrotizing pancreatitis.
Targets:
['Amylases']
Preds:
b'["Biomarkers", "Insulin", "RNA, Messenger", "Transcription Factors", "DNA", "DNA-Binding Proteins", "Antineoplastic Agents", "Calcium"]'
Text:
In this paper, we propose a new 3-D graphical representation of a DNA sequence and prove that it has two properties: (1) there is no circuit in the graph; (2) there exists a one-to-one correspondence between a DNA sequence and the graph. These properties guarantee it has nondegeneracy. Based on the 3-D graphical representation, we characterize a DNA sequence by a 12-dimensional vector whose components are normalized ALE-indexes of the corresponding L/L matrices. The proposed approach is tested by the phylogenetic analysis on three datasets, and the experimental assessment demonstrates its efficiency.
Targets:
['DNA']
Preds:
b'["DNA", "Proteins", "Bacterial Proteins", "Peptides", "Recombinant Proteins", "Ligands", "RNA, Messenger", "Membrane Proteins"]'
Text:
Troponin I is a myofibrillar protein involved in the Ca(2+)-mediated regulation of actomyosin ATPase activity. We report here the isolation and characterization of the gene coding for the slow-muscle-specific isoform of the rat troponin I polypeptide (TpnI). Using restriction mapping, PCR mapping and partial DNA sequencing, we have determined the exon/intron arrangement of this gene. The transcription unit is 10.5-kb long and contains nine exons ranging in size from 4 bp to 330 bp. The rat TpnI(slow) gene is interrupted by large intervening sequences; a 3.3-kb intron separates the 5' untranslated exons from the protein-coding exons. Comparison of the structure of rat TpnI(slow) with that of quail TpnI(fast) reveals that they have a similar intron/exon organization. The 5' untranslated region of the rat gene contains an additional exon, otherwise, the positions of introns and coding exons map to essentially identical regions in both genes.
Targets:
['Troponin', 'Troponin I']
Preds:
b'["RNA, Messenger", "DNA", "DNA-Binding Proteins", "Transcription Factors", "Recombinant Proteins", "Bacterial Proteins", "Proteins", "Carrier Proteins"]'
Text:
Somatomedin-C or insulin-like growth factor I (Sm-C/IGF-I) and insulin-like growth factor II (IGF-II) have been implicated in the regulation of fetal growth and development. In the present study 32P-labeled complementary DNA probes encoding human and mouse Sm-C/IGF-I and human IGF-II were used in Northern blot hybridizations to analyse rat Sm-C/IGF-I and IGF-II mRNAs in poly(A+) RNAs from intestine, liver, lung, and brain of adult rats and fetal rats between day 14 and 17 of gestation. In fetal rats, all four tissues contained a major mRNA of 1.7 kilobases (kb) that hybridized with the human Sm-C/IGF-I cDNA and mRNAs of 7.5, 4.7, 1.7, and 1.2 kb that hybridized with the mouse Sm-C/IGF-I cDNA. Adult rat intestine, liver, and lung also contained these mRNAs but Sm-C/IGF-I mRNAs were not detected in adult rat brain. These findings provide direct support for prior observations that multiple tissues in the fetus synthesize immunoreactive Sm-C/IGF-I and imply a role for Sm-C/IGF-I in fetal development as well as postnatally. The abundance of a 7.5-kb Sm-C/IGF-I mRNA in poly(A+) RNAs from adult rat liver was 10-50-fold higher than in other adult rat tissues which provides further evidence that in the adult rat the liver is a major site of Sm-C/IGF-I synthesis and source of circulating Sm-C/IGF-I. Multiple IGF-II mRNAs of estimated sizes 4.7, 3.9, 2.2, 1.75, and 1.2 kb were observed in fetal rat intestine, liver, lung, and brain. The 4.7- and 3.9-kb mRNAs were the major hybridizing IGF-II mRNAs in all fetal tissues. Higher abundance of IGF-II mRNAs in rat fetal tissues compared with adult tissues supports prior hypotheses, based on serum IGF-II concentrations, that IGF-II is predominantly a fetal somatomedin. IGF-II mRNAs are present, however, in some poly(A+) RNAs from adult rat tissues. The brain was the only tissue in the adult rat where the 4.7- and 3.9-kb IGF-II mRNAs were consistently detected. Some samples of adult rat intestine contained the 4.7- and 3.9-kb IGF-II mRNAs and some samples of adult liver and lung contained the 4.7-kb mRNA. These findings suggest that a role for IGF-II in the adult rat, particularly in the central nervous system, cannot be excluded.
Targets:
['RNA, Messenger', 'Somatomedins', 'Insulin-Like Growth Factor I', 'Insulin-Like Growth Factor II', 'DNA']
Preds:
b'["RNA, Messenger", "Transcription Factors", "Recombinant Proteins", "DNA, Complementary", "DNA-Binding Proteins", "DNA", "DNA Primers", "Membrane Proteins"]'
Text:
A new fluorescent sensor consisting of Cd(II)-cylcen appended aminocoumarin and a substrate peptide for protein kinase A (PKA) has been designed. Upon phosphorylation by PKA, the metal complex moiety binds to a phosphorylated residue, which in turn displaces the coumarin fluorophore, and this event results in ratiometric change of excitation spectrum in neutral aqueous solution.
Targets:
['Anions', 'Coumarins', 'Fluorescent Dyes', 'Peptides', 'Cadmium', 'Water', 'Cyclic AMP-Dependent Protein Kinases']
Preds:
b'["Ligands", "DNA", "Proteins", "Macromolecular Substances", "Adenosine Triphosphate", "Peptides", "Recombinant Proteins", "Membrane Proteins"]'
Text:
The nucleolar Saccharomyces cerevisiae protein Nep1 was previously shown to bind to a specific site of the 18S rRNA and to be involved in assembly of Rps19p into pre-40S ribosome subunits. Here we report on the identification of tma23 and nop6 mutations as recessive suppressors of a nep1(ts) mutant allele and the nep1 deletion as well. Green fluorescent protein fusions localized Tma23p and Nop6p within the nucleolus, indicating their function in ribosome biogenesis. The high lysine content of both proteins and an RNA binding motif in the Nop6p amino acid sequence suggest RNA-binding functions for both factors. Surprisingly, in contrast to Nep1p, Tma23p and Nop6p seem to be specific for fungi as no homologues could be found in higher eukaryotes. In contrast to most other ribosome biogenesis factors, Tma23p and Nop6p are nonessential in S. cerevisiae. Interestingly, the tma23 mutants showed a considerably increased resistance against the aminoglycoside G418, probably due to a structural change in the 40S ribosomal subunit, which could be the result of incorrectly folded 18S rRNA gene, missing rRNA modifications or the lack of a ribosomal protein.
Targets:
['EMG1 protein, S cerevisiae', 'Nop6 protein, S cerevisiae', 'Nuclear Proteins', 'RNA-Binding Proteins', 'Ribosomal Proteins', 'Saccharomyces cerevisiae Proteins', 'Tma23 protein, S cerevisiae']
Preds:
b'["RNA, Messenger", "Transcription Factors", "DNA-Binding Proteins", "DNA Primers", "Bacterial Proteins", "DNA", "Fungal Proteins", "Recombinant Proteins"]'
Text:
Exhaled breath condensate (EBC) contains among a large number of mediators hydrogen peroxide (H2O2) as a marker of airway inflammation and oxidative stress. Similarly EBC pH also changes in respiratory diseases. It was the aim of our investigation to prove if hydrogen peroxide release and changes in pH of EBC changes with exercise.
Targets:
['Hydrogen Peroxide']
Preds:
b'["Biomarkers", "Antioxidants", "Insulin", "RNA, Messenger", "Calcium", "Glucose", "Blood Glucose", "Oxygen"]'
Text:
Abstract Tirasemtiv is a fast skeletal muscle activator that increases the sensitivity of the sarcomere to calcium, increasing the efficiency of muscle contraction when the muscle is stimulated at submaximal contraction frequencies. A previous study showed single doses of tirasemtiv to be well tolerated and associated with potentially important improvements in a variety of functional outcomes. This study determined safety of tirasemtiv when given at doses up to 500 mg daily for three weeks. Tirasemtiv was given as a single daily dose up to 375 mg for two weeks, with and without concomitant riluzole. In a separate cohort, an ascending dose protocol evaluated a total dose of 500 mg daily given in two divided doses. Safety and tolerability were assessed, as well as measures of function, muscle strength and endurance. Results showed that tirasemtiv was well tolerated, with dizziness the most common adverse event. Tirasemtiv approximately doubled the serum concentration of riluzole. Trends were noted for improvement in ALSFRS-R, Maximum Minute Ventilation, and Nasal Inspiratory Pressure. In conclusion, tirasemtiv is well tolerated and can be given safely with a reduced dose of riluzole. Positive trends in multiple exploratory outcome measures support the further study of this agent in ALS.
Targets:
['CK-2017357', 'Imidazoles', 'Pyrazines']
Preds:
b'["Insulin", "Blood Glucose", "Calcium", "Oxygen", "Biomarkers", "Norepinephrine", "Sodium", "Anti-Inflammatory Agents, Non-Steroidal"]'
Text:
An exaggerated release of inflammatory mediators has been implicated in the pathogenesis of necrotizing enterocolitis (NEC). Oral administration of a human immunoglobulin preparation (serum IgA-IgG) has been demonstrated to be an effective prophylaxis for NEC. The aim of the present study was to examine the regulatory effect of a human IgA-IgG preparation on the release of inflammatory cytokines in human monocytes. Our results indicate that the immunoglobulin preparation inhibits TNF-alpha and IL-6 release in monocytes following stimulation with heat-inactivated Hib in a dose-dependent manner. This might have a biological relevance in infants receiving oral immunoglobulin prophylaxis for NEC, since modulation of the release of inflammatory mediators at the level of the gastrointestinal mucosa could interfere with the development of noxious sequelae of acute and/or chronic inflammation initiated by microbial pathogens or their toxins that finally lead to the pathologic changes associated with NEC.
Targets:
['Cytokines', 'Immunoglobulin A', 'Immunoglobulin G', 'Immunoglobulins', 'Interleukin-6', 'Tumor Necrosis Factor-alpha']
Preds:
b'["Cytokines", "Biomarkers", "Anti-Bacterial Agents", "RNA, Messenger", "Tumor Necrosis Factor-alpha", "Antineoplastic Agents", "Antibodies, Monoclonal", "Recombinant Proteins"]'
Text:
Innovative approaches are needed to support patients' adherence to drug therapy. The Real Time Medication Monitoring (RTMM) system offers real time monitoring of patients' medication use combined with short message service (SMS) reminders if patients forget to take their medication. This combination of monitoring and tailored reminders provides opportunities to improve adherence. This article describes the design of an intervention study aimed at evaluating the effect of RTMM on adherence to oral antidiabetics.
Targets:
['Hypoglycemic Agents']
Preds:
b'["Antineoplastic Agents", "Pharmaceutical Preparations", "Antidepressive Agents", "Biomarkers", "Analgesics, Opioid", "Analgesics", "Contrast Media", "Psychotropic Drugs"]'
Text:
Electrical stimulation (ES) is therapeutic to many bone diseases, from promoting fracture regeneration to orthopedic intervention. The application of ES offers substantial therapeutic potential, while optimal ES parameters and the underlying mechanisms responsible for the positive clinical impact are poorly understood. In this study, we assembled an ES cell culture and monitoring device. Mc-3T3-E1 cells were subjected to different frequency to investigate the effect of osteogenesis. Cell proliferation, DNA synthesis, the mRNA levels of osteosis-related genes, the activity of alkaline phosphatase (ALP), and intracellular concentration of Ca2+ were thoroughly evaluated. We found that 100 Hz could up-regulate the mRNA levels of collagen I, collagen II and Runx2. On the contrary, ES could down-regulate the mRNA levels of osteopontin (OPN). ALP activity assay and Fast Blue RR salt stain showed that 100 Hz could accelerate cells differentiation. Compared to the control group, 100 Hz could promote cell proliferation. Furthermore, 1 Hz to 10 Hz could improve calcium deposition in the intracellular matrix. Overall, these results indicate that 100Hz ES exhibits superior potentialities in osteogenesis, which should be beneficial for the clinical applications of ES for the treatment of bone diseases.
Targets:
['Collagen Type I', 'Osteopontin', 'Alkaline Phosphatase', 'Calcium']
Preds:
b'["Collagen", "Antineoplastic Agents", "Calcium", "RNA, Messenger", "Biomarkers", "Recombinant Proteins", "Cytokines", "Oxygen"]'
Text:
While antibiotics are frequently found in the environment, their biodegradability and ecotoxicological effects are not well understood. Ciprofloxacin inhibits active and growing microorganisms and therefore can represent an important risk for the environment, especially for soil microbial ecology and microbial ecosystem services. We investigated the biodegradation of (14)C-ciprofloxacin in water and soil following OECD tests (301B, 307) to compare its fate in both systems. Ciprofloxacin is recalcitrant to biodegradation and transformation in the aqueous system. However, some mineralisation was observed in soil. The lower bioavailability of ciprofloxacin seems to reduce the compound's toxicity against microorganisms and allows its biodegradation. Moreover, ciprofloxacin strongly inhibits the microbial activities in both systems. Higher inhibition was observed in water than in soil and although its antimicrobial potency is reduced by sorption and aging in soil, ciprofloxacin remains biologically active over time. Therefore sorption does not completely eliminate the effects of this compound.
Targets:
['Anti-Bacterial Agents', 'Soil Pollutants', 'Water Pollutants, Chemical', 'Ciprofloxacin']
Preds:
b'["Anti-Bacterial Agents", "Water Pollutants, Chemical", "Biomarkers", "Antineoplastic Agents", "Soil", "Antioxidants", "Oxygen", "Water"]'
Text:
Incubation of gonococci under conditions optimal for autolysis resulted in increased sensitivity and enhancement of the coagglutination reaction of the Phadebact gonococcus test. These conditions included an alkaline pH (pH 8.3) and the presence of divalent cation chelators such as ethylenediaminetetraacetic acid or ethylene glycol-bis(beta-aminoethyl ether)-N,N-tetraacetic acid. Heating cell suspensions at 90 degrees C for 15 min before assay by coagglutination produced a further increase in sensitivity and enhancement of the reaction. Gonococcal lipopolysaccharide was found to be an important antigen in these coagglutination reactions. The detection of lipopolysaccharide was markedly enhanced by the addition of chelating agents.
Targets:
['Antigens, Bacterial', 'Ethylene Glycols', 'Lipopolysaccharides', 'Egtazic Acid', 'Edetic Acid']
Preds:
b'["Calcium", "Oxygen", "Water", "Glucose", "Sodium", "Antioxidants", "Carbon Dioxide", "Potassium"]'
Text:
The purpose of this study was to compare intraosseous graft healing between the doubled flexor tendon (FT) graft and the bone-patellar tendon-bone (BPTB) graft in anterior cruciate ligament (ACL) reconstruction.
Targets:
['Collagen']
Preds:
b'["Biomarkers", "Recombinant Proteins", "Anti-Bacterial Agents", "Collagen", "Calcium", "Oxygen", "RNA, Messenger", "Blood Glucose"]'
Text:
Selection of human cells for resistance to vincristine or doxorubicin often induces overexpression of the multidrug resistance 1 gene (MDR1), which encodes the cell surface P-glycoprotein, as a result of gene amplification or transcriptional activation. Moreover, overexpression of the MDR1 gene has been shown to be associated closely with clinical outcome in various hematological malignancies, including acute myeloid leukemia (AML). However, the precise mechanism underlying overexpression of the MDR1 gene during acquisition of drug resistance remains unclear. We recently described an inverse correlation between the methylation status of CpG sites at the promoter region and expression of the MDR1 gene in malignant cell lines. In this study, we expanded this analysis to 42 clinical AML samples. We adapted a quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay for gene expression and a quantitative PCR after digestion by Hpa II for methylation status of the MDR1 gene. We observed a statistically significant inverse correlation between methylation and MDR1 expression in clinical samples. The hypomethylation status of the MDR1 promoter region might be a necessary condition for MDR1 gene overexpression and establishment of P-glycoprotein-mediated multidrug resistance in AML patients.
Targets:
['ATP Binding Cassette Transporter, Subfamily B, Member 1']
Preds:
b'["RNA, Messenger", "DNA-Binding Proteins", "Transcription Factors", "Tumor Suppressor Protein p53", "RNA, Small Interfering", "NF-kappa B", "Antineoplastic Agents", "Biomarkers, Tumor"]'
Text:
The aim of this study was to assess the relationship between the two types of posttranslational modifications of proteins in RA: glycosylation on the example of carbohydrate-deficient transferrin and citrullination by means of autoantibodies to cyclic citrullinated peptides.
Targets:
['Anti-Citrullinated Protein Antibodies', 'Biomarkers', 'Peptides, Cyclic', 'Transferrin', 'carbohydrate-deficient transferrin', 'cyclic citrullinated peptide', 'Rheumatoid Factor']
Preds:
b'["RNA, Messenger", "DNA", "Transcription Factors", "Bacterial Proteins", "DNA-Binding Proteins", "Proteins", "Recombinant Proteins", "DNA Primers"]'
Text:
The purpose of the present study was to examine the effectiveness of fluorine and silver ions implanted and deposited into acrylic resin (poly(methyl methacrylate)) using a hybrid process of plasma-based ion implantation and deposition. The surface characteristics were evaluated by X-ray photoelectron spectroscopy (XPS), contact angle measurements, and atomic force microscopy. In addition, an antibacterial activity test was performed by the adenosine-5'-triphosphate luminescence method. XPS spectra of modified specimens revealed peaks due to fluoride and silver. The water contact angle increased significantly due to implantation and deposition of both fluorine and silver ions. In addition, the presence of fluorine and silver was found to inhibit bacterial growth. These results suggest that fluorine and silver dual-ion implantation and deposition can provide antibacterial properties to acrylic medical and dental devices.
Targets:
['Anti-Bacterial Agents', 'Ions', 'Resins, Synthetic', 'Fluorine', 'Silver', 'Polymethyl Methacrylate']
Preds:
b'["Polymers", "Biocompatible Materials", "Titanium", "Polyethylene Glycols", "Hydrogels", "Drug Carriers", "Water", "Collagen"]'
Text:
ABSTRACT The goal of this study is to determine whether dermal fibroblasts lacking syndecan-1 (sdc1) show differences in integrin expression and function that could contribute to the delayed skin and corneal wound healing phenotypes seen in sdc-1 null mice. Using primary dermal fibroblasts, we show that after 3 days in culture no differences in alpha-smooth muscle actin were detected but sdc-1 null cells expressed significantly more alphav and beta1 integrin than wildtype (wt) cells. Transforming growth factor beta1 (TGFbeta1) treatment at day 3 increased alphav- and beta1-integrin expression in sdc-1 null cells at day 5 whereas wt cells showed increased expression only of alphav-integrin. Using time-lapse studies, we showed that the sdc-1 null fibroblasts migrate faster than wt fibroblasts, treatment with TGFbeta1 increased these migration differences, and treatment with a TGFbeta1 antagonist caused sdc-1 null fibroblasts to slow down and migrate at the same rate as untreated wt cells. Cell spreading studies on replated fibroblasts showed altered cell spreading and focal adhesion formation on vitronectin and fibronectin-coated surfaces. Additional time lapse studies with beta1- and alphav-integrin antibody antagonists, showed that wt fibroblasts expressing sdc-1 had activated integrins on their surface that impeded their migration whereas the null cells expressed alphav-containing integrins which were less adhesive and enhanced cell migration. Surface expression studies showed increased surface expression of alpha2beta1 and alpha3beta1 on the sdc-1 null fibroblasts compared with wt fibroblasts but no significant differences in surface expression of alpha5beta1, alphavbeta3, or alphavbeta5. Taken together, our data indicates that sdc-1 functions in the activation of alphav-containing integrins and support the hypothesis that impaired wound healing phenotypes seen in sdc-1 null mice could be due to integrin-mediated defects in fibroblast migration after injury.
Targets:
['Actins', 'Fibronectins', 'Integrin alphaV', 'Integrin beta1', 'Sdc1 protein, mouse', 'Syndecan-1', 'Transforming Growth Factor beta1']
Preds:
b'["RNA, Messenger", "Transcription Factors", "DNA-Binding Proteins", "Membrane Proteins", "DNA", "Nuclear Proteins", "Recombinant Proteins", "DNA Primers"]'
Text:
The aim of the current study was to compare sperm quality characteristics of the collared peccary (Pecari tajacu) following freezing in extenders supplemented with whole egg yolk and different concentrations of low-density lipoproteins (LDL). Semen from 11 adult males was obtained by electroejaculation and evaluated for sperm motility, vigor, morphology as well as membrane integrity analyzed by the hypo-osmotic swelling (HOS) test and a fluorescent staining. Moreover, the semen was diluted in a Tris-based extender containing 20% egg yolk (control group) or 5, 10 or 20% LDL (treatment groups). The semen samples were frozen in liquid nitrogen and thawed in a water bath for 60s at 37°C. The treatments did not affect (p>0.05) sperm vigor, morphology or membrane integrity analyzed by the HOS test. However, post-thaw sperm motility was significantly higher (p<0.05) in the extender supplemented with 20% LDL (36.4 ± 5.3%) compared with the egg yolk extender and extender supplemented with 10% LDL. Furthermore, the percentage of membrane-intact frozen-thawed spermatozoa analyzed by the fluorescent staining was significantly higher (p<0.05) in the extender supplemented with 20% LDL (27.4 ± 6.5%) than in the other groups. In conclusion, 20% LDL can be used to substitute the whole egg yolk as a cryoprotective additive for freezing semen of the collared peccary.
Targets:
['Cryoprotective Agents', 'Lipoproteins, LDL']
Preds:
b'["Water Pollutants, Chemical", "Water", "Blood Glucose", "Oxygen", "Glucose", "Lipids", "Amino Acids", "Nitrogen"]'
Text:
The application is in the field of adult neurogenesis and its therapeutic potential. It aims to characterize the activity of apigenin and related compounds on adult neurogenesis in vivo and in vitro. Apigenin and related compounds are derivatives used in food products. They were administered intraperitoneally and orally in adult rodents and assessed for their activity in promoting the generation of neuronal cells and learning and memory performance. They were also tested on adult rat hippocampal-derived neural progenitor and stem cells to assess their neurogenic property. Apigenin and related compounds stimulate adult neurogenesis in vivo and in vitro, by promoting neuronal differentiation. Apigenin promotes learning and memory performance in the Morris water task. The application claims the use of apigenin and related compounds for stimulating adult neurogenesis and for the treatment of neurological diseases, disorders and injuries, by stimulating the generation of neuronal cells in the adult brain.
Targets:
['Apigenin']
Preds:
b'["Cytokines", "Biomarkers", "Transcription Factors", "Dopamine", "RNA, Messenger", "Antineoplastic Agents", "Insulin", "MicroRNAs"]'
Text:
In a biochemical reaction there is generally a change in the binding of hydrogen ions and metal ions. Therefore, calorimetric measurements of enthalpies of reaction have to be adjusted for the enthalpies of reaction of the hydrogen ions and metal ions produced or consumed with the buffer. It can be shown that this yields the standard transformed enthalpy of reaction that determines the change in the apparent equilibrium constant K' (written in terms of sums of concentrations of species of a reactant) with temperature at the chosen pH and concentration of free metal ion. The derivations are based on the assumption that the changes in pH and free metal ion concentrations in the calorimetric experiment are small. This assumption is experimentally realized if a solution is well buffered for hydrogen and metal ions. The derived equations are discussed in terms of the implications they have for the performance and interpretation of calorimetric measurements.
Targets:
['Magnesium']
Preds:
b'["Water", "Polymers", "Proteins", "DNA", "Ligands", "Biocompatible Materials", "Amino Acids", "Titanium"]'
Text:
The present work studied the effect of preoptic catecholamine on acupuncture analgesia. The catecholaminergic terminals were destructed by microinjection of 6-hydroxydopamine into the preoptic area and the destruction was checked by fluorescence histochemical method. The results showed that the destruction of catecholaminergic terminals significantly enhance acupuncture analgesia, suggesting that the reduction of catecholamine content in the preoptic area may enhance acupuncture analgesia.
Targets:
['Hydroxydopamines', 'Receptors, Adrenergic', 'Receptors, Dopamine', 'Oxidopamine', 'Dopamine', 'Norepinephrine']
Preds:
b'["Insulin", "RNA, Messenger", "Calcium", "Dopamine", "Blood Glucose", "Biomarkers", "Glucose", "Norepinephrine"]'
Text:
Patients with a high-output stoma (HOS) (> 2000 ml/day) suffer from dehydration, hypomagnesaemia and under-nutrition. This study aimed to determine the incidence, aetiology and outcome of HOS.
Targets:
['Magnesium']
Preds:
b'["Biomarkers", "Blood Glucose", "Insulin", "Anti-Bacterial Agents", "Oxygen", "Anticoagulants", "Antihypertensive Agents", "Adrenal Cortex Hormones"]'
Text:
Left-sided displacement of the abomasum (LDA) is a common disease in many dairy cattle breeds. A genome-wide screen for QTL for LDA in German Holstein (GH) cows indicated motilin (MLN) as a candidate gene on bovine chromosome 23. Genomic DNA sequence analysis of MLN revealed a total of 32 polymorphisms. All informative polymorphisms used for association analyses in a random sample of 1,136 GH cows confirmed MLN as a candidate for LDA. A single nucleotide polymorphism (FN298674:g.90T>C) located within the first non-coding exon of bovine MLN affects a NKX2-5 transcription factor binding site and showed significant associations (OR(allele) = 0.64; -log(10)P(allele) = 6.8, -log(10)P(genotype) = 7.0) with LDA. An expression study gave evidence of a significantly decreased MLN expression in cows carrying the mutant allele (C). In individuals heterozygous or homozygous for the mutation, MLN expression was decreased by 89% relative to the wildtype. FN298674:g.90T>C may therefore play a role in bovine LDA via the motility of the abomasum. This MLN SNP appears useful to reduce the incidence of LDA in German Holstein cattle and provides a first step towards a deeper understanding of the genetics of LDA.
Targets:
['Transcription Factors', 'Motilin']
Preds:
b'["RNA, Messenger", "DNA", "DNA-Binding Proteins", "Recombinant Proteins", "Transcription Factors", "DNA Primers", "Biomarkers", "Membrane Proteins"]'
Text:
For the last 40 yr, the first line of treatment for anovulation in infertile women has been clomiphene citrate (CC). CC is a safe, effective oral agent but is known to have relatively common antiestrogenic endometrial and cervical mucous side effects that could prevent pregnancy in the face of successful ovulation. In addition, there is a significant risk of multiple pregnancy with CC, compared with natural cycles. Because of these problems, we proposed the concept of aromatase inhibition as a new method of ovulation induction that could avoid many of the adverse effects of CC. The objective of this review was to describe the different physiological mechanisms of action for CC and aromatase inhibitors (AIs) and compare studies of efficacy for both agents for ovulation induction.
Targets:
['Aromatase Inhibitors', 'Clomiphene']
Preds:
b'["Biomarkers", "Anti-Bacterial Agents", "Antineoplastic Agents", "Cytokines", "Antibodies, Monoclonal", "Immunoglobulin G", "Biomarkers, Tumor", "Estrogens"]'
Text:
The Akt/CREB signalling pathway is involved in neuronal survival and protection. Autophagy is also likely to be involved in survival mechanisms. Nimodipine is an L-type calcium channel antagonist that reduces excessive calcium influx during pathological conditions (contributing to its neuroprotective properties). However, the potential role of nimodipine in autophagic and Akt/CREB signalling is not well understood. In addition, little is known about the relationship between autophagic and Akt/CREB signalling. Here, we designed a way to evaluate these issues. Adult male Sprague-Dawley rats were subjected to permanent bilateral occlusion of the common carotid artery (2VO) and randomly divided into three groups: the Vehicle (2VO), Nimodipine10 (2VO+nimodipine 10mg/kg), and Nimodipine20 (2VO+nimodipine 20mg/kg) groups. A fourth group of animals served as Sham controls. Each group was investigated at 4 and 8 weeks post-operatively and assessed using the Morris water maze. Nimodipine significantly alleviated spatial learning and memory impairments and inhibited the loss of neurons in the CA1 region of the hippocampus. These drug effects were more pronounced at 8 weeks than at 4 weeks. The activities of LC3 II p-Akt and p-CREB were examined using immunohistochemistry and western blotting. Suppressing autophagy induced pyramidal cell death without affecting increased pro-survival signalling induced by nimodipine. Nimodipine protected the brain from chronic cerebral hypoperfusion by activating the Akt/CREB signalling pathway. Autophagy has a neuroprotective effect on rats after 2VO. Autophagy is likely part of an integrated survival signalling network involving the Akt/CREB pathway.
Targets:
['CREB1 protein, rat', 'Calcium Channel Blockers', 'Cyclic AMP Response Element-Binding Protein', 'LC3 protein, rat', 'Microtubule-Associated Proteins', 'Neuroprotective Agents', 'Nimodipine', 'Proto-Oncogene Proteins c-akt']
Preds:
b'["RNA, Messenger", "Proto-Oncogene Proteins c-akt", "Transcription Factors", "NF-kappa B", "RNA, Small Interfering", "Nerve Tissue Proteins", "Calcium", "Membrane Proteins"]'
Text:
Several bone resorptive stimuli affect osteoclasts indirectly by modulating the production and release of osteoblastic factors. Using electrophoretic mobility shift assays, we found that not only tumour necrosis factor-alpha (TNF-alpha) but also interleukin-1beta and parathyroid hormone (PTH) caused dose and time-related increases in nuclear factor kappaB (NF-kappaB)-DNA binding in Saos-2 human osteoblastic (hOB) cells. Activation of NF-kappaB by TNF-alpha was reproduced in primary hOBs. In contrast, consistent with their previously reported lack of response to steroid hormones, Saos-2 cells did not respond to 1,25-dihydroxyvitamin D(3). We suggest that NF-kappaB activation in osteoblastic cells constitutes an important pathway in osteoblast-mediated resorptive signalling.
Targets:
['Interleukin-1', 'NF-kappa B', 'Nuclear Proteins', 'Parathyroid Hormone', 'Tumor Necrosis Factor-alpha', 'Vitamin D', '1,25-dihydroxyvitamin D']
Preds:
b'["RNA, Messenger", "Cytokines", "Transcription Factors", "DNA-Binding Proteins", "Tumor Necrosis Factor-alpha", "NF-kappa B", "Membrane Proteins", "Nuclear Proteins"]'
Text:
Intracellular cAMP regulates cell proliferation as a second messenger of extracellular signals in a number of cell types. We investigated, by pharmacological means, whether an increase in intracellular cAMP levels changes proliferation rates of lactotrophs in primary culture, whether there are interactions between signal transduction pathways of cAMP and the growth factor insulin, and where the dopamine receptor agonist bromocriptine acts in the cAMP pathway to inhibit lactotroph proliferation. Rat anterior pituitary cells, cultured in serum-free medium, were treated with cAMP-increasing agents, followed by 5-bromo-2'-deoxyuridine (BrdU) to label proliferating pituitary cells. BrdU-labeling indices indicative of the proliferation rate of lactotrophs were determined by double immunofluorescence staining for PRL and BrdU. Treatment with forskolin (an adenylate cyclase activator) or (Bu)2cAMP (a membrane-permeable cAMP analog) increased BrdU-labeling indices of lactotrophs in a dose- and incubation time-dependent manner. The cAMP-increasing agents were also effective in increasing BrdU-labeling indices in populations enriched for lactotrophs by differential sedimentation. The stimulatory action of forskolin was observed, regardless of concentrations of insulin that were added in combination with forskolin. Inhibition of the action of endogenous cAMP by H89 or KT5720, a protein kinase A inhibitor, attenuated an increase in BrdU-labeling indices by insulin treatment. On the other hand, the specific mitogen-activated protein kinase inhibitor PD98059, which was effective in blocking the mitogenic action of insulin, markedly suppressed the forskolin-induced increase in BrdU-labeling indices. (Bu)2cAMP antagonized not only inhibition of BrdU labeling indices but also changes in cell shape induced by bromocriptine treatment, although forskolin did not have such an antagonizing effect. These results suggest that: 1) intracellular cAMP plays a stimulatory role in the regulation of lactotroph proliferation; 2) cAMP and insulin/mitogen-activated protein kinase signalings require each other for their mitogenic actions; and 3) the antimitogenic action of bromocriptine is, at least in part, caused by inhibition of cAMP production.
Targets:
['Cyclic AMP Response Element-Binding Protein', 'Flavonoids', 'Insulin', 'Colforsin', 'Bromocriptine', 'Bucladesine', 'Cyclic AMP', 'Cyclic AMP-Dependent Protein Kinases', 'Calcium-Calmodulin-Dependent Protein Kinases', '2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one']
Preds:
b'["RNA, Messenger", "Calcium", "Cyclic AMP", "Dopamine", "Nerve Tissue Proteins", "Membrane Proteins", "Adenosine Triphosphate", "Protein Kinase C"]'
Text:
The carbon-14-labeled carbon dioxide that is released by respiration after glucose labeled with carbon-14 is applied to fungal mycelium can be reabsorbed in highly significant amounts by distant mycelium and agar media in the same petri dishes. Atmospheric transfer of carbon-14 must be considered when using labeled organic compounds to study translocation in fungi.
Targets:
['Carbon Isotopes', 'Carbon Dioxide']
Preds:
b'["Water Pollutants, Chemical", "Water", "Culture Media", "Soil", "Soil Pollutants", "Nitrogen", "Carbon", "Sewage"]'
Text:
Cystic fibrosis (CF) is a consequence of defective recognition of the multimembrane spanning protein cystic fibrosis conductance transmembrane regulator (CFTR) by the protein homeostasis or proteostasis network (PN) (Hutt and Balch (2010). Like many variant proteins triggering misfolding diseases, mutant CFTR has a complex folding and membrane trafficking itinerary that is managed by the PN to maintain proteome balance and this balance is disrupted in human disease. The biological pathways dictating the folding and function of CFTR in health and disease are being studied by numerous investigators, providing a unique opportunity to begin to understand and therapeutically address the role of the PN in disease onset, and its progression during aging. We discuss the general concept that therapeutic management of the emergent properties of the PN to control the energetics of CFTR folding biology may provide significant clinical benefit.
Targets:
['CFTR protein, human', 'Cystic Fibrosis Transmembrane Conductance Regulator']
Preds:
b'["Biomarkers", "Proteins", "MicroRNAs", "Transcription Factors", "Antineoplastic Agents", "DNA-Binding Proteins", "Membrane Proteins", "Biomarkers, Tumor"]'
Text:
Excessive bleeding and transfusion increase morbidity and mortality in patients receiving coronary artery bypass grafting (CABG), especially in those exposed to antiplatelet agents.
Targets:
['Antifibrinolytic Agents', 'Platelet Aggregation Inhibitors', 'Tranexamic Acid', 'Clopidogrel', 'Ticlopidine']
Preds:
b'["Immunosuppressive Agents", "Adrenal Cortex Hormones", "Biomarkers", "Anticoagulants", "Antineoplastic Agents", "Antihypertensive Agents", "Antibodies, Monoclonal, Humanized", "Antirheumatic Agents"]'
Text:
Egr-1 is an immediate-early response gene induced transiently and ubiquitously by mitogenic stimuli and also regulated in response to signals that initiate differentiation. The Egr-1 gene product, a nuclear phosphoprotein with three zinc fingers of the Cys2His2 class, binds to the sequence CGCCCCCGC and transactivates a synthetic promoter construct 10-fold in transient-transfection assays. We have analyzed the structure and function of the Egr-1 protein in detail, delineating independent and modular activation, repression, DNA-binding, and nuclear localization activities. Deletion analysis, as well as fusions to the DNA-binding domain of GAL4, indicated that the activation potential of Egr-1 is distributed over an extensive serine/threonine-rich N-terminal domain. In addition, a novel negative regulatory function has been precisely mapped 5' of the zinc fingers: amino acids 281 to 314 are sufficient to confer the ability to repress transcription on a heterologous DNA-binding domain. Specific DNA-binding activity was shown to reside in the three zinc fingers of Egr-1, as predicted by homology to other known DNA-binding proteins. Finally, nuclear localization of Egr-1 is specified by signals in the DNA-binding domain and basic flanking sequences, as determined by subcellular fractionation and indirect immunofluorescence. Basic residues 315 to 330 confer partial nuclear localization on the bacterial protein beta-galactosidase. A bipartite signal consisting of this basic region in conjunction with either the second or third zinc finger, but not the first, suffices to target beta-galactosidase exclusively to the nucleus. Our work shows that Egr-1 is a functionally complex protein and suggests that it may play different roles in the diverse settings in which it is induced.
Targets:
['DNA-Binding Proteins', 'Early Growth Response Protein 1', 'Egr1 protein, mouse', 'Immediate-Early Proteins', 'Nuclear Proteins', 'Oligodeoxyribonucleotides', 'Recombinant Fusion Proteins', 'Repressor Proteins', 'Trans-Activators', 'Transcription Factors']
Preds:
b'["RNA, Messenger", "Transcription Factors", "DNA-Binding Proteins", "Membrane Proteins", "DNA", "Drosophila Proteins", "Recombinant Fusion Proteins", "Recombinant Proteins"]'
Text:
The study of physical organic chemistry in solution is a mature science, over a century old, but over the last 10 years or so, reversible encapsulation has changed the way researchers view molecular interactions. It is now clear that the behavior of molecules in dilute solution is really quite different from their behavior in capsules. Molecules isolated from bulk media in spaces barely large enough to accommodate them and a few neighbors show new phenomena: their activities resemble those of molecules inside biochemical structures--pockets of enzymes, interiors of chaperones, or the inner space of the ribosome--rather than conventional behavior in solution. In this Account, we recount the behavior of molecules in these small spaces with emphasis on structures and reactivities that have not been, and perhaps cannot be, seen in conventional solution chemistry. The capsules self-assemble through a variety of forces, including hydrogen bonds, metal-ligand interactions, and hydrophobic effects. Their lifetimes range from milliseconds to hours, long enough for NMR spectroscopy to reveal what is going on inside. We describe one particular capsule, the elongated shape of which gives rise to many of the effects and unique phenomena. Molecular guests that are congruent to the space of the host can be tightly packed inside and show reduced mobilities such as rotation and translation within the capsule. These mobilities depend strongly on what else is encapsulated with them. We also relate how asymmetric spaces can be created inside the capsule by using a chiral guest. In contrast to the situation in dilute solution, where rapid exchange of solute partners and free molecular motion average out the steric and magnetic effects of chirality, the long lifetimes of the encounters in the capsules magnify the effects of an asymmetric environment. The capsule remains achiral, but the remaining space is chiral, and coencapsulated molecules respond in an amplified way. We probe the various regions of the capsule with guests of different shape. Primary acetylenes, the narrowest of functional groups, can access the tapered ends of the capsule that exclude functions as small as methyl groups. The shape of the capsule also has consequences for aromatic guests, gently bending some and straightening out others. Flexible structures such as normal alkanes can be compressed to fit within the capsule and conform to its shape. We obtain a measure of the internal pressure caused by the compressed guests by determining its effect on the motion of the capsule's components. These forces can also drive a spring-loaded device under the control of external acids and bases. We show that spacer elements can be added to give self-assembled capsules of increased complexity, with 15 or more molecules spontaneously coming together in the assembly. In addition, we analyze the behavior of gases, including the breakdown of ideal gas behavior, inside these capsules. The versatility of these capsule structures points to possible applications as nanoscale reaction chambers. The exploration of these confined spaces and of the molecules within them continues to open new frontiers.
Targets:
['Ligands', 'Metals', 'Organic Chemicals', 'Solutions']
Preds:
b'["Polymers", "Water", "Proteins", "Biocompatible Materials", "Ligands", "Fluorescent Dyes", "Gold", "Collagen"]'
Text:
Three indolocarbazole compounds bearing a tripeptide or a lysine group attached to one of the indole nitrogens via a propylamino chain and two rebeccamycin derivatives bearing a lysine residue on the sugar moiety were synthesised with the aim of improving the binding to DNA and the antiproliferative activities. Four tumour cell lines, from murine L1210 leukemia, human HT29 colon carcinoma, A549 non-small cell lung carcinoma and K-562 leukemia, were used to evaluate the cytotoxicity of the drugs. Their effects on the cell cycle of L1210 cells and their antimicrobial properties against two Gram-positive bacteria Bacillus cereus and Streptomyces chartreusis, a Gram-negative bacterium Escherichia coli and a yeast Candida albicans were also investigated.
Targets:
['12-(2-O-lysyl-4-O-methyl-glucopyranosyl)-6,7,12,13-tetrahydro(5H)-indolo(2,3-a)-pyrrolo(3,4-c)carbazole-5,7-dione dihydrochloride', 'Amino Acids', 'Aminoglycosides', 'Anti-Bacterial Agents', 'Anti-Infective Agents', 'Antineoplastic Agents', 'Carbazoles', 'Indoles', 'Monosaccharides', 'indolo(3,2-b)carbazole', 'rebeccamycin']
Preds:
b'["Recombinant Proteins", "Bacterial Proteins", "Antibodies, Monoclonal", "Antineoplastic Agents", "Peptides", "RNA, Messenger", "DNA", "Peptide Fragments"]'
Text:
A convenient method for isoelectric focusing of intact polymeric IgA and IgM is described. This technique employed composite gels containing 1.0% acrylamide and 0.75% agarose which exhibited minimal electroendosmotic properties. The spectrotypes obtained with mouse IgA myeloma proteins, a human IgA myeloma and rabbit secretory IgA preparations were compared in three gel systems: 5% acrylamide, 0.8% agarose and the composite gel. With respect to resolution of component bands, the composite gel was superior to the other two systems. Hapten binding studies with MOPC-315 IgA and a rabbit secretory IgA anti-DNP antibody indicated that the focused IgA molecules retained their binding site integrity in the composite gel. The pI ranges obtained with microscale sucrose isoelectric focusing and composite gel system showed good correspondence, with the latter exhibiting enhanced resolution. Studies with MOPC-104E IgM revealed improved resolution in the composite gel when compared to the agarose system. Comparison of pI ranges for IgA and IgM immunoglobulins obtained in the present study with those reported previously suggest that IgA spectrotypes are confined to an acidic pI range (3.4--6.4), whereas IgM spectrotypes are not (4.3--8.8).
Targets:
['Acrylamides', 'Gels', 'Haptens', 'Immunoglobulin A', 'Immunoglobulin A, Secretory', 'Immunoglobulin M', 'Myeloma Proteins', 'Polysaccharides', 'Sepharose']
Preds:
b'["Polymers", "Collagen", "Biocompatible Materials", "Polyethylene Glycols", "Antibodies, Monoclonal", "Drug Carriers", "Peptides", "Water"]'
Text:
The frog skin host-defense peptide CPF-SE1 has previously been shown to stimulate the in vitro release of insulin from clonal BRIN-BD11 β-cells. In this study, the in vivo effects of the peptide were investigated in male NIH Swiss mice maintained on a high-fat diet to induce obesity and insulin resistance. Insulin-secretory responses of islets isolated from treated and untreated mice and changes in islet morphology were also examined. Total body fat, plasma glucagon, triglyceride and cholesterol concentrations were measured at the end of the treatment period. Acute intraperitoneal administration of CPF-SE1 (75 nmol body weight) to high-fat fed mice together with glucose (18 mmol/kg body weight) improved glucose tolerance and insulin responses compared to high-fat fed controls. Long term administration of CPF-SE1 (twice-daily administration of 75 nmol/kg body weight for 28 days) did not affect body weight or energy intake but decreased circulating glucose and increased insulin concentrations. Insulin sensitivity and insulin-secretory responses of islets to secretagogues were also significantly improved at 28 days in peptide-treated mice. In addition, significant decreases in plasma glucagon concentrations, pancreatic insulin and glucagon content, islet and beta cell area, body fat and plasma triglyceride levels were observed in CPF-SE1 treated with mice. In conclusion, CPF-SE1 improves beta cell function, insulin sensitivity and glycaemic control whilst reducing total body fat and circulating triglyceride levels. The peptide shows potential for development into an agent for treatment of patients with metabolic syndrome and type 2 diabetes.
Targets:
['Blood Glucose', 'Insulin', 'Lipids', 'Peptides', 'Glucagon']
Preds:
b'["RNA, Messenger", "Biomarkers", "Tumor Necrosis Factor-alpha", "Nitric Oxide", "Cytokines", "Insulin", "Blood Glucose", "Antioxidants"]'
Text:
Genetic and epigenetic alterations play an important role in urothelial cancer pathogenesis. Deeper understanding of these processes could help us achieve better diagnosis and management of this life-threatening disease. The aim of this research was to evaluate the methylation status of selected tumor suppressor genes for predicting BCG response in patients with high grade non-muscle-invasive bladder tumor (NMIBC).
Targets:
['Adjuvants, Immunologic', 'Antineoplastic Agents', 'BCG Vaccine']
Preds:
b'["Biomarkers, Tumor", "Antineoplastic Agents", "Biomarkers", "Contrast Media", "Protein Kinase Inhibitors", "Membrane Proteins", "Antibodies, Monoclonal", "Cisplatin"]'
Text:
The recent identification of an essential RING-H2 finger protein in the SCF E3 ubiquitin ligase complex of budding yeast has uncovered a family of related E3 enzymes, including the other main cell cycle E3 complex, the anaphase promoting complex (APC). Recent insights into APC-dependent proteolysis include a novel protease activity that dissolves cohesion between sister chromatids at anaphase, and a crucial phosphatase, Cdc14, whose release from the nucleolus eliminates cyclin-dependent kinase activity and thereby drives exit from mitosis.
Targets:
['Fungal Proteins', 'Ubiquitin-Protein Ligase Complexes', 'Anaphase-Promoting Complex-Cyclosome', 'SKP Cullin F-Box Protein Ligases', 'Ubiquitin-Protein Ligases', 'Ligases', 'Peptide Synthases']
Preds:
b'["Transcription Factors", "DNA-Binding Proteins", "Saccharomyces cerevisiae Proteins", "Bacterial Proteins", "Recombinant Fusion Proteins", "Arabidopsis Proteins", "Plant Proteins", "RNA, Messenger"]'
Text:
Anti-mitotic compounds (microtubule de-stabilizers) such as vincristine and vinblastine have been shown clinically successful in treating various cancers. However, development of drug-resistance cells limits their efficacies in clinical situations. Therefore, experiments were performed to determine possible drug resistance mechanisms related to the application of anti-mitotic cancer therapy.
Targets:
['Antimitotic Agents', 'Protein Isoforms', 'Tubulin']
Preds:
b'["Antineoplastic Agents", "Anti-Bacterial Agents", "Cytokines", "Protein Kinase Inhibitors", "Antibodies, Monoclonal", "Recombinant Proteins", "Antiviral Agents", "Pharmaceutical Preparations"]'
Text:
A new SERS substrate was prepared using electro-polishing aluminum foils. Based on these high active SERS systems, surface enhanced Raman scattering (SERS) of Azo Dye Sudan were performed and carefully studied based on this highly active SERS substrate. High quality SERS spectra were obtained, which indicates that this kind of coarse aluminum foils is an active SERS substrate. Numbers of additional modes were presented, as well as some split peaks, which may be a consequence of symmetry lowering.
Targets:
['Azo Compounds', 'Coloring Agents', 'Naphthalenes', 'sudan red', 'Sudan Black B', 'Aluminum']
Preds:
b'["Water", "Polymers", "Water Pollutants, Chemical", "Carbon", "Solvents", "Ligands", "Titanium", "Nitrogen"]'
Text:
Graves' ophthalmopathy (GO) is characterized by the infiltration of immune cells into the orbit, a process in which cytokines play a central role. Orbital fibroblasts are potent producers of cytokines on different stimuli. Recently, the authors showed increased expression of the PDGF-B chain in GO orbital tissue. The dimeric PDGF-BB molecule has been described to activate the NF-kappaB pathway, which is well recognized for its role in regulating cytokine production. This study was conducted to determine the role of PDGF-BB in the production of proinflammatory cytokines by orbital fibroblasts in GO.
Targets:
['Angiogenesis Inducing Agents', 'Benzamides', 'Cytokines', 'NF-kappa B', 'Piperazines', 'Platelet-Derived Growth Factor', 'Protein Kinase Inhibitors', 'Proto-Oncogene Proteins c-sis', 'Pyrimidines', 'Becaplermin', 'Imatinib Mesylate', 'PDGF receptor tyrosine kinase', 'Protein-Tyrosine Kinases', 'Receptors, Platelet-Derived Growth Factor']
Preds:
b'["RNA, Messenger", "Cytokines", "Tumor Necrosis Factor-alpha", "Biomarkers", "RNA, Small Interfering", "NF-kappa B", "Reactive Oxygen Species", "Interferon-gamma"]'
Text:
Sulphinpyrazone underwent both reduction to a sulphide and oxidation to a sulphone after parenteral administration to normal Wistar rats. Oral administration was associated with a bioavailability of about 75% and with a 3-fold greater formation of the sulphide. However, no sulphide was detected in the plasma after oral administration of sulphinpyrazone to germ-free (BD/X) rats or normal rats treated with oral antibiotics. In vitro studies showed that the major site of reduction of sulphinpyrazone was the contents of the hind gut with little activity detected in the liver or other tissues. The sulphide was oxidised in vivo to sulphinpyrazone and small amounts of sulphone, while the latter underwent only slight reduction to sulphinpyrazone, but did not give detectable levels of the sulphide. These data suggest that the gut microflora are the main site of reduction of sulphinpyrazone in the rat in vivo.
Targets:
['Sulfides', 'Sulfones', 'Sulfinpyrazone']
Preds:
b'["Antioxidants", "Plant Extracts", "Ethanol", "Drug Combinations", "Antineoplastic Agents", "Zinc", "Glutathione", "Anti-Bacterial Agents"]'
Text:
Liver fibrosis leads to liver cirrhosis and failure, and no effective treatment is currently available. Growing evidence supports a link between mitochondrial dysfunction and liver fibrogenesis and mitochondrial quality control-based therapy has emerged as a new therapeutic target. We investigated the protective mechanisms of melatonin against mitochondrial dysfunction-involved liver fibrosis, focusing on mitophagy and mitochondrial biogenesis. Rats were treated with carbon tetrachloride (CCl4) dissolved in olive oil (0.5 mL/kg, twice a week, i.p.) for 8 wk. Melatonin was administered orally at 2.5, 5, and 10 mg/kg once a day. Chronic CCl4 exposure induced collagen deposition, hepatocellular damage, and oxidative stress, and melatonin attenuated these increases. Increases in mRNA and protein expression levels of transforming growth factor β1 and α-smooth muscle actin in response to CCl4 were attenuated by melatonin. Melatonin attenuated hallmarks of mitochondrial dysfunction, such as mitochondrial swelling and glutamate dehydrogenase release. Chronic CCl4 exposure impaired mitophagy and mitochondrial biogenesis, and melatonin attenuated this impairment, as indicated by increases in mitochondrial DNA and in protein levels of PTEN-induced putative kinase 1 (PINK1); Parkin; peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α); nuclear respiratory factor 1 (NRF1); and transcription factor A, mitochondrial (TFAM). CCl4-mediated decreases in mitochondrial fission- and fusion-related proteins, such as dynamin-related protein 1 (DRP1) and mitofusin 2, were also attenuated by melatonin. Moreover, melatonin induced AMP-activated protein kinase (AMPK) phosphorylation. These results suggest that melatonin protects against liver fibrosis via upregulation of mitophagy and mitochondrial biogenesis, and may be useful as an anti-fibrotic treatment.
Targets:
['Antioxidants', 'Carbon Tetrachloride', 'Melatonin']
Preds:
b'["RNA, Messenger", "Tumor Necrosis Factor-alpha", "Cytokines", "Biomarkers", "Nitric Oxide", "Reactive Oxygen Species", "Antioxidants", "NF-kappa B"]'
Text:
CD26 is a T cell activation antigen that contains dipeptidyl peptidase IV activity and is known to bind adenosine deaminase. The mechanism by which CD26 costimulation potentiates T cell receptor-mediated T cell activation, leading to subsequent exertion of T cell effector function, is still not clearly defined. In this article, we demonstrate that CD26 localizes into lipid rafts, and targeting of CD26 to rafts is necessary for signaling events through CD26. Importantly, aggregation of CD26 by anti-CD26 mAb crosslinking also causes coaggregation of CD45 into rafts. Moreover, we show that CD26 directly binds to the cytoplasmic domain of CD45. Our results therefore indicate a mechanism whereby CD26 engagement promotes aggregation of lipid rafts and facilitates colocalization of CD45 to T cell receptor signaling molecules p56(Lck), ZAP-70, and TCRzeta, thereby enhancing protein tyrosine phosphorylation of various signaling molecules and subsequent interleukin-2 production.
Targets:
['Cross-Linking Reagents', 'Tyrosine', 'Leukocyte Common Antigens', 'Dipeptidyl Peptidase 4']
Preds:
b'["Transcription Factors", "RNA, Messenger", "DNA-Binding Proteins", "Protein-Serine-Threonine Kinases", "Membrane Proteins", "Nuclear Proteins", "RNA, Small Interfering", "Recombinant Proteins"]'
Text:
It is shown that solution composition during immobilization plays a critical role in the properties of fibronectin (FN) surfaces and their bioactivity towards insulinoma (INS-1) cell function. X-ray photoelectron spectroscopy revealed FN grafting onto low-fouling carboxymethyl-dextran (CMD) surfaces was successful with solutions composed of 10 μM CaCl(2), 10 μM MgCl(2), 10 μM MnCl(2), and 10 μM and 1mM NaCl, but unsuccessful with those made of 150 mM NaCl or 1× PBS. Circular dichroism and photon correlation spectroscopy revealed that regardless of solution composition, no measurable differences in free FN conformation prevail. AFM imaging of FN-CMD revealed, while there are no quantitative differences in surface roughness, there are some subtle qualitative differences in topography. FN surface immobilization scheme does not influence INS-1 cell growth after 3 and 7 days regardless of the underlying substrate or solution composition. INS-1 cell insulin secretion in response to glucose is affected by the substrate and solution composition during FN immobilization.
Targets:
['Dextrans', 'Fibronectins', 'Insulin', 'Solutions', 'carboxymethyl dextran', 'Glucose']
Preds:
b'["Water", "Glucose", "Culture Media", "Polyethylene Glycols", "Recombinant Proteins", "Oxygen", "Calcium", "Polymers"]'
Text:
Strobilanthes crispus has been traditionally used as antidiabetic, anticancer, diuretic, antilytic and laxative agent. However, cytotoxicity and antiproliferative effect of S. crispus is still unclear.
Targets:
['Antineoplastic Agents, Phytogenic', 'Hormones', 'Plant Extracts', 'Tumor Suppressor Protein p53', 'X-Linked Inhibitor of Apoptosis Protein', 'XIAP protein, human', 'Cytochromes c', 'Caspase 3', 'Caspase 7']
Preds:
b'["Anti-Bacterial Agents", "Antineoplastic Agents", "Plant Extracts", "Antioxidants", "Antiviral Agents", "Anti-Infective Agents", "Anti-Inflammatory Agents", "Culture Media"]'
Text:
A virus causing Jembrana disease in Bali cattle (Bos javanicus) was demonstrated to have characteristics of a retrovirus. Reverse transcriptase activity was detected in virus purified by sucrose gradient centrifugation. Electron microscopic examination of tissue from the affected cattle indicated that the virus matured by C-type budding through the plasma membrane and into intracytoplasmic vacuoles of cells in lymphoid tissue, with the formation of circular enveloped virus particles ranging in diameter from 96 to 124 nm with an eccentric nucleoid. Western immunoblotting using sera from recovered animals demonstrated virus proteins of M(r) 100K, 45K, 42K, 33K, 26K, 16K and 14K. The 26K protein of Jembrana disease virus cross-reacted in Western blots with the 26K capsid protein of bovine immunodeficiency virus (BIV). The apparent morphogenesis, protein structure and antigenic relationship with BIV suggested the virus was a lentivirus.
Targets:
['Antibodies', 'Antibodies, Monoclonal', 'Antibodies, Viral', 'Antigens, Viral', 'RNA-Directed DNA Polymerase']
Preds:
b'["Recombinant Proteins", "DNA, Bacterial", "Antibodies, Monoclonal", "DNA", "Bacterial Proteins", "Epitopes", "DNA, Viral", "RNA, Messenger"]'
Text:
Herbivorous insects are widespread and often serious constraints to crop production. The use of insect-resistant crops is a very effective way to control insect pests in agriculture, and the development of such crops can be greatly enhanced by knowledge on plant resistance mechanisms and the genes involved. Plants have evolved diverse ways to cope with insect attack that has resulted in natural variation for resistance towards herbivorous insects. Studying the molecular genetics and transcriptional background of this variation has facilitated the identification of resistance genes and processes that lead to resistance against insects. With the development of new technologies, molecular studies are not restricted to model plants anymore. This review addresses the need to exploit natural variation in resistance towards insects to increase our knowledge on resistance mechanisms and the genes involved. We will discuss how this knowledge can be exploited in breeding programmes to provide sustainable crop protection against insect pests. Additionally, we discuss the current status of genetic research on insect-resistance genes. We conclude that insect-resistance mechanisms are still unclear at the molecular level and that exploiting natural variation with novel technologies will contribute greatly to the development of insect-resistant crop varieties.
Targets:
['DNA, Plant']
Preds:
b'["Proteins", "Pharmaceutical Preparations", "Antineoplastic Agents", "Bacterial Proteins", "Anti-Bacterial Agents", "Ligands", "Plant Proteins", "MicroRNAs"]'
Text:
Blebbistatin, a potent inhibitor of myosin II, has inhibiting effects on Ca(2+)-induced contraction and contractile filament organization without affecting the Ca(2+)-sensitivity to the force and phosphorylation level of myosin regulatory light chain (MLC20) in skinned (cell membrane permeabilized) taenia cecum from the guinea pig (Watanabe et al., Am J Physiol Cell Physiol. 2010; 298: C1118-26). In the present study, we investigated blebbistatin effects on the contractile force of skinned tracheal muscle, in which myosin filaments organization is more labile than that in the taenia cecum. Blebbistatin at 10 μM or higher suppressed Ca(2+)-induced tension development at any given Ca(2+) concentration, but had little effects on the Ca(2+)- induced myosin light chain phosphorylation. Also blebbistatin at 10 μM and higher significantly suppressed GTP-γS-induced "sensitized" force development. Since the force inhibiting effects of blebbistatin on the skinned trachea were much stronger than those in skinned taenia cecum, blebbistatin might directly affect myosin filaments organization.
Targets:
['Calcium Channel Blockers', 'Heterocyclic Compounds, 4 or More Rings', 'blebbistatin', "Guanosine 5'-O-(3-Thiotriphosphate)", 'Myosin Type II', 'Calcium']
Preds:
b'["Calcium", "RNA, Messenger", "Membrane Proteins", "Recombinant Proteins", "Carrier Proteins", "Protein-Serine-Threonine Kinases", "DNA-Binding Proteins", "Peptide Fragments"]'
Text:
Lysosomal phospholipid storage disorder in lung tissue was observed during chronic treatment with amphiphilic amine drugs. The prevailing and widely accepted mechanism of phospholipidosis is that amphiphilic drugs bind to phospholipids and make the phospholipids unsuitable substrates for the action of phospholipases. We investigated hydrophobic and hydrophilic binding of fifteen drugs to the phospholipid storage organelle, lung lamellar bodies, isolated from male Sprague-Dawley rats. Hydrophobic interactions were studied using 1,6-diphenyl-1,3,5-hexatriene as a fluorescent probe and hydrophilic binding was studied using 1-anilino-8-naphthalene sulfonate as a fluorescent probe. The binding parameters were calculated using Scatchard equations. Of the fifteen drugs used, nine drugs bound to the hydrophobic moiety of lamellar bodies. The order of binding capacities was promethazine greater than chloramphenicol greater than amiodarone = desethylamiodarone greater than promazine greater than chlorpromazine greater than trimipramine greater than propranolol greater than imipramine much greater than chlorphentermine, phentermine, chloroquine, chlorimipramine, cyclizine and chlorcyclizine. Two binding affinities were calculated for all the bound drugs. Binding affinities to hydrophilic sites of lamellar bodies were calculated in terms of emission coefficients for 1-anilino-8-naphthalene sulfonate in the presence of drugs. Hydrophilic binding was in the order chlorpromazine greater than chlorimipramine greater than promazine greater than trimipramine greater than imipramine greater than chlorcyclizine greater than propranolol greater than promethazine greater than chlorphentermine greater than cyclizine greater than phentermine greater than chloroquine much greater than chloramphenicol, amiodarone and desethylamiodarone. The binding affinities of chlorinated analogs were stronger to hydrophilic sites when compared to the parent compound. Amiodarone, which is known to induce pulmonary phospholipidosis and its major non-polar metabolite, desethylamiodarone, bound strongly to lamellar bodies. These two drugs also inhibit phospholipases in vitro. The drugs with weak phospholipidosis-inducing capacity and extensive in vivo metabolism, namely, imipramine, chlorpromazine and promazine, also bound strongly to lamellar bodies with hydrophilic as well as hydrophobic interactions. On the other hand, chloroquine, which is known to induce phospholipidosis and to inhibit phospholipases, did not bind to lamellar bodies. Two major conclusions could be drawn from this study: one is that the drug interactions with isolated lamellar bodies could be studied using membrane fluorescence probes, 1,6-diphenyl-1,3,5-hexatriene and 1-anilino-8-naphthalene sulfonate; second is that the amphiphilic drugs bind to lamellar bodies, as reported for phospholipid vesicles, and the binding of drugs to lamellar bodies could be correlated with their phospholipidosis-inducing capacity only if
Targets:
['Amines', 'Anilino Naphthalenesulfonates', 'Phospholipids', 'Diphenylhexatriene']
Preds:
b'["Calcium", "Anti-Bacterial Agents", "Amino Acids", "Enzyme Inhibitors", "Glucose", "Peptides", "Recombinant Proteins", "Adenosine Triphosphate"]'
Text:
(+/-)-Mexiletine is a class Ib antiarrhythmic drug useful in the treatment of premature ventricular contractions. It is predominantly metabolized by the liver with less than 15% being excreted in urine as unchanged drug. p-Hydroxymexiletine (PHM) and hydroxymethylmexiletine (HMM) are the two major mammalian metabolites. The purpose of our study was to develop a stereospecific high-performance liquid chromatographic (HPLC) method to determine whether the fungus, Cunninghamella echinulata (UAMH 4145), was able to biosynthesize these same two metabolites from the substrate (+/-)-mexiletine. Furthermore, it was desirable to ascertain whether metabolism of mexiletine was stereoselective. The method requires pre-column derivatization of the drug and metabolites with S-(+)-1-(1-naphthyl)ethyl isocyanate (NEIC) followed by normal-phase HPLC. Mexiletine, PHM, HMM and (+/-)-1-(4-hydroxyphenoxy)-3-isopropylaminopropan-2-ol (internal standard) were extracted from microbial broth using two volumes of diethyl ether after basifying with sodium carbonate. The combined ether extracts were evaporated to dryness, using a gentle stream of nitrogen, and reconstituted in 0.3 ml of chloroform to which was added 0.075 ml of NEIC (0.1%, v/v, in chloroform). This solution was immediately evaporated to dryness under a nitrogen stream. The residue was reconstituted with 0.220 ml of chloroform and 0.030 ml of n-butylamine (0.33%, v/v, in chloroform) and injected into the HPLC system.
Targets:
['Culture Media', 'Indicators and Reagents', 'Mexiletine', '6-hydroxymethylmexiletine', '4-hydroxymexiletine']
Preds:
b'["Anti-Bacterial Agents", "Indicators and Reagents", "Phenols", "Drug Combinations", "Solvents", "Ethanol", "Buffers", "Amino Acids"]'
Text:
The third cytoplasmic loop (C3) of bovine rhodopsin (Rh) is an important site for its interaction with G-protein transducin. The tertiary structure of Rh was determined by X-ray crystallography, although the local conformation around the C3 loop (residues: 236-240) was not visible in electron density maps. We constructed a canonical conformation ensemble at 310 K for the C3 loop (residues: 227-244) using a multicanonical molecular dynamics simulation, and predicted several putative conformations. The conformation ensemble was classified by principal component analysis into several distinct structural clusters, some of which could provide the putative structural models of Rh and the activated state of Rh.
Targets:
['Peptide Fragments', 'Rhodopsin']
Preds:
b'["Bacterial Proteins", "DNA", "Recombinant Proteins", "Ligands", "Saccharomyces cerevisiae Proteins", "Fungal Proteins", "Amino Acids", "Proteins"]'
Text:
In human and rodent models, endocrine disrupting chemicals (EDCs) interfere with the development of cognition and behaviors. Fenvalerate is a potential EDC. The purpose of this study was to examine whether pubertal fenvalerate exposure altered behavioral development. Mice were orally administered with either vehicle or fenvalerate (7.5 or 30 mg/kg/day) from postnatal day (PND) 28 to PND56. Learning and memory were assessed by Morris Water Maze. Aggressive performance was evaluated by aggressive behavior test. Anxiety-related activities were detected by three tests: open-field, plus-maze and black-white alley. Sensorimotor function was analyzed using beam walking and tightrope. Results found that the impairment for spatial learning and memory was more severe in fenvalerate-exposed female mice than in male mice. In addition, pubertal fenvalerate exposure inhibited aggressive behavior in males. Moreover, pubertal fenvalerate exposure increased anxiety activities in females. Altogether, these results suggest that pubertal fenvalerate exposure impairs spatial cognition and behavioral development in a gender-dependent manner. These findings identify fenvalerate as candidate environmental risk factors for cognitive and behavioral development, especially in the critical period of development.
Targets:
['Endocrine Disruptors', 'Insecticides', 'Nitriles', 'Pyrethrins', 'fenvalerate']
Preds:
b'["Biomarkers", "RNA, Messenger", "Blood Glucose", "Tumor Necrosis Factor-alpha", "Insulin", "Cytokines", "Dopamine", "Collagen"]'
Text:
The ability to spatially pattern biochemical signals into nanofibrous materials using thiol-ene reactions of thiolated molecules to presented norbornene groups is demonstrated. This approach is used to pattern three molecules independently within one scaffold, to pattern molecules through the depth of a scaffold, and to spatially control cell adhesion and morphology.
Targets:
['Biocompatible Materials', 'Bridged Bicyclo Compounds', 'Hydrogels', 'bornylene', 'Hyaluronic Acid']
Preds:
b'["Proteins", "Water", "Ligands", "DNA", "Bacterial Proteins", "Polymers", "Plant Proteins", "Oxygen"]'
Text:
We studied how tryptophan methyl ester and related compounds inhibit binding of estrone to rat alpha-fetoprotein and find that: (a) like chymotrypsin, alpha-fetoprotein binds tryptophan esters with higher affinity than tryptophan or its amides; (b) the affinity of alpha-fetoprotein for tryptophan methyl ester is 3.7 . 10(-4) M, which is close to the affinity of chymotrypsin (10(-4) M); (c) alpha-fetoprotein binding of tryptophan methyl ester is stereoselective and pH dependent. All of these observations suggest that there is a specific interaction between alpha-fetoprotein and the chymotrypsin substrate, tryptophan methyl ester, and that rat alpha-fetoprotein contains a site with some structural similarities to the catalytic site in chymotrypsin. Since we also find that tryptophan methyl ester is a competitive inhibitor of estrone binding to alpha-fetoprotein, it is possible that the protease substrate binding site on alpha-fetoprotein is spatially close to the estrone binding site.
Targets:
['alpha-Fetoproteins', 'Estrone', 'tryptophan methyl ester', 'Tryptophan', 'Chymotrypsin']
Preds:
b'["Recombinant Proteins", "DNA", "Calcium", "Amino Acids", "Peptides", "Enzyme Inhibitors", "Adenosine Triphosphate", "Peptide Fragments"]'
Text:
1. Developmental enzyme alterations were investigated in skeletal muscle of the hereditary progressive muscular dystrophy (PMD) mice of C57BL/6J strain. 2. Enzymes examined were classified into three groups according to changes of activities in dystrophy muscle during ageing. Activities of creatine kinase (EC 2.7.3.2), pyruvate kinase (EC 2.7.1.40), glycogen phosphorylase (EC 2.4.1.1), and fructose-biphosphate aldolase (EC 4.1.2.13), each of which had the respective muscle specific isoenzyme of extremely high activity in normal adult skeletal muscle, decreased rapidly in dystrophy muscle from the early stage of the disease with ageing. Activities of glycogen synthase (EC 2.4.1.11) and hexokinase (EC 2.7.1.1) were higher in dystrophy muscle in the early stage but decreased gradually to lower levels than those in the control with ageing. Activities of glucose-6-phosphate dehydrogenase (EC 1.1.1.49) were always much higher in dystrophy muscle than in the control, with no relation to ageing. 3. Isoenzymes of creatine kinase, pyruvate kinase and phosphorylase in dystrophy muscle were mainly the muscle types, indicating that muscle differentiation was not blocked profoundly even in dystrophy muscle. In limited cases, especially in the early stage of the disease, very weak activities of the non-muscle fetal type isoenzymes of creatine kinase and phosphorylase were detected, apparently associated with partial muscle regeneration in dystrophy muscle.
Targets:
['Isoenzymes', 'Phosphorylases', 'Glycogen Synthase', 'Hexokinase', 'Pyruvate Kinase', 'Creatine Kinase', 'Fructose-Bisphosphate Aldolase']
Preds:
b'["Calcium", "Glucose", "Adenosine Triphosphate", "RNA, Messenger", "Sodium", "Insulin", "Potassium", "Isoenzymes"]'
Text:
Thyroid hormone and retinoic acid (RA) are essential for normal neural development in vivo, yet all in vitro differentiation strategies of embryonic stem (ES) cells use only RA. We developed a novel differentiation strategy of mouse ES cells using T(3). A dominant-negative knock-in point mutation (P398H) was introduced into the thyroid hormone receptor alpha gene to determine the influence of T(3) on ES cell differentiation. Differentiation promoted by T(3) (1 nM), RA (1 microM), or combined T(3)/RA was assessed in wild-type (wt) and mutant (m) ES cells on the basis of neuronal-specific gene expression and cell cycle. T(3) alone stimulated neural differentiation in a similar fashion as that seen with RA in both wtES and mES cells. Expression of neurogranin and Ca(2+)/calmodulin-dependent kinase IV mRNA (identified in vivo as T(3)-regulated genes), however, was markedly reduced in mES, compared with wtES cells. RA treatment enhanced apoptosis, significantly greater than that seen with T(3) stimulation. T(3) treatment given with RA significantly reduced the apoptotic effects of RA, an effect not seen in mES cells. T(3)-induced ES cell neural differentiation of thyroid hormone alpha mutant and wtES cells provides an in vitro model to study T(3)-dependent gene regulation in neural development. This system could also be used to identify novel T(3)-regulated genes. The modulation of the apoptotic effects of RA by T(3) may have implications for stem cell therapy.
Targets:
['DNA-Binding Proteins', 'Genetic Markers', 'Neurofilament Proteins', 'RNA, Messenger', 'Receptors, Cytoplasmic and Nuclear', 'Receptors, Thyroid Hormone', 'Thyroid Hormones', 'Triiodothyronine', 'Tretinoin']
Preds:
b'["RNA, Messenger", "Transcription Factors", "Tumor Necrosis Factor-alpha", "Cytokines", "DNA-Binding Proteins", "Recombinant Proteins", "RNA, Small Interfering", "Biomarkers"]'
Text:
Mast cells contain granules packed with a mixture of proteins that are released on degranulation. The proteoglycan serglycin carries an array of glycosaminoglycan (GAG) side chains, sometimes heparin, sometimes chondroitin or dermatan sulphate. Tight packing of granule proteins is dependent on the presence of serglycin carrying these GAGs. The GAGs of mast cells were most intensively studied in the 1970s and 1980s, and though something is known about the fine structure of chondroitin sulphate and dermatan sulphate in mast cells, little is understood about the composition of the heparin/heparan sulphate chains. Recent emphasis on the analysis of mast cell heparin from different species and tissues, arising from the use of this GAG in medicine, lead to the question of whether variations within heparin structures between mast cell populations are as significant as variations in the mix of chondroitins and heparins.
Targets:
['Proteoglycans', 'Vesicular Transport Proteins', 'serglycin', 'Dermatan Sulfate', 'Heparin', 'Chondroitin Sulfates', 'Peptide Hydrolases']
Preds:
b'["RNA, Messenger", "Recombinant Proteins", "Antibodies, Monoclonal", "Bacterial Proteins", "Proteins", "Membrane Proteins", "DNA", "Peptide Fragments"]'
Text:
Limited penetration of antineoplastic agents is one of the contributing factors for chemotherapy failure of many solid tumors. In order to enhance drug penetration into solid cancer, especially, into the avascular regions inside tumors, we proposed cyclic RGD peptide functionalized PEGylated poly(trimethylene carbonate) nanoparticles (c(RGDyK)-NP). By integrin-mediated transcytosis and enhanced drug permeation, c(RGDyK)-NP could access the neoplastic cells distant from blood vessels, and consequently, avoiding the capability of cancer regeneration from these tumor cells. In the present study, the solid tumor penetration, homing specificity and anticancer efficacy were evaluated both on the ex vivo 3D tumor spheroids and on the subcutaneous xenograft mice model. In comparison with conventional nanoparticles (NP/PTX) and Taxol, c(RGDyK)-NP/PTX showed the strongest penetration and accumulation into 3D tumor spheroids, a marked tumor-homing specificity in vivo and the greatest tumor growth inhibitory effect in vitro and in vivo. Histochemistry analysis revealed that no obvious histopathological abnormalities or lesions were observed in major organs after intravenous administration with the treatment doses. In conclusion, cyclic RGD peptide-conjugated PEG-PTMC nanoparticle could facilitate drug penetration and accumulation in tumor tissues and may be a promising vehicle for enhancing the chemotherapy of solid cancers.
Targets:
['Antineoplastic Agents', 'Dioxanes', 'Integrins', 'Polymers', 'polytrimethylene carbonate', 'Polyethylene Glycols', 'Paclitaxel']
Preds:
b'["Antineoplastic Agents", "RNA, Messenger", "Cytokines", "Tumor Necrosis Factor-alpha", "Antibodies, Monoclonal", "Recombinant Proteins", "Biomarkers", "Antioxidants"]'
Text:
Two infants presented with a salt-losing syndrome, the presenting features of which were subtle. One case appeared to be transient. Deficient production of aldosterone was shown by plasma renin activity and plasma aldosterone profile. Gas chromatography-mass spectrometry of urine indicated a defect in 18-dehydrogenation of 18-hydroxycorticosterone. Treatment with salt supplements and 9alpha-fludrocortisone reversed the salt-losing state and in one case treatment was later stopped. Although the disease may appear transient, the biochemical defect is persistent and for adequate growth a positive salt-balance is necessary.
Targets:
['Sodium Chloride', 'Aldosterone', '18-Hydroxycorticosterone', 'Renin', 'Corticosterone']
Preds:
b'["Oxygen", "Calcium", "Anti-Bacterial Agents", "Collagen", "Recombinant Proteins", "Hydrocortisone", "Biomarkers", "Drug Combinations"]'
Text:
Insufficiency fracture of the clavicle is a rare complication that can occur in patients who have undergone neck dissection. The differential diagnoses of this entity include recurrent metastatic disease, post-radiation sarcoma, trauma, and infection. We reviewed the images of seven lesions in six patients who had undergone neck surgery and had stress fractures of the clavicle without tumor metastasis. All lesions involved clavicular fractures and had mass formation around the bone fracture. Two lesions mainly comprised sternoclavicular joint (SCJ) surface destruction, and six mainly comprised fractures of the proximal end of the clavicle. Five (71%) had increased clavicular bone density. Six lesions (86%) had fluid collection in the SCJ, and three of these lesions (in two patients) were complicated by infection. fluorodeoxyglucose-positron emission tomography (FDG-PET) showed relatively weak uptake (SUVmax 0.96-3.09).
Targets:
['Contrast Media', 'Radiopharmaceuticals', 'Fluorodeoxyglucose F18']
Preds:
b'["Biomarkers, Tumor", "Contrast Media", "Anti-Bacterial Agents", "Biomarkers", "Antineoplastic Agents", "Autoantibodies", "Radiopharmaceuticals", "Cisplatin"]'
Text:
Epinephrine, isoproterenol and norepinephrine (10(-6) M - 10(-4) M) reduced the short-circuit current (SCC) across the isolated rabbit iris-ciliary body when added to the blood side (pigmented layer) bathing solution but were without effect when added to the aqueous side (non-pigmented layer) bathing solution. The effect was observed in both HCO-3-rich and HCO-3-free solutions, although it was smaller in the latter. Propranolol and phentolamine (10(-5) M) partially blocked the action of the adrenergic agonists, 8Br-cAMP (1 mM), on the other hand, stimulated the SCC when added to either bathing solution. The apparent contradiction between these results is explained on the basis of separate cyclic AMP compartmentalization in the two epithelial cell layers and the lack of adrenoceptors in the non-pigmented layer.
Targets:
['Adrenergic beta-Antagonists', 'Sympathomimetics', '8-Bromo Cyclic Adenosine Monophosphate', 'Propranolol', 'Cyclic AMP', 'Isoproterenol', 'Norepinephrine', 'Epinephrine', 'Phentolamine']
Preds:
b'["Calcium", "Potassium", "Sodium", "Adenosine Triphosphate", "Glucose", "Cyclic AMP", "Acetylcholine", "Norepinephrine"]'
Text:
Using a magnetic resonance imaging-based volumetry, we quantified the volumes of the hippocampal formation (HF), parahippocampal gyrus (PHG), amygdaloid body (AMB), and anterior temporal neocortex (ATN) in 5 post-herpes simplex encephalitic (post-HSE) patients with temporal lobe damage and memory impairment at 12-52 months after the onset, and in 10 age-matched control subjects. In the post-HSE patients, the HF (p < 0.001) and PHG (p < 0.005) were significantly atrophic, while the AMB (p = 0.155) and ATN (p = 0.102) were smaller but not significantly. Performances on the verbal learning memory tests correlated highly with the HF volume, and length of dense retrograde amnesia with the PHG atrophy. Two patients with severe lasting amnesia had a marked atrophy of the HF and PHG, while 3 patients with good recovery from initial amnesia had temporal lobe structures larger than 50% of the control mean volumes. These results suggest that anterograde and retrograde memory functions involve different neural structures; the former is related to the HF and the latter to the PHG. For producing lasting amnesia, either severe HF damage or a combined damage of the HF and PHG might be necessary.
Targets:
['Acyclovir']
Preds:
b'["Biomarkers", "Biomarkers, Tumor", "Oxygen", "Contrast Media", "Blood Glucose", "Peptide Fragments", "Testosterone", "Insulin"]'
Text:
Effective solar protection is an uncommon practice among young people, increasing the likelihood of sunburn, sunstroke and skin cancers. This fact is more significant in the south of Brazil, where the prevalence of white skinned population is larger, being more prone to sun damage.
Targets:
['Sunscreening Agents']
Preds:
b'["Anti-Bacterial Agents", "Antineoplastic Agents", "Pharmaceutical Preparations", "Antiviral Agents", "Water Pollutants, Chemical", "Biomarkers", "Antibodies, Viral", "Environmental Pollutants"]'
Text:
At conditions commonly applied for trans fatty analyses by gas chromatography, fatty acids naturally occurring in marine lipids may overlap chromatographically with C16 and C18 trans fatty acids and lead to false positives. Elution patterns were studied by tracking retention indices at shifting temperature conditions on two cyanopropyl-coated capillary columns. Most overlaps can be avoided by selecting the right chromatographic conditions, but it was not possible to find a single condition that eliminates the risk of overlap between trans fatty acids and interferents. In total, 17 compounds were identified as potential interferents, and the amounts of these compounds were quantified in various samples of marine origin. The interferents that will most likely contribute to incorrect assessments of trans fatty acids in marine lipids are probably 18:3 n-4 and 18:1 n-11.
Targets:
['Fatty Acids']
Preds:
b'["Water", "Water Pollutants, Chemical", "Proteins", "Ligands", "Carbon", "Amino Acids", "DNA", "Phenols"]'
Text:
4'-methoxy-2-styrylchromone, a new synthetic chromone was identified as a selective proliferation inhibitor of human tumor (MCF-7 and NCI-H460) cell lines than to non-tumor cells (MRC-5). The antiproliferative activity of this chromone was also extensive to peripheral human lymphocytes. 4'-Methoxy-2-styrylchromone was found to block tumor cells in the G2/M phase of the cell cycle. The G2/M arrest of NCI-H460 cells was dose- and time-dependent, reaching a maximum after 12-h treatment while MCF-7 cells reached the maximum value of G2/M accumulation only after a 24-h treatment. Chromone-treated cells evidenced a high frequency of cells in prometaphase, indicating progression beyond G2 and arrest early in mitosis. This mitotic arrest was associated with abnormal mitotic spindles characterized by the formation of a monopolar structure, suggesting that the chromone interferes with microtubules. The results of an in vitro tubulin polymerization assay showed that this chromone stabilizes microtubules in a manner similar to paclitaxel.
Targets:
["4'-methoxy-2-styrylchromone", 'Chromones', 'Styrenes', 'Tubulin Modulators']
Preds:
b'["Antineoplastic Agents", "Recombinant Proteins", "RNA, Messenger", "DNA", "Enzyme Inhibitors", "Antioxidants", "Tumor Necrosis Factor-alpha", "Culture Media"]'
Text:
Hereditary tyrosinemia type I is a disease with a severe prognosis. Main causes of death are acute liver failure, neurologic crises and hepatocarcinoma. NTBC, which acts as an inhibitor of the 4-hydroxyphenylpyruvate dioxygenase, prevents the formation of toxic metabolites involved in hepatic, renal and neurologic lesions.
Targets:
['Cyclohexanones', 'Enzyme Inhibitors', 'Heptanoates', 'Nitrobenzoates', 'Tyrosine', 'succinylacetone', 'Aminolevulinic Acid', 'Methionine', '4-Hydroxyphenylpyruvate Dioxygenase', 'Porphobilinogen Synthase', 'nitisinone']
Preds:
b'["Biomarkers", "Cytokines", "RNA, Messenger", "Tumor Necrosis Factor-alpha", "Antineoplastic Agents", "Transcription Factors", "Recombinant Proteins", "Anti-Bacterial Agents"]'
Text:
The effect of drinking pattern on plasma lipoproteins and body weight was examined in three groups of squirrel monkeys: (1) controls fed isocaloric liquid diet; (2) regular drinkers given liquid diet containing ethanol (EtOH) substituted isocalorically for carbohydrate at 12% of calories daily; and (3) binge drinkers fed 6% EtOH calories daily for a four-day period followed by three days of 20% EtOH to mimic a weekend bout drinking cycle. The number of calories offered per day was the same for all groups, and the average weekly EtOH consumption (12% calories) was identical for the two alcohol treatments. The entire study lasted six months. There were no significant differences in plasma cholesterol, triglyceride or liver function tests. Regular drinkers had the highest high density lipoprotein2/high density lipoprotein3 (HDL2/HDL3) protein and apolipoprotein A-I/B ratios of any group and exhibited a significant elevation in the molar plasma lecithin:cholesterol acyltransferase (LCAT) rate (nmol/min/ml). Binge drinking produced a selective increase in low density lipoprotein (LDL) cholesterol and apolipoprotein B, and a depression in the fractional LCAT rate (% esterified/min). During the course of the study, controls ate 92% of their diet while the alcohol groups each consumed 95% of the liquid diet. Despite this difference, body weight and Quetelet index (weight/height2) decreased progressively in the order controls greater than regular drinkers greater than binge drinkers. Results from our study indicate that moderate, regular daily consumption of EtOH at 12% of calories causes a modest reduction in body weight and produces a coronary protective lipoprotein profile (increases HDL2/HDL3, increases apolipoprotein A-I/B, low LDL cholesterol). By contrast, when this same average weekly dose is concentrated in a binge cycle, unfavorable alterations in lipoprotein composition (increases LDL cholesterol, increases apolipoprotein B) and metabolism (decreases LCAT activity) occur along with weight loss and depletion of body fat. These studies point to the value of the squirrel monkey model in evaluating both favorable and pathophysiological effects of chronic EtOH intake.
Targets:
['Apolipoproteins', 'Lipoproteins', 'Lipoproteins, HDL', 'Ethanol', 'Phosphatidylcholine-Sterol O-Acyltransferase']
Preds:
b'["Blood Glucose", "Triglycerides", "Insulin", "Cholesterol", "Dietary Fats", "Biomarkers", "Lipids", "Estradiol"]'
Text:
Chronic graft-versus-host disease (GVHD) is a major cause of late death and morbidity following allogeneic hematopoietic cell transplantation (HSCT). Retinoic acid (tamibarotene) exerts multiple effects on cell differentiation and is clinically used for the treatment of acute promyelocytic leukemia. Tamibarotene down-regulates both Th1 and Th17 differentiation in donor T cells after allogeneic HSCT, resulting in attenuation of experimental chronic GVHD. Based on preclinical data, we have launched a phase II study of tamibarotene in patients with steroid-refractory chronic GVHD. This study will clarify whether tamibarotene can exert beneficial effects in patients with steroid-refractory chronic GVHD.
Targets:
['Adrenal Cortex Hormones', 'Benzoates', 'Immunosuppressive Agents', 'Tetrahydronaphthalenes', 'tamibarotene']
Preds:
b'["Antineoplastic Agents", "Biomarkers", "Biomarkers, Tumor", "Antibodies, Monoclonal", "Protein Kinase Inhibitors", "Immunosuppressive Agents", "Anti-Bacterial Agents", "Antiviral Agents"]'
Text:
Beta carotene has been associated with a decreased risk of human cancer in many studies employing dietary questionnaires or blood measurements, and it has had protective effects in some animal models of carcinogenesis.
Targets:
['beta Carotene', 'Carotenoids']
Preds:
b'["Antineoplastic Agents", "Anti-Bacterial Agents", "Biomarkers", "Antiviral Agents", "Cytokines", "Recombinant Proteins", "Pharmaceutical Preparations", "Antioxidants"]'
Text:
The survival rate of oral implants in soft-quality bone has been demonstrated to be inferior to that of implants inserted in good-quality bone. A possible way to increase the survival rate in soft-quality bone may be to use a tapered implant. Such an implant has been developed and manufactured by Nobel Biocare AB, Gothenburg, Sweden. So far, there have been only a few publications regarding this implant.
Targets:
['Dental Implants']
Preds:
b'["Antineoplastic Agents", "Anti-Bacterial Agents", "Antiviral Agents", "Antibodies, Monoclonal", "Biomarkers", "Biomarkers, Tumor", "Pharmaceutical Preparations", "Recombinant Proteins"]'
Text:
This phase I/II study determined the maximal tolerable dose, dose limiting toxicities, antitumor activity, the pharmacokinetics and pharmacodynamics of ruthenium compound NAMI-A in combination with gemcitabine in Non-Small Cell Lung Cancer patients after first line treatment.
Targets:
['Organometallic Compounds', 'Ruthenium Compounds', 'imidazolium-bis(imidazole)dimethylsulfoxideimidazotetrachlororuthenate(III)', 'Deoxycytidine', 'Ruthenium', 'gemcitabine', 'Dimethyl Sulfoxide']
Preds:
b'["Antineoplastic Agents", "Cisplatin", "Anticoagulants", "Antiviral Agents", "Anti-Bacterial Agents", "Fluorouracil", "Biomarkers, Tumor", "Anti-Inflammatory Agents, Non-Steroidal"]'
Text:
A combination of calcium phosphates with nanofibrous scaffolds holds promising potential for bone tissue engineering applications. In this study, nanohydroxyapatite (n-HA) was coated on the plasma-treated surface of electrospun poly(l-lactide) (PLLA) nanofibers and the capacity of fabricated scaffolds for bone formation was investigated in vitro using human cord blood derived unrestricted somatic stem cells (USSC) under osteogenic induction and in vivo after subcutaneous implantation. PLLA and n-HA-coated PLLA (n-HA/PLLA) scaffolds exhibited a nanofibrous structure with interconnected pores and suitable mechanical properties. These scaffolds were also shown to support attachment, spreading, and proliferation of USSC, as shown by their flattened normal morphology and MTT assay. During osteogenic differentiation, significantly higher values of ALP activity, biomineralization, and bone-related gene expression were observed on n-HA/PLLA compared to PLLA scaffolds. Subsequently, these markers were measured in higher amounts in USSC on PLLA nanofibers compared to TCPS. According to the in vivo results, ossification and formation of trabeculi was observed in the n-HA/PLLA scaffold compared to PLLA. Taking together, it was shown that nanofibrous structure enhanced osteogenic differentiation of USSC. Furthermore, surface-coated n-HA stimulated the effect of nanofibers on the orientation of USSC toward osteolineage. In addition, the n-HA/PLLA electrospun scaffold showed the capacity for ectopic bone formation in the absence of exogenous cells.
Targets:
['Polyesters', 'poly(lactide)', 'Durapatite']
Preds:
b'["Collagen", "RNA, Messenger", "Tumor Necrosis Factor-alpha", "Biocompatible Materials", "Antioxidants", "Water", "Antibodies, Monoclonal", "Recombinant Proteins"]'
Text:
Evidence of bacterial involvement in precipitation of calcium carbonates has brought a revolution in the field of applied microbiology, geotechnical sciences, environmental and civil engineering with its marked success in restoration of various building materials. For applications of these calcite binder-producing bacterial cultures, different expensive carrier materials have been used but their high costs have come in the way of their successful commercialization. In the present study, we have explored the potential of cheap industrial by-product fly ash as a carrier material for bacterial cells and investigated the viability of calcifying bacterial isolates: Bacillus megaterium, Bacillus cereus, and Lysinibacillus fusiformis in fly ash carrier at varying temperatures and moisture conditions along with biomineralization efficacy of these formulations. We used laser scanning confocal microscopy to analyze the viability of bacteria by florescent dye 5-cyano-2,3-ditolyl tetrazolium chloride (CTC) along with the plate count method. Results revealed that fly ash successfully served as an effective carrier material and bacterial formulations stored at 4 °C provided longer shelf life than those stored at higher temperatures. Up to 10(6) cfu/g was found to sustain in all formulations at 4 °C compared to 10(4)-10(5) cfu/g in case of higher temperatures up to 1 year. For 4 °C, higher moistures (50 %) were found to provide better survivability while for higher temperatures, lower moistures (30 %) favored higher viability. The biomineralization capability of fresh and formulated bacterial cells was compared on the basis of precipitation of carbonates and it was found that carbonate precipitation efficacy of formulated bacterial cells was comparable to fresh bacterial cells.
Targets:
['Coal Ash', 'Industrial Waste', 'Calcium Carbonate']
Preds:
b'["Water Pollutants, Chemical", "Water", "Culture Media", "Polymers", "Anti-Bacterial Agents", "Biocompatible Materials", "RNA, Ribosomal, 16S", "Soil"]'
Text:
Twenty 18beta-glycyrrhetic acid (18beta-GA) derivatives 2-21 including 13 new 18beta-GA derivatives were synthesized and evaluated as anti-inflammatory and antioxidant agents. Compounds 7 and 20 with a 3,4-seco-structure and compound 6 with a lactone moiety showed potent inhibitory effect on superoxide anion generation in rat neutrophils response to fMLP/CB and PMA, respectively. Compound 6 with a lactone moiety revealed stronger inhibitory effect on XO activity than those of compounds 13 and 14 with a 3,4-seco-structure. Compound 14, a 30-isoproylcarbamoyl seco-compound exhibited potent inhibitory effect on NO accumulation and iNOS protein expression while compounds 3, 10, 13, 15, 17, and 21 revealed potent inhibitory effect on tumor necrosis factor-alpha (TNF-alpha) formation in RAW 264.7 cells in response to lipopolysaccharide (LPS). The cleavage of ring A of 3 attenuated the inhibitory effect on TNF-alpha formation in RAW 264.7 cells in response to LPS except for 17. The present results suggested these compounds were potential to be served as anti-inflammatory and antioxidant agents.
Targets:
['Anti-Inflammatory Agents', 'Antioxidants', 'Enzyme Inhibitors', 'Lipopolysaccharides', 'Tumor Necrosis Factor-alpha', 'Superoxides', 'Nitric Oxide', 'Nitric Oxide Synthase Type II', 'Xanthine Oxidase', 'Glycyrrhetinic Acid']
Preds:
b'["Plant Extracts", "Antioxidants", "Antineoplastic Agents", "Enzyme Inhibitors", "Nitric Oxide", "Anti-Bacterial Agents", "Tumor Necrosis Factor-alpha", "Lipopolysaccharides"]'
Text:
Downregulation of microRNA-31 has been linked with enhanced stress resistance, while its overexpression leads to cell death. In this study, we found mediatory role of microRNA-31 in γ-radiation-induced apoptosis in a model insect cell line Sf9 carrying well-conserved apoptotic machinery. Mature microRNA-31 is perfectly conserved amongst insects; hence we used biotinylated probes designed from Bombyx mori sequence for its successful detection in Sf9 cells. Target identification using Bombyx mori 3'UTRs predicted miR-31's potential role in Lepidopteran apoptosis, which prompted us to investigate alterations in its expression during radiation-induced cell death. We found significant overexpression of Sf-miR-31 following lethal dose (1,000Gy-3,000Gy) irradiation. Its mediatory role was finally confirmed as antisense-microRNA-31 could successfully inhibit radiation-induced cytochrome-c release, caspase-3 activation and apoptosis. While Bax/Bcl-2 expression remained unchanged, lethal radiation doses induced Bim overexpression and direct Bim-Bax interaction (co-immunoprecipitation) which is not yet unequivocally demonstrated during apoptosis. Quite important, these events were found to be dependent on radiation-induced miR-31 overexpression, as antisense-miR-31 inhibited both the responses and resulted in significant inhibition of cell death. Pro-apoptotic role of miR-31 was further confirmed when miR-31 mimic induced apoptosis involving similar Bim/Bax alterations. Therefore, our study reveals an important mediatory role of miR-31 in radiation-induced cell death.
Targets:
["3' Untranslated Regions", 'Apoptosis Regulatory Proteins', 'Bcl-2-Like Protein 11', 'Membrane Proteins', 'MicroRNAs', 'Oligonucleotides, Antisense', 'Proto-Oncogene Proteins', 'Proto-Oncogene Proteins c-bcl-2', 'bcl-2-Associated X Protein', 'Cytochromes c', 'Caspase 3']
Preds:
b'["RNA, Messenger", "Cytokines", "Transcription Factors", "Tumor Necrosis Factor-alpha", "RNA, Small Interfering", "Reactive Oxygen Species", "DNA-Binding Proteins", "Antineoplastic Agents"]'
Text:
Male and female New Zealand rabbits were given a single bolus injection of 5 ml/kg of Telebrix, Hexabrix or Omnipaque intravenously. Animals were sacrificed 2, 8 and 24 h after the injection. One group of animals received a continuous i.v. infusion of contrast medium at a constant rate of 2.5 ml/kg/h for 4 h. Animals from this group were killed 30 min after the end of the infusion. Product clearance from plasma was studied in the animals given the i.v. bolus of contrast material and sacrified at 24 h postinjection. Plasma and tissue concentrations of contrast material were determined by high-performance liquid chromatography. Plasma elimination half-lives were identical in males and females and for all three products (approximately 45 min). The same held true for the volume of distribution which comprised between 20 and 26% of body weight. At 2 h postinjection, renal cortical concentrations of contrast medium were 8 to 10 times higher than plasma concentrations. For all three contrast agents, concentrations found in the renal cortex were higher than those in the medulla or the papilla at all observation times. As compared with the evolution of plasma concentrations over time, renal accumulation of the products was found to be persistent. The ionic or non-ionic nature of the tested products and their hydrophilic properties seem to play an essential role in the renal accumulation pattern.
Targets:
['Contrast Media', 'Iothalamic Acid', 'Iohexol', 'ioxitalamic acid', 'Ioxaglic Acid']
Preds:
b'["Oxygen", "Calcium", "Sodium", "Glucose", "Norepinephrine", "Insulin", "Carbon Dioxide", "Estradiol"]'
Text:
To analyze mitochondrial DNA (mtDNA) polymorphisms in coding area and provide a theoretical basis for applying in forensic science.
Targets:
['DNA Primers', 'DNA, Mitochondrial']
Preds:
b'["Biomarkers", "Proteins", "RNA, Messenger", "DNA", "Genetic Markers", "DNA, Mitochondrial", "Insulin", "Pharmaceutical Preparations"]'
Text:
Previous studies suggest that protein synthesis in the liver may be influenced by alterations in hepatic proteolysis and gluconeogenesis. Since proteolysis and gluconeogenesis are accelerated in acute stress states (especially when associated with nutrient deprivation), these alterations may substantially affect hepatic protein synthesis, the integrity of which is important for host survival. In the present study, we have investigated albumin secretion and glucose production in primary cultures of rat hepatocytes in response to nutrient-limiting conditions, including amino acid depletion, proteolysis inhibition, and augmented gluconeogenesis. In nonlimiting nutrient culture medium containing 10 times the normal plasma amino acid concentrations, hepatocytes produced 8.05 +/- 1.62 micrograms/plate-hr of albumin. Short-term (5 hr) inhibition of cellular protein degradation with the lysosomal protease inhibitor leupeptin did not influence albumin production, but caused a profound reduction (17-41%) when amino acid supply was reduced to the physiologic range (1.5-0.5 times, respectively). This indicates the need for active proteolysis for the maintenance of secretory protein production during nutrient limitation. Similarly, leupeptin inhibited glucose production by 22-30% at physiologic (1.5 times and 0.5 times, respectively) amino acid concentrations. Additionally, hepatocyte glucose production could be augmented 168% by epinephrine (2 microM) in 10 times medium, but this response was markedly depressed by leupeptin. Similar catecholamine-mediated effects, but of a smaller magnitude, were noted at lower medium amino acid concentrations. These findings indicate that hepatocyte albumin and glucose production are associated with the common factor of active cellular proteolysis, probably through the regulation of amino acid supply. However, protein synthesis exhibits a higher priority, since stimulated hepatocyte glucose production did not substantially alter albumin secretion.
Targets:
['Amino Acids', 'Culture Media', 'Insulin', 'Leupeptins', 'Serum Albumin', 'Dexamethasone', 'Urea', 'Glucagon', 'leupeptin', 'Epinephrine']
Preds:
b'["RNA, Messenger", "Glucose", "Insulin", "Calcium", "Adenosine Triphosphate", "Recombinant Proteins", "Cyclic AMP", "Blood Glucose"]'
Text:
To summarize the most recent findings concerning the targeting of mitogen-activated protein kinases and small GTP-binding proteins toward vascular remodeling together with molecular mechanisms of their activations in vascular pathophysiology.
Targets:
['Extracellular Signal-Regulated MAP Kinases', 'JNK Mitogen-Activated Protein Kinases', 'p38 Mitogen-Activated Protein Kinases', 'GTP-Binding Proteins']
Preds:
b'["Proteins", "Transcription Factors", "RNA, Messenger", "Ligands", "RNA, Small Interfering", "MicroRNAs", "Calcium", "Cytokines"]'
Text:
Epithelial-mesenchymal transition (EMT) has been proposed as a mechanism in the progression of airway diseases and cancer. Here, we explored the role of acetylcholine (ACh) and the pathway involved in the process of EMT, as well as the effects of mAChRs antagonist.
Targets:
['Piperidines', 'Receptors, Muscarinic', 'Transforming Growth Factor beta1', '4-diphenylacetoxy-1,1-dimethylpiperidinium']
Preds:
b'["Cytokines", "RNA, Messenger", "Tumor Necrosis Factor-alpha", "RNA, Small Interfering", "Reactive Oxygen Species", "NF-kappa B", "Biomarkers", "Transcription Factors"]'
Text:
Central nervous system (CNS) involvement in acute lymphoblastic leukemia (ALL) is diagnosed traditionally by cytopathology (CP) of the cerebrospinal fluid (CSF). Role of flow cytometry (FC) to diagnose CNS involvement has not been extensively investigated.
Targets:
['Biomarkers']
Preds:
b'["Antineoplastic Agents", "Biomarkers, Tumor", "Biomarkers", "Antibodies, Monoclonal", "Anti-Bacterial Agents", "Cisplatin", "Immunosuppressive Agents", "Antiviral Agents"]'
Text:
Macromolecules confined within a nanoporous matrix experience entropic trapping when their dimensions approach the average pore size, leading to emergence of anomalous transport behavior that can be beneficial in separation applications. But the ability to exploit these effects in practical settings (e.g., electrophoretic separation of DNA) has been hindered by additional dispersion introduced as a consequence of the uncorrelated process by which the embedded macromolecules discretely hop from pore to pore. Here, we show how both the source and solution to these difficulties are intimately linked to the inherent dynamics of the underlying activated transport mechanism. By modulating the applied electric field at a frequency tuned to the characteristic activation timescale, a resonance condition can be established that synergistically combines accelerated mobility and reduced diffusion. This resonance effect can be precisely manipulated by adjusting the magnitude and period of the driving electric field, enabling enhanced separation performance and bi-directional transport of different-sized species to be achieved. Notably, these phenomena are readily accessible in ordinary hydrogels (as opposed to idealized nanomachined topologies) suggesting broad potential to apply them in a host of useful settings.
Targets:
['DNA']
Preds:
b'["Proteins", "Water", "Ligands", "Polymers", "Bacterial Proteins", "DNA", "Plant Proteins", "Fluorescent Dyes"]'
Text:
Quantitative experimental data from studies of intracellular processing and transport of secretory and membrane proteins are only rarely evaluated using kinetic modelling. Instead, the analysis of such data is usually limited to calculating either the apparent half-life or the transit time. Neither of these parameters accurately measures rates of cellular processing or transport. This paper describes a formal approach for the calculation of rate constants, half-lives and lag times for single and sequential processing and transport steps. Generalized kinetic models are presented that can be used to analyse data from both pulse-chase and continuous incubation experiments with labelled amino acids or sugars. The results from a number of published studies are reanalysed using the models to demonstrate the usefulness of kinetic modelling in the routine analysis of experimental data.
Targets:
['Membrane Proteins']
Preds:
b'["Proteins", "Water", "Ligands", "DNA", "Oxygen", "Glucose", "Amino Acids", "Pharmaceutical Preparations"]'
Text:
The aim of this study was to highlight the advantages of rapid access to a palliative radiotherapy unit adopting a multidisciplinary approach to symptom management to relieve pain and improve quality of life in patients with bone metastases.
Targets:
['Analgesics']
Preds:
b'["Antineoplastic Agents", "Anti-Bacterial Agents", "Biomarkers, Tumor", "Biomarkers", "Contrast Media", "Pharmaceutical Preparations", "Anticoagulants", "Adrenal Cortex Hormones"]'