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Compton Knox posted an update 6 months, 3 weeks ago
Ipsilateral somatosensory and motor evoked potentials were dynamic, increasing in latency and decreasing in amplitude compared to pre-operative values or the contralateral values, and correlated to varying degrees with behavioral outcomes. A shift in size-frequency distribution of sensory neurons of the DRG was consistent with a loss of large-diameter cells. The present study demonstrated that the NHP SCI model resulted in consistent unilateral limb dysfunction and potential plasticity in the face of loss of spinal cord and DRG tissue.Objective Activation of nicotinic acetylcholine receptors (nAChRs) results in neuroprotection via a poorly understood molecular mechanism. In this study, we aimed to investigate the effect of nAChR stimulation with nicotine on the regulation of microRNA (miRNA) expression and identify the molecular pathway involved in neuroprotection.Methods We conducted miRNA expression profiling using a microarray to identify the miRNAs regulated by nicotine. miR-132-5p expression was validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. Cells were treated with nicotine, a miR-132-5p mimic or its inhibitor, and the cell viability was assessed. CREB, Bcl-2, Bax, cleaved caspase-3, and α-tubulin protein expression levels were determined by Western blotting analysis.Results Using a rodent miRNA microarray, we identified 37 miRNAs regulated by nicotine. The microarray and RT-qPCR results showed 1.67-fold and 1.5-fold increases in miR-132-5p, respectively, upon nicotine treatment. Immunoblotting revealed a >2-fold increase in phosphorylation of CREB with nicotine, peaking at 4 h. Nicotine treatment of cells increased viability from 35% to 54%, and Bcl-2 immunoreactivity increased by 1.4-fold. LYN-1604 mw Overexpression of miR-132-5p increased cell viability from 38% to 70% and increased Bcl-2 expression by 3.9-fold. Inhibition of miR-132-5p decreased cell viability to 25%, whereas no change was observed in Bcl-2. Bax expression remained unchanged following treatment with a miR-132-5p mimic or its inhibitor.Discussion Our results suggest that nAChR activation facilitates cell survival by upregulating miR-132-5p, which upregulates the anti-apoptotic protein Bcl-2. These results present miR-132-5p as a potential novel therapeutic target to achieve neuroprotection via stimulation of nAChRs.Abbreviations CCK-8 Cell counting kit-8; nAChR Nicotinic acetylcholine receptor; NGF Nerve growth factor; WST-8 .Allosteric changes modulate the enzymatic activity, leading to activation or inhibition of the molecular target. Understanding the induced fit accommodation mechanism of a ligand in its lowest-free energy state and the subsequent conformational changes induced in the protein are important questions for drug design. In the present study, molecular dynamics (MD) simulations, binding free energy calculations, and principal component analysis (PCA) were applied to analyze the glycerol-3-phosphate dehydrogenase of Leishmania mexicana (LmGPDH) conformational changes induced by its cofactor and substrate binding. GPDH is a nicotinamide adenine dinucleotide (NAD)-dependent enzyme, which has been reported as an interesting target for drug discovery and development against leishmaniasis. Despite its relevance for glycolysis and pentose phosphate pathways, the structural flexibility and conformational motions of LmGPDH in complex with NADH and dihydroxyacetone phosphate (DHAP) remain unexplored. Here, we analyzed the conformational dynamics of the enzyme-NADH complex (cofactor), and the enzyme-NADH-DHAP complex (adduct), mapped the hydrogen-bond interactions for the complexes and pointed some structural determinants of the enzyme that emerge from these contacts to NADH and DHAP. Finally, we proposed a consistent mechanism for the conformational changes on the first step of the reversible redox conversion of dihydroxyacetone phosphate to glycerol 3-phosphate, indicating key residues and interactions that could be further explored in drug discovery.Communicated by Ramaswamy H. Sarma.The occurrence of 28 common antibiotics in wild and farmed aquatic products from different species was comprehensively investigated in the present study. The results showed that a larger number of antibiotics could be detected quantitatively in wild samples, while the farmed samples had higher concentrations. Twenty, 17, and 14 target compounds were found in the muscles of wild molluscs, wild fish and farmed fish with total concentrations of 2.02-16.4 ng g-1, 0.51-11.9 ng g-1, and less then LOD – 144 ng g-1, respectively. Quinolones could be frequently detected in all investigated samples with higher concentrations, while sulphonamides were only detected more frequently in wild molluscs. For wild samples, sulfamethoxazole, sulphamethazine, clarithromycin, and ciprofloxacin are the main antibiotics that were detected in molluscs and fish with different residues. However, there was almost no significant residue difference among different wild fish. Compared with other studies in China or overseas, antibiotic residues in the investigated fish were almost always at a relative low level. Monte Carlo simulation showed that the farmed fish posed higher health risks than the wild fish, while the proportion of the consumers with chronic toxic risk (HI) of farmed fish higher than 0.05 (a distinct risk) was only 1.15 %.PURPOSE Triple-negative breast cancer is characterized by fast progression with high possible for metastasis and poor survival. Dysfunction of microRNAs plays an important role in the initiation and progression of cancer. Our previous microRNA-seq data indicated the downregulation of miR-331-3p in triple-negative breast cancer tissues compared with that of the noncancer tissues. However, the function of miR-331-3p in triple-negative breast cancer remains largely unknown. Herein, the involvement of miR-331-3p in triple-negative breast cancer was investigated and the therapeutic potential of miR-331-3p was also explored. METHODS Real-time quantitative polymerase chain reaction was performed to detect the expression of miR-331-3p in triple-negative breast cancer tissues and cell lines. The cell proliferation was determined by the cell counting kit-8 assay. Apoptosis of triple-negative breast cancer cells was examined by annexin V/propidium iodide staining. miRDB database was used to predict the potential targets of miR-331-3p.
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