فهرست مطالب jun ma
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Introduction
Diabetic nephropathy (DN) belongs to the major cause of end-stage kidney disease. We probed the functions of a microRNA miR-33a in inducing podocytes injury during childhood DN (CDN).
MethodsKidney samples were collected from 20 children with DN. Matrix deposition and glomerular basement membranes thickness were examined by periodic acid-Schiff staining. Immunofluorescence staining was performed to assess kidney function-related proteins. MicroRNA (MiR)-33a mimic together with miR-33a inhibitor was transfected into podocytes for determining the roles of miR-33a. Glomerular podocyte apoptosis was determined by terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) staining along with flow cytometry.
ResultsDown-regulation of Nephrin and Podocin and increased podocyte apoptosis rate were observed in the glomerulus of CDN as well as podocytes treated with high glucose. MiR-33a was up-regulated in the glomeruli and glucose-treated podocytes. Injury in podocytes was aggravated with miR-33a elevation but alleviated with miR-33a inhibition. Moreover, the expression of Sirtuin 6 (Sirt6) was decreased while the levels of notch receptor 1 (Notch1) and notch receptor 4 (Notch4) were elevated in the glomerulus and glucose-treated podocytes. Decreased level of Sirt6 upon glucose treatment was abrogated by miR-33a inhibition, and the podocytes injury induced by glucose exposure was relieved by Sirt6 via Notch signaling.
ConclusionThese findings indicated that miR-33a promoted podocyte injury via targeting Sirt6-dependent Notch signaling in CDN, which might provide a novel sight for CDN treatment
Keywords: Children Diabetic Nephropathy, Microrna, Podocyte Injury, Sirt6, Notch Signaling} -
Background
This study aimed to establish a clinically relevant animal model for peripheral arterial disease (PAD) that better replicates the complexity observed in human patients.
Materials and MethodsThirty male rats were randomly assigned into the sham (SM), femoral artery resection (FE), constrictor-induced ischemia (CI), two-stage ischemia (TS), or diabetic two-stage ischemia (DT) groups. In the FE group, rats underwent femoral artery resection, whereas the SM group had sham surgery. The CI group received progressive ischemia using two ameroid constrictors, and the TS and DT groups underwent a two-stage ischemia procedure involving initial gradual narrowing with two ameroid constrictors and subsequent femoral artery resection in healthy and diabetic rats, respectively. Perfusion evaluation and functional assessment were conducted at postoperative days 14, 28, and 42. On day 42, hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) protein expression were measured, along with histological examination and immunofluorescence analysis.
ResultsMotor function deficits and reduced limb reperfusion were most prominent in the TS and DT groups on days 28 and 42 (P < 0.05), exacerbated by type 2 diabetes. Gastrocnemius exhibited upregulated HIF-1α and VEGF protein expression, as well as increased capillary density in response to ischemia. However, the DT group showed significantly lower protein expression and capillary density, along with more severe structural damage compared to other groups (P < 0.05).
ConclusionA clinically relevant rat model of PAD was established by implementing a twostage ischemia procedure involving initial progressive narrowing and subsequent femoral artery excision in the context of diabetes.
Keywords: Angiogenesis, diabetes, limb ischemia, peripheral artery disease} -
BackgroundBody pain is an important issue among elderly. The objective of this study was to access the association between the socioeconomic status and pain among elderly Chinese.MethodsThis nationally representative sample cohort study, China Health and Retirement Longitudinal Study (CHARLS), was conducted to estimate pain prevalence and risk factors from Jun 2011 to Mar 2012. Body pain was evaluated by the questionnaires. Logistic regression model was applied to estimate the odds ratio (OR) and 95% Confidence Interval (95% CI) of body pain to identify the potential risk factors.ResultsThe prevalence of pain was increased with age (PConclusionSocioeconomic variables such as education, occupation and health conditions are associated with both moderate severe pains.Keywords: Pain, Prevalence, Socioeconomic, Elderly, China}
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Objective(s)The purpose of this study was to investigate the role of chloride channel protein 2 (ClC-2) in glutamate-induced apoptosis in the retinal ganglion cell line (RGC-5).Materials And MethodsRGC-5 cells were treated with 1 mM glutamate for 24 hr. The expression of ClC-2, Bax, and Bcl-2 was detected by western blot analysis. Cell survival and apoptosis were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays, respectively. Caspase-3 and -9 activities were determined by a colorimetric assay. The roles of ClC-2 in glutamate-induced apoptosis were examined by using ClC-2 complementary deoxyribonucleic acid (cDNA) and small inference ribonucleic acid (RNA) transfection technology.ResultsOverexpression of ClC-2 in RGC-5 cells significantly decreased glutamate-induced apoptosis and increased cell viability, whereas silencing of ClC-2 with short hairpin (sh) RNA produced opposite effects. ClC-2 overexpression increased the expression of Bcl-2, decreased the expression of Bax, and decreased caspase-3 and -9 activation in RGC-5 cells treated with glutamate, but silencing of ClC-2 produced opposite effects.ConclusionOur data suggest that ClC-2 chloride channels might play a protective role in glutamate-induced apoptosis in retinal ganglion cells via the mitochondria-dependent apoptosis pathway.Keywords: Apoptosis_Chloride channels_Chloride channel protein 2 Neuroprotection_Retinal ganglion cells}
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A quantitative analysis method for fudosteine in human serum by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI/MS/MS) was established, which shows high sensitivity and selectivity. The mobile phase composition was 75% 20 mM acetic acid and 25% acetonitril, which was pumped at a flow rate of 0.40 mL/min. The overall chromatographic run time was approximately 7 min. The autosampler was set with an injection volume of 10 μl. The calibration curve was linear in the concentration range of 0.1~15.0 µg/mL. The coefficient of determination (r) was greater than 0.9998. This method has been fully validated and shown to be specific, accurate and precise. The method was simple, rapid and the sample preparation was minimal. It was successfully applied to the analysis of healthy volunteer serum samples during a phaseⅠclinical pharmacokinetic study of fudosteine.Keywords: Fudosteine, HPLC, ESI, MS, MS, Human serum, Pharmacokinetics}
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