Diabetic nephropathy (DN) remains one of the severe complications associated with diabetes mellitus. It is worthwhile to uncover the underlying mechanisms of clinical benefits of human urine‐derived ...stem cells (hUSCs) in the treatment of DN. At present, the clinical benefits associated with hUSCs in the treatment of DN remains unclear. Hence, our study aims to investigate protective effect of hUSC exosome along with microRNA‐16‐5p (miR‐16‐5p) on podocytes in DN via vascular endothelial growth factor A (VEGFA). Initially, miR‐16‐5p was predicated to target VEGFA based on data retrieved from several bioinformatics databases. Notably, dual‐luciferase report gene assay provided further verification confirming the prediction. Moreover, our results demonstrated that high glucose (HG) stimulation could inhibit miR‐16‐5p and promote VEGFA in human podocytes (HPDCs). miR‐16‐5p in hUSCs was transferred through the exosome pathway to HG‐treated HPDCs. The viability and apoptosis rate of podocytes after HG treatment together with expression of the related factors were subsequently determined. The results indicated that miR‐16‐5p secreted by hUSCs could improve podocyte injury induced by HG. In addition, VEGA silencing could also ameliorate HG‐induced podocyte injury. Finally, hUSC exosomes containing overexpressed miR‐16‐5p were injected into diabetic rats via tail vein, followed by qualification of miR‐16‐5p and observation on the changes of podocytes, which revealed that overexpressed miR‐16‐5p in hUSCs conferred protective effects on HPDCs in diabetic rats. Taken together, the present study revealed that overexpressed miR‐16‐5p in hUSC exosomes could protect HPDCs induced by HG and suppress VEGFA expression and podocytic apoptosis, providing fresh insights for novel treatment of DN.
Long non‐coding RNA (lncRNA) lnc‐ISG20 has been found aberrantly up‐regulated in the glomerular in the patients with diabetic nephropathy (DN). We aimed to elucidate the function and regulatory ...mechanism of lncRNA lnc‐ISG20 on DN‐induced renal fibrosis. Expression patterns of lnc‐ISG20 in kidney tissues of DN patients were determined by RT‐qPCR. Mouse models of DN were constructed, while MCs were cultured under normal glucose (NG)/high glucose (HG) conditions. The expression patterns of fibrosis marker proteins collagen IV, fibronectin and TGF‐β1 were measured with Western blot assay. In addition, the relationship among lnc‐ISG20, miR‐486‐5p, NFAT5 and AKT were analysed using dual‐luciferase reporter assay and RNA immunoprecipitation. The effect of lnc‐ISG20 and miR‐486/NFAT5/p‐AKT axis on DN‐associated renal fibrosis was also verified by means of rescue experiments. The expression levels of lnc‐ISG20 were increased in DN patients, DN mouse kidney tissues and HG‐treated MCs. Lnc‐ISG20 silencing alleviated HG‐induced fibrosis in MCs and delayed renal fibrosis in DN mice. Mechanistically, miR‐486‐5p was found to be a downstream miRNA of lnc‐ISG20, while miR‐486‐5p inhibited the expression of NFAT5 by binding to its 3'UTR. NFAT5 overexpression aggravated HG‐induced fibrosis by stimulating AKT phosphorylation. However, NFAT5 silencing reversed the promotion of in vitro and in vivo fibrosis caused by lnc‐ISG20 overexpression. Our collective findings indicate that lnc‐ISG20 promotes the renal fibrosis process in DN by activating AKT through the miR‐486‐5p/NFAT5 axis. High‐expression levels of lnc‐ISG20 may be a useful indicator for DN.
To conduct a metaanalysis in order to determine the association between matrix metalloproteinase (MMP)-2 expression and renal cell carcinoma (RCC) progression.
Cohort studies were identified after an ...exhaustive search of the following electronic databases: PubMed, China Biomedicine, Web of Science, Wanfang database, and China National Knowledge Infrastructure. Summary odds ratios with 95% confidence interval were calculated.
Seventeen clinical studies were eligible for the present metaanalysis. Overall, increased MMP-2 protein expression levels had a positive correlation with several RCC clinical parameters, such as tumor node metastasis (TNM) stage, differentiation grade, lymph node metastasis (LNM), and tumor size (all p < 0.05). Country-stratified analysis revealed statistically significant differences in MMP-2 expression levels, based on the 4 clinical parameters studied, in the Chinese population (all p < 0.05). The results indicated that the MMP-2 protein level in RCC patients with non-clear cell type was higher than that in the patients with clear cell carcinoma (p < 0.05). A positive correlation was found between RCC differentiation grade and MMP-2 protein levels in only the streptavidin-peroxidase subgroup (p < 0.05), while there were significant associations between MMP-2 protein level and TNM stage, LNM, and tumor size (p < 0.05).
Our metaanalysis suggests that RCC patients with a high MMP-2 expression level exhibit rapid progression of RCC and that high MMP-2 expression level is associated with poor prognosis.
We use conditional nonlinear optimal perturbation （CNOP） to investigate the optimal precursory disturbances in the Zebiak- Cane El Nino-Southern Oscillation （ENSO） model. The conditions of the ...CNOP-type precursors are highly likely to evolve into El Nino events in the Zebiak-Cane model. By exploring the dynamic behaviors of these nonlinear El Nino events caused by the CNOP-type precursors, we find that they, as expected, tend to phase-lock to the annual cycles in the Zebiak-Cane model with the SSTA peak at the end of a calendar year. However, E1 Nino events with CNOPs as initial anomalies in the linearized Zebiak-Cane model are inclined to phase-lock earlier than nonlinear E1 Nino events despite the existence of annual cycles in the model. It is clear that nonlinearities play an important role in El Nino＇s phase-locking. In particular, nonlinear temperature advection increases anomalous zonal SST differences and anomalous westerlies, which weakens anomalous upwelling and acts on the increasing anomalous vertical temperature difference and, as a result, enhances E1 Nino and then delays the peak SSTA. Finally, we demonstrate that nonlinear temperature advection, together with the effect of the annual cycle, causes El Nino events to peak at the end of the calendar year.
Aim： To study the relationship between the antihypertensive response of iptakalim and KCNJ11 polymorphisms in Chinese Han hypertensive patients. Methods： One hundred sixty two Chinese Hart ...hypertensive patients were administered iptakalim （5 or 10 mg/d, po） for 8 weeks. Before the treatment and 24 h after completing the treatment blood pressure （BP） was measured. Genotyping was performed using direct sequencing. Results： Four common A190A, E23K, 1337V and 3＇UTR ＋62 G/A polymorphisms were found in KCNJ11. The E23K, 1337V and 3＇UTR ＋62 G/A polymorphisms were in complete linkage disequilibrium, and 1337V was used as a representative. There were no significant differences in age, body mass index, sex, baseline systolic BP （SBP） and diastolic BP （DBP） among the 3 genotypes for the four polymorphisms. Significant association was found between SBP response and the polymorphisms （adjusted regression coefficient： 3.5 1.2 mmHg; P=0.003 for the A190A polymorphism; adjusted regression coefficient： 3.1 1.2 mmHg; P=0.012 for the 1337V polymorphism）. The patients with TT genotype for A190A polymorphism had higher clinical efficacy than those with CC genotype. Conclusion： The results suggest the KCNJ11 polymorphisms are associated with the SBP-Iowering response of short-term iptakalim therapy in Chinese Han hypertensive patients.
Two-dimensional （2D） layered transition metal dichalcogenide （TMD） materials （e.g., MoS2） have attracted considerable interest due to their atomically thin geometry and semiconducting electronic ...properties. With ultrahigh surface to volume ratio, the electronic properties of these atomically thin semiconductors can be readily modulated by their environment. Here we report an investigation of the effects of mercury（II） （Hg^2＋） ions on the electrical transport properties of few-layer molybdenum disulfide （MoS2）. The interaction between Hg^2＋ ions and few-layer MoS2 was studied by field-effect transistor measurements and photoluminescence. Due to a high binding affinity between Hg2. ions and the sulfur sites on the surface of MoS2 layers, Hg^2＋ ions can strongly bind to MoS2. We show that the binding of Hg^2＋ can produce a p-type doping effect to reduce the electron concentration in n-type few-layer MoS2. It can thus effectively modulate the electron transport and photoluminescence properties in few-layer MoS2. By monitoring the conductance change of few-layer MoS2 in varying concentration Hg2~ solutions, we further show that few-layer MoS2 transistors can function as highly sensitive sensors for rapid electrical detection of Hg^2＋ ion with a detection limit of 30 pM.
An efficient synthesis of cyanoalkylated heteroarenes via iron-catalyzed direct C–H cyanoalkylation of heteroarenes has been developed. Structurally diverse cyanoalkyl motifs generated through C–C ...bond cleavage of cyclobutanone oxime esters have been introduced into quinoxalin-2(1H)-ones, flavone, benzothiazoles, and caffeine in good to excellent yields. Remarkably, less-strained cyclopentanone and unstrained cyclohexanone oxime esters were also amenable substrates in this cyanoalkylation reaction.
A direct C–H cyanoalkylation of heteroaromatic N-oxides and quinones with cyclobutanone oximes is reported. This redox-neutral, operationally simple cyanoalkylation reaction is successfully amenable ...to a wide range of heteroaromatic N-oxides, quinones, and cyclobutanone oximes. A novel catalytic system consisting of a nickel source proved crucial for cleavage of the C–C bond of cyclobutanone oximes and for selective C–C bond formation over β-hydride elimination. Mechanistic studies suggest that a radical intermediate might be involved in this transformation.
A visible‐light mediated γ‐hydroxyalkylation of ketones via C(sp3)‐H functionalization has been developed under redox neutral conditions. This protocol relies on the iminyl radical‐triggered 1,5‐HAT ...followed by oxyalkylation of alkenes, wherein C−C and C−O bonds were constructed in one step. This three‐component reaction features mild conditions, wide substrate scope and excellent functional group tolerance, thus providing a facile and highly efficient access to complex valuable ketones.
An iron-catalyzed redox-neutral, decarboxylative olefination of cycloketone oxime esters with α,β-unsaturated carboxylic acids has been developed. This reaction involves an iminyl radical mediated ...C–C bond cleavage/radical addition/decarboxylation cascade. This protocol is highlighted by its low-cost catalytic system and readily accessible starting materials, as well as broad substrate scope, thus providing facile access to structurally diverse cyano-containing alkenes.
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