Deletion of diacylglycerol-responsive TRPC genes attenuates diabetic nephropathy by inhibiting activation of the TGFβ1 signaling pathway

TRPC6 plays a critical role in proteinuric kidney diseases, and TRPC3 is involved in tubulointerstitialdamage and renal fibrosis in obstructed kidneys. Podocyte loss is a characteristic event in diabetic nephropathy(DN). The aim of this study was to examine whether deletion of the closely related diacylglycerol (DAG)-responsiveTRPCs in mice (TRPC3/6/7-/-) affects diabetes-induced renal dysfunction and podocyte loss. We compared urinevolume, kidney hypertrophy, glomerular enlargement, albuminuria and podocyte loss between wild type (WT) andTRPC3/6/7-/- diabetic mice. Finally, we examined whether the TGFβ1 signaling pathway is changed in diabetic WTand TRPC3/6/7-/- mice. TRPC6 protein in the renal cortex was increased in WT diabetic mice. High glucose (HG)treatment increased TRPC6 expression in human podocytes. TRPC3 protein, however, was not altered in eitherdiabetic mice or HG-treated human podocytes. Although diabetic WT and TRPC3/6/7-/- mice had similar levels ofhyperglycemia, the TRPC3/6/7-/- diabetic mice showed less polyuria, kidney hypertrophy, glomerular enlargement,albuminuria, and had lost less podocytes compared with WT diabetic mice. In addition, we observed decreasedexpression of anti-apoptotic Bcl2 and increased expression of pro-apoptotic cleaved caspase 3 in WT diabetic mice,but such changes were not significant in TRPC3/6/7-/- diabetic mice. Western blot and immunohistochemistry revealedthat TGFβ1, p-Smad2/3, and fibronectin were upregulated in WT diabetic mice; however, expression of thesesignaling molecules was not changed in TRPC3/6/7-/- diabetic mice. In conclusion, deletion of DAG-responsiveTRPCs attenuates diabetic renal injury via inhibiting the upregulation of TGFβ1 signaling in diabetic kidneys.Fil: Liu, Benju. Huazhong University of Science and Technology; ChinaFil: He, Xiju. Huazhong University of Science and Technology; ChinaFil: Li, Shoutian. Yangtze University; ChinaFil: Xu, Benke. Yangtze University; ChinaFil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Liao, Yanhong. Huazhong University of Science and Technology; Chin

Intranasal Delivery of Cationic PLGA Nano/Microparticles- Loaded FMDV DNA Vaccine Encoding IL-6 Elicited Protective Immunity against FMDV Challenge

Mucosal vaccination has been demonstrated to be an effective means of eliciting protective immunity against aerosol infections of foot and mouth disease virus (FMDV) and various approaches have been used to improve mucosal response to this pathogen. In this study, cationic PLGA (poly(lactide-co-glycolide)) nano/microparticles were used as an intranasal delivery vehicle as a means administering FMDV DNA vaccine encoding the FMDV capsid protein and the bovine IL-6 gene as a means of enhancing mucosal and systemic immune responses in animals. Three eukaryotic expression plasmids with or without bovine IL-6 gene (pc-P12A3C, pc-IL2AP12A3C and pc-P12AIL3C) were generated. The two latter plasmids were designed with the IL-6 gene located either before or between the P12A and 3C genes, respectively, as a means of determining if the location of the IL-6 gene affected capsid assembly and the subsequent immune response. Guinea pigs and rats were intranasally vaccinated with the respective chitosan-coated PLGA nano/microparticles-loaded FMDV DNA vaccine formulations. Animals immunized with pc-P12AIL3C (followed by animals vaccinated with pc-P12A3C and pc-IL2AP12A3C) developed the highest levels of antigen-specific serum IgG and IgA antibody responses and the highest levels of sIgA (secretory IgA) present in mucosal tissues. However, the highest levels of neutralizing antibodies were generated in pc-IL2AP12A3C-immunized animals (followed by pc-P12AIL3C- and then in pc-P12A3C-immunized animals). pc-IL2AP12A3C-immunized animals also developed stronger cell mediated immune responses (followed by pc-P12AIL3C- and pc-P12A3C-immunized animals) as evidenced by antigen-specific T-cell proliferation and expression levels of IFN-γ by both CD4+ and CD8+ splenic T cells. The percentage of animals protected against FMDV challenge following immunizations with pc-IL2AP12A3C, pc-P12AIL3C or pc-P12A3C were 3/5, 1/5 and 0/5, respectively. These data suggested that intranasal delivery of cationic PLGA nano/microparticles loaded with various FMDV DNA vaccine formulations encoding IL-6 as a molecular adjuvant enhanced protective immunity against FMDV, particularly pc-IL2AP12A3C with IL-6 gene located before P12A3C gene

On the “Double Adaptation” of Teaching and its Comprehensive Effect

The teaching methods of various subjects should not only meet the inner needs of students, but also conform to the objective laws of external development. So as to realize “double adaptation”. After repeated research and experimentation, we found that the “guided learning method” implemented with a “four-step procedure” can better solve this problem. On this basis, we can achieve a high degree of integration of “teaching” and “learning”, a high degree of integration of lesson plan, textbooks, assignments and examination papers, a high degree of integration of teaching methods of various disciplines, and a high degree of integration of many teaching steps such as explanation, practice, consolidation and review. The role and power of this “high level of integration” All kinds of effects should not be underestimated. With the “high level of integration”, it is easy to knock on the door of simple, efficient and effective teaching and learning, thereby making the education to step on a healthy track

First-principles prediction of low-energy structures for AlH3

We report density-functional calculations that predict ten different low-energy structures for aluminum hydride AlH3 with space groups Pnma, P6/mmm, I4/mcm, P4/mbm, P4/nmm, Pmm, P21/m, P21/c, Pbcm, and P4/n. Phonon calculations within harmonic approximation reveal unstable modes in the P6/mmm, I4/mcm, P4/mbm, P4/nmm, Pmm, P21/m, and P21/c structures, indicating that they are unstable at low temperatures. The calculations show that the thermodynamic stabilities for AlH3 with space groups Pnma, Pbcm, and P4/n are overall close to the existing - and -AlH3. From x-ray powder-diffraction patterns, the simulated main-peak positions for AlH3 (P4/n) are in good agreement with experimental -AlH3. A full Rietveld analysis reveals that the fitting space groups Rc, Pbcm, and Pnma to the experimental x-ray powder-diffraction pattern of -AlH3 gives almost the same satisfactory result

Chemical genetics approach reveals the role of Raf kinase inhibitor protein in cell migration.

Chemical genetics approach reveals the role of Raf kinase inhibitor protein in cell migration

Research progress on the role of canonical transient receptor potential channels in skeletal muscle diseases

Canonical transient receptor potential(TRPC) is a kind of non-selective cation channel located in the cell membrane, which plays an important role in electrophysiological activity of cells. Under pathological conditions, TRPC channels are more selective for Ca2+, which will break the Ca2+ homeostasis in skeletal muscle cells and lead to calcium overload and subsequent occurrence of a variety of skeletal muscle diseases. To study the role and mechanism of TRPC channels in skeletal muscle diseases is helpful to provide new ideas for disease treatment

Effects of Straw Return Mode on Soil Aggregates and Associated Carbon in the North China Plain

Crop straw is widely used to manage soil organic carbon (SOC) sequestration as an environmentally friendly practice in the North China Plain. However, little is known about the effects of straw returning modes on SOC sequestration in this region. Thus, a field experiment was conducted to study SOC accumulation and mineralization as well as aggregate stability and aggregate-associated SOC for the following three straw returning modes: no straw returning (NSR), only wheat straw returning (WR), and both wheat and maize straw returning (WR-MR). SOC concentration and storage were higher for WR and WR-MR than for NSR in the 0–20 cm soil layer, respectively (p < 0.05). Although WR and WR-MR resulted in higher mineralization per unit of soil than NSR, no significant difference in mineralization per unit of soil carbon was observed among straw returning modes in the upper soil layer. The mean weight diameters of aggregates at 0–5 cm were higher under treatments with crop retention than under NSR. At this soil depth, the aggregate-associated C concentration and stock for each soil size were significantly decreased by NSR. These findings suggest that WR-MR and WR are effective residue management practices. In particular, WR is the optimal strategy to enhance SOC sequestration, considering other applications of straw (e.g., forage, fuel, or biomass)

First-principles prediction of low-energy structures for AlH3

We report density-functional calculations that predict ten different low-energy structures for aluminum hydride AlH3 with space groups Pnma, P6/mmm, I4/mcm, P4/mbm, P4/nmm, Pmm, P21/m, P21/c, Pbcm, and P4/n. Phonon calculations within harmonic approximation reveal unstable modes in the P6/mmm, I4/mcm, P4/mbm, P4/nmm, Pmm, P21/m, and P21/c structures, indicating that they are unstable at low temperatures. The calculations show that the thermodynamic stabilities for AlH3 with space groups Pnma, Pbcm, and P4/n are overall close to the existing - and -AlH3. From x-ray powder-diffraction patterns, the simulated main-peak positions for AlH3 (P4/n) are in good agreement with experimental -AlH3. A full Rietveld analysis reveals that the fitting space groups Rc, Pbcm, and Pnma to the experimental x-ray powder-diffraction pattern of -AlH3 gives almost the same satisfactory result