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Recent studies suggested that DNA double-strand breaks (DSBs) were associated with the pathogenesis of chronic kidney disease (CKD). The purpose of this investigation was to determine the role of Sirtuin6 (Sirt6), a histone deacetylase related to DNA damage repair, in angiotensin (Ang) II-induced DNA DSBs and the cell injury of podocytes and explore the possible mechanism. Here we showed that an increase of DNA DSBs was accompanied by a reduction in Sirt6 expression in the glomeruli of patients with hypertensive nephropathy (HN). Similar results were found in rat kidneys infused with Ang II and in cultured podocytes stimulated with Ang II. Sirt6 overexpression inhibited Ang II-induced ROS generation and DNA DSBs, and thus served as a protection against Ang II-induced apoptosis in podocytes. Moreover, Sirt6 activation enhanced Nrf2 and HO-1 gene expressions in podocytes after Ang II treatment. Furthermore, Nrf2 knockdown could partly reverse the cytoprotective effects of Sirt6 activation. In conclusion, our observations demonstrated that the Sirt6-Nrf2-HO-1 pathway played a vital role in relieving Ang II-mediated oxidative DNA damage and podocyte injury.

Multiple radial fractures have brought great pain to the patients, and the treatment takes a long time and the effect is slow, which seriously affects people’s production and life. Traditional conservative treatment methods are mostly used for radius fractures. However, with the development of science and technology of the times, the level of medical treatment is also constantly improving. For radius fractures, the embedded wearable device fixation frame absorption bone nail treatment method has attracted attention. In order to study whether the embedded wearable device fixation frame can treat radius fractures, this article conducted a related survey of radius fracture patients in a hospital in a certain city, reviewed related literature, conducted interviews with professionals and so forth, and collected relevant information. A case template was constructed, and a clinical research model was created using a comprehensive quantitative and qualitative analysis method. The results of the study found that using the research embedded wearable device fixation frame to treat radius fractures with absorption bone nails can achieve good results, and its healing efficiency is about 20% faster than conservative treatment. With decoction, its treatment efficiency can be improved; and the prognostic treatment of the decoction can reduce the complications of the patient’s treatment by about 13%. This shows that the embedded wearable device holder absorption bone nail combined with decoction can play an important role in the treatment of multiple radius fractures.

Herein, we successfully synthesized, for the first time, a diameter of 340 nm hollow yolk-shell type CdS–graphene composite photocatalyst with a hollow core and an independent void space with 5~10 nm between hollow CdS core and graphene (GR) shell with the thickness of about 2 nm (denoted as hollow CdS@@GR), by the bottom-up method using the template-guided layer-by-layer self-assembly process. The formation mechanism of hollow CdS@@GR nanocomposites was proposed. Due to the unique hollow structure that can absorb more light, more dye, and catalyst molecules and the synergistic effect between hollow CdS core and GR shell with void space, hollow CdS@@GR showed enhanced photocatalytic performance. In addition, GR shell can effectively protect CdS from photocorrosion, and even after five repeated runs, the recycled nanocomposites exhibited superior stability. Moreover, we also proposed the possible photocatalytic mechanism of such nanostructures based on free radical capturing experiments and fluorescent probe technique. The design and fabrication of the hollow yolk-shell structured nanocomposites will provide a new potential route for other stable and efficient photocatalysts to satisfy versatile solar energy conversion.

Hidradenitis suppurativa is a chronic skin disease characterised by repeated skin abscesses with sinus tracts and scar formation. Currently, the aetiology and pathogenesis of hidradenitis suppurativa remain unclear. Genetic factors, immune disorders, hormonal abnormalities, skin-microbial dysbiosis, smoking, obesity and mechanical friction all influence hidradenitis suppurativa pathogenesis. Moreover, hidradenitis suppurativa has a familial subset with autosomal dominant transmission proposed and is related to a mutation of γ-secretase component genes. In this review, we analyse and summarise research progress regarding the relationship between the γ-secretase gene dysfunction and the pathogenesis of hidradenitis suppurativa.

Increasing data have shown that angiotensin II (Ang II) perpetuates podocyte injury and promotes progression to end-stage kidney disease. The mechanism underlying Ang II-induced podocyte apoptosis has not been established. C-terminal Src kinase (Csk) is a cytoplasmic kinase that interacts with scaffolding proteins involved in cell growth, adhesion, and polarization, and the role of Csk in regulating cellular apoptosis has gradually attracted attention. This study evaluates the role of Csk in Ang II-induced podocyte apoptosis. In vivo, Wistar rats were randomly subjected to a normal saline or Ang II infusion. In vitro, we exposed differentiated mouse podocytes to Ang II. Ang II increased Csk expression and induced podocyte apoptosis, stimulated Csk translocation and binding to Caveolin-1, and stimulated decreased Fyn pY416, increased Fyn pY529, and nephrin dephosphorylation. Csk knockdown prevented Ang II-induced podocyte apoptosis, reduced Fyn kinase inactivation, and increased the interaction between nephrin and the activated form of Fyn, accompanied by a reduced interaction between Csk and Caveolin-1. These findings indicate that Ang II induces podocyte injury via a Csk-dependent pathway.

Aim To investigate the role of the non-receptor tyrosine kinase c-Abl in high glucose-induced podocyte injury and its possible signal transduction pathway. Methods Sixteen C57BL/6 mice were randomly assigned to a group with diabetes and a normal control group. Subsequently, differentiated mouse podocytes were exposed to high-glucose conditions, and podocyte apoptosis was then assessed by flow cytometry and Hoechst 33258 staining. Western blot and immunofluorescence assay were used to measure c-Abl expression. Co-immunoprecipitation assay was used and c-Abl siRNA was applied to evaluate the interaction between c-Abl and p53. Results High glucose promotes podocyte apoptosis. The c-Abl expression in podocytes was increased after exposure to high glucose, stimulating the p53 signaling pathway. Conversely, treatment with c-Abl siRNA restored high glucose-promoted podocyte apoptosis and resulted in the reduction of p53 expression . Conclusion c-Abl contributes to high glucose-induced podocyte apoptosis via p53 signaling pathway.

Angiotensin II (Ang II) has been reported to cause podocyte apoptosis in rats both in vivo and in vitro studies. However, the underlying mechanisms are poorly understood. In the present study, we investigated the role of the nonreceptor tyrosine kinase c-Abl in Ang II-induced podocyte apoptosis. Male Sprague-Dawley rats in groups of 12 were administered either Ang II (400 kg/kg/min) or Ang II + STI-571 (50 mg/kg/day) by osmotic minipumps. In addition, 12 rats-receiving normal saline served as the control. Glomeruli c-Abl expression was carried out by real time PCR, Western blotting and immunolabeled, and occurrence of apoptosis was carried out by TUNEL staining and transmission electron microscopic analysis. In vitro studies, conditionally immortalized mouse podocytes were treated with Ang II (10(-9)-10(-6) M) in the presence or absence of either c-Abl inhibitor, Src-I1, specific c-Abl siRNA, or c-Abl plasmid alone. Quantification of podocyte c-Abl expression and c-Abl phosphorylation at Y245 and Y412 was carried out by real time PCR, Western blotting and immunofluorescence imaging. The nuclear c-Abl and p53 were quantified by co-immunoprecipitation and Western blotting studies. Podocyte apoptosis was analysed by flow cytometry and Hoechst-33342 staining. c-Abl expression was demonstrated in rat kidney podocytes in vivo and cultured mouse podocytes in vitro. Ang II-receiving rats displayed enhanced podocyte c-Abl expression. And Ang II significantly stimulated c-Abl expression in cultured podocytes. Furthermore Ang II upregulated podocyte c-Abl phosphorylation at Y245 and Y412. Ang II also induced an increase of nuclear p53 protein and nuclear c-Abl-p53 complexes in podocytes and podocyte apoptosis. Down-regulation of c-Abl expression by c-Abl inhibitor (Src-I1) as well as specific siRNA inhibited Ang II-induced podocyte apoptosis; conversely, podoctyes transfected with c-Abl plasmid displayed enhanced apoptosis. These findings indicate that c-Abl may mediates Ang II-induced podocyte apoptosis, and inhibition of c-Abl expression can protect podocytes from Ang II-induced injury.

Nephrin, an important structural and signal molecule of podocyte slit-diaphragm (SD), has been suggested to contribute to the angiotensin II (Ang II)-induced podocyte injury. Caveolin-1 has been demonstrated to play a crucial role in signaling transduction. In the present study, we evaluated the role of caveolin-1 in Ang II-induced nephrin phosphorylation in podocytes. Wistar rats-receiving either Ang II (400 ng/kg/min) or normal saline (via subcutaneous osmotic mini-pumps, control) were administered either vehicle or telmisartan (3 mg/kg/min) for 14 or 28 days. Blood pressure, 24-hour urinary albumin and serum biochemical profile were measured at the end of the experimental period. Renal histomorphology was evaluated through light and electron microscopy. In vitro, cultured murine podocytes were exposed to Ang II (10(-6)M) pretreated with or without losartan (10(-5) M) for variable time periods. Nephrin and caveolin-1 expression and their phosphorylation were analyzed by Western-blotting and immunofluorescence. Caveolar membrane fractions were isolated by sucrose density gradient centrifugation, and then the distribution and interactions between Ang II type 1 receptor (AT1), nephrin, C-terminal Src kinase (Csk) and caveolin-1 were evaluated using Western-blotting and co-immunoprecipitation. Podocyte apoptosis was evaluated by cell nucleus staining with Hoechst-33342. Ang II-receiving rats displayed diminished phosphorylation of nephrin but enhanced glomerular/podocyte injury and proteinuria when compared to control rats. Under control conditions, podocyte displayed expression of caveolin-1 in abundance but only a low level of phospho moiety. Nonetheless, Ang II stimulated caveolin-1 phosphorylation without any change in total protein expression. Nephrin and caveolin-1 were co-localized in caveolae fractions. AT1 receptors and Csk were moved to caveolae fractions and had an interaction with caveolin-1 after the stimulation with Ang II. Transfection of caveolin-1 plasmid (pEGFPC3-cav-1) significantly increased Ang II-induced nephrin dephosphorylation and podocyte apoptosis. Furthermore, knockdown of caveolin-1 expression (using siRNA) inhibited nephrin dephosphorylation and prevented Ang II-induced podocyte apoptosis. These findings indicate that Ang II induces nephrin dephosphorylation and podocyte injury through a caveolin-1-dependent mechanism.

Ang II plays a vital role in the initiation and progression of proteinuric kidney diseases, but the mechanism is still elusive. It is shown that c-Abl is a molecular chaperone of nephrin signaling and the SHIP2-Akt pathway, and released c-Abl from nephrin is involved in Ang II–induced podocyte injury., Recent studies have shown that nephrin plays a vital role in angiotensin II (Ang II)–induced podocyte injury and thus contributes to the onset of proteinuria and the progression of renal diseases, but its specific mechanism remains unclear. c-Abl is an SH2/SH3 domain–containing nonreceptor tyrosine kinase that is involved in cell survival and regulation of the cytoskeleton. Phosphorylated nephrin is able to interact with molecules containing SH2/SH3 domains, suggesting that c-Abl may be a downstream molecule of nephrin signaling. Here we report that Ang II–infused rats developed proteinuria and podocyte damage accompanied by nephrin dephosphorylation and minimal interaction between nephrin and c-Abl. In vitro, Ang II induced podocyte injury and nephrin and Akt dephosphorylation, which occurred in tandem with minimal interaction between nephrin and c-Abl. Moreover, Ang II promoted c-Abl phosphorylation and interaction between c-Abl and SH2 domain–containing 5′-inositol phosphatase 2 (SHIP2). c-Abl small interfering RNA (siRNA) and STI571 (c-Abl inhibitor) provided protection against Ang II–induced podocyte injury, suppressed the Ang II-induced c-Abl–SHIP2 interaction and SHIP2 phosphorylation, and maintained a stable level of nephrin phosphorylation. These results indicate that c-Abl is a molecular chaperone of nephrin signaling and the SHIP2-Akt pathway and that the released c-Abl contributes to Ang II–induced podocyte injury.

Background/Aims: The mechanism underlying angiotensin II (AngII)-promoted podocyte apoptosis has not been established. IQ domain GTPase-activating protein 1 (IQGAP1) is a scaffolding protein of the mitogen-activated protein kinases (MAPK) signaling pathway, and plays a significant role in apoptosis. The present study evaluates the role of IQGAP1 in AngII-induced podocyte apoptosis. Methods: We randomly assigned 36 male Wistar rats to a normal saline-infused group, an AngII-infused group, or a normal control group, and measured podocyte apoptosis by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay and transmission electron microscopic analysis. In addition, we exposed differentiated mouse podocytes to AngII and then assessed apoptosis by flow cytometry and Hoechst-33258 staining. Expression of IQGAP1 was measured by Western blotting, real-time PCR and immunofluorescence assay in vivo and in vitro. IQGAP1 siRNA and MAPK pathway inhibitors were further introduced to investigate the role of IQGAP1 and MAPK signaling in the process. Coimmunoprecipitation was used to evaluate the interaction between ERK1/2 and IQGAP1. Results: AngII promoted podocyte apoptosis in vivo and in vitro. IQGAP1 had a linear distribution along the capillary loops of glomeruli in vivo, and was in the cellular membrane and cytoplasm of cultured podocytes. AngII stimulated IQGAP1 expression and increased phosphorylation of P38, JNK, and ERK1/2. Knockdown of IQGAP1 with siRNA prevented AngII-induced apoptosis of podocytes and reduced AngII-induced phosphorylation of ERK1/2, but not that of P38, JNK. This was accompanied by a reduced interaction between ERK1/2 and IQGAP1. Conclusion: IQGAP1 contributes to AngII-induced apoptosis of podocytes by interacting with the ERK1/2 signaling protein.

Atomic layer deposition has attracted much attention recently in fabricating noble metal nanoparticles for a wide range of applications. We have explored synthesizing palladium nanoparticles via atomic layer deposition on self-assembled monolayers modified silicon substrate. Using alkyltrichlorosilanes as the passivating agents, our results show the method is capable of fabricating Pd nanoparticles with well controlled density and particle diameter on the modified silicon substrate.

Introduction Podocytes play an important role in the pathogenesis and progression of glomerulosclerosis. Various elements of the renin-angiotensin-aldosterone system can induce podocyte apoptosis. However, little is known about the direct effects of renin on podocytes. Methods The authors used the mouse podocyte cell line to investigate the apoptotic effects mediated by the renin receptor. The authors used fluorescent staining and reverse-transcriptase polymerase chain reaction to detect renin receptor expression. Podocytes were incubated with renin for variable time periods. Apoptosis was evaluated by cell nucleus staining, and caspase-3, p38 and phospho-p38 mitogen-activated protein kinase (MAPK) were measured. Results The authors found that both renin receptor mRNA and protein were expressed in the mouse podocyte cell line. Exposure of podocytes to renin induced podocyte apoptosis in a time- and dose-dependent manner, which was accompanied by upregulation of active caspase-3 and increased expression of p38 MAPK. p38 MAPK phosphorylation and apoptosis were inhibited when the cells were pretreated with p38 MAPK inhibitor. Transfection of renin receptor small interfering RNA attenuated the above changes induced by renin. Furthermore, the effects of renin were not altered by inhibition of angiotensin II-mediated effects using enalaprilat or losartan. Conclusion The authors conclude that the effects of renin are mediated through the activation of rennin receptor and are independent of angiotensin II generation.

Summary Surfactant protein D (SP-D), a member of the C-type lectin (collectin) protein family, plays a critical role in innate host defence against various microbial pathogens and in the modulation of inflammatory responses in the lung. However, little is known about its expression and biological function in the kidney. In this work, we studied SP-D expression in human kidney and cultured human renal proximal tubular epithelial cells (HK-2), and examined the effect of SP-D on proinflammatory cytokine production after lipopolysaccharide (LPS) stimulus. We observed the expression of both SP-D mRNA and protein in human kidney and in-vitro HK-2 cells by immunohistochemistry, Western blot analysis, reverse transcription–polymerase chain reaction (RT–PCR) and real-time PCR. To explore the potential role of SP-D in the pathogenesis of tubulointerstitial fibrosis in kidney infection, we examined the production of monocyte chemoattractant protein-1 (MCP-1) in HK-2 cells after LPS treatment. Results showed that the level of MCP-1 in the conditioned medium increased significantly when HK-2 cells were cultured with LPS (>0·1 µg/ml) for 8 h. Of interest, LPS treatment inhibited SP-D expression in HK-2 cells. Furthermore, over-expression of SP-D reduced significantly the LPS-induced expression of MCP-1 in transfected cells. These findings suggest that SP-D in the kidney functions as an anti-inflammatory factor in renal tubular epithelial cells and may modulate tubulointerstitial fibrosis in kidney.

Background. Several studies in patients with primary aldosteronism (PA) have suggested that aldosterone (ALD) is directly contributing to albuminuria. However, there are limited data pertaining to the direct role of ALD in in vivo models in regard to the induction of renal injury and the involved mechanisms. In the present study, we established a high-dose ALD-infused rat model to evaluate urinary albumin excretion rate (UAER) and podocyte damage. Moreover, we studied the effect of eplerenone (EPL), telmisartan (TEL) and amlodipine (AML) on ALD-induced renal structural and functional changes. Methods. Immunohistochemical and real-time PCR analyses, and TUNEL assays were performed to evaluate nephrin expression and podocyte injury. Results. ALD-receiving rats (ARR) showed a progressive increase in BP, UAER and proteinuria when compared with control rats (CR). Conversely, BP was significantly reduced in ALD + EPL (A/ERR)-, ALD + AML (A/ARR)- and ALD + TEL (A/TRR)-treated rats. However, UAER and proteinuria were decreased only in A/ERR and A/TRR, but not in A/ARR. Only EPL administration provided protection against ALD-induced podocyte apoptosis. Renal tissue of ARR revealed enhanced expression of nephrin protein and mRNA. This effect of ALD was inhibited by EPL, but not by TEL or AML. Conclusions. ALD induces direct glomerular injury independent of its haemodynamic effects; this effect of ALD is, at least in part, mediated through activation of the mineralocorticoid receptor.