Penehyclidine hydrochloride suppresses inflammation response and reduces podocyte injury in diabetic nephropathy by targeting fibrinogen-like protein 2.

BACKGROUND: Diabetic nephropathy (DN) is one of the main complications of diabetes. Penehyclidine hydrochloride (PHC) has anti-inflammatory, anti-apoptotic and anti-oxidative stress effects. Nevertheless, whether PHC can be used to prevent podocyte injury has not been reported. OBJECTIVES: This present study aimed to identify the functional role of PHC in DN as well as its underlying mechanism. METHODS: The high-glucose (HG)-induced podocyte damage in vitro model was established. The proliferation, apoptotic rate, inflammatory factors, and gene/protein expressions of HG-induced MPC5 cells were determined using CCK-8 assay, flow cytometry, ELISA, real-time PCR, and Western blot upon PHC treatment. Co-immunoprecipitation experiments and pull-down assay were performed to verify the interactions between fibrinogen-like protein 2 (Fgl2) and toll-like receptor 4 (TLR4) as well as TLR4 and NLRP3. A rat in vivo model was used to confirm the effect of PHC treatment. RESULTS: PHC treatment reduced Fgl2 expression and inhibited HG-induced podocyte injury and DN-induced kidney damage. Flg2 was associated with TLR4 and NLRP3. It was further proved that PHC treatment suppressed the TLR4-NF-кB and NLRP3-Caspase-1 pathways through Fgl2, which eventually inhibited inflammatory cytokines and prevented HG-induced podocyte injury both in vitro and in vivo. CONCLUSION: PHC treatment possibly ameliorates DN by preventing podocyte injury via inactivating the TLR4-NF-кB and NLRP3-Caspase-1 signaling pathways by Flg2.

[Effects of dexmedetomidine on the proliferation, invasiveness and tumorigenesis of human prostate cancer PC3 cells and its action mechanism].

OBJECTIVE: To investigate the effects of dexmedetomidine (Dex) on the proliferation, invasiveness and tumorigenesis of human PCa PC3 cells and its action mechanism. METHODS: We treated human PCa PC3 cells with Dex at 0 µmol/L (the control group), 1 µmol/L (Dex group 1), 2 µmol/L (Dex group 2), and 5 µmol/L (Dex group 3). After 24, 48 and 72 hours of treatment, we examined the proliferation, apoptosis and invasiveness of the cells using cell counting kit-8 (CCK8), flow cytometry and Transwell assay respectively, measured the tumorigenicity of the transplanted tumors in the nude mice, and determined the expressions of mitogen-activated protein kinase (MAPK) signaling pathway-related proteins in the cells by Western blot. RESULTS: After treatment, the A value of the PC3 cells was significantly increased in all the four groups (P < 0.05). Compared with the control group, the three Dex groups showed a decrease in the A value, an elevated rate of apoptotic cells (P < 0.05), an increased number of membrane-penetrating cells (P < 0.05), reduced volume of the transplanted tumors (P < 0.05), and down-regulated expressions of phosphorylated extracellular signal-regulated kinase (p-ERK) / ERK and phosphorylated c-Jun N-terminal kinase (p-JNK) / JNK (P < 0.05) with the increased dose of Dex. The volume of the transplanted tumors in the nude mice was increased in all the four groups in a time-dependent manner (P < 0.05). CONCLUSION: Dex inhibits the proliferation and invasiveness, promotes the apoptosis, and reduces the tumorigenicity of human PCa PC3 cells by decreasing the phosphorylation of ERK and JNK in the MAPK signaling pathway.

LncRNA TUG1 regulates the development of ischemia-reperfusion mediated acute kidney injury through miR-494-3p/E-cadherin axis.

BACKGROUND: Acute kidney injury (AKI) results from renal dysfunction caused by various causes, resulting in high mortality. The underlying mechanisms of ischemia-reperfusion (I/R) induced AKI is very complicated and needed for further research. Here, we sought to found out the functions of lncRNA TUG1 in I/R-induced AKI. METHODS: In vivo model was constructed by I/R-induced mice and in vitro model was constructed by hypoxia/reoxygenation (H/R)-induced HK-2 cell. Kidney tissue damage was evaluated through H&E staining in mice. Cell flow cytometry was used to detect the degree of apoptosis. TUG1, miR-494-3p and E-cadherin were determined both by RT-PCR and western blot. Dual luciferase assay was employed to validate the relationships between TUG1, miR-494-3p and E-cadherin. Inflammatory factors including IL-1ß, TNFɑ and IL-6 were evaluated by ELISA. RESULTS: lncRNA TUG1 was decreased while miR-494-3p was elevated in vivo and in vitro. Overexpression of TUG1 or transfection with miR-494-3p inhibitor significantly alleviated cell apoptosis. MiR-494-3p directly targeted E-cadherin and TUG1 suppressed cell apoptosis via serving as a miR-494-3p sponge to disinhibit E-cadherin. CONCLUSION: lncRNA TUG1 alleviated I/R-induced AKI through targeting miR-494-3p/E-cadherin.

[Preliminary construction of three-dimensional visual educational system for clinical dentistry based on world wide web webpage].

OBJECTIVE: To establish a new visual educational system of virtual reality for clinical dentistry based on world wide web (WWW) webpage in order to provide more three-dimensional multimedia resources to dental students and an online three-dimensional consulting system for patients. METHODS: Based on computer graphics and three-dimensional webpage technologies, the software of 3Dsmax and Webmax were adopted in the system development. In the Windows environment, the architecture of whole system was established step by step, including three-dimensional model construction, three-dimensional scene setup, transplanting three-dimensional scene into webpage, reediting the virtual scene, realization of interactions within the webpage, initial test, and necessary adjustment. RESULTS: Five cases of three-dimensional interactive webpage for clinical dentistry were completed. The three-dimensional interactive webpage could be accessible through web browser on personal computer, and users could interact with the webpage through rotating, panning and zooming the virtual scene. CONCLUSIONS: It is technically feasible to implement the visual educational system of virtual reality for clinical dentistry based on WWW webpage. Information related to clinical dentistry can be transmitted properly, visually and interactively through three-dimensional webpage.