Search

Background: Mitral valve prolapse (MVP) is a common cardiovascular disease defined as a late systolic click or mitral valve lobes that move up into the left atrium during ventricular systole, with or without mitral insufficiency. Dachsous catherin‐related 1 (DCHS1) is one of the two known pathogenic genes associated with MVP. However, there is little information about the renal dysfunction caused by MVP and DCHS1 mutations. Methods: We analyzed the genetic etiology in a rare case of 9‐year‐old boy affected by chronic renal failure with MVP. Subsequently, we constructed stable cell lines overexpressing wild‐type DCHS1 or mutant DCHS1 (c.8309G>A, p.R2770Q) to evaluate the influence of the DCHS1 mutation on the proliferation, apoptosis, and autophagy. Results: Complete exome sequencing and pedigree verification revealed a mutation p.R2770Q (c.8309G>A) in exon 21 of the DCHS1 gene carried by the patient, which may affect the DNA binding. No such mutation was detected in his parents, indicating that this was a new mutation. Potential functional impact of sequence variants was predicted using in silico prediction programs including SIFT, Polyphen2, and Condel. This variant was determined to be a pathogenic mutation that has not been reported elsewhere. Subsequently, we used a stable DCHS1 gene‐mutated HK‐2 cell line to analyse proliferation, apoptosis, and autophagy, showed that kidney volume decreased with increasing cell death associated with a reduced proliferation. Conclusions: Our analysis revealed a heterozygous variation of DCHS1 in a child with MVP. Our observations highlight previously unrecognized phenotypes of the currently recognized MVP genotype, including distinct chronic renal failure. [ABSTRACT FROM AUTHOR]

Fused deposition modeling (FDM) technology decreases production time and cost in engineering industry, but with typical low surface quality. In this study, laser polishing was employed to improve surface quality of copper fiber/polylactide acid (Cu/PLA) composite parts fabricated by FDM. Surface roughness, surface morphology, dynamic mechanical analysis (DMA), and tensile properties were studied. The results showed that after laser polishing, the surface roughness was reduced by more than 91% (from 10.52 to 0.87 μm Sa) at the optimized parameters (the laser power of 5 W and the laser beam diameter of 200 μm). Laser polishing can effectively remove surface defects formed during FDM. DMA showed that the storage modulus, loss modulus, and glass transition temperature of Cu/PLA composites were significantly improved, because the Cu fibers and PLA matrix formed a strong interfacial adhesion after treatment. Moreover, the tensile strength and Young's modulus of the Cu/PLA composites sample also improved by laser polishing. The fracture morphologies were observed, and the possible strengthening mechanism was also discussed. [ABSTRACT FROM AUTHOR]

This study aims to investigate the effects of TNF receptors associated factor 3 (TRAF3) on the signaling pathway and expression of downstream products of nuclear factor kappa B (NF-κB) in the epithelial cells of renal ducts in individuals with polycystic kidney disease (PKD). We observe the TRAF3 genic overexpression of the epithelial cells, which form a tubular branch structure, in polycystic kidneys and to explore the protective effect of TRAF3 on the cystogenesis and progression of PKD. Western blotting analysis was conducted to examine the signaling changes of NF-κB in PKD the epithelial cells and TRAF3 transgenic PKD epithelial cells. Changes in the downstream apoptosis factor and cell proliferation in PKD epithelial cells and TRAF3 transgenic PKD epithelial cells were detected. A three-dimensional matrigel culture experiment was performed to examine abnormal tubulomorphogenesis in vitro. The overexpression of TRAF3 significantly inhibited the signaling pathway of NF-κB in the PKD epithelial cells, downregulated the expression of downstream factors Bcl-2 and Bcl-xl, and significantly decreased cystic epithelial cell proliferation. Additional branch structures were observed in the PKD epithelial cells with a three-dimensional culture compared to wildtype cells. TRAF3 may likely induce apoptosis and resistance to proliferation and may be a new target to inhibit the cyst formation in PKD by regulating the NF-κB signaling pathway Bcl-2 and Bcl-xl activity. © 2017 IUBMB Life, 69(3):170-178, 2017 [ABSTRACT FROM AUTHOR]

Using extreme high‐speed laser cladding technology, Ni60 coatings are laser cladded onto stainless‐steel, 20# steel, and 45# steel substrates. The effect of substrate material properties on the cracking behavior, microstructure, and tribological properties of the Ni60 coating is systematically studied. The results show that as the difference of the coefficient of thermal expansion between the substrate and cladding material decreases, the tendency for crack generation in the cladding layer is reduced. In addition, the difference of the thermal physical properties of the substrate has an important effect on the temperature gradient during the cooling process of the coating, and then affects the growth rate of the grain in the coating and the overall mechanical properties of the coating. Finer grain size, fewer macroscopic coating cracks, and the evenly distributed hard phase in the Ni60 coating on the 20# steel substrate lead to better wear resistance. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Delayed intestinal perforation has various manifestations. For peritonitis with delayed treatment and multi‐bacterial peritonitis, we should be alert to the occurrence of this rare complication. Abdominal CT examination and imaging results judgment based on clinical conditions are particularly important for diagnosis. Delayed intestinal perforation of peritoneal dialysis catheter is a rare but serious complication. We reported a 49‐year‐old patient who had been hospitalized twice within 3 months due to poor drainage of the peritoneal dialysis catheter. During the first hospitalization, peritoneal dialysis‐related peritonitis was diagnosed, and a variety of bacterial infections were cultivated. However, at that time, the actual peritoneal dialysis catheter‐related intestinal perforation was missed, and he was discharged after anti‐infection treatment until a clinical cure was met. After more than 2 months of normal peritoneal dialysis after returning home, the patient again had poor drainage of the peritoneal dialysis catheter, accompanied by the outflow of yellowish‐brown sediment. It was found that the peritoneal dialysis catheter had evidence of intestinal perforation. After the removal of the catheter and intestinal repair, he recovered and was discharged from the hospital and received long‐term hemodialysis treatment. In the case of delayed intestinal perforation, peritoneal dialysis was maintained normally for more than 2 months, which was an unprecedented situation in previous case reports. In addition, we should be alert to the occurrence of this rare complication, especially when we find the occurrence of polybacterial Peritonitis. Abdominal CT examination and imaging results judgment based on clinical conditions are particularly important for diagnosis. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the molecular mechanism of miR‐182 in kidney fibrosis in polycystic kidney disease (PKD). We measured the expression of miR‐182 in kidney tissue of autosomal dominant PKD. Additionally, we investigated the relationship between miR‐182 and fibrotic protein by transfecting miR‐182 mimics and miR‐182 inhibitor into polycystic kidney cyst‐lined epithelial cells, respectively. Furthermore, we observed the interaction between transforming growth factor β1 (TGF‐β1) and miR‐182 and fibrinogen factors of cyst‐lined epithelial cells after TGF‐β1 intervention, and measured the expression of Smad2 and Smad3 protein. Results are presented as follows: (a) MiR‐182 was positively correlated with fibrosis of cyst‐lined epithelial cells; (b) TGF‐β1 could induce fibrosis of cyst‐lined epithelial cells; (c) the expression of miR‐182 had a remarkably impact on the fibrosis induced by TGF‐β1, but had little effect on the expression of TGF‐β1; (d) the expression of Smad3 protein in TGF‐β1 induce‐cyst‐lined epithelial cells was increased. TGF‐β1 and miR‐182 promoting the fibrosis of polycystic kidney cyst‐lined epithelial cells may be mediated by the TGF‐β1/Smad3 signaling pathway, of which Smad3 was an important regulator. [ABSTRACT FROM AUTHOR]

The metabolism and homeostasis of the skeletal system have historically been considered to be associated with the endocrine system. However, this view has been expanded with the recognition of several neural pathways playing important roles in the regulation of bone metabolism via central relays. In particular, bone metabolism and homeostasis have been reported to be precisely modulated by the central neural signaling. Initiated by the finding of leptin, the axis of neural regulation on bone expands rapidly. The semaphorin–plexin system plays an important role in the cross‐talk between osteoclasts and osteoblasts; a complex system has also been identified and includes neuropeptide Y and cannabinoids. These findings facilitate our understanding of the central neuropeptides and neural factors in the modulation of bone metabolism and homeostasis, and these neuronal pathways also represent an area of research scenario that identifies the novel regulation between brain and bone. These regulatory mechanisms correlate with other homeostatic networks and demonstrate a more intricate and synergetic bone biology than previously envisioned. As such, this review summarizes the current knowledge of the neural regulation of bone metabolism and homeostasis, as well as its role in skeletal diseases and discusses the emerging challenges presented in this field. This review summarizes the current knowledge of the neural regulation of bone metabolism and homeostasis, as well as its role in skeletal diseases and discusses the emerging challenges presented in this field. [ABSTRACT FROM AUTHOR]