The miR-486-5p plays a causative role in prostate cancer through negative regulation of multiple tumor suppressor pathways The miR-486-5p plays a causative role in prostate cancer through negative regulation of multiple tumor suppressor pathways

This study systematically evaluated five microbial and four mitochondrial DNA (mtDNA) markers, including sensitivities and specificities under PCR method, and fecal concentrations and decay rates in water under qPCR method. The microbial DNA markers were the three human-associated (BacH, HF183 and B.adolescentis) and two pig-associated (Pig-2-Bac and L.amylovorus), while the mtDNA ones were two human- (H-ND6 and H-ND5) and two pig-associated (P-CytB and P-ND5). All the mtDNA markers showed higher sensitivity (100%) than the microbial ones (84.0–88.8%) except Pig-2-Bac (100%). Specificities of the human mtDNA markers (99.1 and 98.1%) were higher than those of the human-associated microbial ones (57.0–88.8%). But this pattern was not observed in the pig-associated markers where Pig-2-Bac had 100% specificity. The reliability of H-ND6 and H-ND5 was further evidenced to identify locations of the most polluted within the Taihu Lake watershed of China. In general, the microbial DNA markers demonstrated a higher fecal concentration than the mtDNA ones; increasing temperature and sunlight exposure accelerated significantly the decay of all the DNA markers. Results of this study suggest that DNA markers H-ND6, H-ND5, and Pig-2-Bac may be among the best for fecal source tracking in water.

Here we elucidated the pathogenesis of a 14-year-old Chinese female who initially developed an isolated nephropathy followed by a complex clinical presentation with brain and muscle problems, which indicated that the disease process was possibly due to a mitochondrial dysfunction. Careful evaluation of renal biopsy samples revealed a decreased staining of cells induced by COX and NADH dehydrogenase activities, and a strong fragmentation of the mitochondrial network. These anomalies were due to the presence of a mutation in the mitochondrialATP6gene, G8969>A. This mutation leads to replacement of a highly conserved serine residue at position 148 of thea-subunit of ATP synthase. Increasing the mutation load in cybrid cell lines was paralleled by the appearance of abnormal mitochondrial morphologies, diminished respiration and enhanced production of reactive oxygen species. An equivalent of the G8969>A mutation in yeast had dramatic consequences on ATP synthase, with a block in proton translocation. The mutation was particularly abundant (89%) in the kidney compared to blood and urine, which is likely the reason why this organ was affected first. Based on these findings, we suggest that nephrologists should pay more attention to the possibility of a mitochondrial dysfunction when evaluating patients suffering from kidney problems.

Inflammation has recently been attributed to dysbiosis of the gut microbiome, which has been linked to proteinuria in chronic kidney disease. Since Adriamycin® (ADR) is widely used to induce proteinuria in mouse models, the aim of this study was to explore the potential effect of gut microbiome on this process. Both ADR resistant (C57BL/6) and susceptible (BALB/C) strains were part of the induced nephropathy with ADR injection. BALB/C mice significantly presented increased urinary albumin/creatinine ratio (UACR) with renal lesions in pathology, but C57BL/6 mice were absent from kidney damage. Species and genus level resolution analysis showed a shift in gut microbial profile between BALB/C and C57BL/6 mice. ADR further altered the stool microbiome in BALB/C mice, particularly with enrichment of Odoribacter and depletion of Turicibacter, Marvinbryantia and Rikenella. Moreover, the level of UACR in BALB/C mice was marked related to the abundance of Marvinbryantia, Odoribacter and Turicibacter in stool. Meanwhile, ADR remarkably increased the serum levels of interleukin (IL)-2 in BALB/C mice, but not in C57BL/6 mice. It is suggested that the favorably altered stools as shown in the microbiome might promote the inflammation and proteinuria in ADR-sensitive mice, which provides a new insight on the pathogenicity of chronic kidney disease.

C3 glomerulopathy often presents with a membranoproliferative glomerulonephritis (MPGN) pattern, and is principally caused by unrestricted activation of the complement alternative pathway. Genetic abnormalities of the complement system critically implicate in the pathogenesis of C3 glomerulopathy, but a systemic profile remains open, especially in Asia. In this study, we completed a comprehensive screen of 11 candidate alternative pathway genes by using targeted genomic enrichment and massively parallel sequencing on 43 patients with sporadic C3 glomerulopathy, which were classified as dense deposit disease (DDD; n = 10) and C3 glomerulonephritis (C3GN; n = 33) cases. An additional 24 patients with immune complex-mediated MPGN were also enrolled. In total, 4 novel and 16 rare variants were identified: one was classified as likely pathogenic, and the remaining 19 were of uncertain significance. Three variants reportedly led to functional deficiency with supporting evidences. Variants in the CFH, CFI, CD46 and C3 genes were most frequently detected. A defective control of the complement alternative pathway due to hereditary abnormalities was found at frequencies of 50%, 27% and 17% in DDD, C3GN and immune complex-mediated MPGN, respectively. Irrespective of histological type, the patients with likely pathogenic and uncertain significant variants were clinically similar to those without. Accurate genetic screening can give rise to progress in understanding the pathogenesis of C3 glomerulopathy, and the correct assignment of pathogenicity classification is of great importance for better patient care and prognostic or therapeutic advice.