Metabonomics analysis of aqueous humor samples from cataract patients with branch retinal vein occlusion.

Cataract (CAT) has a very high incidence rate among the middle-aged and elderly, with most patients complicated by branch retinal vein occlusion (BRVO), a key cause of blindness. In this study, through metabolomic analysis of aqueous humor samples from CAT patients with BRVO, a total of 319 different metabolites were found, most of which belonged to the categories of carboxylic acids and derivatives, fatty acyls, and organooxygen compounds. The most typical metabolites were 3-methylhistidine and biliverdin, which were up-regulated, as well as the down-regulated beta-glycerophosphoric acid. Tricosanoic acid showed the most significant correlation with CAT+BRVO. According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, the most commonly related keywords for differentially expressed metabolites were biosynthesis of unsaturated fatty acids and synaptic vesicle cycle. These results can not only help to further understand the pathogenesis of CAT complicated by BRVO in clinical practice, but also provide some new therapeutic research directions.

sPLA2-IB and PLA2R mediate insufficient autophagy and contribute to podocyte injury in idiopathic membranous nephropathy by activation of the p38MAPK/mTOR/ULK1ser757 signaling pathway.

Secretory phospholipase A2 group IB (sPLA2-IB) and M-type phospholipase A2 receptor (PLA2R) are closely associated with proteinuria in idiopathic membranous nephropathy (IMN). Podocytes constitute an important component of glomerular filtration, and high basal autophagy is indispensable for podocyte function. The current study aimed to analyze the relationship between sPLA2-IB and podocyte autophagy in IMN and determine whether sPLA2-IB mediates abnormal autophagy regulation in podocytes. The serum sPLA2-IB level and podocyte autophagy were detected, and clinical data were collected from IMN patients with different proteinuria levels. Then, the effects of sPLA2-IB on autophagy signaling pathways were evaluated in cultured human podocytes treated with sPLA2-IB, rapamycin, p38 inhibition, and PLA2R-siRNA in vitro. We found that IMN patients with nephrotic-range proteinuria have a significantly higher level of sPLA2-IB and fewer autophagosomes than those with non-nephrotic-range proteinuria. In vitro sPLA2-IB-induced insufficient autophagy in podocytes and promoted podocyte injury via activation of the mTOR/ULK1ser757 signaling pathway. Moreover, inhibition of p38 MAPK evidently abrogated sPLA2-IB-induced autophagy and the activation of mTOR/ULK1ser757 . Additionally, PLA2R silencing demonstrated that sPLA2-IB-induced abnormal autophagy was also PLA2R-dependent. In conclusion, the results revealed that sPLA2-IB downregulated autophagy and contributed to podocyte injury via PLA2R though activation of the p38MAPK/mTOR/ULK1ser757 signaling pathway.

Excessive arachidonic acid induced actin bunching remodeling and podocyte injury via a PKA-c-Abl dependent pathway.

Recent studies have shown that serum secretory phospholipase A2 group IB (sPLA2-IB) is associated with proteinuric kidney diseases and plays a pivotal role in podocyte injury via its natural receptor. Arachidonic acid (AA), as a major metabolite of sPLA2-IB, regulates the actin bungling remodeling and contributes to the podocyte injury. However, the underlying mechanism of AA in the regulation of podocyte actin remodeling and human podocyte injury is unclear. Here, we reported that AA induced F-actin cytoskeletal ring formation and promoted protein kinase A (PKA), nephrin and c-Abl phosphorylation. Moreover, AA promoted c-Abl translocation from the nucleus to the cytoplasm and increased the recruitment of c-Abl to p-nephrin by the interaction between them. H89 (PKA inhibitor) provided protection against AA-induced F-actin bunching remodeling, down-regulated nephrin phosphorylation, and suppressed the c-Abl translocation and activation. STI571 (c-Abl inhibitor) also improved the AA associated F-actin bunching remodeling. In addition, H89 and STI571 both alleviated apoptosis and adhesion damage of podocyte. These results indicate that an excess of AA treatment is detrimental to the podocyte actin cytoskeleton and promotes podocyte injury due to the activation of PKA-c-Abl signaling.

Effects of Probiotics on Malnutrition and Health-Related Quality of Life in Patients Undergoing Peritoneal Dialysis: A Randomized Controlled Trial.

OBJECTIVE: Alterations in the gut microbiota and host responses have been implicated in the progression of end-stage renal disease, increased cardiovascular risk, uremic toxicity, and inflammation. The purpose of this study was to evaluate the clinical efficacy of probiotics on malnutrition and health-related quality of life in patients undergoing peritoneal dialysis (PD). DESIGN AND METHODS: A total of 116 patients undergoing PD were randomly divided into an intervention group (n = 58) and a control group (n = 58). The intervention group received a daily dose of probiotics (1 × 109 CFU/day, i.e., 2 capsules, tid) for 2 months, while the control group did not receive probiotics during the same period. Biochemical indicators, physical measurements, and scores on the SF-36 were measured before and 2 months after the intervention. RESULTS: A total of 98 patients completed the study (50 in the intervention group and 48 in the control group). Among patients receiving probiotics, the levels of high-sensitivity C-reactive protein and interleukin-6 decreased after 2 months of treatment, while the serum albumin levels, upper arm circumference, and triceps skinfold thickness increased significantly. The probiotic group had higher scores on the physical functioning and social functioning domains than the control group after 2 months. CONCLUSIONS: Probiotics could significantly decrease the serum levels of high-sensitivity C-reactive protein and interleukin-6 and increase the serum albumin levels, upper arm circumference, and triceps skinfold thickness in patients undergoing PD. As a result, malnutrition and health-related quality of life partially improved after probiotic supplementation in patients undergoing PD.

Retinal Transcriptomics Analysis Reveals the Underlying Mechanism of Disturbed Emmetropization Induced by Wavelength Defocus.

PURPOSE: Wavelength signals play a vital role in refractive development. This study aimed to explore the retinal transcriptome signature in these processes. METHODS: Guinea pigs were randomly divided into three groups exposed to white, blue, or green environmental light for eight weeks. Refraction and axial length were evaluated every 4 weeks, and the retinal transcriptome was profiled at 8 weeks. RESULTS: Compared with the white group, ocular refraction significantly decreased and ocular axial length significantly extended in the green group whereas these parameters showed opposite trends in the blue group. RNA-sequencing showed that, compared with the white group, 184 and 171 differentially expressed genes (DEGs) were found in the blue and green groups, respectively. Among these DEGs, only 31 overlapped. These two sets of DEGs were enriched in distinct biological processes and pathways. There were 268 DEGs between the blue and green groups, which were primarily enriched in the extracellular matrix, and metabolism, receptor activity, and ion binding processes. In addition, nine human genes, including ECEL1, CHRND, SHBG, PRSS56, OVOL1, RDH5, WNT7B, PEBP4, CA12, were identified to be related to myopia development and wavelength response, indicating the potential role of these genes in human wavelength-induced myopia. CONCLUSIONS: In this study, we identified retinal targets and pathways involved in the response to wavelength signals in emmetropization.

Emodin ameliorates renal injury in BXSB mice by modulating TNF-α/ICAM-1.

The purpose of the present study was to explore the effects of emodin on renal injury in a BXSB mouse model of lupus and its mechanisms. BXSB mice were fed different concentrations of emodin (0, 5, 10 and 20 mg/kg.d), and the levels of intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α) and fibronectin (FN) levels in the glomeruli and serum levels of the anti-dsDNA antibody were determined. Mesangial cells (MCs) were cultured in vitro, and IgG-type anti-dsDNA antibody and/or emodin were added to the MC culture supernatant. In addition, TNF-α small interfering RNA (siRNA) was transfected into MCs to explore the mechanism of action of emodin. The results showed that the mice fed emodin presented decreases in the urinary protein content and glomerular TNF-α, ICAM-1 and FN levels (P<0.05). Moreover, the urine protein, TNF-α, ICAM-1 and FN levels were decreased in a dose-dependent manner (P<0.05). In vitro, the anti-dsDNA antibody group exhibited increased levels of ICAM-1 and TNF-α (P<0.05), and the anti-dsDNA antibody group showed myofibroblast-like structural changes. The aforementioned indexes were decreased in the emodin group (P<0.05), and the extent of transdifferentiation was significantly reduced. Moreover, the level of ICAM-1 decreased with the down-regulation of TNF-α (P<0.05). Emodin reduced the urine protein levels and serum levels of the anti-dsDNA antibody in a mouse model of lupus nephritis (LN). The underlying mechanism may be related to decreased levels of TNF-α, ICAM-1 and FN and the inhibition of dsDNA antibody-induced MC damage.

Novel conservative treatment for peritoneal dialysis-related hydrothorax: Two case reports.

BACKGROUND: Peritoneal dialysis (PD) is an important renal replacement therapy for patients with end-stage renal disease. PD-related hydrothorax is a rare but serious complication in PD patients, produced by the movement of peritoneal dialysate through pleuroperitoneal fistulas. In previous reports, patients with hydrothorax secondary to PD were usually recommended to discontinue PD and transfer to hemodialysis (HD). Herein, we describe another method of managing this complication-with an adjusted PD prescription and continuous drainage of pleural effusion, patients could continue PD without recurrence of hydrothorax. CASE SUMMARY: In this report, we present the medical records of 2 patients with hydrothorax secondary to PD. We recommended intermittent PD with continuous drainage of pleural effusion. A type 18Ga soft catheter was placed to drain pleural effusion. Ultrasound-guided thoracentesis was performed, and the soft catheter was placed in the pleural cavity for a long period (3 mo and 2 mo, respectively). The pleural catheter was removed when no fluid was drained from the pleural cavity. After several months, pleuroperitoneal fistulas were closed in both patients and PD was continued. These patients did not transfer to HD, had no recurrence of hydrothorax and were still treated with PD after 1 year. CONCLUSION: These 2 case reports show that continuous drainage of pleural effusion with an 18Ga soft catheter is a useful method for hydrothorax secondary to PD.

sPLA2-IB Level Correlates with Hyperlipidemia and the Prognosis of Idiopathic Membranous Nephropathy.

Recent studies suggested that serum secretory phospholipase A2 group IB (sPLA2-IB) was increased in idiopathic membranous nephropathy (IMN). However, the interference of high lipemia on the sPLA2-IB levels was not taken into account in these studies. The present study aimed to investigate the correlation between sPLA2-IB and lipemia, and the clinical merit of sPLA2-IB in the prediction of prognosis of IMN patients. A total of 64 IMN patients, 39 immunoglobulin A nephropathy (IgAN) patients and 64 healthy controls were included in the study. The levels of serum sPLA2-IB, lipemia and proteinuria were measured. Fifty IMN patients were followed up for 6 months. Pathologic stages were made for all IgAN and IMN patients. The results showed that the levels of serum sPLA2-IB, cholesterol and low-density lipoprotein cholesterol (LDL-C) were significantly higher, and the levels of albumin and high-density lipoprotein cholesterol (HDL-C) were significantly lower in IMN patients than in healthy controls and IgAN patients. Serum sPLA2-IB levels were also found to be higher in IgAN patients than in heathy controls, but the association of serum sPLA2-IB levels with proteinuria, cholesterol and albumin was only shown in IMN patients. Antibody against M-type receptor for secretory phospholipase A2 (PLA2R1) was positive in 81.3% IMN patients. Glomerular sPLA2-IB deposition, podocyte fused processes, and density deposition on thickened basement membrane were seen in IMN patients, but not in IgAN patients. IMN patients with lower sPLA2-IB and proteinuria levels were found to have better outcome after the 6-month follow-up. In IMN patients, sPLA2-IB levels were significantly increased in both serum and renal tissue. In conclusion, serum sPLA2-IB was closely correlated with proteinuria, albumin and cholesterol, and IMN patients with lower sPLA2-IB levels were more likely to achieve a better outcome.