c-Cbl induced podocin ubiquitination contributes to the podocytes injury in diabetic nephropathy.

The ubiquitination function in diabetic nephropathy (DN) has attracted much attention, but there is a lack of information on its ubiquitylome profile. To examine the differences in protein content and ubiquitination in the kidney between db/db mice and db/m mice, we deployed liquid chromatography-mass spectrometry (LC-MS/MS) to conduct analysis. We determined 145 sites in 86 upregulated modified proteins and 66 sites in 49 downregulated modified proteins at the ubiquitinated level. Moreover, 347 sites among the 319 modified proteins were present only in the db/db mouse kidneys, while 213 sites among the 199 modified proteins were present only in the db/m mouse kidneys. The subcellular localization study indicated that the cytoplasm had the highest proportion of ubiquitinated proteins (31.87%), followed by the nucleus (30.24%) and the plasma membrane (20.33%). The enrichment analysis revealed that the ubiquitinated proteins are mostly linked to tight junctions, oxidative phosphorylation, and thermogenesis. Podocin, as a typical protein of slit diaphragm, whose loss is a crucial cause of proteinuria in DN. Consistent with the results of ubiquitination omics, the K261R mutant of podocin induced the weakest ubiquitination compared with the K301R and K370R mutants. As an E3 ligase, c-Cbl binds to podocin, and the regulation of c-Cbl can impact the ubiquitination of podocin. In conclusion, in DN, podocin ubiquitination contributes to podocyte injury, and K261R is the most significant site. c-Cbl participates in podocin ubiquitination and may be a direct target for preserving the integrity of the slit diaphragm structure, hence reducing proteinuria in DN.

ACSF2 and lysine lactylation contribute to renal tubule injury in diabetes.

AIMS: Lactate accumulation is reported to be a biomarker for diabetic nephropathy progression. Lactate drives lysine lactylation, a newly discovered post-translational modification that is involved in the pathogenesis of cancers and metabolic and inflammatory disease. Here, we aimed to determine whether lysine lactylation is involved in the pathogenesis of diabetic nephropathy. METHODS: Renal biopsy samples from individuals with diabetic nephropathy (n=22) and control samples from individuals without diabetes and kidney disease (n=9) were obtained from the First Affiliated Hospital of Zhengzhou University for immunohistochemical staining. In addition, we carried out global lactylome profiling of kidney tissues from db/m and db/db mice using LC-MS/MS. Furthermore, we assessed the role of lysine lactylation and acyl-CoA synthetase family member 2 (ACSF2) in mitochondrial function in human proximal tubular epithelial cells (HK-2). RESULTS: The expression level of lysine lactylation was significantly increased in the kidneys of individuals with diabetes as well as in kidneys from db/db mice. Integrative lactylome analysis of the kidneys of db/db and db/m mice identified 165 upregulated proteins and 17 downregulated proteins, with an increase in 356 lysine lactylation sites and a decrease in 22 lysine lactylation sites decreased. Subcellular localisation analysis revealed that most lactylated proteins were found in the mitochondria (115 proteins, 269 sites). We further found that lactylation of the K182 site in ACSF2 contributes to mitochondrial dysfunction. Finally, the expression of ACSF2 was notably increased in the kidneys of db/db mice and individuals with diabetic nephropathy. CONCLUSIONS: Our study strongly suggests that lysine lactylation and ACSF2 are mediators of mitochondrial dysfunction and may contribute to the progression of diabetic nephropathy. DATA AVAILABILITY: The LC-MS/MS proteomics data have been deposited in the ProteomeXchange Consortium database ( https://proteomecentral.proteomexchange.org ) via the iProX partner repository with the dataset identifier PXD050070.

Surfactant-Induced Reconfiguration of Urea-Formaldehyde Resins Enables Improved Surface Properties and Gluability of Bamboo.

The high-efficiency development and utilization of bamboo resources can greatly alleviate the current shortage of wood and promote the neutralization of CO2. However, the wide application of bamboo-derived products is largely limited by their unideal surface properties with adhesive as well as poor gluability. Herein, a facile strategy using the surfactant-induced reconfiguration of urea-formaldehyde (UF) resins was proposed to enhance the interface with bamboo and significantly improve its gluability. Specifically, through the coupling of a variety of surfactants, the viscosity and surface tension of the UF resins were properly regulated. Therefore, the resultant surfactant reconfigured UF resin showed much-improved wettability and spreading performance to the surface of both bamboo green and bamboo yellow. Specifically, the contact angle (CA) values of the bamboo green and bamboo yellow decreased from 79.6° to 30.5° and from 57.5° to 28.2°, respectively, with the corresponding resin spreading area increasing from 0.2 mm2 to 7.6 mm2 and from 0.1 mm2 to 5.6 mm2. Moreover, our reconfigured UF resin can reduce the amount of glue spread applied to bond the laminated commercial bamboo veneer products to 60 g m-2, while the products prepared by the initial UF resin are unable to meet the requirements of the test standard, suggesting that this facile method is an effective way to decrease the application of petroleum-based resins and production costs. More broadly, this surfactant reconfigured strategy can also be performed to regulate the wettability between UF resin and other materials (such as polypropylene board and tinplate), expanding the application fields of UF resin.

Prevalence and risk factors of chronic kidney disease and diabetic kidney disease in a central Chinese urban population: a cross-sectional survey.

BACKGROUND: This study was conducted to evaluate and update the current prevalence of and risk factors for chronic kidney disease (CKD) and diabetic kidney disease (DKD) in a central Chinese urban population. METHODS: From December 2017 to June 2018, a total of 5231 subjects were randomly enrolled from 3 communities in 3 districts of Zhengzhou. CKD was defined as estimated glomerular filtration rate (eGFR) < 60 mL/min.1.73m2 or urinary albumin to creatinine ratio ≥ 30 mg/g (albuminuria). Diabetic subjects with systolic blood pressure > 140 mmHg, albuminuria or an eGFR less than 60 mL/min/1.73 m2 were classified as having DKD. Participants completed a questionnaire assessing lifestyle and relevant medical history, and blood and urine specimens were taken. Serum creatinine, uric acid, total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein and urinary albumin were assessed. The age- and sex-adjusted prevalences of CKD and DKD were calculated, and risk factors associated with the presence of reduced eGFR, albuminuria, DKD, severity of albuminuria and progression of reduced renal function were analyzed by binary and ordinal logistic regression. RESULTS: The overall adjusted prevalence of CKD was 16.8% (15.8-17.8%) and that of DKD was 3.5% (3.0-4.0%). Decreased renal function was detected in 132 participants (2.9, 95% confidence interval [CI]: 2.5-3.2%), whereas albuminuria was found in 858 participants (14.9, 95% CI: 13.9-15.9%). In all participants with diabetes, the prevalence of reduced eGFR was 6.3% (95% CI = 3.9-8.6%) and that of albuminuria was 45.3% (95% CI = 40.4-50.1%). The overall prevalence of CKD in participants with diabetes was 48.0% (95% CI = 43.1-52.9%). The results of the binary and ordinal logistic regression indicated that the factors independently associated with a higher risk of reduced eGFR and albuminuria were older age, sex, smoking, alcohol consumption, overweight, obesity, diabetes, hypertension, dyslipidemia and hyperuricemia. CONCLUSIONS: Our study shows the current prevalence of CKD and DKD in residents of Central China. The high prevalence suggests an urgent need to implement interventions to relieve the high burden of CKD and DKD in China.

Vitamin D protects podocytes from autoantibodies induced injury in lupus nephritis by reducing aberrant autophagy.

SUBJECT: The aim of this study was to investigate whether vitamin D plays a protective role in podocyte injury induced by autoantibodies purified from the serum of patients with lupus nephritis (LN) via reducing aberrant autophagy. METHODS: Autophagic activities of renal tissues of patients with LN were evaluated under transmission electronic microscope (TEM). Immunoglobulin G (IgG) from patients with LN was purified to induce human podocyte injury, and the role of vitamin D in injury was observed. Podocytes were observed under TEM, autophagic activity was evaluated by western blot analysis and quantitative real-time polymerase chain reaction, and mRFP-GFP-LC3B adenovirus was infected into human podocytes in vitro. RESULTS: Significantly higher autophagic levels were observed in patients with LN (P <0.05), and apparently greater autophagic levels in podocytes were shown (P <0.05). Among different classifications of LN, class V (n = 5), III + V (n = 5), and IV + V (n = 5) gained higher autophagic levels than class III (n = 5) and IV (n = 5). Induced autophagy, which was evident by increased LC3B-II and Beclin 1 level, caused consumption of p62, more autophagosomes observed under TEM, and more LC3B dots observed under confocal microscope in the IgG group, along with decreased nephrin expression, which suggests podocyte injury. Reduction of autophagy as well as alleviated podocyte injury was observed in the IgG+ vitamin D group. CONCLUSION: This study demonstrates that vitamin D plays a protective role in podocyte injury induced by autoantibodies from patients with LN and appears to be a novel therapy target in LN.

Cecropin suppresses human hepatocellular carcinoma BEL- 7402 cell growth and survival in vivo without side-toxicity.

Conventional chemotherapy against hepatocellular carcinoma typically causes various side effects. Our previous study showed that cecropin of Musca domestica can induce apoptosis in human hepatocellular carcinoma BEL-7402 cells in vitro. However, whether cecropin inhibits BEL-7402 cell in vivo and the question of possible side effects remained undentified. The present study confirmed tumor-inhibitory effects of cecropin in vivo, and furthermore strongly suggested that cecropin cytotoxicity in BEL-7402 cells in vivo may be mainly derived from its pro-apoptotic action. Specifically, we found that cecropin exerted no obvious side effects in tumor-bearing mice as it had no significant hematoxicity as well as visceral toxicity. Therefore, cecropin may be a potential candidate for further investigation as an antitumor agent against hepatocellular carcinoma.