Application of Proteomics and Machine Learning Methods to Study the Pathogenesis of Diabetic Nephropathy and Screen Urinary Biomarkers.

Diabetic nephropathy (DN) has become the main cause of end-stage renal disease worldwide, causing significant health problems. Early diagnosis of the disease is quite inadequate. To screen urine biomarkers of DN and explore its potential mechanism, this study collected urine from 87 patients with type 2 diabetes mellitus (which will be classified into normal albuminuria, microalbuminuria, and macroalbuminuria groups) and 38 healthy subjects. Twelve individuals from each group were then randomly selected as the screening cohort for proteomics analysis and the rest as the validation cohort. The results showed that humoral immune response, complement activation, complement and coagulation cascades, renin-angiotensin system, and cell adhesion molecules were closely related to the progression of DN. Five overlapping proteins (KLK1, CSPG4, PLAU, SERPINA3, and ALB) were identified as potential biomarkers by machine learning methods. Among them, KLK1 and CSPG4 were positively correlated with the urinary albumin to creatinine ratio (UACR), and SERPINA3 was negatively correlated with the UACR, which were validated by enzyme-linked immunosorbent assay (ELISA). This study provides new insights into disease mechanisms and biomarkers for early diagnosis of DN.

Schisandrin B ameliorates high-glucose-induced vascular endothelial cells injury by regulating the Noxa/Hsp27/NF-κB signaling pathway.

BACKGROUND: To address the molecular mechanism of the anti-inflammation effects of schisandrin B (Sch B) in atherosclerosis, we examined injured HMEC-1, HBMEC, and HUVEC-12 cells induced by high glucose (HG). METHODS: Western blot was performed to detect the levels of the proteins Hsp27, Noxa, TLR5, p-IκBα, and p-p65 in HG-induced cells, while ELISA was used to analyze the inflammatory cytokines TNF-α, IL-6, MCP-1, and IL-1ß in cells with Hsp27 or Noxa stable expression. RESULTS: Overexpression of Hsp27 upregulated the inflammatory cytokines and the release of IκBα, promoted transportation of p65 into the nucleus, and lastly, affected the inflammation process, while Sch B counteracted the upregulation. In addition, the effect of Noxa overexpression, which is different from Hsp27 overexpression, was consistent with that of Sch B treatment. CONCLUSIONS: Sch B may inhibit the inflammatory cascade and alleviate the injury to HMEC-1, HBMEC, and HUEVC-12 cells caused by HG by regulating the Noxa/Hsp27/NF-κB signaling pathway.

Photodegradation of bisphenol A in Fe(III)-oxalate complexes solution.

The aqueous photodegradation of bisphenol A (BPA) in the presence of Fe(III)-oxalate complexes (Fe(III)-Ox), which are common compositions of natural water, was investigated in this study. BPA underwent rapid indirect photolysis in Fe(III)-Ox solution under simulated solar irradiation, proceeding pseudo-first-order kinetics. The photolysis rate increased with decreasing pH or initial BPA level and increasing Fe(III)/oxalate concentration ratio. Hydroxyl radicals (*OH), which were generated from the photochemical processes of Fe(III)-Ox complexes and contributed to the photooxidation of BPA, were determined by molecular probe and electron spin resonance (ESR) methods with the steady-state concentration of 2.56 x 10(-14) mol/L. Superoxide anion radical (O2*-) was considered as the precursor of *OH and qualitatively determined by adding nitro blue tetrazolium as well as ESR experiments. Based on the structural analysis of the intermediate photoproducts of BPA in Fe(III)-Ox complexes solution, the possible degradation pathways of BPA were proposed, involving *OH addition, alkyl scission and alky oxidation. The results indicate that the photochemical reactivity of Fe(III) may affect the environmental fate of BPA in natural water significantly.

[Photodegradation of bisphenol A in presence of Suwannee River fulvic acid].

Under simulated solar irradiation, the degradation of bisphenol A (BPA) was studied in the presence of Suwannee River Fulvic Acid (SRFA). The results demonstrate that the photodegradation of BPA followed a pseudo-first-order kinetics and the photodegradation rate increased rapidly with increasing initial concentration of SRFA. Hydroxyl radical, singlet oxygen were found in the SRFA solutions of BPA with molecular probes and the technique of electronic spin resonance. The electronic energy transfer of triplet state fulvic acid was also studied with various aerated conditions. The results showed that the photodegradation of BPA was related with triplet state fulvic acid. The photodegradation products of BPA in the presence of SRFA were identified with GC/MS methods. The photodegradation pathways of BPA were also discussed.

Determination of hydroxyl radicals with salicylic acid in aqueous nitrate and nitrite solutions.

The qualitative and quantitative analyses of reactive oxygen species are essential to determine their steady-state concentration and related reaction mechanisms in environmental aquatic systems. In this study, salicylic acid was employed as an innovative molecular probe of hydroxyl radical(OH) generated in aqueous nitrate and nitrite solutions through photochemical reactions. Kinetic studies showed that the steady-state concentrations of OH in aqueous NO3- (10 mmol/L, pH = 5) and NO2- (10 mmol/L, pH = 5) solutions under ultraviolet irradiation were at a same magnitude, 10(-15) mol/L. Apparent quantum yields of OH at 313 nm were measured as 0.011 and 0.07 for NO3- and NO2- respectively, all comparable to the results of previous studies.