Correlation Between Plasma NLRP3, IL-1ß, and IL-18 and Diabetic Nephropathy in Patients With Type 2 Diabetes.

Context: Diabetic nephropathy (DN) is a common microvascular complication in diabetic patients. The pathogenesis of DN is complex. Inflammatory response may play a key role as a common downstream pathway. Objective: The study intended to explore the relationship between the levels of plasma nucleotide-binding oligomeric domain-like receptor protein 3 (NLRP3 inflammasome), interleukin-1ß (IL-1ß), and IL-18 and the progression of type 2 diabetic nephropathy to clarify their relationship with type 2 diabetes mellitus (T2DM) and to provide evidence for clinical treatment. Design: The research team performed a controlled observational study. Setting: The study took place at Baoding No. 1 Central Hospital in Baoding, Hebei, China. Participants: Participants were 153 patients with T2DM who received treatment at the hospital between October 2020 and October 2021. The research team allocated 30 participants without evidence of DN to the control group. Based on the DN stage, the team assigned the 123 remaining participants to one of five observation groups: (1) 32 participants with stage 1 DN to the DN1 group, (2) 31 participants with stage 2 DN to the DN2 group, (3) 30 participants with stage 3 DN to the DN3 group, (4) 30 participants with stage 4 DN to the DN4 group, and (5) 29 participants with stage 5 DN to the DN5 group. Outcome Measures: The research team measured participants' levels of "nucleotide binding oligomeric domain-like receptor protein 3" (NLRP3), interleukin-1 beta (IL-1ß), and IL-18 and used the Spearman rank correlation analysis to determine the correlation between those levels and the DN stages. Results: The levels of NLRP3 , IL-1ß and IL-18 in all the five observation groups were significantly higher than those in the control group (all P < .01). The levels were also significantly higher: (1) in the DN2, DN3, DN4, and DN5 groups than those in the DN1 group (all P < .01); (2) in the DN3, DN4, and DN5 groups than those in the DN2 group (all P < .01); (3) in the DN4 and DN5 groups than those in the DN3 group (all P < .01); and (4) in the DN5 groups than those in the DN4 group (all P < .01). The Spearman rank correlation analysis showed that the NLRP3, IL-1ß, and IL-18 levels were significantly positively correlated with the DN stage (P = .01). Conclusions: NLRP3, IL-1ß and IL-18 played an important role in the progression of T2DM, and their levels increased with the aggravation of DN. Therefore, the plasma levels of NLRP3, IL-1ß and IL-18 can be useful as indicators of the occurrence and development of DN and can provide clinical guidance for the early diagnosis of DN and for the determination and adjustment of treatment plans.

Triclocarban evoked neutrophil extracellular trap formation in common carp (Cyprinus carpio L.) by modulating SIRT3-mediated ROS crosstalk with ERK1/2/p38 signaling.

Triclocarban (TCC), an antimicrobial ingredient in personal care products, is associated with immunosuppression and physiological dysfunctions of aquatic organisms. The aim of this study was to investigate whether TCC can induce common carp NETosis (neutrophil death by neutrophil extracellular trap (NET) release) and then to attempt to identify the potential molecular mechanisms. Herein, scanning electron microscopy and flow cytometric assays showed that revealed that TCC triggers DNA-containing web-like structures and increases extracellular DNA content. In the proteomic analysis, we observed that NET-related proteins, extracellular regulated protein kinase (Mapk1, Mapk14, Jak2) and apoptotic protein (caspase3) were significantly increased, and defender against cell death 1 (Dad1) was significantly decreased after TCC treatments. Meanwhile, we confirmed that TCC stress can trigger NETosis in common carp by activating the reactive oxygen species (ROS)/ERK1/2/p38 signaling. We think that the upregulated NDUFS1 expression is closely related to oxidative stress induced by TCC. Importantly, we discovered that SIRT3 expression was significantly decreased in the process of TCC-induced NETs. Importantly, pretreatment with the SIRT3 agonist honokiol (HKL) effectively suppressed TCC-induced NET release. In contrast, the SIRT3 antagonist 3-TYP escalated TCC-induced NET formation. Mechanistically, SIRT3 degradation serves as a potential mediator for regulating oxidative stress crosstalk between ERK1/2/p38 signals in the process of TCC-induced NET formation. These findings unveil new insights into the TCC-evoked health risk of fish and other aquatic organisms and suggest that SIRT3 is a potential pharmacological intervention target to alleviate TCC-induced common carp NETosis.

Effect of 5:2 Fasting Diet on Liver Fat Content in Patients with Type 2 Diabetic with Nonalcoholic Fatty Liver Disease.

Background: The prevalence of nonalcoholic fatty liver disease (NAFLD) is rapidly growing in China, especially in patients with type 2 diabetes mellitus (T2DM). Weight loss strategies have been shown to treat NAFLD effectively. We conducted a 24-week, prospective, randomized study in T2DM patients with NAFLD to evaluate the effects of a 5:2 fasting diet on liver fat content. Methods: Sixty-one T2DM patients with NAFLD were enrolled and randomly divided into a 5:2 fasting diet intervention group (5:2 diet group, n = 31) and 1.8 mg/day liraglutide intervention group (Lira group, n = 30). The study was performed for 24 weeks. Data of the body weight, waist circumference, plasma lipids and glucose profile, fasting plasma insulin, and liver function parameters were collected. Controlled attenuation parameter (CAP) was measured to assess the liver fat content. Superoxide dismutase (SOD) and malondialdehyde (MDA) were measured to evaluate oxidative stress status. Results: At 24 weeks after intervention, compared with those at baseline, CAP was significantly decreased in both the 5:2 diet group and Lira group, which was 7.4% and 5.5%, respectively. Body weight, plasma lipids and glucose profile, and liver function parameters improved significantly, while homeostasis model assessment-ß (HOMA-ß) was significantly increased in both groups (all P < 0.05). Stepwise linear regression showed that increased HOMA-ß and SOD, as well as reduced body mass index (BMI), were the independent predictors of CAP decrease in the Lira group (P = 0.000, 0.000, 0.015). In contrast, reduced BMI and MDA were the independent influencing factors of CAP decrease in the 5:2 diet group (P = 0.011, 0.043). The common side effects in the 5:2 diet group were hunger (60%), weakness (10%), and constipation (0.3%). Conclusions: A 5:2 fasting diet achieved comparable effects with liraglutide on liver fat content in patients with T2DM with NAFLD by reducing BMI and oxidative stress. Both treatment strategies were safe and effective for glucose control.

Potential Therapeutic Targets of Obesity-Related Glomerulopathy.

The global increase of obesity parallels the obesity-related glomerulopathy (ORG) epidemic. The purpose of this review is to emphasize the potential therapeutic targets of ORG as well as the corresponding possible mechanisms. We systematically identified surveys, reports, and published studies that included data for the purpose of this review and did literature analysis. Under circumstance of obesity, weight loss, and renin-angiotensin-aldosterone blockade are the most studied therapies, effective to induce antiproteinuric effects and reversal of hyperfiltration in ORG. Glucagon-like peptide-1-based therapies led to improvement in proteinuria. Newer therapies directed to lipid metabolism, including farnesoid X receptor and takeda G protein-coupled receptor 5 agonists, peroxisome proliferator-activated receptor α agonists, hold therapeutic promise. Prevention and treatments of obesity and ORG are of great importance.

Keap1-Nrf2 pathway up-regulation via hydrogen sulfide mitigates polystyrene microplastics induced-hepatotoxic effects.

Microplastics, which are new types of environmental pollutants, are recently receiving widespread attention worldwide. Hydrogen sulfide (H2S) as the third endogenous gaseous mediator had protective effects in multiple physiological and pathological conditions. However, the protective role of H2S in microplastics-induced hepatotoxocity remain unclear. In this study, our data showed that H2S significantly suppressed inflammation, apoptosis and oxidative stress induced by polystyrene microplastics (mic-PS) (20 mg/kg b.w.) in the liver. Strikingly, although mic-PS exposure increased the expression of nuclear factor-E2-related factor (Nrf2), it did not influence the levels of heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQOl) in the L02 hepatocytes. Immunofluorescence assay showed that sodium hydrosulfide (NaHS) reduced micro-Ps-induced hepatic apoptosis by facilitating nuclear accumulation of Nrf2. Simultaneously, flow cytometry also showed that NaHS could prevent mic-PS-induced accumulation of reactive oxygen species (ROS) by increasing the expression of HO-1 and NQO1. Furthermore, inhibition of HO-1 could reverse the hepatic protective effects of NaHS during mic-PS exposure. Mechanistically, H2S elevating the HO-1 and NQO1 expression by facilitating nuclear accumulation of Nrf2, and consequently reducing mic-PS-induced hepatic apoptosis and inflammation. This study unveils the hepatotoxic effects of MPs and suggest NaHS have protective effects on mic-PS-induced liver damage.

Study on the Correlation between Metabolism, Insulin Sensitivity and progressive weight loss change in Type-2 Diabetes.

OBJECTIVE: To observe the changes of lipid metabolism, blood glucose level and insulin sensitivity in patients with Type-2 diabetes after progressive weight loss of their body weight, so as to lay a theoretical foundation for diabetes treatment and education in the future. METHODS: One hundred obese patients with Type-2 diabetes (BMI ≥ 25 kg/m2) who visited the endocrinology department of our hospital from April 2017 to April 2018 were given diabetes health education, diabetic diet, exercise and other measures to control their weight. The changes of blood glucose, blood lipid, insulin level and insulin release test before weight loss (T1), and at the time points of weight loss reached 5% (T2), 10% (T3) and 15% (T4) were recorded respectively to understand the influence of progressive weight loss on relevant indexes of patients. RESULTS: With the decrease of body weight, the differences of TC, TG, LDL-C and HDL-C at different weight loss points were significant (p < 0.05), and the changes of fasting blood glucose in 5% and 10% weight loss were significant (p = 0.02). The 2h postprandial blood glucose showed the most significant difference when the weight loss reached 15% (p = 0.00). There was no statistical difference in the change of glycosylated hemoglobin among different weight loss points (p = 0.08). When the weight loss reached 10%, the blood insulin level was significantly lower than that before the weight loss, while the insulin level was not significantly changed when the weight loss reached 15%, but the peak of secretion was shifted forward. It is suggested that insulin sensitivity gradually increases with weight loss. CONCLUSION: Obese patients with Type-2 diabetes can benefit from weight loss, with abnormal blood glucose and lipid metabolism improved, insulin resistance relieved, and insulin sensitivity increased.

Diabetic nephropathy: serum miR-9 confers a poor prognosis in and is associated with level changes of vascular endothelial growth factor and pigment epithelium-derived factor.

OBJECTIVE: To investigate the relationship between the serum level of miR-9 and the progression of diabetic nephropathy (DN) and related molecular mechanisms. RESULTS: Thirty-five healthy subjects and 140 DN patients were divided into five groups: control, DN I-II, DN III, DN IV and DN V. Serum level of miR-9 was measured by real-time qPCR. Serum levels of vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF) lipids, fasting glucose, insulin, hemoglobin A1c (HBA1c), creatinine, fibrinogen and insulin resistance (HOMA-IR) were also measured. The results show that the levels of miR-9, PEDF and VEGF are increased with DN progression (P < 0.05). miR-9, VEGF and PEDF are independent risk factors of DN (R2 = 0.430). Spearman rank correlation analysis showed that miR-9 level is positively related to the levels of VEGF, PEDF, cholesterol, triglyceride, fasting glucose, fasting insulin, HBA1c, creatinine, fibrinogen and HOMA-IR (P < 0.05). CONCLUSIONS: Serum miR-9 is a potential marker for conferring a poor prognosis in DN and associated with the levels of VEGF, PEDF and biochemical indices.

Development of cesium phosphotungstate salt and chitosan composite membrane for direct methanol fuel cells.

A novel composite membrane has been developed by doping cesium phosphotungstate salt (CsxH3-xPW12O40 (0≤x≤3), Csx-PTA) into chitosan (CTS/Csx-PTA) for application in direct methanol fuel cells (DMFCs). Uniform distribution of Csx-PTA nanoparticles has been achieved in the chitosan matrix. The proton conductivity of the composite membrane is significantly affected by the Csx-PTA content in the composite membrane as well as the Cs substitution in PTA. The highest proton conductivity for the CTS/Csx-PTA membranes was obtained with x=2 and Cs2-PTA content of 5 wt%. The value is 6×10(-3) S cm(-1) and 1.75×10(-2) S cm(-1) at 298 K and 353 K, respectively. The methanol permeability of CTS/Cs2-PTA membrane is about 5.6×10(-7), 90% lower than that of Nafion-212 membrane. The highest selectivity factor (φ) was obtained on CTS/Cs2-PTA-5 wt% composite membrane, 1.1×10(4)/Scm(-3)s. The present study indicates the promising potential of CTS/Csx-PTA composite membrane as alternative proton exchange membranes in direct methanol fuel cells.