As a new way of programmed cell death, pyroptosis plays a vital role in many diseases. In recent years, the relationship between pyroptosis and type 2 diabetes (T2D) has received increasing attention. Although the current treatment options for T2D are abundant, the occurrence and development of T2D appear to continue, and the poor prognosis and high mortality of patients with T2D remain a considerable burden in the global health system. Numerous studies have shown that pyroptosis mediated by the NLRP3 inflammasome can affect the progression of T2D and its complications; targeting the NLRP3 inflammasome has potential therapeutic effects. In this review, we described the molecular mechanism of pyroptosis more comprehensively, discussed the most updated progress of pyroptosis mediated by NLRP3 inflammasome in T2D and its complications, and listed some drugs and agents with potential anti-pyroptosis effects. Based on the available evidence, exploring more mechanisms of the NLRP3 inflammasome pathway may bring more options and benefits for preventing and treating T2D and drug development.

No abstract

Polymyxin B (PMB) is a polypeptide antibiotic widely used in treating multidrugresistant Gram-negative bacteria. However, nephrotoxicity is a serious adverse effect that limits its clinical use. Therefore, clarification of the molecular mechanism of PMB-induced renal injury is essential. Our study aimed to explore possible mechanisms of PMB-induced nephrotoxicity in vivo and in vitro. Mice were treated with PMB to construct the kidney injury model. The antioxidant capacity was assessed by measuring the superoxide dismutase (SOD) and catalase (CAT) activities and the glutathione (GSH) and malondialdehyde (MDA) contents. The pathway of the nuclear factor erythroid 2-related factor 2/NADH quinone oxidoreductase 1 (Nrf2/NQO1) was examined after PMB treatment in NRK-52E cells and mice. Finally, the expressions of genes and proteins (Bax, Bcl-2, Caspase-3, Caspase-9) related to apoptosis were evaluated through quantitative polymerase chain reaction and western blot assay. The study verified PMB-induced nephrotoxicity in mice and NRK-52E cells in a dose-and time-dependent manner. PMB treatment significantly decreased the expression of Nrf2 and its downstream target gene NQO1 and increased the apoptosis-related proteins expression. In summary, our results suggested that PMB-induced oxidative stress damage by inhibiting the Nrf2/ NQO1 pathway and promoting apoptosis in kidney tissues.

Background and objectives:This study aimed to summarize the clinical pharmacokinetics and bioequivalence of generic and branded linagliptin tablets during fasting and fed conditions, and the influence of food on the pharmacokinetics (PK) of linagliptin tablets was also explored in healthy Chinese subjects.Methods: An open-label, randomized, single-center, two-period, and single-dose crossover bioequivalence study was performed in this research. Healthy subjects in fasting (n = 32) and fed (n = 32) conditions received 5 mg of generic (test) linagliptin or a commercial (reference) capsule, respectively. Blood sample collection was conducted at the baseline and post-dose. Plasma concentrations of linagliptin were detected by an HPLC-MS/MS method. A non-compartmental method was performed to analyze pharmacokinetic parameters, and safety was monitored.Results: A total of 64 subjects completed the study, 32 for the fasting and 31 for the fed study. The major PK parameters of linagliptin, including C max and AUC 0-72, were similar between the preparations under fasting and fed conditions. Under fasting conditions, the 90% confidence intervals (CI) of the test/reference ratios (T/R) of C max and AUC 0-72 were 95.9∼110.9% and 96.8∼101.9%, respectively. Under fed conditions, the 90% CI of T/R of C max and AUC 0-72 were 98.2∼103.4% and 97.7∼103.5%, respectively. None of the volunteers had a severe adverse event.Conclusions: Generic linagliptin tablet is bioequivalent to the reference drug under both fasting and feeding conditions. Food delays the absorption of linagliptin. Chinese subjects taking a single dose of linagliptin of 5 mg have good tolerance to the drug.

Polymyxin B (PMB) is a Polypeptide antibiotic widely applied in multidrug-resistant Gram-negative bacteria. However, nephrotoxicity is one of the serious adverse effects that limit its clinical use. Therefore, clarification of the molecular mechanism of PMB-induced renal injury appears to be particularly important. Our study aimed to explore the possible mechanism of PMB-induced nephrotoxicity in vivo and in vitro. Mice were treated with PMB to construct models of kidney injury. The antioxidant capacity was assessed by measuring the activity of SOD and CAT and the contents of GSH and MDA, and the Nrf2/NQO1 pathway was examined after PMB treatment in NRK-52E cells and mice. Finally, we assessed the expression of apoptosis-related genes and proteins (Bax, Bcl-2, Caspase-3, Caspase-9) through qPCR and WB assay. The study verified PMB-induced nephrotoxicity in mice and NRK-52E cells by a dose- and time-dependent manners. PMB treatment significantly down-regulated the expression of Nrf2 and its downstream target genes NQO1 and up-regulated the apoptosis-related protein expression. In summary, our results suggested PMB induced oxidative stress damage by inhibiting the Nrf2/NQO1 pathway and promoting apoptosis in kidney tissue.