ObjectiveGPR142 agonists are being pursued as novel diabetes therapies by virtue of their insulin secretagogue effects. But it is undetermined whether GPR142's functions in pancreatic islets are limited to regulating insulin secretion. The current study expands research on its action.Methods and ResultsWe demonstrated by in situ hybridization and immunostaining that GPR142 is expressed not only in β cells but also in a subset of α cells. Stimulation of GPR142 by a selective agonist increased glucagon secretion in both human and mouse islets. More importantly, the GPR142 agonist also potentiated glucagon-like peptide-1 (GLP-1) production and its release from islets through a mechanism that involves upregulation of prohormone convertase 1/3 expression. Strikingly, stimulation of insulin secretion and increase in insulin content via GPR142 engagement requires intact GLP-1 receptor signaling. Furthermore, GPR142 agonist increased β cell proliferation and protected both mouse and human islets against stress-induced apoptosis.ConclusionsCollectively, we provide here evidence that local GLP-1 release from α cells defines GPR142's beneficial effects on improving β cell function and mass, and we propose that GPR142 agonism may have translatable and durable efficacy for the treatment of type 2 diabetes.

To deal with the Cd contaminant of agricultural soil, pollution-safe cultivar (PSC) is developed to minimize the Cd accumulation risk in crops. The present study aimed to investigate the different proteomic responses related to Cd accumulation in different tissues between two Amaranthus gangeticus cultivars, Pen and Nan. A significantly higher Cd accumulation in Pen than in Nan was unraveled, especially in shoot. The proportions of soluble Cd in root and stem of Nan were significantly lower than those of Pen, implying lower Cd transportation from root to shoot in Nan. Higher contents of NaCl-extracted Cd in Pen than in Nan were probably attributed to the enhancement of GSH related metabolism in Pen, which activated the transportation of Cd from root to shoot. Alteration of other proteins involved in Cd detoxification and energy production also demonstrated that Pen had exhibited a stronger tolerance than Nan in dealing with Cd stress. Thus, differences in the proteomic processes associated with biochemical differences between the two typical cultivars suggested a cultivar-dependent capacity of Cd tolerance and accumulation in amaranth for the first time.

No abstract

AimTo investigate the clinical significance of Oct-4 in the development and progression of gastric cancer.MethodsImmunohistochemistry was used to analyze Oct-4 expression in 412 gastric cancer cases. Oct-4 protein levels were upregulated in gastric cancer tissues compared with adjacent noncancerous tissues.ResultsPositive expression of Oct-4 correlated with age, depth of invasion, Lauren classification, lymph node metastasis, distant metastasis, and TNM stage. In stages I, II, and III, the 5-year survival rate of patients with high expression of Oct-4 was significantly lower than that in patients with low expression of Oct-4. In stage IV, Oct-4 expression did not correlate with the 5-year survival rate. Furthermore, multivariate analysis suggested that the depth of invasion, lymph node metastasis, distant metastasis, TNM stage, and upregulation of Oct-4 were independent prognostic factors of gastric cancer.ConclusionOct-4 protein is a useful marker in predicting tumor progression and prognosis.

Background. The inflammatory response is an important part of the pathogenesis of acne vulgaris. Auriculotherapy has been shown to have a good therapeutic effect on this disease. The aim of this study was to explore the mechanism underlying the anti-inflammatory effect of auriculotherapy in the treatment of acne vulgaris. Methods. Propionibacterium acnes was injected subcutaneously into the ears of rats to establish an animal model of acne. The auriculotherapy intervention in rats consisted of auricular bloodletting therapy (ABT), auricular point sticking (APS), or a combination of both (ABPS). The anti-inflammatory effects of auriculotherapy were evaluated by measuring changes in ear thickness, local body surface microcirculation in the ear, and serum inflammatory factors in rats. The polarization of macrophages was analyzed by flow cytometry, and the expression of TLR2/NF-κB signaling pathway in the target tissues was analyzed using western blot. Results. ABT, APS, and ABPS all reduced the erythema of ear acne, decreased microcirculation in localized ear acne, and decreased serum levels of TNF-α and IL-1β in rats. Meanwhile, the three interventions reduced M1-type macrophages and increased M2-type macrophages; only APS could reduce the expression of TLR2/NF-κB signaling pathway. Conclusion. ABT, APS, and ABPS can improve the inflammatory symptoms of acne and reduce inflammatory cytokines. APS may exert anti-inflammatory effects by altering macrophage polarization and decreasing TLR2/NF-κB expression.