Bisphenol A (BPA) is widely used in plastic products, through which humans are exposed to it. Accumulating evidence suggests that BPA exposure is associated with b-cell dysfunction. Mitochondrial defects can cause impairment and failure of b cells, but there is little information about the effects of BPA on the mitochondrial function of b cells. In this study, we assessed the role of mitochondria-mediated mechanisms underlying BPA-induced b-cell dysfunction and resulting b-cell apoptosis. INS-1 cells were cultured with 0, 0.0020, 0.020, 0.20, or 2.0 lM BPA. Cell viability, glucose-stimulated insulin secretion (GSIS), and mitochondrial function were examined. The mitochondrial apoptotic pathway was also analyzed at molecular level. We found that BPA suppressed cell viability and disturbed GSIS in a dose-dependent manner. Positive Annexin-propidium iodide (PI) staining and altered expression of Bcl-2 family members and caspases in INS-1 cells indicated that the cells progressively became apoptotic after BPA exposure. Additionally, BPA-induced apoptosis was associated with mitochondrial defects in b cells, as evidenced by depletion of ATP, release of cytochrome c, loss of mitochondrial mass and membrane potential, and alterations in expression of genes involved in mitochondrial function and metabolism. Taken together, these findings provide strong evidence that BPA triggers INS-1 cells dysfunction and apoptosis may be meditated via the mitochondrial pathway.

Introduction Early and precise diagnosis and staging of gastric cancer are important for its treatment and management. However, the low sensitivity of 18 F-uorodeoxyglucose ( 18 F-FDG) for gastric cancer diagnosis limits its application. Currently, the tracer 68 Ga-FAPI, which targets broblast activation protein (FAP), is widely used to diagnose various cancers. However, the diagnostic value of 68 Ga-FAPI in gastric cancer is still unclear. In this study, we aimed to investigate the potential advantage of 68 Ga-FAPI-04 over 18 F-FDG in the evaluation of gastric cancer.Methods: Thirty-eight patients with gastric cancer (31 with adenocarcinoma and 7 with signet ring cell carcinoma) were recruited for this study. All of the participants underwent 68 Ga-FAPI-04 and 18 F-FDG imaging by positron emission tomography (PET)/computed tomography (CT) or PET/magnetic resonance (MR). The results were interpreted by two experienced nuclear medicine physicians, and the maximum standardized uptake value (SUV max ) was calculated.Results: For the detection of primary gastric cancer, the sensitivities of 68 Ga-FAPI-04 PET and 18 F-FDG PET were 100% (38/38) and 81.6% (31/38), respectively. Four cases of adenocarcinoma and three cases of signet ring cell carcinoma were missed by 18 F-FDG PET. The SUV max of 68 Ga-FAPI-04 in tumors greater than 4 cm (11.0 ± 4.5) was higher than tumors less than 4 cm (4.5 ± 3.2) (P = 0.0015). The SUV max of 68 Ga-FAPI-04 was higher in T2-4 tumors (9.7 ± 4.4) than in T1 tumors (3.1 ± 1.5) (P = 0.0002). For the detection of metastatic lesions, the sensitivities of 68 Ga-FAPI-04 PET and 18 F-FDG PET in 10 patients with regional lymph node metastasis and distant metastasis were 6/10 and 5/10, respectively. Conclusion: Compared to 18 F-FDG PET, 68 Ga-FAPI-04 PET had superior potential in detecting primary gastric cancers and metastatic lymph nodes, 68 Ga-FAPI-04 PET also had a better performance on small gastric cancer detection. 68 Ga-FAPI-04 PET could provide better performance for gastric cancer diagnosis and staging.

Although Panax ginseng is a famous traditional Chinese medicine and has been widely used to treat a variety of metabolic diseases including hyperglycemia, hyperlipidemia, and hepatosteatosis, the effective mediators and molecular mechanisms remain largely unknown. In this study we found that ginsenoside Rb2, one of the major ginsenosides in Panax ginseng, was able to prevent hepatic lipid accumulation through autophagy induction both in vivo and in vitro. Treatment of male db/db mice with Rb2 significantly improved glucose tolerance, decreased hepatic lipid accumulation, and restored hepatic autophagy. In vitro, Rb2 (50 µmol/L) obviously increased autophagic flux in HepG2 cells and primary mouse hepatocytes, and consequently reduced the lipid accumulation induced by oleic acid in combination with high glucose. Western blotting analysis showed that Rb2 partly reversed the high fatty acid in combination with high glucose (OA)-induced repression of autophagic pathways including AMP-activated protein kinase (AMPK) and silent information regulator 1 (sirt1). Furthermore, pharmacological inhibition of the sirt1 or AMPK pathways attenuated these beneficial effects of Rb2 on hepatic autophagy and lipid accumulation. Taken together, these results suggested that Rb2 alleviated hepatic lipid accumulation by restoring autophagy via the induction of sirt1 and activation of AMPK, and resulted in improved nonalcoholic fatty liver disease (NAFLD) and glucose tolerance.