內(nèi)容: Patients with glioma have a very high mortality rate, thus improving the poor prognosis of glioma has been the goal in the therapeutic field. Searching for more effective drugs for gliomas from natural compounds is a promising strategy. In this study, both oleanonic acid and oleanolic acid inhibited proliferation of glioma cells and reduced expression of cyclin D1 and E1, but the former has a lower IC50 than the latter. Oleanonic acid reduced the expression of p-STAT3 but not p-STAT1 and 5, and also reducing the expression of STAT3 in the nucleus and its transcriptional activity in glioma cells. Furthermore, knockdown of STAT3 expression inhibited proliferation and migration of glioma cells. Next, the expressions of the upstream regulators such as SIRT6 and p-JAK2 but not SIRT1, p-ERK1/2, p300 were increased by oleanonic acid. The overexpression of SIRT6 not only reduced the expression of p-STAT3 and its transcriptional activity but also inhibited the proliferation and migration of glioma cells. In addition, the effects that oleanonic acid reduced the expression of p-STAT3 and its transcriptional activity and inhibited the proliferation and migration were attenuated by the knockdown of SIRT6. Furthermore, oleanonic acid effectively suppressed glioma growth and extended survival in nude mice bearing intracerebral U87 xenografts, but not in nude mice bearing intracerebral SIRT6-knockdown U87 xenografts. In conclusion, oleanonic acid upregulates the expression of SIRT6 to inactivates STAT3 and then inhibits glioma growth.

內(nèi)容: Viable but non-culturable (VBNC) bacteria after chlorination disinfection pose a considerable threat to the public health and environment. The current work aimed to uncover the stress adaptation mechanisms of VBNC Salmonella Enteritidis to sodium hypochlorite. In this study, we investigated the morphology, gene expressions and proteomic profile in VBNC S. Enteritidis. It demonstrated that 109 cells/mL of bacteria could transition into the VBNC state after exposure to 50 mg/L chlorine for 2.5 h. The VBNC state cells exhibited cellular membrane impairment, decreased size, and intracellular ATP depletion compared to the culturable cells. In the VBNC state cells, there was a significant increase in intracellular reactive oxygen species (ROS) levels and NAD+/NADH ratios. This observation suggested an imbalance in the intracellular redox status of the VBNC bacteria. Transcriptome and proteomic analysis revealed significant upregulation of the resistance-nodulation-division (RND) efflux systems (arcA, tolC, ramA), oxidative stress response genes (soxR, trxA, grxB), DNA repair genes (lexA, radA, mutH, mutL), and virulence factor genes (sseA, sseL, eutS, and eutE). Our findings indicated that it is important to formulate disinfection protocols that are specifically designed for food processing plants and healthcare facilities, focusing on implementing a more thorough disinfection method to effectively eradicate VBNC cells.

內(nèi)容: Depression poses a considerable threat to global health, underscoring the critical need for safe treatments. Because of its homology of medicine and food, Gardeniae Fructus is widely used in clinical and every-day life contexts. Gardeniae Fructus oil (OGF) is a waste byproduct of the food industry with promising recycling potential. While previous research has demonstrated the antidepressant effects of OGF, the precise mechanism remains unclear. To fill this gap in the literature, this paper elucidates the composition and potential antidepressant mechanism of OGF. According to the results, OGF is mainly composed of fatty acids and unsaponifiable matter. OGF could effectively attenuate depression-like behaviors in mice with chronic unpredictable mild stress by modulating the microbiota-gut-brain axis. Mechanisms include improving gut dysbiosis, regulating short-chain fatty acids, protecting the intestinal barrier function, reducing hippocampal damage, and alleviating neuroinflammation by inhibiting the activation of the TLR4/NF-κB/NLRP3 pathway. Fecal microbiota transplantation experiments confirmed the involvement of the gut microbiota in the modulation of depression-like behavior by OGF. This study establishes the antidepressant effects of OGF as well as the underlying mechanism, demonstrating its potential as a novel dietary intervention for depression treatment.