Associations between dietary inflammatory index and stroke risk: based on NHANES 2005-2018.

The dietary inflammatory index (DII) is a measure of the inflammatory potential of the diet and is closely associated with insulin resistance (IR) and stroke. And IR may play an important role in the development of stroke. Therefore, this study aimed to evaluate the relationship between DII and stroke risk while delving into the potential role of IR in this association. We analyzed data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018, performing weighted univariate analyses, logistic regression, and mediation analyses. At baseline, 3.89% of participants developed stroke, and we observed stroke patients exhibited higher DII scores. After adjusting for covariates, compared to participants in the first quartile of DII scores, those in the third quartile and fourth quartile had increased odds of experiencing a stroke (OR: 1.78, 95% CI: 1.18-2.68) and (OR: 1.70, 95% CI: 1.16-2.50), respectively. Moreover, a significant dose-response relationship was observed (P-trend < 0.05). However, there was no observed interaction between DII and homeostatic model assessment-IR (HOMA-IR) concerning stroke risk, and HOMA-IR did not mediate the association between DII and stroke. In summary, our study elucidated the significant association between DII and stroke risk, independent of IR. This insight suggests that an anti-inflammatory diet may serve as an effective strategy for stroke prevention.

A novel curcumin derivative CL-6 exerts antitumor effect in human gastric cancer cells by inducing apoptosis through Hippo-YAP signaling pathway.

PURPOSE: Gastric carcinoma is the second most frequently diagnosed cancer and leading cause of cancer death in China. As a new generation of cancer therapeutic drug, CL-6, a curcumin derivative, shows better bioavailability than curcumin, which has shown anticancer effects in gastric cancer (GC). However, whether CL-6 shows similar activities in GC has not been examined. MATERIALS AND METHODS: Cell proliferation assay, colony-forming assay, flow cytometric analysis, wound healing assay, and Transwell invasion assay were performed to examine the effects of CL-6 on proliferation, apoptosis, migration, and invasion on human AGS and MGC-803 cell lines. Western blot was used to evaluate protein levels of Bax, Bcl-2, YAP, p-YAP, and Lats, and gene expression was measured by real-time quantitative PCR (RT-qPCR). RESULTS: CL-6 dose dependently reduced proliferation, increased apoptosis, and inhibited the migration and invasion abilities of AGS and MGC-803 cells. CL-6 also increased levels of pro-apoptotic protein Bax, decreased levels of antiapoptotic protein Bcl-2, and increased the Bax/Bcl-2 ratio. CL-6 treatment also inhibited YAP and YAP protein and mRNA expression, while it induced the expression of Lats and p-YAP (Ser127). CONCLUSION: CL-6 induces apoptosis of GC cells by activating the Hippo-YAP signaling pathway. These results indicate the therapeutic potential of the novel curcumin derivative CL-6 in GC.

Nrf2-miR-129-3p-mTOR Axis Controls an miRNA Regulatory Network Involved in HDACi-Induced Autophagy.

Histone deacetylase inhibitors (HDACis) are the recommended treatment for many solid tumors; however, resistance is a major clinical obstacle for their efficacy. High levels of the transcription factor nuclear factor erythroid 2 like-2 (Nrf2) in cancer cells suggest a vital role in chemoresistance, and regulation of autophagy is one mechanism by which Nrf2 mediates chemoresistance. Although the molecular mechanisms underlying this activity are unclear, understanding them may ultimately improve therapeutic outcomes following HDACi treatment. In this study, we found that HDACi treatment increased Nrf2 mRNA and protein levels and enhanced Nrf2 transcriptional activity. Conversely, Nrf2 knockdown or inhibition blocked HDACi-induced autophagy. In addition, a microRNA (miRNA) array identified upregulation of miR-129-3p in response to Nrf2 overexpression. Chromatin immunoprecipitation assays confirmed miR-129-3p to be a direct Nrf2 target. RepTar and RNAhybrid databases indicated mammalian target of rapamycin (mTOR) as a potential miR-129-3p target, which we experimentally confirmed. Finally, Nrf2 inhibition or miR-129-3p in combination with HDACis increased cell death in vitro and in vivo. Collectively, these results demonstrated that Nrf2 regulates mTOR during HDACi-induced autophagy through miRNA-129-3p and inhibition of this pathway could enhance HDACi-mediated cell death.