Antitumor activity of galaxamide involved in cell apoptosis and stemness by inhibiting Wnt/ß-catenin pathway in cervical cancer.

Our previous work reported that galaxamide, a cyclopeptide extracted from the seaweed Galaxaura filamentosa, showed antiproliferative activity against HeLa cells by MTT assay. In this study, the growth-inhibitory effects of galaxamide in HeLa cells and xenograft mouse models were investigated. It was found galaxamide significantly inhibited cell growth, colony formation, migration, and invasion and induced cell apoptosis by inhibiting the Wnt signaling pathway in HeLa cells. RNA sequencing revealed that galaxamide regulated stemness by Wnt6 signaling pathway in HeLa cells. By analyzing The Cancer Genome Atlas database, Wnt6 was found to be negatively/positively correlated with stemness- and apoptosis-related genes in human cervical cancer. Cancer stem-like cells (CSCs) isolated and enriched from HeLa cells demonstrated elevated Wnt6 and ß-catenin genes compared with nonstem HeLa cells. After galaxamide treatment, CSCs showed abrogation of sphere-forming ability, along with inhibition of stemness-related and Wnt pathway genes. Galaxamide treatment was also accompanied by the induction of apoptosis in HeLa cells, which was consistent with the results in BALB/c nude mice. Our results provide evidence that suppression of stemness by downregulating the Wnt signaling pathway is the molecular mechanism by which galaxamide effectively inhibits cell growth and induces apoptosis in cervical cancer cells.

Serum sirtuin-1 a potential marker in the diagnosis of rheumatoid arthritis.

Introduction: To explore the value of serum sirtuin-1 (SIRT1) in the diagnosis and evaluation of joint mobility of rheumatoid arthritis (RA). Materials and Methods: Serum was randomly obtained from 212 RA patients,210 non-RA patients and 58 healthy controls in a large tertiary first-class hospital in Jiangxi province from November 2021 to June 2022. The level of serum Sirt1,anti-cyclic citrulline polypeptide antibody (anti-CCP), anti-mutant citrulline vimentin antibody (anti-MCV), rheumatoid factor (RF),high-mobility group box 1 (HMGB1), collagen triple helix repeat containing 1 (CTHRC1), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were detected by ELISA, to explore the correlation between them and their value in the diagnosis and evaluation of joint range of motion of RA and statistically analyse their diagnostic efficiency. Results: ① The level of all markers was higher in the RA group than in the non-RA group and the healthy controls (p < 0.05). ② The AUC of the SIRT1 was 0.882, second only to the anti-MCV and anti-CCP. ③ The anti-CCP showed the highest sensitivity to RA diagnosis of 0.948. The specificity and positive predictive value of SIRT1 for the diagnosis of RA were the highest, which are 0.959 and 0.934 respectively. ④ In serial combination, SIRT1/anti-CCP、SIRT1/anti-MCV showed the highest specificity.SIRT1/anti-CCP in parallel combination had the highest sensitivity. ⑤ SIRT1 showed a significant correlation with other markers and DAS28 scores (p < 0.01). Conclusion: SIRT1 can be used as a new serological marker for RA diagnosis, which has a significant correlation with RA joint mobility and has a certain reference value in RA differential diagnosis, providing a new detection basis for RA differential diagnosis.

SIRT1 upregulation promotes epithelial-mesenchymal transition by inducing senescence escape in endometriosis.

Endometrial epithelial cells carry distinct cancer-associated alterations that may be more susceptible to endometriosis. Mouse models have shown that overexpression of SIRT1 associated with oncogene activation contributes to the pathogenesis of endometriosis, but the underlying reason remains elusive. Here, we used integrated systems biology analysis and found that enrichment of endometrial stromal fibroblasts in endometriosis and their cellular abundance correlated negatively with epithelial cells in clinical specimens. Furthermore, endometrial epithelial cells were characterized by significant overexpression of SIRT1, which is involved in triggering the EMT switch by escaping damage or oncogene-induced induced senescence in clinical specimens and in vitro human cell line models. This observation supports that genetic and epigenetic incident favors endometrial epithelia cells escape from senescence and fuel EMT process in endometriosis, what could be overcome by downregulation of SIRT1.