OBJECTIVES: To elucidate the anti-aging effect of β-sitosterol (BS), an important component in the fruits of Alpinia oxyphylla Miq., in C. elegans and its regulatory effect on ETS-5 gene to modulate ferroptosis. METHODS: C. elegans treated with 10 µg/mL BS were monitored for survival time and changes in body length, motility, and reproductive function. The effect of ETS-5 gene knockdown on survival time of C. elegans was observed, and the changes in fat accumulation and lipid redox homeostasis in the transfected C. elegans were assessed using Oil Red O staining and by detecting MDA levels and the GSH/GSSG ratio. The mRNA expression levels of ferroptosis-related genes (FTN-1, GPX-1 and AAT-9) were detected using qPCR. The effects of BS treatment and ETS-5 knockdown on AAT-9 enzyme activity in C. elegans were examined. The effect of BS on nuclear localization of FEV (the human homolog of ETS-5) was validated in cultured human umbilical venous endothelial cells (HUVECs). RESULTS: Both BS treatment and ETS-5 knockdown significantly prolonged the lifespan, promoted lipid accumulation and reduced lipid peroxidation in C. elegans. ETS-5 knockdown resulted in upregulated expressions of the ferroptosis repressors GPX-1, AAT-9 and FTN-1 and increased the GSH/GSSG ratio in C. elegans. CONCLUSIONS BS inhibits ferroptosis in C. elegans by suppressing the expression of ETS-5 transcription factor and hence the activity of AAT-9 enzyme, a key gene for ferroptosis, which in turn prolongs the lifespan of C. elegans.
Animals ; Caenorhabditis elegans/physiology* ; Ferroptosis/drug effects* ; Alpinia/chemistry* ; Sitosterols/pharmacology* ; Longevity/drug effects* ; Fruit/chemistry* ; Humans

Objective:To analyze the short-term efficacy and safety of tislelizumab combined with neoadjuvant chemotherapy in the treatment of resectable esophageal squamous cell carcinoma (ESCC) .Methods:The clinical data of 56 patients with ESCC who received neoadjuvant therapy combined with surgical resection in the Department of Thoracic Surgery, Affiliated Hospital of Guangdong Medical University from April 2021 to October 2023 were collected. According to the different preoperative neoadjuvant therapy methods, the patients were divided into neoadjuvant chemotherapy combined with immunotherapy group (chemoimmunization group, n=24) and neoadjuvant chemotherapy group (chemotherapy group, n=32). The postoperative tumor regression grade, objective response rate (ORR), disease control rate (DCR), pathological complete response (pCR) rate, major pathological remssion (MPR) rate, R0 resection rate, perioperative indicators, and security were compared between the two groups. Results:In chemoimmunization group, the tumor regression grade was better than that in chemotherapy group, with a statistically significant difference ( Z=9.39, P=0.025). The ORR and the DCR were 75.00% (18/24) and 91.67% (22/24) in chemoimmunization group, and 46.88% (15/32) and 65.62% (21/32) in chemotherapy group, with statistically significant differences ( χ2=4.48, P=0.034; χ2=5.21, P=0.022). The R0 resection rate was 87.50% (21/24) in chemoimmunization group, which was higher than that of the chemotherapy group [59.38% (19/32) ], with a statistically significant difference ( χ2=5.31, P=0.021). The pCR rate and MPR rate were 29.17% (7/24) and 54.17% (13/24) in chemoimmunization group, and 6.25% (2/32) and 28.12% (9/32) in chemotherapy group, there was no statistically significant difference in pCR rate ( χ2=3.78, P=0.052), but there was a statistically significant difference in MPR rate ( χ2=3.89, P=0.048). The interval between the end of neoadjuvant treatment and the start of surgery was (42.71±8.29) days in chemoimmunization group, and (42.25±8.03) days in chemotherapy group. The intraoperative blood loss of patients was (215.54±57.85) ml in chemoimmunization group, and (229.65±57.74) ml in chemotherapy group. The operation time of patients was (293.52±37.50) minutes in chemoimmunization group, and (295.31±37.66) minutes in chemotherapy group. The postoperative hospitalization time of patients was (17.90±3.49) days in chemoimmunization group, and (18.42±3.82) days in chemotherapy group, all with no statistically significant differences ( t=0.21, P=0.835; t=0.90, P=0.370; t=0.18, P=0.861; t=0.52, P=0.603). In terms of postoperative complications, there was no statistically significant difference in the total incidence of postoperative complications between the two groups [62.50% (15/24) vs. 84.38% (27/32), χ2=0.59, P=0.440]. The main adverse drug reactions in the two groups included decreased white blood cell count, nausea and vomiting, liver dysfunction, pruritus, hypothyroidism, etc. Most of them were grade 1-2, 3 cases were grade 3, and no grade 4 adverse reactions occurred. The total incidence of adverse reactions was 62.50% (15/24) in chemoimmunization group, and 65.62% (21/32) in chemotherapy group, with no statistically significant difference ( χ2=0.06, P=0.809) . Conclusion:For the preoperative neoadjuvant therapy of resectable ESCC, the combination of tislelizumab and chemotherapy has better short-term efficacy and better safety than the single chemotherapy scheme, which can improve the surgical efficacy.