Aberrant expression of AKR1B1 indicates poor prognosis and promotes gastric cancer progression by regulating the AKT-mTOR pathway.

Gastric cancer (GC) is a common malignant tumor in the digestive tract and a major cause of global cancer death. Due to the limited access to early screening, many patients are diagnosed with advanced GC. Therefore, postoperative radiotherapy and chemotherapy possess limited efficacy in treating GC. AKR1B1 has been associated with tumorigenesis and metastasis across various tumors, becoming a potential therapeutic target for GC. However, its role and mechanism in GC remain unclear. In this study, AKR1B1 was elevated in GC tissue, depicting a poor prognosis. AKR1B1 is closely related to age, vascular and neural invasion, lymph node metastasis, and the TNM stage of GC. The developed survival prediction model suggested that AKR1B1 expression level is crucial in the prognosis of GC patients. Moreover, the expression level of AKR1B1 in GC tissues is closely associated with the AKT-mTOR pathway. In vitro and in vivo assays functional assays helped determine the oncogenic role of AKR1B1. Additionally, the knockdown of AKR1B1 expression level in GC cell lines could effectively suppress the AKT-mTOR pathway and inhibit the proliferation and migration of tumor cells. In conclusion, this study provides a theoretical basis to establish the potential association and regulatory mechanism of AKR1B1 while offering a new strategy for GC-targeted therapy.

Bile acid metabolism and liver fibrosis following treatment with bifid triple viable capsules in nonalcoholic fatty liver disease.

PURPOSE: This study investigated liver enzymes, bile acid metabolism, and liver fibrosis in nonalcoholic fatty liver disease (NAFLD) to evaluate the therapeutic effects of microecological preparations on fatty liver. METHODS: Liver enzymes, liver fibrosis, and bile acids were assessed in 40 healthy volunteers and 124 NAFLD patients. All patients were retested for liver enzymes, bile acids, and liver fibrosis after two months of bifid triple viable capsule therapy. Results: (1) Prior to treatment, alanine aminotransferase, aspartate aminotransferase, glutamyl transpeptidase, FibroScan liver stiffness, total bile acid, chenodeoxycholic acid, deoxycholic acid, glycocholic acid, glycochenodeoxycholic acid, glycodeoxycholic acid, taurocholic acid, taurochenodeoxycholic acid, taurodeoxycholic acid, and taurolithocholic acid increased with the severity of NAFLD (P<0.05). Primary/secondary bile acids increased in patients compared to healthy controls; free/conjugated bile acids decreased (P<0.05). (2) We detected a positive correlation between total bile acid, cholic acid, chenodeoxycholic acid, deoxycholic acid, ursodeoxycholic acid, glycocholic acid, glycochenodeoxycholic acid, glycodeoxycholic acid, taurocholic acid, taurochenodeoxycholic acid, taurodeoxycholic acid, taurolithocholic acid, tauroursodeoxycholic acid, and FibroScan liver stiffness. (3) Following treatment, liver enzymes decreased. Bile acids were impacted by decreasing primary/secondary bile acids and increasing free/conjugated bile acids. Improvements were observed in the fibrosis of mild fatty liver. No effects were observed for moderate and severe fatty liver. CONCLUSIONS: Liver enzymes, bile acids, and liver fibrosis were correlated with the severity of NAFLD. There were positive correlations between bile acids and liver fibrosis. Bifid triple viable capsules could decrease liver enzymes and impact bile acid metabolism but failed to effectively improve liver fibrosis.

High expression of piwi-like RNA-mediated gene silencing 1 is associated with poor prognosis via regulating transforming growth factor-ß receptors and cyclin-dependent kinases in breast cancer.

Previous studies have demonstrated that abnormal expression levels of PIWI may serve a crucial role in tumorigenesis. However, the pathological role and its association with prognosis remains to be fully elucidated. In the present study, the expression levels of piwi­like RNA­mediated gene silencing 1 (HIWI) and piwi­like RNA­mediated gene silencing 2 (HILI) in breast cancer tissues were reported to be high. The high expression levels of HIWI are correlated with poor prognosis in detected patients. In addition, by overexpression and interference, it was demonstrated that HIWI promotes the activity of breast cancer cells while depression of HIWI may induce apoptosis of breast cancer cells. It was additionally identified that suppression of HIWI may arrest the cells at the G2/M stage. The expression levels of transforming growth factor­ß receptor (TßR)I, TßRII, cyclin­dependent kinase (CDK)4, CDK6 and CDK8 were observed to be regulated by HIWI, which indicated a novel mechanism of HIWI in the regulation of breast cancer progression. The present study provides novel insight into the HIWI expression in breast cancer, providing a potential biomarker for assessment of prognosis and therapy of breast cancer.