Notoginsenoside Ft1 inhibits colorectal cancer growth by increasing CD8+ T cell proportion in tumor-bearing mice through the USP9X signaling pathway.

The management of colorectal cancer (CRC) poses a significant challenge, necessitating the development of innovative and effective therapeutics. Our research has shown that notoginsenoside Ft1 (Ng-Ft1), a small molecule, markedly inhibits subcutaneous tumor formation in CRC and enhances the proportion of CD8+ T cells in tumor-bearing mice, thus restraining tumor growth. Investigation into the mechanism revealed that Ng-Ft1 selectively targets the deubiquitination enzyme USP9X, undermining its role in shielding ß-catenin. This leads to a reduction in the expression of downstream effectors in the Wnt signaling pathway. These findings indicate that Ng-Ft1 could be a promising small-molecule treatment for CRC, working by blocking tumor progression via the Wnt signaling pathway and augmenting CD8+ T cell prevalence within the tumor environment.

The function of tRNA-derived small RNAs in cardiovascular diseases.

tRNA-derived small RNAs (tsRNAs) constitute a subgroup of small noncoding RNAs (ncRNAs) originating from tRNA molecules. Their rich content, evolutionary conservatism, high stability, and widespread existence makes them significant in disease research. These characteristics have positioned tsRNAs as key players in various physiological and pathological processes. tsRNA actively participates in regulating many cellular processes, such as cell death, proliferation, and metabolism. tsRNAs could be promising diagnostic markers for cardiovascular diseases (CVDs). tsRNAs have been identified in serums, suggesting their utility as early indicators for the diagnosis of CVDs. Moreover, the regulatory roles of tsRNAs in CVDs make them promising targets for therapeutic intervention. This review provides a succinct overview of the characteristics, classification, and regulatory functions of tsRNAs in the context of CVDs. By shedding light on the intricate roles of tsRNAs, this knowledge could pave the way for the development of innovative diagnostic tools and therapeutic strategies for CVDs.

Fibroblast growth factor 15, induced by elevated bile acids, mediates the improvement of hepatic glucose metabolism after sleeve gastrectomy.

BACKGROUND: Fibroblast growth factor (FGF) 15/19, which is expressed in and secreted from the distal ileum, can regulate hepatic glucose metabolism in an endocrine manner. The levels of both bile acids (BAs) and FGF15/19 are elevated after bariatric surgery. However, it is unclear whether the increase in FGF15/19 is induced by BAs. Moreover, it remains to be understood whether FGF15/19 elevations contribute to improvements in hepatic glucose metabolism after bariatric surgery. AIM: To investigate the mechanism of improvement of hepatic glucose metabolism by elevated BAs after sleeve gastrectomy (SG). METHODS: By calculating and comparing the changes of body weight after SG with SHAM group, we examined the weight-loss effect of SG. The oral glucose tolerance test (OGTT) test and area under the curve of OGTT curves were used to assess the anti-diabetic effects of SG. By detecting the glycogen content, expression and activity of glycogen synthase as well as the glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (Pepck), we evaluated the hepatic glycogen content and gluconeogenesis activity. We examined the levels of total BA (TBA) together with the farnesoid X receptor (FXR)-agonistic BA subspecies in systemic serum and portal vein at week 12 post-surgery. Then the histological expression of ileal FXR and FGF15 and hepatic FGF receptor 4 (FGFR4) with its corresponding signal pathways involved in glucose metabolism were detected. RESULTS: After surgery, food intake and body weight gain of SG group was decreased compare with the SHAM group. The hepatic glycogen content and glycogen synthase activity was significantly stimulated after SG, while the expression of the key enzyme for hepatic gluconeogenesis: G6Pase and Pepck, were depressed. TBA levels in serum and portal vein were both elevated after SG, the FXR-agonistic BA subspecies: Chenodeoxycholic acid (CDCA), lithocholic acid (LCA) in serum and CDCA, DCA, LCA in portal vein were all higher in SG group than that in SHAM group. Consequently, the ileal expression of FXR and FGF15 were also advanced in SG group. Moreover, the hepatic expression of FGFR4 was stimulated in SG-operated rats. As a result, the activity of its corresponding pathway for glycogen synthesis: FGFR4-Ras-extracellular signal regulated kinase pathway was stimulated, while the corresponding pathway for hepatic gluconeogenesis: FGFR4- cAMP regulatory element-binding protein- peroxisome proliferator-activated receptor γ coactivator-1α pathway was suppressed. CONCLUSION: Elevated BAs after SG induced FGF15 expression in distal ileum by activating their receptor FXR. Furthermore, the promoted FGF15 partly mediated the improving effects on hepatic glucose metabolism of SG.

Improved LSTM-based deep learning model for COVID-19 prediction using optimized approach.

Individuals in any country are badly impacted both economically and physically whenever an epidemic of infectious illnesses breaks out. A novel coronavirus strain was responsible for the outbreak of the coronavirus sickness in 2019. Corona Virus Disease 2019 (COVID-19) is the name that the World Health Organization (WHO) officially gave to the pneumonia that was caused by the novel coronavirus on February 11, 2020. The use of models that are informed by machine learning is currently a major focus of study in the field of improved forecasting. By displaying annual trends, forecasting models can be of use in performing impact assessments of potential outcomes. In this paper, proposed forecast models consisting of time series models such as long short-term memory (LSTM), bidirectional long short-term memory (Bi-LSTM), generalized regression unit (GRU), and dense-LSTM have been evaluated for time series prediction of confirmed cases, deaths, and recoveries in 12 major countries that have been affected by COVID-19. Tensorflow1.0 was used for programming. Indices known as mean absolute error (MAE), root means square error (RMSE), Median Absolute Error (MEDAE) and r2 score are utilized in the process of evaluating the performance of models. We presented various ways to time-series forecasting by making use of LSTM models (LSTM, BiLSTM), and we compared these proposed methods to other machine learning models to evaluate the performance of the models. Our study suggests that LSTM based models are among the most advanced models to forecast time series data.

Ginsenosides: Allies of gastrointestinal tumor immunotherapy.

In the past decade, immunotherapy has been the most promising treatment for gastrointestinal tumors. But the low response rate and drug resistance remain major concerns. It is therefore imperative to develop adjuvant therapies to increase the effectiveness of immunotherapy and prevent drug resistance. Ginseng has been used in Traditional Chinese medicine as a natural immune booster for thousands of years. The active components of ginseng, ginsenosides, have played an essential role in tumor treatment for decades and are candidates for anti-tumor adjuvant therapy. They are hypothesized to cooperate with immunotherapy drugs to improve the curative effect and reduce tumor resistance and adverse reactions. This review summarizes the research into the use of ginsenosides in immunotherapy of gastrointestinal tumors and discusses potential future applications.

Efficacy and Safety of Totally Laparoscopic Gastrectomy Compared with Laparoscopic-Assisted Gastrectomy in Gastric Cancer: A Propensity Score-Weighting Analysis.

Objectives: To compare the short- and long-term outcomes of totally laparoscopic gastrectomy (TLG) with laparoscopic-assisted gastrectomy (LAG) in gastric cancer (GC) patients and evaluate the efficacy and safety of TLG. Methods: This retrospective study was based on GC patients who underwent laparoscopic radical gastrectomy in the Qilu Hospital from January 2017 to December 2020. The groups' variables were balanced by using the propensity score-based inverse probability of treatment weighting (PS-IPTW). The primary outcomes were 3-year relapse-free survival (RFS) and 3-year overall survival (OS). Postoperative recovery and complications were the secondary outcomes. Results: A total of 250 GC patients were included in the study. There were no significant differences in baseline and pathological features between the TLG and the LAG groups after the PS-IPTW. TLG took around 30 min longer than LAG, while there were more lymph nodes obtained and less blood loss throughout the procedure. TLG patients had less wound discomfort than LAG patients in terms of short-term prognosis. There were no significant differences between groups in the 3-year RFS rate [LAG vs. TLG: 78.86% vs. 78.00%; hazard ratio (HR) = 1.14, 95% confidence interval (CI), 0.55-2.35; p = 0.721] and the 3-year OS rate (LAG vs. TLG: 78.17% vs. 81.48%; HR = 0.98, 95% CI, 0.42-2.27; p = 0.955). The lymph node staging was found to be an independent risk factor for tumor recurrence and mortality in GC patients with laparoscopic surgery. The subgroup analysis revealed similar results of longer operation time, less blood loss, and wound discomfort in totally laparoscopic distal gastrectomy, while the totally laparoscopic total gastrectomy showed benefit only in terms of blood loss. Conclusion: TLG is effective and safe in terms of short- and long-term outcomes, with well-obtained lymph nodes, decreased intraoperative blood loss, and postoperative wound discomfort, which may be utilized as an alternative to LAG.