RESUMO
Background Gastric cancer (GC) is the second most common cause of cancer-related death worldwide. Novel anticancer drugs against gastric cancer are urgently needed. Methods Compound 10 was designed and synthesized via a molecular hybridization strategy based on the natural product formononetin. It was evaluated for their antiproliferative activity against three gastric cancer cell lines (SGC7901, MKN45 and MGC803). Results Derivative 10 displayed potently antiproliferative activity with an IC50 value of 1.07 µM against SGC7901 cells. Derivative 10 could inhibit the growth and migration against gastric cancer SGC7901 cells through the Wnt/ß-Catenin and AKT/mTOR pathways. From the in vivo expremints, it could effectively inhibited SGC7901 xenograft tumor growth in vivo without significant loss of the body weight. Conclusion Derivative 10 is an novel antitumor agent with potential for further clinical applications to treat gastric cancer. Graphical abstract.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Cumarínicos/uso terapêutico , Isoflavonas/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cumarínicos/química , Cumarínicos/farmacologia , Humanos , Isoflavonas/química , Isoflavonas/farmacologia , Camundongos Nus , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Serina-Treonina Quinases TOR/metabolismo , Carga Tumoral/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacosRESUMO
Objectives: Dysphagia is a common complication in stroke patients, widely affecting recovery and quality of life after stroke. The objective of this systematic review is to identify the gaps that between evidence and practice by critically assessing the quality of clinical practice guidelines (CPGs) for management of dysphagia in stroke. Methods: We systematically searched academic databases and guideline repositories between January 1, 2014, and August 1, 2023. The Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument was used by two authors to independently assess CPG quality. Results: In a total of 14 CPGs included, we identified that three CPGs obtained a final evaluation of "high quality," nine CPGs achieved "moderate quality" and two CPGs received "low quality." The domain of "scope and purpose" achieved the highest mean score (91.1%) and the highest median (IQR) of 91.7% (86.1, 94.4%), while the domain of "applicability" received the lowest mean score (55.8%) and the lowest median (IQR) of 55.4% (43.2, 75.5%). Conclusion: The CPG development group should pay more attention to improving the methodological quality according to the AGREE II instrument, especially in the domain of "applicability" and "stakeholder involvement;" and each item should be refined as much as possible.
RESUMO
The major pathogenic feature of liver fibrosis is that oxidative stress motivation of hepatic stellate cells (HSCs) alters the balance between the synthesis and degradation of extracellular matrix (ECM) and HSCs into proliferative myofibroblasts. Green tea and selenium (Se) can protect the liver from damage; however, the precise mechanism of green tea and the action of Se in green tea on hepatic fibrosis remain unclear. Several studies have demonstrated the profibrogenic role of 5-hydroxytryptamine (5-HT) and 5-hydroxytryptamine receptor (5-HTR) 2A/2B in the liver. The current study aimed to investigate the protective effects and possible mechanisms of selenium-enriched green tea on carbon tetrachloride (CCl4)-induced liver fibrosis in male C57BL/6 J mice. After a 4-week intervention with tea solution, histological analysis of the liver showed that green tea interventions alleviated hepatic fibrosis, which was supported by the changes in collagen type I, collagen type III, and α-smooth muscle actin in the liver. Tea interventions significantly inhibited the CCl4-provoked increase of duodenal 5-HT and tryptophan hydroxylase and hepatic 5-HT and 5-HTR2A/2B levels. All of them were lower in the selenium-enriched green tea group than in regular green tea group. Se-enriched green tea had a more pronounced improvement in liver ECM deposition and scar formation and peripheral 5-HT signals than regular green tea. Thus, green tea, especially those enriched with selenium, can improve liver fibrosis through intestinal 5-HT-hepatic 5-HTR signaling.