The antitumor action of endocannabinoids in the tumor microenvironment of glioblastoma.

Approximately 80% of all malignant brain tumors are gliomas, which are primary brain tumors. The most prevalent subtype of glioma, glioblastoma multiforme (GBM), is also the most deadly. Chemotherapy, immunotherapy, surgery, and conventional pharmacotherapy are currently available therapeutic options for GBM; unfortunately, these approaches only prolong the patient's life by 5 years at most. Despite numerous intensive therapeutic options, GBM is considered incurable. Accumulating preclinical data indicate that overt antitumoral effects can be induced by pharmacologically activating endocannabinoid receptors on glioma cells by modifying important intracellular signaling cascades. The complex mechanism underlying the endocannabinoid receptor-evoked antitumoral activity in experimental models of glioma may inhibit the ability of cancer cells to invade, proliferate, and exhibit stem cell-like characteristics, along with altering other aspects of the complex tumor microenvironment. The exact biological function of the endocannabinoid system in the development and spread of gliomas, however, is remains unclear and appears to rely heavily on context. Previous studies have revealed that endocannabinoid receptors are present in the tumor microenvironment, suggesting that these receptors could be novel targets for the treatment of GBM. Additionally, endocannabinoids have demonstrated anticancer effects through signaling pathways linked to the classic features of cancer. Thus, the pharmacology of endocannabinoids in the glioblastoma microenvironment is the main topic of this review, which may promote the development of future GBM therapies.

Efficacy and safety of dulaglutide compared with the first-line hypoglycemic drugs in Asian patients with type 2 diabetes: a systematic review and meta-analysis.

To assess the efficacy and safety of dulaglutide in the treatment of Asian type 2 diabetes mellitus (T2DM), along with first-line hypoglycemic drugs. Systematic review and meta-analysis. Cochrane Library, Pubmed, Embase, and www.clinicaltrials.gov databases were searched from inception to September 27, 2022. The studies evaluating adults (≥ 18 years) undergoing dulaglutide (0.75 mg and 1.5 mg) and first-line hypoglycemic drugs were considered. There were only English languages. We used Stata 12.0 software to detect the risk of bias. 4 randomized controlled trials (RCTs), and 1 observational study. Both dulaglutide 0.75 mg dose group and 1.5 mg dose group could significantly reduce HbA1c [Dulaglutide 0.75 mg: WMD = - 0.20, 95% CI (- 0.28, - 0.11), P < 0.0001; Dulaglutide 1.5 mg: WMD = - 0.49, 95% CI (- 0.67, - 0.30), P < 0.0001] in Asian T2DM patients. In reducing fasting blood glucose (FBG) level, there was no significant difference observed in 2 dose groups. The body weight of patients in both dulaglutide dose groups was significantly reduced. In safety, the incidence of adverse events in the dulaglutide 0.75 mg dose group was slightly higher than that in the first-line drug group, but there was no statistically significant difference in the incidence of adverse events between the 1.5 mg dose group and the first-line drug group. Furthermore, the incidences of hypoglycemic events in both groups were higher than that in the first-line drug group. Two doses of dulaglutide showed better efficacy for Asian T2DM patients, but patients should be vigilant about the occurrence of hypoglycemia and gastrointestinal discomfort. However, more number and better quality of RCTs are suggested to confirm long-term safety and efficacy.

Exploring the role of Xingren on COVID-19 based on network pharmacology and molecular docking.

Since the outbreak of novel Coronavirus Pneumonia 2019 (COVID-19), the role of Almonds (Xingren) in the protection and treatment of COVID-19 is not clear. Network pharmacology and molecular docking were used to explore the potential mechanism and potential key targets of Xingren on COVID-19. A total of nine common targets between them were obtained, and these targets were involved in multiple related processes of GO and KEGG pathway enrichment analysis. Molecular docking showed that licochalcone B has the best binding energy (-9.33 kJ·mol-1 ) to PTGS2. They are maybe the important ingredient and key potential target. Its possible mechanism is to intervene anxiety disorder in the process of disease development, such as regulation of blood pressure, reactive oxygen species metabolic process, leishmaniasis peroxisome, and IL-17 signaling pathway. PRACTICAL APPLICATIONS: Xingren is a traditional Chinese medicine that has been used and developed in China for many years. It contains a variety of active ingredients and also has the functions of relieving cough, relieving asthma, enhancing human immunity, delaying aging, regulating blood lipids, nourishing brain, and improving intelligence. In this article, the possible mechanisms of action and important targets of Xingren in the prevention and treatment of COVID-19 were discussed through network pharmacology and molecular docking. We also found that active ingredient licochalcone B and the potential target PTGS2 are worthy of further research and analysis. At the same time, the study also provides a theoretical basis and reference for the prevention and treatment of COVID-19 and the development of new drugs.

Investigating the Role of Dahuang in Hepatoma Treatment Using Network Pharmacology, Molecular Docking, and Survival Analysis.

Hepatoma is one of the most common malignant tumors. The incidence rate is high in developing countries, and China has the most significant number of cases. Dahuang is a classic traditional antitumor drug commonly used in China and has also been applied to treat hepatoma. However, the potential mechanism of Dahuang in treating hepatoma is not clear. Therefore, this study is aimed at elucidating the possible molecular mechanism and key targets of Dahuang using methods of network pharmacology, molecular docking, and survival analysis. Firstly, the active ingredients and key targets of Dahuang were analyzed through public databases, and then the drug-ingredient-target-disease network diagram of Dahuang against hepatoma was constructed. Five main active components and five core targets were determined according to the enrichment degree. Enrichment analysis demonstrated that Dahuang treated hepatoma through the multiple pathways in cancer. Additionally, molecular docking predicted that aloe-emodin and PIK3CG depicted the best binding energy. Survival analysis indicated that a high/ESR1 gene expression had a relatively good prognosis for patients with hepatoma (p < 0.05). In conclusion, the current study results demonstrated that Dahuang could treat hepatoma through a variety of active ingredients, targets, and multiantitumor pathways. Moreover, it effectively improved the prognosis of hepatoma patients. ESR1 is the potential key gene that is beneficial for the survival of hepatoma patients. Also, aloe-emodin and beta-sitosterol are the two main active crucial ingredients for hepatoma treatment. The study also provided some functional bases and references for the development of new drugs, target mining, and experimental animal research of hepatoma in the future.