First total synthesis, antitumor evaluation and target identification of mornaphthoate E: A new tubulin inhibitor template acting on PI3K/Akt signaling pathway.

Mornaphthoate E (MPE) is a prenylated naphthoic acid methyl ester isolated from the roots of a famous Chinese medicinal plant Morinda officinalis and shows remarkable cytotoxicity against several human tumor cell lines. In the current project, the first total synthesis of (±)-MPE was achieved in seven steps and 5.6% overall yield. Then the in vitro anti-tumor activity of MPE was first assessed for both enantiomers in two breast cancer cells, with the levoisomer exerting slightly better potency. The in vivo anti-tumor effect was further verified by applying the racemate in an orthotopic autograft mouse model. Notably, MPE exerted promising anti-metastasis activity both in vitro and in vivo and showed no obvious toxicity on mice at the therapeutic dosage. Mechanistic investigations demonstrated that MPE acted as a tubulin polymerization stabilizer and disturbed the dynamic equilibrium of microtubules via regulating PI3K/Akt signaling. In conclusion, our work has provided a new chemical template for the future design and development of next-generation tubulin-targeting chemotherapies.

Risk factors of chronic kidney disease in cisplatin-based hyperthermia intraperitoneal chemotherapy.

PURPOSE: Cisplatin is commonly prescribed in hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal malignancy. Acute kidney injury (AKI) is regarded as a common complication after HIPEC combined with cytoreductive surgery (CRS). However, post-HIPEC chronic kidney disease (CKD) is scarce and less investigated. This study aims to investigate the incidence of CKD following cisplatin-based HIPEC and to analyse the associated risk factors. MATERIALS AND METHODS: From January 2016 to August 2021, a total of 55 patients treated with CRS and cisplatin-based HIPEC for peritoneal carcinomatosis were categorized retrospectively into groups, with and without CKD. Demographics, comorbidity, surgery, postoperative management, and complications were collected to evaluate risk factors for cisplatin-based HIPEC-related CKD. Univariate and multivariate analyses were conducted to confirm the correlation between different variables and CKD occurrence. RESULTS: Of the 55 patients, 24 (43.6%) patients developed AKI and 17 (70.8%) patients of these AKI patients progressed to CKD. Multivariate regression analysis identified intraoperative use of parecoxib (Odds Ratio (OR) = 4.39) and intraoperative maximum temperature > 38.5°C (OR = 6.40) as major risk factors for cisplatin-based HIPEC-related CKD occurrence. Though type II diabetes mellitus and intraoperative complications were the independent risk factors of AKI following cisplatin-based HIPEC, but they were not shown in CKD analysis. CONCLUSION: Intraoperative use of parecoxib during cisplatin-based HIPEC emerged as a significant risk factor for postoperative CKD. Clinicians should exercise caution in prescribing parecoxib during HIPEC procedures. Additionally, maintaining intraoperative body temperature below 38.5°C might be crucial to mitigate the risk of CKD development. This study underscores the importance of identifying and preventing specific risk factors to improve long-term renal outcomes in patients undergoing cisplatin-based HIPEC.

The antioxidant activity of polysaccharides from Armillaria gallica.

The purpose of this study was to investigate the antioxidant activity of Armillaria gallica polysaccharides. It explored whether Armillaria gallica polysaccharides (AgP) could prevent HepG2 cells from H2O2-induced oxidative damage. The results demonstrated that HepG2 cells were significantly protected by AgP, and efficiently suppressed the production of reactive oxygen species (ROS) in HepG2 cells. Additionally, AgP significantly decreased the abnormal leakage of alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) caused by H2O2, protecting cell membrane integrity. It was discovered that AgP was also found to regulate the activities of antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX), while reducing malondialdehyde (MDA), thus protecting cells from oxidative damage. According to the flow cytometry analysis and measurement of caspase-3, caspase-8, and caspase-9 activities, AgP could modulate apoptosis-related proteins and attenuate ROS-mediated cell apoptosis.

Isolation, Structure Characterization, Total Synthesis and Biological Evaluation of Cinnamic Acid Derivatives from Tinospora sagittata.

Thirteen cinnamic acid derivatives (1-13), including six formerly unreported hybrids incorporating different short-chain fatty acid esters (1-6), have been obtained and structurally elucidated from an ethnological herb Tinospora sagittata. The structures of them have been established by spectroscopic data analyses and NMR comparison with known analogs, while those of 1, 2, 4 and 6 have been further supported by total synthesis, and it is the first report of this type of metabolites from the title species. All the isolates have been assessed in an array of bioassays encompassing cytotoxic, antibacterial, anti-inflammatory, antioxidant, as well as α-glucosidase and HDAC1 inhibitory models. Compound 7 showed significant inhibitory activity against α-glucosidase, and half of the isolates also displayed moderate antiradical effect.

The Therapeutic Effect of Coriolus versicolor Fruiting Body on STZ-Induced ICR Diabetic Mice.

Coriolus versicolor is a natural drugs which has many pharmacological effects such as antitumor and enhanced immune activity. This paper studies the therapeutic effect of Coriolus versicolor fruiting body (CVFB) on streptozotocin (STZ)-induced Institute of Cancer Research (ICR) diabetic mice, the STZ solution was administered intraperitoneally at a dose of 150 mg/kg after fasting the mice, and ICR mice with fasting blood glucose >16.7 mmol/l were selected for research. Metformin was the positive control, and the dose of CVFB powder (1000 mg/kg, 2000 mg/kg, and 4000 mg/kg) for 28 consecutive days by gavage. The serum and liver of mice were collected for relevant index content testing. The results showed that CVFB can control or reduce the fasting blood glucose of mice and accelerate the rate of glucose metabolism, can reduce the levels of total cholesterol (T-CHO), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) in mice, and regulate the abnormal symptoms of blood lipid metabolism commonly found in diabetes. It can increase the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) antioxidant enzymes and enhance the ability of antioxidative stress in diabetic mice. In the H&E staining and apoptosis experiments of pancreatic tissue, CVFB can greatly reduce the inflammatory factors present in islets, increase the islet cells, and reduce the apoptotic rate caused by diabetes. All data confirmed the therapeutic effect of CVFB on diabetic ICR mice. The present study provides a scientific basis for the development of drugs for the prevention and treatment of diabetes, it is of great significance to the in-depth study of Coriolus versicolor.