Int J Med Sci
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Hepatocellular carcinoma (HCC) is a primary liver cancer commonly found in adults. Previously, we showed the anticancer effects of Thai herbal plant extract, Dioscorea membranacea Pierre (DM), in HCC-bearing rats. In the present study, we further examined the proposed mechanism of DM, including apoptosis and antioxidant activity. ⋯ DM extract expanded the Bax protein-positive pericentral zone in the tumor areas and decreased hepatic malondialdehyde levels, implying a decrease in lipid peroxidation in liver. However, DM treatment did not ameliorate the molecular pathways induced in DEN/TAA-treated livers. Our findings indicate that DM extract has antioxidant activity and exerts its pro-apoptotic effect on rat HCCs in vivo at the (post-)translational level.
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RRx-001 is a small molecule NLRP3 inflammasome inhibitor with anti-CD47 and antiangiogenic/vascular normalization properties in a Phase 3 clinical trial that has been designated as a drug-device combination by the FDA. In the Phase 1 first-in-man dose escalation clinical trial, where RRx-001 was given by direct intravenous (IV) infusion, the main adverse event was a sterile painful infusion phlebitis (IP). Less pain was experienced when RRx-001 was infused at a slower rate over multiple hours which was impractical on an outpatient basis. ⋯ In this 13-week toxicology study of once weekly IV RRx-001 administration to Wistar Han rats followed by a recovery period of 28 days. The main observed toxicity was a significant inflammatory response in the vein wall, consistent with superficial venous thrombosis observed in man. Due to this development, direct IV infusion of RRx-001 is relatively contraindicated in favor of co-administration with autologous blood.
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More and more reports have pointed out that rotenone, as an insecticide, has high neurotoxicity and reproductive toxicity to livestock and mammals. As a highly physiological correlation system of internal organs, quasi-organs have great potential in the fields of drug toxicity and efficacy test, toxicology research, developmental biology and so on. In this study, brain organs (mBOs) derived from mouse neural stem cells were used to investigate the effects of rotenone on the physiological activity and epigenetic modification of mBOs. ⋯ In addition, the results of RRBS-Seq sequencing showed that the methylation modification at DMR level in Rotenone-treated mBOs group was significantly higher than that in Ctrl group. The results of KEGG analysis showed that compared with Ctrl, the genes with hypermethylation of promoter and Genebody in Rotenone-treated mBOs were mainly located in the Neuro active ligand-receptor interaction signal transduction pathway. In summary, rotenone can significantly lead to abnormal methylation of mouse brain organs, and lead to the loss of normal physiological function of neurons by inducing ferroptosis.
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Traumatic brain injury is a medical event of global concern, and a growing body of research suggests that circular RNAs can play very important roles in traumatic brain injury. To explore the functions of more novel and valuable circular RNA in traumatic brain injury response, a moderate traumatic brain injury in rats was established and comprehensive analysis of circular RNA expression profiles in rat cerebral cortex was done. ⋯ This study showed that differentially expressed circular RNAs existed between rat cerebral cortex after moderate traumatic brain injury and control. And this will provide valuable information for circular RNA research in the field of traumatic brain injury.
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Retroperitoneal liposarcoma (RLPS) is one of the most common subtypes of retroperitoneal soft tissue sarcomas. It is characterized by poor sensitivity to radiotherapy and chemotherapy and a low success rate of complete surgical resection. However, there are few reliable preclinical RLPS models for target discovery and therapy research. ⋯ Treatment with MDM2 inhibitor RG7112 significantly suppressed tumor growth of DDLPS PDX in mice. In conclusion, we successfully established RLPS PDX models that were histologically, genetically, and molecularly consistent with the original tissues. These models might provide opportunities for advancing RLPS tumor biology research, facilitating the development of novel drugs, particularly those targeting MDM2 amplification, adipose differentiation process, angiogenesis, cancer-associated fibroblasts, and so on.