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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Background: We previously found that intermediate conductance Ca2+-activated K+ channel (SK4) might be an important target in atrial fibrillation (AF). Objective: To investigate the role of SK4 in AF maintenance. Methods: Twenty beagles were randomly assigned to the sham group (n=6), pacing group (n=7), and pacing+TRAM-34 group (n=7). ⋯ Compared with the sham group, the expression of SK4 in atria was higher in the pacing group, which was associated with an increased number of myofibroblasts and levels of extracellular matrix in atrium (all P<0.05), and this effect was reversed by TRAM-34 treatment (all P<0.05). In atrial fibroblasts, the increased expression of SK4 induced by angiotensin II stimulation or Ad-SK4 transfection contributed to higher levels of P38, ERK1/2 and their downstream factors c-Jun and c-Fos, leading to the increased expression of α-SMA (all P<0.05), and all these increases were markedly reduced by TRAM-34 treatment. Conclusion: SK4 blockade suppressed AF by attenuating cardiac fibroblast activity and atrial fibrosis, which was realized through not only a decrease in fibrogenic factors but also inhibition of fibrotic signaling pathways.
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Among geriatric diseases, cerebrovascular disease ranks fourth according to the Causes of Death Statistics in 2019, Korea, and is the most common cause of acquired disorders in adults. Daehwang-Hwanglyoun-Sasim-Tang (DHST), a herbal prescription consisting of two herbal medicines, Rhei Rhizoma and Coptidis Rhizoma, has been reported to have anti-inflammatory, antioxidant, and anticancer effects. This study was conducted to confirm the anti-inflammatory mechanism of DHST treatment in ischemic brain injury and to confirm the role of DHST in cognitive function improvement. ⋯ In the 50 mL/kg DHST (H-DHST) group, the expression of apoptosis-related proteins was reduced and neuronal damage was suppressed in the hippocampal CA1 region. However, cognitive improvement was observed in the H-DHST group that was attributable to anti-inflammatory and antiapoptotic pathways. In the 5 mL/kg DHST group, no significant effect was observed compared with the control group.
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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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N6-methyladenosine (m6A) RNA methylation has been implicated in various malignancies. This study aimed to identify prognostic signature based on m6A methylation regulators for hepatocellular carcinoma (HCC) and provide candidate targets for HCC treatment. In this study, the expression levels, prognostic values, correlation with tumor grades and genetic variations of m6A-related genes in HCC were evaluated using bioinformatics analyses. ⋯ Functional and pathway enrichment analyses indicated that ZC3H13 might be involved in transcriptional dysregulation or the JAK-STAT signaling pathway in cancer. Additionally, ZC3H13 expression was significantly correlated with lymphocytes and immunomodulators. Therefore, ZC3H13 is a promising candidate as a novel biomarker and therapeutic target for HCC.