Int J Med Sci
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Omega-3 fatty acids from fish oil (FO) and selenium (Se) potentiate some conventional therapies and have anticancer immune potential. This study aims to determine whether FO/Se modulates G-protein-coupled polyunsaturated fatty acid receptors (GPR-40 and GPR-120) and selenoproteins (Sel-H, Sel-W, and GPx4), and increases the therapeutic effect of doxorubicin in a dose-dependent manner on triple-negative breast cancer (TNBC) mouse. Mice were randomized into 5 groups (n = 7/group) and treated with physiological saline (control), low-dose doxorubicin, and doxorubicin in combination with low, medium, or high doses of FO/Se. ⋯ Dose-dependent inhibition of proliferation index Ki-67, cell cycle, and stem-cell-related markers were observed. Decreased immune check-points PD-L1/CTLA-4/Foxp3/CD86 and increased PD-1/CD28/IL-2 expression was also found. These observations suggest that the nutritional supplements FO/Se increase the chemotherapeutic efficacy of doxorubicin against TNBC by modulating GPR-40 and selenoprotein and targeting multiple signaling pathways in tumor tissues.
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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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Purpose: Mutations (K11E or E271K) of DEAD-box RNA helicase 24 (DDX24) were related to multi-organ venous lymphatic malformation syndrome (MOVLD). However, the relationship between these mutations and DDX24-function still remains unknown. Understanding whether K11E and E271K cause "loss-of-function" or "gain-of-function" for DDX24 is significant for related diseases. ⋯ Moreover, mice, inoculated with CHO-K11E-DDX24 or CHO-E271K-DDX24 cells, showed lower tumor formation rate, slower tumor growth rate, better prognosis, reduced standard uptake value and Ki of glucose in subcutaneous tumors. Sequencing indicated CHO-K11E-DDX24 or CHO-E271K-DDX24 caused increasing expression of TNF or chemokines and alteration in immune-related signal pathways. Conclusion: K11E or E271K mutation could lead to "loss-of-function" of DDX24 in cell proliferation and tumor bearing mice, which may be acted by non-specific immune killing to inhibit tumor growth.
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Spontaneous intracerebral hemorrhage (ICH) is associated with high mortality and disability rates. The microglia-induced inflammatory response is a critical factor determining brain tissue damage after ICH. ⋯ Mechanistically, RA downregulated the TLR4-mediated pro-inflammatory effectors, reduced infiltration of microglia in peri-intracerebral hemorrhage and inhibited apoptosis of neurons co-cultured with activated microglia. In conclusion, RA can alleviate ICH-related tissue damage and promote the recovery of neuronal function by suppressing microglia-induced inflammation and apoptosis.
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The injury of Schwann cells is an important pathological feature of peripheral neuropathy. However, the explicit molecular mechanism and blocking method remains to be explored. In this study, we identified an pivotal executor of necroptosis-RIPK1, performed an unique function in response to oxidative stress-induced injury in Rat Schwann cells. ⋯ While administration of Necrostatin-1 (Nec-1) failed to influence the levels of ROS and mitochondrial membrane potential, revealing that RIPK1 served as the down-stream regulators of ROS. Lastly, pharmacological inhibition of RIPK1 by Nec-1 attenuated the levels of necroptosis, increased proliferation, as indicated by Annexin V/PI evaluation, CCK-8 detection, TEM scanning and EdU staining. Our results indicate a previous un-recognized post-translational change of RIPK1 in response to oxidative stress in Schwann cells.