Diabetic cardiomyopathy (DCM) is one of the most common complications of diabetes without effective treatment options. Its pathogenesis is complex and remains unclear. Long non-coding RNA (lncRNA) MIAT allele has been reported to be enriched in DCM patients and activate a pyroptosis program in hypoxia-induced H9c2 cells. Thus, whether MIAT played a role in DCM pyroptosis remains to be clarified. In the study, the expression of MIAT was found elevated in the serum of diabetic patients, as well as in high-glucose induced cardiomyocytes and diabetic mice. Further, the expression levels of CASP1 and pyroptosis correlation factors (IL-1 and IL-18) were downregulated after silencing MIAT. Through modeling and validation experiments, we then confirmed that the MIAT-miR-214-3p-CASP1 axis serves as an essential point in pyroptosis of DCM mice. These results suggested that silencing MIAT would be a potential treatment strategy for DCM.
29 May 2023 in European Journal of Medicinal Chemistry
While endocrine therapy is considered as an effective way to treat breast cancer, it still faces many challenges, such as drug resistance and individual discrepancy. Therefore, novel preventive and therapeutic modalities are still in great demand to decrease the incidence and mortality rate of breast cancer. Numerous studies suggested that G protein-coupled estrogen receptor (GPER), a membrane estrogen receptor, is a potential target for breast cancer prevention and treatment. It was also shown that not only endogenous estrogens can activate GPERs, but many phytoestrogens can also function as selective estrogen receptor modulators (SERMs) to interact GPERs. In this review, we discussed the possible mechanisms of GPERs pathways and shed a light of developing novel phytoestrogens based dietary supplements against breast cancers.
Clinically, antioxidant therapy is a potential strategy for myocardial ischemia-reperfusion injury (MI/RI), a common complication of acute myocardial ischemia. The H-D-Arg-Dmt-Ly-Phe-NH2 (SS31) peptide is shown to have amazing antioxidant properties, but its utilization is limited by the peptide characteristics, such as the destruction by proteases and rapid metabolism. Silica nanoparticles (MSNs) comprise an excellent material for peptide delivery, owing to the protection effect relating to peptides. Moreover, platelet membrane (PLTM) is shown to be advantageous as a coat for nanosystems because of its specific protein composition, such that a PLTM-coated nanosystem has a stealth effect in vivo, able to target injury in the cardiovascular system. Based on this feature, we designed and prepared a novel nanocarrier to target SS31 delivery. This carrier is encapsulated by a platelet membrane and loaded with SS31 peptide into MSNs. The results reveal that this delivery system can target SS31 to the injured cardiovascular site, exert antioxidant function, and alleviate MI/RI.
The prevalence of diabetes mellitus is increasing in resource limited settings. Simultaneously, there has been an increase in the number of novel therapies for the management of diabetes mellitus. However, use of novel antidiabetic therapies is limited because of major market access challenges in resource limited settings. Niching products to those patients with the highest absolute risk for major adverse cardiovascular outcomes, and thus most likely to benefit from the therapy, are less likely to have negative budget impact for funders. To improve access, and reduce morbidity and mortality, requires alignment amongst key stakeholders including patient advocacy groups, health care professional councils, national departments of health, the pharmaceutical industry, treasury and finance departments.