Translational research : the journal of laboratory and clinical medicine
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Non-HDL cholesterol is a simple measure to analyze the total amount of proatherogenic lipoproteins in the blood and to predict development of cardiovascular disease. However, it is unclear whether non-HDL cholesterol has a relationship with incident type 2 diabetes. This study aimed to evaluate the association between non-HDL cholesterol and incident type 2 diabetes with a large-sample, community-based Korean cohort over a 12-year period. ⋯ In total, 1442 individuals (18.9%: 1442 of 7608) developed type 2 diabetes during the 12-year follow up period, with an incident rate of 3.0-5.0. Compared to the reference first quartile, the HRs (95% CIs) of incident type 2 diabetes for the second, third, and fourth quartiles increased in a dose-response manner after adjusting for potentially confounding variables, including the HOMA-IR marker. Non-HDL cholesterol level at baseline could be a future predictor of type 2 diabetes even when prior glucose or insulin (HOMA-IR) levels are normal.
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Biomarkers of mineral bone disorders (MBD) including phosphorus, fibroblast growth factor (FGF)-23 and Klotho are strongly altered in patients with acute kidney injury (AKI) who have high cardiac outcomes and mortality rates. However, the crosslink between MBD and cardiac damage after an AKI episode still remains unclear. We tested MBD and cardiac biomarkers in an experimental AKI model after 24 or 72 hours of folic acid injection and we analyzed structural cardiac remodeling, intracellular calcium (Ca2+) dynamics in cardiomyocytes and cardiac rhythm. ⋯ In a translational retrospective longitudinal clinical study, we determined that combining FGF-23 and phosphorus with cardiac troponin T levels achieved a better prediction of mortality in AKI patients at hospital admission. Thus, monitoring MBD and cardiac damage biomarkers could be crucial to prevent mortality in AKI patients. In this setting, Klotho might be considered as a new cardioprotective therapeutic tool to prevent deleterious cardiac events in AKI conditions.
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The balance between cardiac sympathetic and parasympathetic activities has been intricately linked to mitochondrial function, cellular oxidative status, and immunomodulation in healthy and diseased myocardium. Cardiac autonomic neuropathy, along with the associated mitochondrial and cellular dysfunction, is an important pathophysiological feature of doxorubicin-induced cardiotoxicity (DIC). We tested the hypothesis that autonomic modulation by activation of acetylcholine receptors (AChR) effectively attenuates DIC. ⋯ Contrarily, activation of mAChR by BET attenuated mitochondrial fission and mitophagy. The in vitro experiments confirmed the cytoprotective effects of AChR activation in DOX-treated H9c2 cells without compromising the anticancer effect of DOX in cancer cells. In conclusion, α7nAChR and mAChR agonists exerted cardioprotection against DIC via rebalancing autonomic function, improving mitochondrial function, reducing oxidative stress, and decreased cardiomyocyte apoptosis and inflammation, leading to improved cardiac function.
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Spectrin, as one of the major components of a plasma membrane-associated cytoskeleton, is a cytoskeletal protein composed of the modular structure of α and β subunits. The spectrin-based skeleton is essential for preserving the integrity and mechanical characteristics of the cell membrane. ⋯ Dysfunction of spectrins is implicated in various human diseases including hemolytic anemia, neurodegenerative diseases, ataxia, heart diseases, and cancers. Here, we briefly discuss spectrins function as well as the clinical manifestations and currently known molecular mechanisms of human diseases related to spectrins, highlighting that strategies for targeting regulation of spectrins function may provide new avenues for therapeutic intervention for these diseases.
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Endometriosis has been shown to increase the risk of gynecological cancers. However, the effect of gestrinone, a clinical endometriosis drug, on gynecological cancers remains unclear. This study aimed to understand the effect of gestrinone on gynecological cancers. ⋯ Cellular experiments verified the anticancer effects of gestrinone, which effectively and specifically inhibited the growth of HeLa cervical cancer cells, decreased P21 expression via JNK phosphorylation, and induced apoptosis. Combining the results of clinical database analysis and cell experiments, our findings prove that gestrinone has the potential to protect against cancer through regulation of the JNK-P21 axis. Repurposing the anticancer efficacy of gestrinone may be a strategy for targeted therapy in the future.