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Plasma biomarkers are useful tools in the diagnosis and prognosis of heart failure (HF). In the last decade, numerous studies have aimed to identify novel HF biomarkers that would provide superior and/or additional diagnostic, prognostic, or stratification utility. Although numerous biomarkers have been identified, their implementation in clinical practice has so far remained largely unsuccessful. Whereas cardiac-specific biomarkers, including natriuretic peptides (ANP and BNP) and high sensitivity troponins (hsTn), are widely used in clinical practice, other biomarkers have not yet proven their utility. Galectin-3 (Gal-3) and soluble suppression of tumorigenicity 2 (sST2) are the only novel HF biomarkers that are included in the ACC/AHA HF guidelines, but their clinical utility still needs to be demonstrated. In this review, we will describe natriuretic peptides, hsTn, and novel HF biomarkers, including Gal-3, sST2, human epididymis protein 4 (HE4), insulin-like growth factor-binding protein 7 (IGFBP-7), heart fatty acid-binding protein (H-FABP), soluble CD146 (sCD146), interleukin-6 (IL-6), growth differentiation factor 15 (GDF-15), procalcitonin (PCT), adrenomedullin (ADM), microRNAs (miRNAs), and metabolites like 5-oxoproline. We will discuss the biology of these HF biomarkers and conclude that most of them are markers of general pathological processes like fibrosis, cell death, and inflammation, and are not cardiac- or HF-specific. These characteristics explain to a large degree why it has been difficult to relate these biomarkers to a single disease. We propose that, in addition to clinical investigations, it will be pivotal to perform comprehensive preclinical biomarker investigations in animal models of HF in order to fully reveal the potential of these novel HF biomarkers. [ABSTRACT FROM AUTHOR]

Reperfusion stands as a pivotal intervention for ischemic heart disease. However, the restoration of blood flow to ischemic tissue always lead to further damage, which is known as myocardial ischemia/reperfusion injury (MIRI). Ramelteon is an orally administered drug used to improve sleep quality, which is famous for its high bioadaptability and absence of notable addictive characteristics. However, the specific mechanism by which it improves MIRI is still unclear. Sirtuin-3 (Sirt3), primarily located in mitochondria, is crucial in mitigating many cardiac diseases, including MIRI. Based on the structure of Sirt3, we simulated molecular docking and identified several potential amino acid binding sites between it and ramelteon. Therefore, we propose a hypothesis that ramelteon may exert cardioprotective effects by activating the Sirt3 signaling pathway. Our results showed that the activation levels and expression level of Sirt3 were significantly decreased in MIRI tissue and H 2 O 2 stimulated H9C2 cells, while ramelteon treatment upregulated Sirt3 activity and expression. After treat with 3-TYP, a classic Sirt3 activity inhibitor, we constructed myocardial ischemia/reperfusion surgery in vivo and induced H9C2 cells with H 2 O 2 in vitro. The results showed that the myocardial protection and anti-apoptotic effects of ramelteon were antagonized by 3-TYP, indicating that the activation of Sirt3 is a key mechanism for ramelteon to exert myocardial protection. In summary, our results confirm a novel mechanism by which ramelteon improves MIRI by activating Sirt3 signaling pathway, providing strong evidence for the treatment of MIRI with ramelteon. [ABSTRACT FROM AUTHOR]

• We for the first time investigated that Melatonin exerted anti-tumor activities in Hodgkin lymphoma via inhibiting cell proliferation and promoting cell apoptosis. • Melatonin treatment induced autophagy in Hodgkin lymphoma cells. • Melatonin induces autophagy by increasing the expression of RORC. Melatonin (Mel) has been shown to involve in many essential cell functions via modulating many signaling pathways. We for the first time investigated that Mel exerted anti-tumor activities in Hodgkin lymphoma (HL) via inhibiting cell proliferation and promoting cell apoptosis. Further study revealed that Mel treatment increased expression of LC3-II and decreased p62 proteins with the enhanced production of autolysosome, indicating it induced activation of autophagy. Nevertheless, Mel treatment together with autophagy inhibitors 3-MA or CQ exacerbated the damage effect of Mel in HL cells, which means autophagy plays a protective role in this process. Furthermore, we found Mel treatment increased the expression of G protein-coupled receptors MT2 and retinoic acid-related orphan receptors (RORs), eg. RORA, RORB and RORC. While RORC has the highest increase in Mel treated HL cells. In addition, RORC overexpression induced autophagy activation. Therefore, Mel showed tumor-suppressive role due to an increased level of RORC induced autophagy in HL. [ABSTRACT FROM AUTHOR]