Neuraminidase1 Inhibitor Protects Against Doxorubicin-Induced Cardiotoxicity via Suppressing Drp1-Dependent Mitophagy

Anthracyclines, such as doxorubicin (DOX), are among the effective chemotherapeutic drugs for various malignancies. However, their clinical use is limited by irreversible cardiotoxicity. This study sought to determine the role of neuraminidase 1 (NEU1) in DOX-induced cardiomyopathy and the potential cardio-protective effects of NEU1 inhibitor oseltamivir (OSE). Male Sprague–Dawley (SD) rats were randomized into three groups: control, DOX, and DOX + OSE. NEU1 was highly expressed in DOX-treated rat heart tissues compared with the control group, which was suppressed by OSE administration. Rats in the DOX + OSE group showed preserved cardiac function and were protected from DOX-induced cardiomyopathy. The beneficial effects of OSE were associated with the suppression of dynamin-related protein 1 (Drp1)-dependent mitochondrial fission and mitophagy. In detail, the elevated NEU1 in cardiomyocytes triggered by DOX increased the expression of Drp1, which subsequently enhanced mitochondrial fission and PINK1/Parkin pathway-mediated mitophagy, leading to a maladaptive feedback circle towards myocardial apoptosis and cell death. OSE administration selectively inhibited the increased NEU1 in myocardial cells insulted by DOX, followed by reduction of Drp1 expression, inhibition of PINK1 stabilization on mitochondria, and Parkin translocation to mitochondria, thus alleviating excessive mitochondrial fission and mitophagy, alleviating subsequent development of cellular apoptotic process. This work identified NEU1 as a crucial inducer of DOX-induced cardiomyopathy by promoting Drp1-dependent mitochondrial fission and mitophagy, and NEU1 inhibitor showed new indications of cardio-protection against DOX cardiotoxicity.

The Gasotransmitter Hydrogen Sulfide and the Neuropeptide Oxytocin as Potential Mediators of Beneficial Cardiovascular Effects through Meditation after Traumatic Events

Trauma and its related psychological and somatic consequences are associated with higher cardiovascular morbidity. The regulation of both the gasotransmitter hydrogen sulfide (H2S) and the neuropeptide oxytocin (OT) have been reported to be affected during physical and psychological trauma. Both mediators are likely molecular correlates of trauma-induced cardiovascular complications, because they share parallel roles and signaling pathways in the cardiovascular system, both locally as well as on the level of central regulation and the vagus nerve. Meditation can alter the structure of specific brain regions and can have beneficial effects on cardiovascular health. This perspective article summarizes the evidence pointing toward the significance of H2S and OT signaling in meditation-mediated cardio-protection.

Presynaptic Release-Regulating Alpha2 Autoreceptors: Potential Molecular Target for Ellagic Acid Nutraceutical Properties

Polyphenol ellagic acid (EA) possesses antioxidant, anti-inflammatory, anti-carcinogenic, anti-diabetic and cardio protection activities, making it an interesting multi-targeting profile. EA also controls the central nervous system (CNS), since it was proven to reduce the immobility time of mice in both the forced swimming and the tail-suspension tests, with an efficiency comparable to that of classic antidepressants. Interestingly, the anti-depressant-like effect was almost nulled by the concomitant administration of selective antagonists of the noradrenergic receptors, suggesting the involvement of these cellular targets in the central effects elicited by EA and its derivatives. By in silico and in vitro studies, we discuss how EA engages with human α2A-ARs and α2C-AR catalytic pockets, comparing EA behaviour with that of known agonists and antagonists. Structurally, the hydrophobic residues surrounding the α2A-AR pocket confer specificity on the intermolecular interactions and hence lead to favourable binding of EA in the α2A-AR, with respect to α2C-AR. Moreover, EA seems to better accommodate within α2A-ARs into the TM5 area, close to S200 and S204, which play a crucial role for activation of aminergic GPCRs such as the α2-AR, highlighting its promising role as a partial agonist. Consistently, EA mimics clonidine in inhibiting noradrenaline exocytosis from hippocampal nerve endings in a yohimbine-sensitive fashion that confirms the engagement of naïve α2-ARs in the EA-mediated effect.

Exosomes Derived from miR-146a-5p-Enriched Mesenchymal Stem Cells Protect the Cardiomyocytes and Myocardial Tissues in the Polymicrobial Sepsis through Regulating MYBL1

Background. At present, the study has confirmed that the mesenchymal stem cell-derived exosomes (MCSs-Exo) possess cardio-protection in sepsis. Nevertheless, the molecular mechanism of the protection of MSCs-Exo in sepsis remains unknown. Therefore, this research is aimed at studying the molecular mechanism. Methods. The effects of MSCs-Exo and miR-146a-5p in LPS-induced cardiomyocytes (H9C2 cells) in vitro were verified by CCK-8, EdU assay, flow cytometry, Western blot assay, and RT-qPCR. The effect of MSCs-Exo in vivo was evaluated by CLP-induced sepsis model. The potential gene in MSCs-Exo was verified by bioinformatics analysis, and the potential target of miR-146a-5p was identified by bioinformatics analysis and luciferase reporter assay. At last, the function of miR-146a-5p and its target genes on LPS-induced cardiomyocytes (H9C2 cells) in vitro was validated by recuse experiment. Results. Our findings revealed that MSCs-Exo could effectively protect cardiomyocytes of inflammation model in vitro and myocardial tissues of sepsis model in vivo. Meanwhile, we found that miR-146a-5p was a potential gene in MSCs-Exo, and MYBL1 was the target gene of miR-146a-5p and negatively regulated by miR-146a-5p. In addition, miR-146a-5p overexpression promoted proliferation and inhibited apoptosis of LPS-induced cardiomyocytes. The rescue experiment demonstrated that miR-146a-5p could effectively repress the inflammatory response of cardiomyocytes via decreasing MYBL1 expression. Conclusion. This study suggests that miR-146a-5p-bearing MSC-derived exosomes may become an effective treatment for sepsis.

Assessing the effect of sevoflurane anesthesia on cardiac and brain protection compared with propofol in patients undergoing cardiac surgery: A meta-analysis

Objective: Whether sevoflurane anesthesia is superior to propofol anesthesia in cardiac protection is still unknown. Here, we aim to compare the cardio-/neuro-protective efficacy of sevoflurane and propofol on patients undergoing cardiac surgery. Design: We searched studies based on predefined strategies in MEDLINE, the Cochrane Library, Web of Science and EMBASE. Standardized mean difference (SMD) and relative risk were employed to combine continuous and binary measurements respectively using R packages “metafor”. Subgroup analysis was performed and publication bias was evaluated.. Results: A total of 26 studies were included in our meta-analysis, with 1510 in the sevoflurane group and 1494 in the propofol group. Compared with propofol anesthesia, sevoflurane anesthesia could not significantly reduce the all-cause mortality (OR = 0.79[0.36, 1.74], p-value = 0.564). Although sevoflurane anesthesia was superior to propofol in reducing postoperative cTnI (SMD = -0.93[-1.36, -0.50], p-value < 0.001), such cardio-protection effect would diminish with time since the differences of postoperative 12h and 24h cTnI became insignificant after Bonferroni correction. The results of neuroprotection are rather contradictory and needs further investigation. Conclusion: The sevoflurane anesthesia cannot result in a lower all-cause mortality rate than propofol anesthesia among patients undergoing cardiac surgery despite of its minor protective effects.

Pharmacological actions and underlying mechanisms of Catechin: A review

Background: Catechin is a phytochemical and is a major component of our daily use beverages, which has shown great potential in improving general health and fighting against several medical conditions. Clinical studies have confirmed its effectiveness in conditions ranging from acute upper respiratory tract infection, neuroprotection, to cardio-protection effects. Though most studies relate their potential to anti-oxidative action and radical scavenging action, still the mechanism of action is not clearly understood. Objective: The present review article is focused on addressing various pharmacological actions and underlying mechanisms of catechin. Additionally, we will try to figure out the major adverse effect and success in trials with catechin and lead to a conclusion for its effectiveness. Methods: This review article is based on the recent/ most cited papers of PubMed and Scopus databases. Description: Catechin can regulate Nrf2 and NFkB pathways in ways that impact oxidative stress and inflammation by influencing gene expression. Other pathways like MAPKs and COMT and receptor tyrosine kinase are also affected by catechin and EGCG that alter their action and barge the cellular activity. This review article explored the structural aspect of catechin and its different isomers and analogs. It also evaluated its various therapeutic and pharmacological arrays . Conclusion: Catechin and its stereo-isomers have shown their effectiveness as anti-inflammatory, anti-diabetic, anti-cancer, anti-neuroprotective, bactericidal, memory enhancer, anti-arthritis, and hepato-protective mainly through its activity to alter the pathway by NF-κB, Nrf-2, TLR4/NF-κB, COMT, and MAPKs.