Combined systemic inflammatory indexes as reflectors of outcome in patients with COVID­19 infection admitted to ICU.

INTRODUCTION: The principal etiology of mortality in COVID-19 patients is the systemic pro-inflammatory processes which may lead to acute respiratory distress syndrome. Hematologic indices are reachable representatives of inflammation in patients with COVID-19 infection. The purpose of the current study was to evaluate the potential predictive value of these inflammatory indices in the in-hospital mortality of ICU-admitted COVID-19 patients. The studied indexes included AISI, dNLR, NLPR, NLR, SII, and SIRI. METHOD: 315 COVID-19 patients admitted to ICU managed in Imam Khomeini Hospital of Urmia, Iran, during the last 6 months of 2020 were retrospectively enrolled in the study and divided into two subgroups based on their final outcome, discharge or death. RESULTS: Total leucocyte count (TLC), absolute neutrophil count (NLC), urea, Cr, RDW, AISI, dNLR, NLPR, NLR, SII, and SIRI were drastically elevated in the dead patients (P < 0.05). The optimal cut-off points for AISI (378.81), dNLR (5.66), NLPR (0.03), NLR (5.97), SII (1589.25), and SIRI (2.31) were obtained using ROC curves. NLR and SII had the highest sensitivity (71.4%) and specificity (73.6%), respectively. Patients with above-cut-off levels of ISI, dNLR, NLPR, NLR, and SII had lower average survival time. Age (OR = 1.057, CI95%: 1.030-1.085, p < 0.001) and dNLR (OR = 1.131, CI95%: 1.061-1.206, p < 0.001) were the independent predictors for mortality in the studied COVID-19 patients based on multivariate logistic regression. CONCLUSION: Age and dNLR are valuable predictive factors for in-hospital death of ICU-admitted COVID-19 patients. Besides, other indices, AISI, NLPR, NLR, SII, and SIRI, may have an additional role that requires further investigation.

Inhibitory effect of microRNA-21 on pathways and mechanisms involved in cardiac fibrosis development.

Cardiac fibrosis is a pivotal cardiovascular disease (CVD) process and represents a notable health concern worldwide. While the complex mechanisms underlying CVD have been widely investigated, recent research has highlighted microRNA-21's (miR-21) role in cardiac fibrosis pathogenesis. In this narrative review, we explore the molecular interactions, focusing on the role of miR-21 in contributing to cardiac fibrosis. Various signaling pathways, such as the RAAS, TGF-ß, IL-6, IL-1, ERK, PI3K-Akt, and PTEN pathways, besides dysregulation in fibroblast activity, matrix metalloproteinases (MMPs), and tissue inhibitors of MMPs cause cardiac fibrosis. Besides, miR-21 in growth factor secretion, apoptosis, and endothelial-to-mesenchymal transition play crucial roles. miR-21 capacity regulatory function presents promising insights for cardiac fibrosis. Moreover, this review discusses numerous approaches to control miR-21 expression, including antisense oligonucleotides, anti-miR-21 compounds, and Notch signaling modulation, all novel methods of cardiac fibrosis inhibition. In summary, this narrative review aims to assess the molecular mechanisms of cardiac fibrosis and its essential miR-21 function.

Unraveling cardiac fibrosis: insights into microRNA-21's key role and promising approaches for controlCardiac fibrosis poses a significant global health threat and plays a central role in cardiovascular diseases. This examination delves into recent research revealing the participation of microRNA-21 (MiR-21) in the progression of cardiac fibrosis, providing insight into its critical function in this process. The investigation explores diverse molecular interactions, underscoring MiR-21's contribution to the development of cardiac fibrosis. Various signaling pathways, including the Renin-Angiotensin-Aldosterone System, TGF-ß, IL-6, IL-1, ERK, PI3K-Akt, and PTEN pathways, coupled with disturbances in fibroblast activity, matrix metalloproteinases (MMPs), and tissue inhibitors of MMPs (TIMPs), contribute to cardiac fibrosis. MiR-21's influence on growth factor secretion, apoptosis, and endothelial-to-mesenchymal transition further emphasizes its crucial role. What adds promise to MiR-21 is its capacity for regulation, providing potential insights into controlling cardiac fibrosis. The review also investigates various methods to modulate MiR-21 expression, such as antisense oligonucleotides, anti-miR-21 compounds, and Notch signaling modulation ­ innovative approaches showing potential in inhibiting cardiac fibrosis. In summary, this narrative review aims to dissect the complex molecular mechanisms behind cardiac fibrosis, explicitly emphasizing the indispensable role of MiR-21. By comprehending these mechanisms, researchers can lay the groundwork for inventive interventions and therapeutic strategies to hinder cardiac fibrosis, ultimately contributing to advancing cardiovascular health.

Putative effect of melatonin on cardiomyocyte senescence in mice with type 1 diabetes mellitus.

Background: To date, many investigators have tried to clarify the molecular mechanism of cardiovascular injuries after T1D. In present study, we evaluated the possible effects of melatonin on the levels of aging-related factors in the heart tissue of streptozotocin-induced diabetic mice. Methods: 40 male mice were enrolled in this study and randomly allocated into 4 groups (n = 10) as follows: Control group (C), Control group + melatonin (CM), Diabetic group (D), Diabetic + melatonin (DM) group. Single Streptozotocin (50 mg/kbW) was applied for the induction of T1D. 3 mg/kg melatonin was injected intraperitoneally twice a week for consequent four weeks. After the completion of this period, the animals were sacrificed and their heart tissue was obtained for histological examination (IHC analysis of vWF and α-SMA cells), aging and inflammation-related gene analysis. Result: Hematoxylin and Eosin staining indicated cardiomyocyte toxicity in T1D mice. IHC analysis of vascular tissue showed the detachment of vWF and α-SMA cells and disintegration into the vascular lumen. Additionally, real-time PCR assay showed the up-regulation of ß-galactosidase and suppression of SOX2, Klotho, and Telomerase genes in T1D mice compared to the control group (p < 0.05). We noted that melatonin administration can revert these condition and closed near-to-control levels. Along with these conditions, the levels of IL-1ß were also decreased after melatonin treatment. Conclusions: In general, one can hypothesize that modulation of different effectors associated with aging is beneficial to alleviate cardiac injuries under hypergylcemic condition. Melatonin can exert its therapeutic effects, in part, through anti-aging capacity.