Cardiovascular & Haematological Disorders - Drug Targets - Online First

Diabetic Cardiomyopathy (DCM) remains a significant health concern, necessitating innovative therapeutic approaches. This study explores the potential of a polyherbal combination (PHC) in mitigating DCM and delves into the underlying molecular mechanisms.

Rat models with induced diabetes and cardiomyopathy were administered the polyherbal combination. Molecular analyses included the assessment of ICAM-1, VCAM-1, and NF-κB expression in cardiac tissue. Histopathological and functional evaluations of cardiac health were performed.

The polyherbal-treated group showed a significant reduction in blood glucose levels and improved cardiac function, as indicated by increased ejection fraction and cardiac output. Cardiac injury markers, CK-MB and hs-CRP, were significantly reduced by 66.6% and 50% respectively. Lipid profile improvements included lower total cholesterol and triglycerides by 28.5% and 31.1%, respectively. TGF-β levels were markedly reduced, suggesting an anti-fibrotic effect. Additionally, NF-κB, ICAM-1, and VCAM-1 expression were significantly downregulated, confirming the polyherbal formulation's anti-inflammatory potential. These findings highlight its cardioprotective effects, making it a promising therapeutic approach for mitigating diabetic cardiomyopathy.

The study unveils a promising therapeutic strategy for DCM, characterized by the PHC's ability to modulate ICAM-1, VCAM-1, and NF-κB expression. This molecular insight underscores the potential for innovative interventions in managing DCM and offers hope for improved cardiac health in individuals with diabetes.

Metabolism dysfunction associated with fatty liver disease During metabolic hepatic inflammation (MAFLD), is characterized by systemic metabolism deregulation leading to increased hepatic erythrophagocytosis and subsequent iron overload and ferroptosis. Studies in animal models have shown that erythrocyte phosphatidylserine exposure drives erythrophagocytosis. However, the mechanism of erythrophagocytosis in human MAFLD has not been fully elucidated yet. Therefore, in this study, we explored the opsonins recognizing phosphatidylserine. In particular, we measured the levels of erythrocyte calreticulin, lactadherin, mannose-binding lectin, and thrombospondin-1.

Twenty-four patients (15 men and 9 women) with MAFLD and 9 healthy controls (4 men and 5 women) were enrolled. Erythrocytes were isolated from EDTA-containing blood through multiple centrifugations and isotonic buffer. Protein levels were measured in erythrocyte lysates (triton X-100 0.1% v/v) or plasma with enzyme-linked immunosorbent assays.

Erythrocyte TSP-1 levels were reduced in MAFLD patients. This reduction was not followed by changes in plasma TSP-1 levels or erythrocyte calreticulin, lactadherin, and mannose-binding protein

Our results suggest that erythrophagocytosis in human MALFD, unlike animal models, is not mediated by opsonization of exposed phosphatidylserine.

Our study underlines the need for disease models that could better reflect the molecular pathogenesis of human MAFLD.

Acute lymphoblastic leukemia (ALL), a hematopoietic cancer of T or B lymphoblasts, is the most prevalent cancer in children. Ongoing research aims to better understand the factors contributing to ALL and create more successful treatment options. Therefore, the current study presented cytogenetic, genetic, and hematologic features from 318 ALL patients under eighteen years of age who were referred to Ali Asghar Hospital of Tehran, Iran, from 2013 to 2023.

This study was designed as a retrospective cross-sectional analysis, focusing on 318 children in Tehran, Iran, who had been newly diagnosed with ALL. All data were extracted from the patient case files that included additional information, such as clinical data, and demographic information. The Flow cytometry technique was employed to perform immunophenotyping for various markers. Moreover, the standardized protocol was carried out for conventional cytogenetic analysis.

Out of 318, 179 (56.3%) and 139 (43.7%) were males and females, respectively. The most common subtype of ALL was Common B Cell ALL, accounting for 182 cases (57.23%), followed by Pre B cell ALL with 74 cases (23.27%) and T cell ALL with 27 cases (8.49%). Out of 222 patients, 17 (7.7%) had genetic abnormalities, with the highest incidence of abnormalities being associated with Runx 1 (four cases). Additionally, out of 228 patients, 143 (62.7%) were identified as having cytogenetic abnormalities, with the most prevalent abnormalities being hyperdiploidy (54 cases) and t (12;21) (28 cases).

Our findings showed that some cytogenetic abnormalities, such as t (9;22) and hyperdiploidy, were consistent with previous studies. These results offer valuable foundational insights that can help direct future research on ALL patients and inform potential treatment strategies.

Myocardial ischemia/reperfusion injuries (MI/RI) are responsible

for fatal cardiovascular diseases. Myocardial infarction may lead to ischemic cardiomyopathy (ICM). Thereby, illustrating the MI/RI molecular basis could lead to the emergence of novel therapeutic options. PIM1/ASK1 (MAP3K5) pathway is well-known in renal ischemia/

reperfusion. PIM1 protein can promote autophagy after hypoxia.

We selected the dataset GSE46224 from the National Center of Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database for evaluation. This dataset was analyzed using tools such as the Kyoto Encyclopedia of Genes and Genomes, GeneCodis, and BioGRID. Three groups of patients were selected from the dataset. ICM group (n=8), non-failing (NF) group (n=8), and non-ischemic cardiomyopathy (NICM) group (n=8) evaluated for 15 genes expression levels. P-value <0.05 is statistically significant.

JAK1 showed significantly lower gene expression in the ICM group compared to the NF group (p-value = 0.012, difference = -6.24). ASK1 was also significantly down-regulated in the ICM group compared to the NF group (p-value =0.0159, difference = -1.478). In contrast, STAT5B and NF-κB were significantly up-regulated in the ICM group (STAT5B: p-value = 0.0238, difference = 2.388; NF-κB: p-value = 0.0158, difference = 1.11). The analysis of differences and the volcano plot confirmed these findings, highlighting key dysregulated genes in ICM.

In conclusion, ICM patients have altered ASK1 expression compared to NF individuals. The significant down-regulation of ASK1 and JAK1, along with the up-regulation of STAT5B and NF-κB, suggests that targeting ASK1 could be an important strategy to ameliorate ischemia-related cardiomyocyte damage.