Globally acute myocardial infarction is the leading independent cause of unexpected death. This study aimed to explore the diagnostic and molecular impact of miR-21, miR-488, and miR-126 in acute myocardial infarction patients (AMI). We enrolled 95 non-ST-elevation myocardial infarction (NSTEMI) patients, 152 ST-elevation myocardial infarction (STEMI) patients, and 95 healthy individuals, additionally using three-month-old mice and their ventricular-derived H9c2 cells. The circulatory plasma miR-21 and miR-488 levels were significantly upregulated, while plasma miR-126 levels were remarkably downregulated in NSTEMI and STEMI subjects. The receiver operating characteristic curve showed that plasma miR-21, miR-488, and miR-126 were able to clearly differentiate NSTEMI and STEMI from healthy subjects. Moreover, H9c2 hypoxic cells treated with inhibitor miR-21 markedly reduced intracellular ROS levels, capase-3 activities levels, and cellular apoptosis rates and significantly enhanced cellular viability through up regulation of Smad-7 mRNA and protein expressions. In geriatric STEMI and NSTEMI subjects, plasma miR-21 levels were evidently higher than in comparatively younger subjects. Upregulated plasma miR-21 and miR-488 levels and downregulated miR-126 levels might be considered potential clinical biomarkers for myocardial infarction patients, while inhibition of miR-21, which significantly reduced hypoxia-exposed H9c2 cellular injury via targeting Smad-7, could be a new therapeutic target for AMI patients. Low levels plasma miR-21 may have a significant impact on delaying the aging process.

Background/Objectives: Type 2 diabetes mellitus (T2-DM) is a continuing national and global health challenge. Retinoic acid (RA), the major transcription-regulating ligand, plays a critical role in energy metabolism, and pancreatic β-cell homeostasis. However, human data linking circulating RA levels to T2-DM and its clinical outcomes are sparse and inconsistent. In this ethically approved cross-sectional study of consented hospital-diagnosed adult T2-DM patients (n = 292) and matched healthy controls (n = 64), variation in plasma RA levels and its relationship with disease and patient characteristics were investigated. Methods: RA concentrations assayed via specific ELISA were related to glycemic control indices [fasting blood glucose (FBG) and HbA1c], the triglyceride–glucose ratio for insulin resistance (TyG-IR), treatment modalities, and complications derived from patients’ medical records. Results: RA concentrations were substantially lower in patients with T2-DM (mean ± SD 2.63 ± 1.54 ng/mL) than in controls (5.21 ± 4.3 ng/mL; p < 0.001). Within the diabetic cohort, RA was inversely correlated with indices of glycemic dysregulation and insulin resistance. Plasma RA exhibited strong discriminatory performance for distinguishing diabetic patients from healthy adults. Its AUC is 0.870 (p < 0.0001 and 95% CI = 0.832–0.902) with a sensitivity of 79.7% and a specificity of 81.3%, at an optimal cutoff of ≤3.061 ng/mL. Conclusions: Circulating RA is associated with metabolic perturbations that define T2-DM, and therefore is promising as a clinically useful biomarker. It may reflect pathophysiological processes linking nutrient signaling, energy handling and β-cell function in T2-DM that merit further evaluation.

Background/Objectives: Sphingosine-1-phosphate (S1P) is implicated in glycemic control. However, its circulating levels and clinical significance in type 2 diabetes mellitus (T2DM) remain controversial. We assessed plasma S1P levels in T2DM patients, its associations with metabolic parameters and complications, and explored its biomarker potential and non-linear (U-/J-shaped) relationships. Methods: This cross-sectional study enrolled 140 patients with T2DM and 63 matching healthy controls. Plasma S1P was measured by competitive ELISA. Statistical analyses included comparisons, correlation, ROC analysis, multivariable logistic regression, and quadratic/spline regression for U-shaped relationships. Results: Plasma S1P was significantly elevated in T2DM patients [1256.7 (149.4–1510.0) ng/mL] compared to controls [1075.1 (202.0–1510.0) ng/mL; p < 0.001]. S1P correlated positively with age, disease duration, HbA1c, insulin resistance, TyG index, triglycerides, systolic blood pressure, and negatively with HDL-C. Patients with complications had higher S1P than those without (p = 0.001), with progressive increases from retinopathy to nephropathy to mixed complications. Insulin-treated patients exhibited the highest S1P levels (p < 0.001). ROC analysis showed moderate diagnostic accuracy (AUC = 0.724). S1P is an independent associated factor with complications (OR = 1.18 per 100 ng/mL, p = 0.003). Non-linear analysis revealed a U-shaped relationship with HDL-C (optimal S1P: 1100–1350 ng/mL) and a J-shaped relationship with complication risk (threshold ~1250 ng/mL). Conclusions: Plasma S1P is elevated in T2DM and correlates with disease severity, glycemic control, insulin resistance, and complications. S1P demonstrates moderate biomarker potential and exhibits non-linear U-/J-shaped relationships with metabolic parameters, suggesting an optimal therapeutic window of 1100–1280 ng/mL. These findings support S1P as a marker of cumulative disease burden and a potential therapeutic target.

The link between ABO/Rh blood groups and COVID-19 severity remains a topic of debate. We aimed to investigate the role ABO/Rh blood groups, rs8176746 and rs495828 single nucleotide polymorphisms (SNPs), in COVID-19 severity among COVID-19 patients in Mansoura City, Egypt. A total of 306 Egyptian patients were included in this cross-sectional study. They were grouped into 86 cases with non-severe infection and 220 with severe infection according to clinical, laboratory, and radiological findings. ABO/Rh blood groups were confirmed. A TaqMan real-time PCR SNP genotyping assay was used to examine the allelic discrimination of rs8176746 and rs495828 SNPs. Older age, male gender, and the presence of comorbidities were associated with severe COVID-19. AB blood group was significantly associated with a protective effect against severe COVID-19 (p = 0.029) in the unadjusted analysis. There was no statistically significant association between Rh type and disease severity. GT genotype was significantly associated with a higher frequency of AB blood groups in both rs8176746 and rs495828 (p < 0.001). However, there was no statistically significant association between the studied SNPs and COVID-19 severity. After adjusting for age, gender, and the presence of comorbidities, the protective effect of the AB blood group with severe COVID-19 did not remain significant. No association was observed between Rh type rs8176746 and rs495828 SNPs and COVID-19 severity. The impact of ABO/Rh blood types and related SNPs on COVID-19 severity can vary by the ethnic group and population being studied. This diversity emphasizes the need for specialized research approaches to better understand the demographic, clinical, and genetic factors that lead to variations in COVID-19 outcomes among various groups.

Background/Objectives: Endogenously produced ethanol (EndoEth) from a dysbiotic microbiome is an under-recognized pathogenic factor in metabolic diseases, including type-2 diabetes (T2DM). EndoEth is any systemically detectable alcohol in abstinent individuals. We aimed to assess EndoEth changes, its correlation with patients’ characteristics, metabolic indices, the disease outcomes, and its biomarker and independent risk factor characteristics as compared to healthy controls. Methods: EndoEth was cross-sectionally assayed using a specific enzymatic colorimetric method in 125 abstinent T2DM patients and 55 matching healthy controls. Its associations with glycemic control [fasting blood glucose (FBG), HbA1c, and triglyceride–glucose insulin resistance (TyG-IR) index], lipid profile [total, LDL-(LDL-C), and HDL-cholesterol (HDL-C), and triglycerides (TGs)], and the disease duration, treatment and microvascular complication profile (ophthalmopathy, neuropathy and nephropathy) were assessed. Its biomarker ability was assessed using the area under the ROC curve (AUC). Results: Significantly higher levels of EndoEth were detected in T2DM patients. EndoEth had significant associations with disease duration, complications particularly ophthalmopathy, insulin treatment, fasting blood glucose, TyG-IR index, and plasma triglycerides. Complications were also significantly associated with age, male gender, disease duration, FBG and total cholesterol. ROC curve analysis showed acceptable moderate ability of plasma EndoEth to discriminate against T2DM complications (AUC mean ± standard error = 0.766 ± 0.047, p = 0.001, and at a cut-off ≥ 0.016 µmol/mL, sensitivity = 75.7% and specificity = 61.0%). Conclusions: EndoEth is higher in abstinent T2DM patients than in healthy controls, and is correlated with disease duration, insulin resistance and treatment and complications, particularly for ophthalmopathy. It had a moderate biomarker performance (AUC = 0.766) in discriminating against diabetic complications.

Background: Lipoprotein(a) [Lp(a)] is a genetically determined, pro-atherogenic lipoprotein enriched in oxidized phospholipids and increasingly recognized as a key potential contributor to residual cardiovascular and inflammatory risk. However, data on its distribution and cardiometabolic associations in Middle Eastern populations remain limited. This study aimed to evaluate the prevalence of elevated Lp(a) and its association with type 2 diabetes (T2D), systemic inflammation, and ethnic variation in a multiethnic cohort. Methods: In this cross-sectional study, data from 2083 adults aged ≥ 18 years residing in Kuwait were collected through the Kuwait Diabetes Epidemiology Program (KDEP) at Dasman Diabetes Institute between 2011 and 2014 using random sampling. Plasma Lp(a) concentrations, cardiometabolic parameters, and high-sensitivity C-reactive protein (CRP) were measured. Elevated Lp(a) was defined as ≥ 50 mg/dL according to established clinical guidelines. Associations of elevated Lp(a) with T2D and CRP were assessed using multivariable Poisson regression models to estimate adjusted prevalence ratios. Results: The overall prevalence of elevated Lp(a) was 41.2%, exceeding global estimates. Significant ethnic variation was observed, with Arabs exhibiting the highest prevalence. After adjustment for potential confounders, individuals with T2D had a higher prevalence of elevated Lp(a) (APR = 1.166) and diabetes status significantly modified the association between CRP and elevated Lp(a) interaction (APR = 1.015), thus supporting a link between Lp(a) and systemic inflammation. Conclusions: Elevated Lp(a) was highly prevalent in this multiethnic Middle Eastern population and was independently associated with T2D and systemic inflammation. These findings support the emerging concept that Lp(a) may function as a molecular-inflammatory mediator potentially contributing to residual cardiovascular risk and highlight the importance of incorporating Lp(a) assessment into cardiometabolic risk stratification, particularly in high-risk populations.