Familial dyslipidemia (FD), particularly familial hypercholesterolemia (FH), is a major contributor to premature cardiovascular disease (CVD), especially in regions with high consanguinity and underut Show more
Familial dyslipidemia (FD), particularly familial hypercholesterolemia (FH), is a major contributor to premature cardiovascular disease (CVD), especially in regions with high consanguinity and underutilized genetic screening, such as Egypt. This study aimed to assess clinical, biochemical, and genetic factors that differentiate FD patients with and without CVD, and to develop a composite risk score for individualized stratification. A cross-sectional study was conducted on 60 Egyptian patients aged 15-25 years with genetically confirmed FD, equally divided based on CVD status. All participants underwent detailed clinical assessment, lipid profiling, and targeted next-generation sequencing of LDLR, APOB, and PCSK9 genes. Missense variants were evaluated using SIFT, PolyPhen-2, CADD, and ΔΔG stability scores, and classified according to ACMG criteria. Compared to non-CVD patients, those with CVD had significantly higher triglyceride levels (median: 356.5 vs. 236.5 mg/dL; p < 0.001) and a higher frequency of heterozygous pathogenic LDLR variants (30.0% vs. 3.3%; p = 0.006), while homozygous variants were more common in non-CVD patients (26.7% vs. 0%; p = 0.002). Deleterious missense variants were notably more frequent in the CVD group (56.7% vs. 10.0%; p < 0.001). A 10-variable composite risk score integrating clinical, lipid, and bioinformatic predictors effectively distinguished high- and moderate-risk cases (AUC = 0.742; p = 0.022), with 89.5% sensitivity and 81.8% negative predictive value. The study highlights the importance of combining clinical and genomic data for early risk stratification and introduces a pragmatic tool for identifying high-risk youth in resource-limited, consanguineous populations. Show less
Transforming growth factor beta (TGFβ) plays a key role in liver carcinogenesis. However, its action is complex, since TGFβ exhibits tumor-suppressive or oncogenic properties, depending on the tumor s Show more
Transforming growth factor beta (TGFβ) plays a key role in liver carcinogenesis. However, its action is complex, since TGFβ exhibits tumor-suppressive or oncogenic properties, depending on the tumor stage. At an early stage TGFβ exhibits cytostatic features, but at a later stage it promotes cell growth and metastasis, as a potent inducer of epithelial to mesenchymal transition (EMT). Here, we evaluated DNA methylation as a possible molecular mechanism switching TGFβ activity toward tumor progression in hepatocellular carcinoma (HCC). We report that decitabine, a demethylating agent already used in the clinic for the treatment of several cancers, greatly impairs the transcriptional response of SNU449 HCC cells to TGFβ. Importantly, decitabine was shown to induce the expression of EMT-related transcription factors (e.g., Show less
various extracts of Moringa oleifera Lam. leaves, were reported to possess antiobesity effect in experimental animals models, yet its active doses and mechanism of action are still unclear. The metabo Show more
various extracts of Moringa oleifera Lam. leaves, were reported to possess antiobesity effect in experimental animals models, yet its active doses and mechanism of action are still unclear. The metabolic profiling of 70% ethanol extract of M. oleifera (MO) leaves was performed using HPLC-MS/MS analysis. The antiobesity activity of MO was tested in high fat diet induced obesity in rats at 200 and 400 mg/kg body weight orally for 1 month. Total cholesterol (TC), high density lipoproteins (HDL-C), low density lipoprotein-cholesterol (LDL-C), triglycerides (TGs), insulin resistance, insulin sensitivity, and adipose tissue index were monitored. In addition, fatty acid synthase (FAS) and HMG-CoA reductase mRNA from liver tissue, Peroxisome Proliferator-Activated Receptor alpha (PPARα) and Melanocortin-4 receptor (MC4R) RNA from adipose tissue were quantified using qRT-PCR. MO hard gelatin capsules (400 mg/capsule) were formulated and standardized using HPLC-RP analysis and tested on fifteen female participants, aged 45-55 with a BMI of 29-34 kg/m Thirteen metabolites were tentatively identified using HPLC-MS/MS analysis including flavonols, flavones and a phenolic acid. MO 400 showed a prominent effect on reducing the rats' final weights, % weight increase and adiposity index (P < 0.05). Glucose, insulin and HOMA-IR were significantly reduced and R-QUICKI was significantly increased by MO 400 (P < 0.001). Mean tissue level of leptin and vaspin were significantly reduced, adiponectin, omentin and GLUT-4 expression were increased significantly by MO 400 (P < 0.01). MO 400 significantly suppressed FAS and HMG-CoA reductase and increased mRNA expression of MC4R and PPAR-α (P < 0.01). Eight weeks administration of MO hard gelatin capsules to obese patients showed significant reduction of the average BMI, TC and LDL compared to the baseline values (p < 0.05). Our results presented a scientific evidence for the traditional use of M. oleifera leaves as antiobesity herbal medicine. Show less