👤 Froogh Aziz

Endothelial to mesenchymal transition (EndMT), the transformation of endothelial cells into a mesenchymal-like state, is regulated by various factors, including transcription factors such as activator protein 1 (AP-1). While recent studies have confirmed the role of EndMT in atherosclerosis, the involvement of AP-1 in EndMT, particularly in the context of human diabetes, remains unclear. This study aimed to elucidate the role of the AP-1 transcription factor complex in EndMT associated with atherosclerosis in diabetes, utilising both an in vivo preclinical model and an ex vivo model using patient-derived serum for translational relevance. Additionally, it sought to profile gene expression changes following AP-1 inhibition in an EndMT model under high glucose conditions. Serum from patients with and without type 2 diabetes mellitus (T2DM) was used to assess EndMT in primary human aortic endothelial cells (HAECs) in the presence and absence of the AP-1 inhibitor T-5224. EndMT was evaluated through immunofluorescent staining of these cells and of aortic sections from a murine model of diabetes-associated atherosclerosis in a preclinical early intervention study. Furthermore, HAECs were used to explore the effects of AP-1 inhibition on the transcriptional signature of EndMT. Patient-derived serum induced EndMT in HAECs, which T-5224 effectively prevented, as confirmed by immunofluorescent staining. Immunofluorescent analysis of the aortic sinus also revealed that T-5224 treatment inhibited EndMT, leading to reduced atherosclerosis in Apoe This study identifies AP-1 inhibition with T-5224 as a potential therapeutic approach for EndMT resulting in reduced atherosclerosis in diabetes. The use of human serum underscores the translational relevance of these findings. Show less

Sex differences in Alzheimer disease (AD) neuropathology have not been examined extensively across multiple pathological constructs within broadly representative samples. To examine sex differences in neuroimaging biomarkers of AD-related pathologies in a racially and ethnically diverse cohort. Data for this cross-sectional study were collected from a community-based sample of adults without cognitive impairment aged 60 to 69 years in New York City from March 1, 2016, to September 31, 2022, and analyzed in March 2025. The primary exposure was self-reported sex (women or men). The outcomes were global amyloid burden measured with florbetaben labeled with fludeoxyglucose 18 (18F) positron emission tomography (PET), tau burden in Braak stages I to VI measured with 18F-MK-6240 PET, and magnetic resonance imaging (MRI)-derived AD signature cortical thickness and white matter hyperintensity volumes. Linear regression analyses were performed to examine sex differences in the outcomes. Covariates included demographics, APOE ε4 status, and vascular health-related factors. Sex × age, sex × APOE ε4, and sex × race and ethnicity interactions were additionally examined on the outcomes. False discovery rate (FDR) correction for multiple comparisons were also performed. A total of 503 participants (mean [SD] age, 64.6 [2.8] years; 321 [63.8%] women; 305 [60.6%] Hispanic, 120 [23.9%] non-Hispanic Black, and 78 [15.5%] non-Hispanic White) with Aβ PET, MRI (n = 501), and tau PET (n = 355) data were studied. Compared with men, women had greater amyloid burden (B = 0.05; 95% CI, 0.02-0.07; P < .001), Braak stages III and IV (B = 0.05; 95% CI, 0.02-0.08; P = .003) and Braak stages V and VI (B = 0.09; 95% CI, 0.06-0.12; P < .001) tau burden, and AD signature thickness (B = 0.04; 95% CI, 0.02-0.05; P < .001). A significant sex × APOE ε4 interaction was observed, with women showing greater Braak stages I and II (B = 0.15; 95% CI, 0.04-0.25; P = .006) and Braak stages III and IV (B = 0.08; 95% CI, 0.02-0.14; P = .01) tau burden than men among APOE ε4 carriers. All findings remained statistically significant after FDR correction. No significant sex × age or sex × race and ethnicity interactions were observed on any outcome. This cross-sectional study of community-based adults found greater AD pathology yet better preserved structural brain integrity in women compared with men. Sex differences in tau burden across early to middle Braak stages were more pronounced among APOE ε4 carriers compared with noncarriers. These findings were not modified by age or race and ethnicity. Overall, the results underscore sex-specific distinctions in AD pathology burden and brain structure at the cross-sectional level. Show less

Apolipoprotein B (apoB) is the primary structural protein in low-density lipoprotein (LDL) and plays a crucial role in atherogenesis. The Framingham Risk Score (FRS) is a widely used tool for assessing cardiovascular disease (CVD) risk. However, the correlation between apoB and FRS in Iraqi individuals remains underexplored. This study aims to evaluate the association between serum apoB levels and FRS, establishing its potential utility as a predictive biomarker for coronary artery disease (CAD) risk. A cross-sectional study was conducted on 201 individuals aged ≥30 years attending a clinical laboratory in Baghdad between November 2022 and October 2023. Serum apoB and lipid profiles were measured, and FRS was calculated for all participants. Correlation analysis between apoB and FRS was performed using Spearman's test, while group comparisons were conducted The median age of participants was 48 years, with males constituting 51.2% of the cohort. Median apoB and FRS values were 130 mg/dL and 4, respectively. A strong positive correlation was observed between serum apoB and FRS ( These findings suggest that apoB may serve as a reliable biomarker for CAD risk assessment in the Iraqi population, where its predictive value has been underexplored. The identified cutoff value (97.75 mg/dL) highlights its potential role in refining risk stratification beyond traditional lipid markers. Further prospective studies are needed to validate these findings and assess their clinical impact. Show less

Atherosclerosis is partially driven by the accumulation of oxidised low-density lipoprotein (oxLDL), which facilitates foam cell formation and vascular inflammation. This research examines the efficacy of bamboo charcoal (BC) as a bioactive agent for neutralising oxLDL using both in silico and in vitro methodologies. Molecular docking demonstrated significant binding affinities between BC and essential constituents of oxLDL, such as oxidised cholesterol and apolipoprotein B-100, facilitated by π-π stacking and electrostatic interactions. Molecular dynamics simulations demonstrated the stability of these complexes over 300 ns, indicating sustained molecular interactions. Quantum chemical calculations employing density functional theory showed a narrow HOMO-LUMO gap of 0.45 eV and a significant dipole moment of approximately 45 D, underscoring the reactive and polar characteristics of BC. Electrostatic potential mapping and thermodynamic analyses provided additional evidence for BC's spontaneous and stable binding to oxLDL components. The Oil Red O staining and total cholesterol estimation assays were conducted on oxLDL-treated RAW 264.7 macrophages in vitro indicated that BC significantly decreased macrophage-derived foam cell formation, thereby confirming its ability to reduce oxLDL-induced lipid accumulation. The findings suggest that BC functions as a physical adsorbent and a participant in direct chemical interactions with oxLDL, providing a dual-action therapeutic approach to atherosclerosis. Show less

Vitamin D may play a role in cardiovascular health, particularly in lipid metabolism and atherosclerosis. This study examines the correlation between serum vitamin D levels with Apolipoprotein B (Apo B), and the Framingham Risk Score (FRS) and evaluates the impact of correcting severe vitamin D deficiency on Apo B levels and FRS among a group of Iraqi population. This two-phase study was conducted in Baghdad between November 2022 and October 2023 and included a cross-sectional phase examining the association between vitamin D, with Apo B, and the FRS, followed by a prospective phase assessing the impacts of vitamin D correction. A total of 201 participants were recruited, including 60 individuals with severe vitamin D deficiency (≤ 10 ng/ml) who received supplementation and 40 with sufficient vitamin D levels (≥ 30 ng/ml) serving as controls. Levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), Apo B, and FRS were evaluated at baseline and after six months. The Thai Clinical Trials Registry (TCTR) has retrospectively registered and approved the study under the identification number TCTR20250301003 on the 1st of March 2025. Vitamin D levels correlated significantly with age (p < 0.001), Apo B (p = 0.007), and FRS (p = 0.003) in the cross-sectional phase. After supplementation TC (p = 0.004) and FRS (p = 0.007) significantly decreased in the treatment group, with no significant changes in Apo B. Males only showed significant decrease in FRS and TC. Vitamin D correction significantly decreased TC and FRS reinforcing its role in lipid metabolism and cardiovascular health. However, Apo B levels remained unchanged, suggesting that vitamin D may not directly influence Apo B metabolism in the short term. These findings emphasize the importance of correcting severe vitamin D deficiency before calculating FRS due to its impact on lipid parameters. Show less

Colorectal cancer (CRC) is the second most common cancer in men and third in females, a heterogeneous disease involving multistep mechanisms that represents 10% of all cancers globally. This study investigates gene mutation profiling in CRC using Next-Generation sequencing machine. Formalin-fixed paraffin-embedded tissues of 30 CRC patients were retrieved and reviewed. DNA was isolated from selected tissues. Desirable quality check using Qubit and Nanoquant machine was done, and desirable libraries prepared were loaded into the sequencer for sequencing. Using Illumina BaseSpace and Illumina Variant interpreter, generated FastQ data were treated for annotation, alignment, and mapping with reference genome. Sequencing-runs with Phred-score ≥ 30 were selected as desirable runs. Finally, the variants were validated on NCBI-dsSNP and Ensembl databases for clinical consequence interpretations. Overall, patient distribution consists of 12(40%) females and 18 (60%) males with mean age (53.2 + 5.3). most patients were in TNM stage-3: 53.3% (15/30) and the least was Stage-4: 20%(6/30) respectively. Overall, 73.3%: (22/30) completed the sequencing, and 552 mutations involving 29 genes and 12 chromosomes were detected. The most upregulated variants are KIT:68(12.3%), FGFR4:61(11.1%), EGFR:60(10.9%), ALK:53(9.6%), DCUN1D1:41(7.4%), PDGFR:40(7.2%), KRAS:33(6.0%), CDK4:27(4.9%), FGFR3:26(4.7%), MTOR:14(2.6), while NRAS, CDK6, PIK3CA, and RET each has 13(2.4%) apiece. Chromosomes 4:134/55(24.2%), chr7:84/552(15.2%), chr12:71/552(12.9%), chr5:64/552(11.6%), chr2:61/552(11.1%), chr3:54/552(9.8%), and chr1:43/552(7.8%) are the most involved chromosomes. Nine genes (APC, NRAS, ALK, PIK3CA, KRAS, IDH1, FGFR1, ERBB2, and ESR1) are identified as pathogenic-causing variants in CRC. This is the first NGS-based molecular study on FFPE-CRC tissues in hospital-USM that showed the most upregulated variants in CRC and identified nine genes as crucial pathogenic variants. Show less

This work involved the preparation of pristine and iron nanoparticle-loaded biochar from a water chestnut shell to remove diclofenac sodium (DCF) containing effluent of pharmaceutical origin. To create suitable forecasting equations for the modelling of the DCF adsorption onto the adsorbent, response surface methodology (RSM) was used. The parameters, e.g. pH, adsorbent mass, DCF concentration and contact time, were used for the modeling of adsorption. The RSM model predicts that for 98.0% DCF removal, the ideal conditions are pH 6, an adsorbent dose of 0.5 g L Show less

Genome-wide studies related to neurological disorders and neurodegenerative diseases have pointed to the role of epigenetic changes such as DNA methylation, histone modification, and noncoding RNAs. DNA methylation machinery controls the dynamic regulation of methylation patterns in discrete brain regions. This review aims to describe the role of DNA methylation in inhibiting and progressing neurological and neurodegenerative disorders and therapeutic approaches A Systematic search of PubMed, Web of Science, and Cochrane Library was conducted for all qualified studies from 2000 to 2022. For the current need of time, we have focused on the DNA methylation role in neurological and neurodegenerative diseases and the expression of genes involved in neurodegeneration such as Alzheimer's, Depression, and Rett Syndrome. Finally, it appears that the various epigenetic changes do not occur separately and that DNA methylation and histone modification changes occur side by side and affect each other. We focused on the role of modification of DNA methylation in several genes associated with depression (NR3C1, NR3C2, CRHR1, SLC6A4, BDNF, and FKBP5), Rett syndrome (MECP2), Alzheimer's, depression (APP, BACE1, BIN1 or ANK1) and Parkinson's disease (SNCA), as well as the co-occurring modifications to histones and expression of non-coding RNAs. Understanding these epigenetic changes and their interactions will lead to better treatment strategies. This review captures the state of understanding of the epigenetics of neurological and neurodegenerative diseases. With new epigenetic mechanisms and targets undoubtedly on the horizon, pharmacological modulation and regulation of epigenetic processes in the brain holds great promise for therapy. Show less

Nonalcoholic fatty liver disease (NAFLD) is a condition that affects about 24% of people worldwide. Increased liver fat, inflammation, and, in the most severe cases, cell death are all characteristics of NAFLD. However, NAFLD pathogenesis and therapy are still not clear enough. Thus, this study aimed to determine the effect of a high-cholesterol diet (HCD) inducing NAFLD on lipolytic gene expression, liver function, lipid profile, and antioxidant enzymes in rabbits and the modulatory effects of probiotic Lactobacillus acidophilus (L. acidophilus) on it. A total of 45 male New Zealand white rabbits, eight weeks old, were randomly divided into three groups of three replicates (5 rabbits/replicate). Rabbits in group I were given a basal diet; rabbits in group II were given a high-cholesterol diet that caused NAFLD; and rabbits in group III were given a high-cholesterol diet as well as probiotics in water for 8 weeks. The results showed that a high-cholesterol diet caused hepatic vacuolation and upregulated the genes for lipoprotein lipase (LPL), hepatic lipase (HL), and cholesteryl ester transfer protein (CETP). Downregulated low-density lipoprotein receptor (LDLr) gene, increased liver enzymes [alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH)], cholesterol, triglycerides (TG), low-density lipoprotein (LDL), glucose, and total bilirubin. On the other hand, it decreased high-density lipoprotein (HDL), total protein, albumin, and liver antioxidants [glutathione peroxidase (GPx), catalase (CAT), reduced glutathione (GSH), and superoxide dismutase (SOD)]. Supplementing with probiotics helped to return all parameters to normal levels. In conclusion, probiotic supplementation, especially L. acidophilus, protected against NAFLD, and restored lipolytic gene expression, liver functions, and antioxidants to normal levels. Show less

Hypotrichosis is a human hereditary hair loss disorder in which affected individuals show sparse to complete absence of hair on scalp and/or on different body parts. To date, at least eight isolated autosomal recessive and dominant forms of hypotrichosis loci have been mapped on different human chromosomes, and the corresponding genes have been identified. Detailed clinical and molecular studies were undertaken of the hereditary hypotrichosis observed in the two consanguineous families (A and B) presented here. Human genome scan, using >500 highly polymorphic microsatellite markers, identified equal evidence of linkage of the hypotrichosis phenotype on chromosomes 12q21.2-q22 and 16q21-q23.1 in both the families. The novel hypotrichosis locus on chromosome 12q21.2-q22 spans 16.3 cM (17.62 Mb), flanked by markers D12S326 and D12S101. At this locus, maximum multipoint logarithm of the odds ratio (LOD) scores of 3.68 and 3.31 were obtained in families A and B, respectively. The second hypotrichosis locus on chromosome 16q21-q23.1, identified in the two families, spans 5.58 cM (8.28 Mb) and is flanked by markers D16S3031 and D16S512. Maximum multipoint LOD scores of 3.17 and 3.31 were obtained with markers mapped at this locus in families A and B, respectively. DNA sequence analysis of six candidate genes (PLEKHG7, SLC6A15, VEZT, DUSP6, KERA and KITLG), located in the linkage interval on chromosome 12q21.2-q22, failed to detect potential sequence variants in the affected individuals of the two families. However, DNA sequence analysis of CDH3 gene, located on chromosome 16q21-q23.1, detected a single base pair homozygous insertion (c.1024₁₀₂₅insG and p.342insGfsX345) in exon 9 in family A and deletion of four base pair (c.1859₁₈₆₂delCTCT and p.620delSfsX629) in exon 13 in family B. We described for the first time digenic inheritance of an autosomal recessive hypotrichosis phenotype in two unlinked loci on chromosomes 12q21.2-q22 and 16q21-q23.1 in two unrelated consanguineous Pakistani families. Show less

Tamarindus indicaL. (T. indica) or locally known as asam jawa belongs to the family of Leguminosae. The fruit pulp had been reported to have antioxidant activities and possess hypolipidaemic effects. In this study, we attempted to investigate the gene expression patterns in human hepatoma HepG2 cell line in response to treatment with low concentration of the fruit pulp extracts. Microarray analysis using Affymetrix Human Genome 1.0 S.T arrays was used in the study. Microarray data were validated using semi-quantitative RT-PCR and real-time RT-PCR. Amongst the significantly up-regulated genes were those that code for the metallothioneins (MT1M, MT1F, MT1X) and glutathione S-transferases (GSTA1, GSTA2, GST02) that are involved in stress response. APOA4, APOA5, ABCG5 and MTTP genes were also significantly regulated that could be linked to hypolipidaemic activities of the T. indica fruit pulp. Show less