👤 Mohammed M Alanazi

Obesity and diabetes are escalating worldwide health concerns, prompting the use of non-caloric sweeteners such as aspartame and stevia as substitutes for sucrose; however, their long-term physiological and behavioral consequences remain incompletely understood. This work presents a comparative experimental study examining the long-term effects of sucrose, aspartame, and stevia intake on liver, heart, and brain functions in rats, while exploring the capacity of astaxanthin (ASTX) to attenuate the resulting tissue impairments. Seven rat groups-including control, sucrose, aspartame, stevia, and each sweetener combined with ASTX-were treated for 8 weeks to compare the organ-specific toxicity of the sweeteners and assess the protective effects of ASTX. Comprehensive evaluations of liver, heart, and brain were conducted using biochemical, behavioral, and histopathological analyses. All three sweeteners induced hyperglycemia, disrupted lipid metabolism (triglycerides, LDL, HDL), and increased oxidative stress (MDA), suppressing Nrf2/HO-1 antioxidant pathway and activating TLR4/NF-κB-mediated inflammation, leading to apoptosis. Biomarkers revealed liver dysfunction (ALT, AST, ALP), cardiac injury (troponin I, CK-MB, MEF2), and cognitive impairment (amyloid-beta, tau, BDNF), alongside altered monoamine neurotransmitters and Wnt3a/GSK-3β/β-catenin dysregulation. Bax/Bcl-2 ratio indicated enhanced apoptosis, with aspartame exerting the highest toxicity and stevia the least. While ASTX effectively alleviated these biochemical, histological, and functional changes. These findings suggest that aspartame has the strongest negative impact on liver, heart, and brain health, while stevia has the least, and that ASTX may serve as a potential protective agent against these harmful impacts. Show less

Genetic variations within the Lipoprotein Lipase (LPL) gene have been shown to influence the risk of cardiometabolic diseases. However, their associations with cardiometabolic disease-related markers remain underexplored in Arab Qatari populations. Hence, we examined the association between a genetic risk score (GRS) based on three LPL single nucleotide polymorphisms (SNPs) and cardiometabolic indicators in a healthy Qatari population. A cross-sectional genetic association study was conducted using data from the Qatar Biobank population-based cohort, involving a sample of metabolically healthy Qatari adults (n = 6,919). The LPL-GRS was computed as the unweighted sum of risk alleles from three LPL SNPs: rs295 (C/A), rs301 (C/T), and rs320 (G/T). Associations between the GRS and metabolic markers were assessed using a generalized linear model, adjusting for age, sex, and body mass index. Individuals with high GRS (>5 risk alleles) showed a significant association with lower fat-free mass index values (β = -0.064, p = 0.029). In addition, a positive association was observed between GRS and fasting insulin levels (β = 0.035, p = 0.016). In addition, high GRS was significantly associated with lower high-density lipoprotein cholesterol (β = -0.025, p = 0.001) and higher triacylglycerol concentrations (β = 0.027, p = 0.0003) and systolic blood pressure (β = 0.007, p = 0.002), respectively. Our study shows that the LPL-GRS is associated with key cardiometabolic risk factors in this self-reported healthy Qatari population. These findings highlight the need for additional research to replicate these findings in independent and ethnically diverse cohorts, as well as the use of longitudinal studies to evaluate the predictive value of the GRS for future metabolic outcomes. Show less

Variants linked to the risk of ischemic stroke have been discovered through genome-wide association studies (GWASs). These variations frequently have little consequences that lack apparent biological significance. Hence, these findings demonstrate that exome sequencing can be highly relevant to stroke, even though stroke is a complex phenotype with various diseases and risk factors. In this case-control investigation, we used ARMS genotyping to investigate the distribution of polymorphic variations in genes associated with stroke susceptibility. In addition to examine the novel gene variations associated with ischemic stroke we utilized the Illumina NovaSeq 6000 platform for whole-exome sequencing (WES). Results identified 11 novel gene variants in the GSTT4 gene by targeted whole-exome sequencing, including one deletion GSTT4p.Asn232LysfsTer6, one insertion c.688₆₈₉insCG, and 9 SNVs c.699 T > C, c.701C > G, c.708G > T, c.710 T > G, c.712A > G, c.712A > G, c.718A > T, c.719G > A, c.721A > T, c.722G > T in the ischemic stroke patients. We also identified several rare, intermediate, and most common gene variants in cholesterol associated genes LDLR, LDLRAD2, LDLRAD3, APOA2, APOA3, APOA4, APOA5, and PCSK9. Also, several common gene variants were reported in MTHFR, KLF14, eNOS3, and ACE by whole-exome sequencing. Furthermore, the eNOS3-GG and eNOS3-GT genotypes were associated with susceptibility to ischemic stroke (OR = 1.95, This case-control study identified 11 novel GSTT4 variants and several known polymorphisms associated with ischemic stroke risk in Saudi patients. These findings highlight population-specific genetic factors that warrant further functional and large-scale validation. Show less

The increased prevalence of metabolic diseases in the Arab countries is mainly associated with genetic susceptibility, lifestyle behaviours, such as physical inactivity, and an unhealthy diet. The objective of this review was to investigate and summarise the findings of the gene-lifestyle interaction studies on metabolic diseases such as obesity and type 2 diabetes in Arab populations. Relevant articles were retrieved from a literature search on PubMed, Web of Science, and Google Scholar starting at the earliest indexing date through to January 2024. Articles that reported an interaction between gene variants and diet or physical activity were included and excluded if no interaction was investigated or if they were conducted among a non-Arab population. In total, five articles were included in this review. To date, among three out of twenty-two Arab populations, fourteen interactions have been found between the Show less

The incidence and mortality of endometrial cancer (EC) have increased in recent years. There is mounting evidence that diabetes may play a role in the greater incidence of EC. The molecular mechanisms of the interaction between type 2 diabetes and EC are not yet clearly understood yet. The present study was undertaken to investigate the plasma proteomics of EC patients with diabetes in comparison to those of EC patients without diabetes. Plasma samples were obtained from age-matched patients (EC diabetic and EC nondiabetic). Untargeted proteomic analysis was carried out using a two-dimensional differential gel electrophoresis coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Of the 33 proteins identified, which significantly differed in the plasma abundance between groups, 17 were upregulated and 16 were downregulated. The majority of the altered proteins are involved in the acute phase reaction, cholesterol metabolism, scavenging of heme from plasma, and plasma lipoprotein assembly and mobilization. α-2-macroglobulin, Ras association domain-containing protein 3, apolipoprotein A-I, α-1B-glycoprotein, and zinc-α-2-glycoprotein were significantly upregulated. The significantly downregulated proteins included haptoglobin, apolipoprotein A-IV, hemopexin, and α-1-antichymotrypsin. The differential expression of proteins found in patients who had EC and diabetes indicated severe disease and a poor prognosis. The protein interaction analysis showed dysregulation of cholesterol metabolism and heme scavenging pathways in these patients. Show less

Multiple sclerosis (MS), an immune-mediated and neurodegenerative disorder of the central nervous system (CNS), is characterized by infiltrating myelin-reactive T lymphocytes and demyelinating lesions. Experimental autoimmune encephalomyelitis (EAE) is a well-established animal model used to study MS. To explore the impact of chemokine receptor CCR1 blockade in EAE and the underlying mechanisms, we used CCR1 antagonist J-113863 in PLP Show less

Familial hypercholesterolemia (FH) is an autosomal dominant inherited genetic disorder and results in the development of coronary artery disease (CAD). Clinical diagnosis of homozygous HH patients is usually straightforward because persistent hypercholesterolemia can produce xanthoma and corneal arcus. However, xanthoma may also be misdiagnosed as skin lesions and could therefore be mistreated. The aim of this case study report is to highlight the plight of patients with FH as means of raising awareness of the condition among dermatologists and health care practitioners, also to determine the genotype-phenotype correlation in severely affected homozygous FH proband patients. Genetic screening of FH associated genes was performed by Ion Torrent next-generation sequencing and cascade screening by capillary sequencing. We present two clinical cases with prominent skin lesions seen in a dermatology clinic that were referred to plastic surgery for excision. Genetic testing was performed later, and confirmed common single nucleotide deletion variant (c.2027delG) in the The present report indicates the need for increased awareness of FH, among the public and healthcare practitioners and supports the need for diagnostic screening and cascade genetic testing of this high-risk condition, which could ultimately lead to better prevention of CHD in this lethal condition. Show less

Colorectal cancer is a major health concern as it ranks third in incidence and second major cause of cancer-related deaths worldwide. A leading cause of treatment failure has been attributed to cancer stem cells that can invariably resist existing chemotherapeutic regimens. Notch signaling pathway has been involved in the maintenance of stem cells besides being crucial in cell fate decision and embryonic development. This pathway has also been implicated in several human malignancies including colorectal cancer. We investigated mRNA expression of four Notch receptors (Notch1-4), five ligands (Jag1, Jag2, Dll1, Dll3, and Dll4), and four target genes (Hes1, Hes5, Hey1, and Hey2) using highly specific TaqMan gene expression assays in colorectal adenomas and cancers. Upregulated expression of Notch receptors ranged between 29 and 73% in colorectal cancers and between 11 and 56% in adenomas. Expression of Notch3 and Notch4 receptors was significantly higher in colorectal cancers compared to normal and adenoma tissues. The Jagged and Delta-like ligands were overexpressed between 25 and 52% in colorectal cancers, while in adenomas, it ranged between 0 and 33%. Combining the data for upregulation of receptors and ligands suggests that 86% colorectal cancers and 56% adenomas exhibited overexpression of Notch pathway genes in our cohort. Notch target genes were upregulated between 24 and 33% in colorectal cancers and between 11 and 22% in adenomas. Collating upregulation of Notch receptors and ligands with the target genes showed concordance in 58% colorectal tumors. Additionally, we evaluated expression of Notch receptors, ligands, and target genes with prognosis using the TCGA mRNA expression dataset. Patients overexpressing Notch3, Notch4, and Hey1 had significantly poorer overall survival relative to those having lower levels of these genes. Taken together, Notch signaling components are aberrantly overexpressed in colorectal tumors, and development of therapeutics targeting the Notch pathway may prove to be beneficial in the management of colorectal cancers. Show less

Several studies have suggested that chemokine receptors are important mediators of inflammatory response in rheumatoid arthritis (RA). B cells are also known to play an important role in RA pathology. C-X-C chemokine receptor type 3 (CXCR3) is considered a potential therapeutic target in different inflammatory diseases; however, the mechanism remains unclear. Here, we evaluated the potentially protective effect of AMG487, a selective CXCR3 antagonist, in collagen-induced arthritis (CIA) mouse model. CIA mice were treated with AMG487 (5 mg/kg) every 48 h, from day 21 until day 41. We then investigated the effect of AMG487 on NF-κB p65-, NOS2-, MCP-1-, TNF-α-, IFN-γ, IL-4-, and IL-27-producing CD19 Show less