Fahad Zadjali

Fahad Zadjali
Sultan Qaboos University | SQU · Department of Biochemistry

PhD

About

69
Publications
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909
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Publications

Publications (69)
Article
Full-text available
Background : Limited data on short versus long-term changes in adaptive immune response across different COVID-19 disease severity groups. Methods : A multi-center prospective study of 140 adult patients with COVID-19 (a total of 325 samples) were analysed for inflammatory markers and lymphocyte subsets at presentation, weeks 2 and 24. Results :...
Article
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Patients with autosomal dominant polycystic kidney disease (ADPKD) and tuberous sclerosis complex (TSC) are born with normal or near-normal kidneys that later develop cysts and prematurely lose function. Both renal cystic diseases appear to be mediated, at least in part, by disease-promoting extracellular vesicles (EVs) that induce genetically inta...
Article
Electronic nicotine delivery systems (ENDS) can reduce the health risks associated with chronic smoke exposure, and their potential benefits are the subject of intense scientific debate. The international "Replica Study Group" replicated independently three relevant studies from the tobacco industry on the cytotoxic and inflammatory effects of ciga...
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Familial hypertriglyceridemia (F-HTG) is an autosomal disorder that causes severe elevation of serum triglyceride levels. It is caused by genetic alterations in LPL, APOC2, APOA5, LMF1, and GPIHBP1 genes. The mutation spectrum of F-HTG in Arabic populations is limited. Here, we report the genetic spectrum of six families of F-HTG of Arab ancestry i...
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Purpose To describe the effect of seasonal variations on sleep patterns in a hot climate Arab region. Methods This is a cross-sectional study that included healthy Omani subjects of both genders between ages 18 and 59 years. Data for sleep pattern identification in summer and winter were collected from participants using an actigraphy wristband....
Preprint
Inter-laboratory comparison is widely used to ensure quality control among laboratories. In in vitro toxicology studies for tobacco harm reduction (THR), exposure system performance and laboratory proficiency along with product smoke and aerosol stream are tested for variability to assess accuracy. Here we aim to test a novel inter-laboratory setup...
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Mucolipidosis Type IV (MLIV) is caused by a deficiency of the mucolipin cation channel encoded by Mucolipin TRP Cation Channel 1 gene (MCOLN1). It is a slowly progressive neurodevelopmental and neurodegenerative disorder causing severe psychomotor developmental delay and progressive visual impairment, which is often misdiagnosed as cerebral palsy....
Preprint
Background: Serum creatinine and estimated glomerular filtration rate (eGFR) are keys to assess kidney function and suggest a propensity for development of renal failure. Genetic factors are reported in different ethnic groups to play a role in the variability of these phenotypes. In this study, we investigate the heritability and quantitative trai...
Article
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Electronic nicotine delivery systems (ENDS) may reduce health risks associated with chronic exposure to smoke and their potential benefits have been the matter of intense scientific debate. We aimed to replicate three published studies on cytotoxic and inflammatory effects of cigarette smoke and ENDS aerosol in an independent multi-center ring stud...
Article
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PurposeTo investigate the agreement in sleep pattern recording by self-reported sleep questionnaires and actigraphy in adults.Methods This is a cross-sectional study. Men and women who met inclusion criteria were recruited for this study. The inclusion criteria were apparently healthy Omani nationals ages 19 to 50 years. Sleep questionnaires were r...
Article
Ulcerative colitis is a chronic inflammation of the colonic mucosa. Gum Arabic (GA) has been reported to exert anti-inflammatory and antifibrotic activity. This study aimed to evaluate the effect of GA on disease activity in an experimental model of colitis. Dextran sodium sulfate (DSS) was used to induce colitis in C57BL/6 mice and the animals wer...
Article
Tuberous sclerosis complex (TSC) is associated with TSC1 or TSC2 gene mutations resulting in hyperactivation of the mTORC1 pathway. This mTORC1 activation is associated with abnormal tissue development and proliferation such that in the kidney there are both solid tumors and cystic lesions. This review summarizes recent advances in tuberous scleros...
Article
Background: PTRHD1 was proposed as a disease-causing gene of intellectual disability, spasticity, and parkinsonism. Objectives: To characterize the clinical phenotype and the molecular cause of intellectual disability in four affected individuals of a consanguineous family. Methods: Clinical evaluation, whole-exome sequencing, Sanger sequencin...
Article
Ovarian cancer (OC) is characterized by a high morbidity and mortality, highlighting a great need for a better understanding of biological mechanisms that affect OC progression and improving its early detection methods. This study investigates effects of prolactin (PRL) on ovarian cancer cells, analyzes PRL receptors (PRLR) in tissue micro arrays a...
Article
Background The development of anti-cancer drugs with the ability to inhibit brain metastasis through the blood-brain barrier (BBB) is substantially limited due to the lack of reliable in vitro models. Main methods In this study, the Geltrex™-based Transwell® and microfluidic BBB models were applied to screen the effect of β-boswellic acid (β-BA) o...
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Background and aims Familial hypercholesterolemia (FH) is a common autosomal dominant disorder that can result in premature atherosclerotic cardiovascular disease (ASCVD). Limited data are available worldwide about the prevalence and management of FH. Here, we aimed to estimate the prevalence and management of patients with FH in five Arabian Gulf...
Article
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In tuberous sclerosis complex (TSC), Tsc2 mutations are associated with more severe disease manifestations than Tsc1 mutations and the role of extracellular vesicles (EVs) in this context is not yet studied. We report a comparative analysis of EVs derived from isogenic renal cells except for Tsc1 or Tsc2 gene status and hypothesized that in spite o...
Article
Objective: This paper describes an unsupervised Machine Learning approach to estimate the HOMA-IR cutoff identifying subjects at risk of insulin resistance in a given ethnic group, based on the clinical data of a representative sample. Method: We apply the approach to clinical data of individuals of Arab ancestors obtained from a family study condu...
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TSC renal cystic disease is poorly understood and has no approved treatment. In a new principal cell-targeted murine model of Tsc cystic disease, the renal cystic epithelium is mostly composed of type A intercalated cells with an intact Tsc2 gene confirmed by sequencing, although these cells exhibit a Tsc-mutant disease phenotype. We used a newly d...
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The suppressor of cytokine signaling 3 (SOCS3) is a major regulator of immune responses and inflammation as it negatively regulates cytokine signaling. Here, the role of SOCS3 in thymic T cell formation was studied in Socs3fl/fl Actin-creER mice (Δsocs3) with a tamoxifen inducible and ubiquitous Socs3 deficiency. Δsocs3 thymi showed a 90% loss of c...
Article
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Objectives: We sought to describe the clinical and genetic characteristics of patients with familial hypercholesterolemia (FH) that presented to the lipid clinic at Sultan Qaboos University Hospital, Muscat, Oman. Methods: Patients who presented with high low-density lipoprotein cholesterol (LDL-C) levels (> 189.0 mg/dL or 4.9 mmol/L) were recruite...
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Inflammatory bowel disease (IBD) is an immunologically mediated chronic intestinal disorder. Growth hormone (GH) administration enhances mucosal repair and decreases intestinal fibrosis in patients with IBD. In the present study, we investigated the effect of cellular sensitivity to GH via suppressor of cytokine signaling 2 (SOCS2) deletion on coli...
Poster
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Daytime siesta is associated with increased HbA1c community cross-sectional study M Al-Abri, I Al-lawati, F Al-Zedjali JOURNAL OF SLEEP RESEARCH 27
Article
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Background: Sleep patterns have changed continuously worldwide and it can be influenced by social, cultural, and environmental factors. These patterns may be associated with poor sleep quality and daytime sleepiness. The aim of the study was to investigate sleep patterns and quality in Omani adults using actigraphy. Subjects and methods: This wa...
Article
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The tuberous sclerosis complex (Tsc) proteins regulate the conserved mTORC1 growth regulation pathway. We identified that loss of the Tsc2 gene in mouse inner medullary collecting duct (mIMCD) cells induced a greater than two-fold increase in extracellular vesicle (EV) production compared to the same cells having an intact Tsc axis. We optimized EV...
Article
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A series of new 11-keto-b-boswellic acid were partially-synthesized by modifying the hydroxyl and carboxylic acid functional groups of ring A. The structures of the new analogs were confirmed by detailed spectral data analysis. Compounds 4, 5 and 9 exhibited potent anti-cancer results against two human tumor cancer cell lines having IC 50 value of...
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The endothelium contributes to the maintenance of vasodilator tone by releasing endothelium-derived relaxing factors, including nitric oxide (NO). In hypertension, endothelial nitric oxide synthase (eNOS) produces less NO and could be one of the contributing factors to the increased peripheral vascular resistance. Agonist-induced Ca2+ entry is esse...
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Tuberous sclerosis complex (TSC) is a tumor predisposition syndrome with significant renal cystic and solid tumor disease. While the most common renal tumor in TSC, the angiomyolipoma, exhibits a loss of heterozygosity associated with disease, we have discovered that the renal cystic epithelium is composed of type A intercalated cells that have an...
Article
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Aim: To determine the prevalence, genetic characteristics, current management and outcomes of familial hypercholesterolaemia (FH) in the Gulf region. Method: Adult (18-70 years) FH patients were recruited from 9 hospitals and centres across 5 Arabian Gulf countries. The study was divided into 4 phases and included patients from 3 different categ...
Article
Recently, with the advancement in Next Generation Sequencing (NGS) along with the improvement of bioinformatics tools, Whole Exome Sequencing (WES) has become the most efficient diagnostic test for patients with intellectual disability (ID). This study aims to estimate the yield of a reanalysis of ID negative exome cases after data re‐annotation. T...
Article
Aminoacyl‐tRNA synthetases (ARSs) canonical function is to conjugate specific amino acids to cognate tRNA that are required for the first step of protein synthesis. Genetic mutations that cause dysfunction or absence of ARSs result in various neurodevelopmental disorders. The human phenylalanine‐tRNA synthetase (PheRS) is a tetrameric protein made...
Article
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Introduction: Sleep patterns have changed continuously worldwide. These patterns may be associated with poor sleep quality and daytime sleepiness. The aim of the study is to investigate the sleep patterns and quality in Omani adults using actigraphy. Subjects and methods: This is a cross sectional study conducted between June 2015 and February 2017...
Article
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SOCS2 is a pleiotropic E3 ligase. Its deficiency is associated with gigantism and organismal lethality upon inflammatory challenge. However, mechanistic understanding of SOCS2 function is dismal due to our unawareness of its protein substrates. We performed a mass spectrometry based proteomic profiling upon SOCS2 depletion and yield quantitative da...
Article
Recent observational cohort studies indicated that the incidence of connective tissue diseases such as systemic lupus erythematous (SLE), in adult patients with sickle cell disease (SCD), appears to be increasing. The exact causes underlying this increased risk are still unknown, but patients with SCD are at risk of infections due to immune dysfunc...
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Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in humans and is characterized with poor outcome. In this study, we investigated components of prolactin (Prl) system in cell models of GBM and in histological tissue sections obtained from GBM patients. Expression of Prolactin receptor (PrlR) was detected at high l...
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Toll-like receptors (TLRs) are essential elements of the innate immune response to different infections including the infection with human immunodeficiency virus (HIV). Single nucleotide polymorphisms (SNPs) in TLRs such as TLR4 1063A/G and 1363C/T have been found to be associated with changes in CD4 count, viral load (VL), and disease progression...
Article
Around 15 to 30% of AIDS patients fail to recover their CD4(+) T cell levels following combined antiretroviral therapy despite successful inhibition of HIV-1 replication. The exact reasons for this immune recovery failure are not completely understood. HLA alleles are among the candidate that may explain this failure. A total of 65 adult AIDS patie...
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Objective: Globally obesity has reached epidemic proportions with alarming rates in the Arabian Gulf countries. The impact of behavioral eating habits and in particular night eating syndrome (NES) have not been emphasized in the region. This study assessed the proportion of NES in an Omani Arab adult population sample. Method: A night eating syn...
Article
Objectives: This study aimed to assess the distribution of missense mutations in the adrenoceptor β2 (ADRB2) gene in an Omani cohort. Methods: This study was carried out between May 2014 and March 2015 at the Sultan Qaboos University, Muscat, Oman. Blood samples were taken from 316 unrelated Omani subjects. Genotyping for rs1042713 (c.46A>G, p.A...
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Background: Diabetes type 1 is characterized by the failure of beta cells to produce insulin. Suppressor of cytokine signaling (SOCS) proteins are important regulators of the Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway. Previous studies have shown that GH can prevent the development of type I diabetes in mice a...
Article
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The large intestine is a home for trillions of microbiota, which confer many benefits on the host including production of vitamin, absorption of nutrients, pathogen displacement and development of the immune system. For several decades, germ free animals have been used to study the interaction between the host and its microbiota. This minireview de...
Article
Bisphenol A (BPA) is a byproduct of polycarbonate plastic widely present in food containers. BPA is historically a known endocrine disruptor and due to its oestrogen agonist activity, BPA consumption is associated with hypothyroidism and reproductive disorder. Recent studies have shown that oestrogen antagonised GH actions. Since BPA has oestrogen...
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Objectives: This study examined the utility of a family-based model for replicating the results of genome-wide association studies (GWAS) of type 2 diabetes (T2D). Methods and results: In a total of 232 members of a large consanguineous Omani Arab pedigree (age: 16-80years), there were 27 diabetics and 50 prediabetics (17 with impaired fasting g...
Article
Toll-like receptors (TLRs) are essential elements of the innate immune response to different infections including HIV-1 infection. The single-nucleotide polymorphisms (SNPs) in TLRs have been associated with CD4T cell count and HIV disease progression. The TLR7 (Gln11Leu) SNP was shown to be associated with a rapid decline of CD4T cell count. A rel...
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Polymorphisms in the regulatory region of the CCR5 gene affect protein expression and modulate the progress of HIV-1 disease. Because of this prominent role, variations in this gene have been under differential pressure and their frequencies vary among human populations. The CCR2V64I mutation is tightly linked to certain polymorphisms in the CCR5 g...
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Familial hypercholesterolemia (FH) is an autosomal dominant disorder typified by elevated low-density lipoprotein cholesterol (LDL-C) levels caused by mutations in the LDL receptor (LDLR), apolipoprotein B (ApoB), or proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. Previously, we reported a novel mutation in the exon-3 of LDLR gene, obs...
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C-C motif chemokine receptor-5 (CCR5) is a pro-inflammatory receptor that binds to chemokines and facilitates the entry of the R5 strain of HIV-1. A number of polymorphisms were identified within the promoter and coding regions of the CCR5 gene, some of which have been found to affect the protein expression and thus receptor function. Although seve...
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The receptor tyrosine kinase Flt3 is an important growth factor receptor in hematopoiesis, and gain-of-function mutations of the receptor contribute to the transformation of acute myeloid leukemia. SOCS6 (suppressor of cytokine signaling 6) is a member of the SOCS family of E3 ubiquitin ligases that can regulate receptor tyrosine kinase signal tran...
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Mammalian brain development is initiated in utero and internal and external environmental signals can affect this process all the way until adulthood. Recent observations suggest that one such external cue is the indigenous microbiota which has been shown to affect developmental programming of the brain. This may have consequences for brain maturat...
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Hepatic steatosis is a prominent feature in patients with growth hormone (GH) deficiency. The ubiquitin ligase SOCS2 attenuates hepatic GH signaling by inhibiting the Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5b (STAT5b) axis. Here, we investigated the role of SOCS2 in the development of diet-induced hepatic steatosis a...
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Stem cell transplantation (SCT) is a curative treatment for malignant and non malignant diseases. However, transplantation-related complications including cardiovascular disease deteriorate the clinical outcome and quality of life. We have investigated the acute effects of conditioning regimen on the pharmacology, physiology and structure of large...
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Liver X receptor (LXR) agonists have been shown to influence the development of hyperlipidemia and atherosclerosis in mouse models. It has also been demonstrated that some LXR agonists can cause hepatic steatosis in experimental animals. Growth hormone (GH) is known to regulate hepatic metabolism and the absence of hepatic GH receptors (GHR) leads...