Papers by Vidya Mohamed-Ali
COVID-19 complications present a huge burden on healthcare systems and warrant a predictive risk ... more COVID-19 complications present a huge burden on healthcare systems and warrant a predictive risk model for disease severity of SARS-CoV-2 infection to enable early intervention, prospective decision-making and triaging of patients. We profiled plasma proteins from COVID-19 patients (severe n=50, and mild n=50) and controls (n=50) using function- and pathway-based panels developed with the highly specific proximity extension assays. Several biological pathways were specific for patients with severe complications. Based on these dysregulated profiles, we propose candidate FDA-approved drugs that target multiple upregulated proteins to treat severe complications. In addition, the set of differentially expressed plasma proteins in severe disease contained a robust 46-protein signature, the COVID-19 molecular severity score, which predicts the risk of severe complications. We cross-validated this molecular severity score in an independent cohort and found it useful within three days afte...
International Journal of Environmental Research and Public Health, 2022
Background: South Asian workers have a greater predisposition to non-communicable diseases (NCDs)... more Background: South Asian workers have a greater predisposition to non-communicable diseases (NCDs) that is exacerbated by migration and length of residence in host countries. Aims: To examine the association between length of residence in Qatar with diagnosis of NCDs in male blue-collar workers. Methods: A retrospective investigation of the electronic health records (EHRs) of 119,581 clinical visits by 58,342 patients was conducted. Data included age, nationality and confirmed ICD-10 diagnosis. Based on duration of residence, the population was divided into groups: ≤6 months, 6–12 months, 1–≤2 years, 2–≤5 years, 5–≤6 years, >6 years. It was assumed that the group that had been resident in Qatar for ≤6 months represented diseases that had been acquired in their countries of origin. Results: South Asian (90%) patients presented with NCDs at a younger (mean ± SD age of 34.8 ± 9.0 years) age. Diabetes and hypertension were higher in those who had just arrived (<6 months’ group), co...
Nature Communications, 2022
COVID-19 complications still present a huge burden on healthcare systems and warrant predictive r... more COVID-19 complications still present a huge burden on healthcare systems and warrant predictive risk models to triage patients and inform early intervention. Here, we profile 893 plasma proteins from 50 severe and 50 mild-moderate COVID-19 patients, and 50 healthy controls, and show that 375 proteins are differentially expressed in the plasma of severe COVID-19 patients. These differentially expressed plasma proteins are implicated in the pathogenesis of COVID-19 and present targets for candidate drugs to prevent or treat severe complications. Based on the plasma proteomics and clinical lab tests, we also report a 12-plasma protein signature and a model of seven routine clinical tests that validate in an independent cohort as early risk predictors of COVID-19 severity and patient survival. The risk predictors and candidate drugs described in our study can be used and developed for personalized management of SARS-CoV-2 infected patients.
The role of autoantibodies in coronavirus disease (COVID-19) complications is not yet fully under... more The role of autoantibodies in coronavirus disease (COVID-19) complications is not yet fully understood. The current investigation screened two independent cohorts of 97 COVID-19 patients (Discovery (Disc) cohort from Qatar (n = 49) and Replication (Rep) cohort from New York (n = 48)) utilizing high-throughput KoRectly Expressed (KREX) immunome protein-array technology. Autoantibody responses to 57 proteins were significantly altered in the COVID-19 Disc cohort compared to healthy controls (P ≤ 0.05). The Rep cohort had altered autoantibody responses against 26 proteins compared to non-COVID-19 ICU patients that served as controls. Both cohorts showed substantial similarities (r2 = 0.73) and exhibited higher autoantibodies responses to numerous transcription factors, immunomodulatory proteins, and human disease markers. Analysis of the combined cohorts revealed elevated autoantibody responses against SPANXN4, STK25, ATF4, PRKD2, and CHMP3 proteins in COVID-19 patients. KREX analysis ...
Viruses, 2021
The COVID-19 pandemic has affected all individuals across the globe in some way. Despite large nu... more The COVID-19 pandemic has affected all individuals across the globe in some way. Despite large numbers of reported seroprevalence studies, there remains a limited understanding of how the magnitude and epitope utilization of the humoral immune response to SARS-CoV-2 viral anti-gens varies within populations following natural infection. Here, we designed a quantitative, multi-epitope protein microarray comprising various nucleocapsid protein structural motifs, including two structural domains and three intrinsically disordered regions. Quantitative data from the microarray provided complete differentiation between cases and pre-pandemic controls (100% sensitivity and specificity) in a case-control cohort (n = 100). We then assessed the influence of disease severity, age, and ethnicity on the strength and breadth of the humoral response in a multi-ethnic cohort (n = 138). As expected, patients with severe disease showed significantly higher antibody titers and interestingly also had s...
Phytomedicine Plus, 2021
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Clinical Chemistry, 1996
dependence of tissue plasminogen activator concentrations in plasma, as studied by an improved en... more dependence of tissue plasminogen activator concentrations in plasma, as studied by an improved enzyme-linked immunosorbent assay. Clin Chem
International Journal of Obesity, 2000
Objectives: To investigate the effects of b b-adrenergic stimulation on IL-6 secretion in humans,... more Objectives: To investigate the effects of b b-adrenergic stimulation on IL-6 secretion in humans, and to determine the potential contribution to this response of adipocytes and peripheral blood cells (PBC). Design: Experimental study in 8 human volunteers, and in vitro studies on murine adipocyte cell-line, 3T3.L1 and 3T3.F442A, and human PBC. Measurements: Plasma IL-6 and TNFa responses to isoprenaline infusion. Cytokine secretion from differentiated adipocyte cell-lines and PBC in response to isoprenaline. Results: Plasma IL-6 levels increased ninefold (median) by 180 min (baseline median 0.51 [interquartile range 0.47 ± 1.4] vs 180 mins 4.53 [2.58 ± 5.69] pg ml 71 , P 0.01). One hour after infusion, IL-6 levels (2.9 [1.27 ± 3.98]) were lower than at 180 min (P 0.05), but higher than baseline (P 0.01). TNFa levels were unchanged. Differentiated adipocytes incubated in isoprenaline (0 ± 0.1 mM) released signi®cantly increased amounts of IL-6 whereas no response was elicited from PBC. Conclusions: The induction of IL-6 observed in vivo may be attributed to the b b-adrenergic stimulation of IL-6 release speci®cally from adipocytes, as opposed to circulating blood cells.
Diabetologia, Nov 24, 2016
A subset of obese individuals remains insulin sensitive by mechanisms as yet unclear. The hypothe... more A subset of obese individuals remains insulin sensitive by mechanisms as yet unclear. The hypothesis that maintenance of normal subcutaneous (SC) adipogenesis accounts, at least partially, for this protective phenotype and whether it can be abrogated by chronic exposure to IL-6 was investigated. Adipose tissue biopsies were collected from insulin-sensitive (IS) and insulin-resistant (IR) individuals undergoing weight-reduction surgery. Adipocyte size, pre-adipocyte proportion of stromal vascular fraction (SVF)-derived cells, adipogenic capacity and gene expression profiles of isolated pre-adipocytes were determined, along with local in vitro IL-6 secretion. Adipogenic capacity was further assessed in response to exogenous IL-6 application. Despite being equally obese, IR individuals had significantly lower plasma leptin and adiponectin levels and higher IL-6 levels compared with age-matched IS counterparts. Elevated systemic IL-6 in IR individuals was associated with hyperplasia of ...
American journal of physiology. Endocrinology and metabolism, Jan 15, 2015
The POU4F2/Brn-3b transcription factor has been identified as a potentially novel regulator of ke... more The POU4F2/Brn-3b transcription factor has been identified as a potentially novel regulator of key metabolic processes. Loss of this protein in Brn-3b knockout (KO) mice causes profound hyperglycemia and insulin resistance (IR), normally associated with type II diabetes (T2D), whilst Brn-3b is reduced in tissues taken from obese mice fed on high-fat diets (HFD), which also develop hyperglycemia and IR. Furthermore, studies in C2C12 myocytes show that Brn-3b mRNA and proteins are induced by glucose but inhibited by insulin, suggesting that this protein is itself highly regulated in responsive cells. Analysis of differential gene expression in skeletal muscle from Brn-3b KO mice showed changes in genes that are implicated in T2D such as increased glycogen synthase kinase-3 beta (GSK3) and reduced GLUT4 glucose transporter. The GLUT4 gene promoter contains multiple Brn-3b binding sites and is directly transactivated by this transcription factor in co-transfection assays whereas chromat...
Molecular medicine (Cambridge, Mass.)
Obesity is associated with an array of health problems in adult and pediatric populations. Unders... more Obesity is associated with an array of health problems in adult and pediatric populations. Understanding the pathogenesis of obesity and its metabolic sequelae has advanced rapidly over the past decades. Adipose tissue represents an active endocrine organ that, in addition to regulating fat mass and nutrient homeostasis, releases a large number of bioactive mediators (adipokines) that signal to organs of metabolic importance including brain, liver, skeletal muscle, and the immune system--thereby modulating hemostasis, blood pressure, lipid and glucose metabolism, inflammation, and atherosclerosis. In the present review, we summarize current data on the effect of the adipose tissue-derived hormones adiponectin, chemerin, leptin, omentin, resistin, retinol binding protein 4, tumor necrosis factor-alpha and interleukin-6, vaspin, and visfatin on insulin resistance.
Fibrinolysis and Proteolysis, 1997
Functional sequence changes in the 13-gene promoter may have a direct effect on the rate of trans... more Functional sequence changes in the 13-gene promoter may have a direct effect on the rate of transcription and thus on plasma fibrinogen levels. A common G/A sequence variation has been detected at position-455 of the l~-fibrinogen promoter, with carriers of the A allele, representing roughly 20% of the population, consistently having higher fibrinogen levels than those with the genotype G/G (0.17 g/I higher, averaged over 8 published studies in Caucasian men). The magnitude of this genotype effect indicates that it is likely to be of biological significance in causing an elevated risk of thrombosis. However, the magnitude of this effect is modulated by several environmental factors and data will be presented to demonstrate interaction between genotype and age, smoking and physical exercise, in the determination of an individual's plasma fibrinogen levels.
Disease models & mechanisms, 2011
The close correspondence between energy intake and expenditure over prolonged time periods, coupl... more The close correspondence between energy intake and expenditure over prolonged time periods, coupled with an apparent protection of the level of body adiposity in the face of perturbations of energy balance, has led to the idea that body fatness is regulated via mechanisms that control intake and energy expenditure. Two models have dominated the discussion of how this regulation might take place. The set point model is rooted in physiology, genetics and molecular biology, and suggests that there is an active feedback mechanism linking adipose tissue (stored energy) to intake and expenditure via a set point, presumably encoded in the brain. This model is consistent with many of the biological aspects of energy balance, but struggles to explain the many significant environmental and social influences on obesity, food intake and physical activity. More importantly, the set point model does not effectively explain the 'obesity…
International Journal of Obesity, 2008
Obesity, 2009
nature publishing group articles intervention and Prevention IntroductIon Obesity, and especially... more nature publishing group articles intervention and Prevention IntroductIon Obesity, and especially abdominal obesity, is a risk factor for insulin resistance (IR), type 2 diabetes, and cardiovascular disease. "Dysfunctional" adipose tissue, which cannot properly handle the energy surplus resulting from a sedentary lifestyle combined with excessive calorie consumption, plays a central role in obesity-associated IR and type 2 diabetes (1). In general, IR develops as a consequence of exposure of insulin-responsive tissues to elevated dietary nutrients, resulting in the accumulation of lipid-derived metabolites and impairment of interorgan communication networks that are mediated by peptide hormones and inflammatory molecules (2). Lifestyle modification therapies, such as reduced caloric intake and increased physical activity, for the obesity-associated IR and metabolic abnormalities have proved to be difficult for the general population. However, current pharmacological interventions often require the use of multiple agents and are also associated with adverse side effects, as documented in the case of the thiazolidinediones (3). Therefore, new treatment strategies are sought. At the same time, the quality of dietary lipids is important. The n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA), namely, eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3), which are abundant in marine fish oils, act as potent hypolipidemics in both rodents (4-6) and humans (7). The n-3 LC-PUFA also prevented development of obesity and IR in rodents fed high-fat diets (8). However, their beneficial effect on body weight and IR in overweight patients was only apparent when n-3 LC-PUFA were combined with
Molecular and Cellular Endocrinology, 2010
Obesity, defined by an excess of adipose tissue, is often associated with the development of vari... more Obesity, defined by an excess of adipose tissue, is often associated with the development of various metabolic diseases. The increased and inappropriate deposition of this tissue contributes to hyperglycemia, hyperlipidemia, insulin resistance, endothelial dysfunction and chronic inflammation. Recent evidence suggests that factors expressed and secreted by the adipose tissue, adipokines, may contribute to the development of these abnormalities by mechanisms including inhibition of adipogenesis, adipocyte hypertrophy and death, immune cell infiltration and disruption of tissue metabolism. The presence of adipokine receptors in adipocytes renders these cells available to autocrine and paracrine effects of adipokines. In this review the reported local effects of adipokines on adipose tissue structure, inflammation and regulation of metabolic functions, in the face of over-nutrition and consequent obesity, are outlined. Elucidating the local regulation of white adipocyte development and function could help in the design of effective, tissue-specific therapies for obesity-associated diseases. Introduction. Obesity, affected by the expanding adipose tissue mass, has necessitated the study and understanding of this organ. It is now accepted that the adipose tissue is an important, dynamic participant in regulating whole-body metabolism and is crucial for glucose and energy homeostasis (Rosen and Spiegelman, 2006). Various diseases are closely associated with increased adipose tissue mass, including type 2 diabetes, atherosclerosis, hypertension, osteoarthritis and certain cancers (Greenberg and Obin, 2006). Obesity-associated changes in the structure and function of adipose tissue and its distribution are affected by and effect changes in the adipokine secretory repertoire and profoundly influence the susceptibility of an individual to the associated pathologies (Björntorp, 1991). Obesity has been described as a low grade inflammatory condition, with both the cellularity and the secretions of adipose tissue reflecting these changes. Current evidence suggests that over-nutrition leads to adipocyte hypertrophy, followed by cell death, which may act as a stimulus for immune cell infiltration into the tissue (Strissel et al., 2007; Murano et al., 2008). Monocyte infiltration and differentiation in particular has been shown to correlate with adipocyte hypertrophy, as well as body mass (Weisberg et al 2003). These macrophages, in response to the endocrine and metabolic milieu prevalent in the obese adipose tissue, switch their phenotype from one of a non-inflammatory resident macrophage to that of a lipid engorged foam cell, expressing dendritic cell markers, such as CD11c (Lumeng et al., 2007). The secretions of these macrophages, such as IL-6 and TNFα along with those from the hypertrophied adipocyte, such as MCP-1 and leptin, regulate the pathological changes of obesity, like insulin resistance and endothelial dysfunction (Figure 1). These autocrine/paracrine effects augment the endocrine changes mediated by the molecules in other organs such as liver, heart and skeletal muscle. All the signals released from or expressed by the adipose tissue are referred to as adipokines here, even though these include cytokines, chemokines and products of tissue enzyme activity (Table 1).
Mediators of Inflammation, 2013
Recent studies from the Gulf region suggest that compared to men, women have a greater risk of de... more Recent studies from the Gulf region suggest that compared to men, women have a greater risk of developing metabolic syndrome (MeS).Objective. To investigate gender differences in body composition, adipokines, inflammatory markers, and aerobic fitness in a cohort of healthy Qatari adults.Participants. Healthy Qatari (n=58) were matched for age, gender, and body mass index.Methods. Body composition and regional fat distribution were determined by dual-energy X-ray absorptiometry and computerized tomography. Laboratory assessments included serum levels of fasting glucose, insulin, lipid profile analysis, adipokines, and inflammatory markers. Subjects were also evaluated for aerobic fitness.Results. Women had more adipose tissue in the total abdominal (P=0.04) and abdominal subcutaneous (P=0.07) regions compared to men. Waist circumference and indices of insulin sensitivity were similar; however, women had a more favourable lipid profile than men. Serum adiponectin and leptin levels wer...
Kidney International, 2003
Endothelial dysfunction and inflammation in asymptomatic Proteinuria is associated with an increa... more Endothelial dysfunction and inflammation in asymptomatic Proteinuria is associated with an increased prevalence proteinuria. of vascular disease in both diabetic [1] and non-diabetic Background. Proteinuria is associated with vascular risk and populations [2, 3]. a systemic increase in vascular permeability. Endothelial dys-Evidence suggests that proteinuria does not solely refunction occurs early in atherosclerosis and modulates vascular flect renal pathology but is also associated with a systemic permeability. Vascular risk and chronic inflammation are associated. This study investigates whether the increased vascular increase in vascular permeability. In the normal physiopermeability in proteinuria reflects systemic endothelial dyslogical response to exercise or to passive ascent to altitude, function and chronic inflammation. for example, the development of proteinuria and a raised Methods. Twenty-one patients with asymptomatic proteincapillary fluid permeability in the calf are contemporaneuria (1.29 g/24 h; range 0.18 to 3.17) and 21 matched controls ous [4]. Capillary fluid permeability is also increased in were studied. Microvascular endothelial function was assessed using acetylcholine iontophoresis. Maximum microvascular hy-otherwise healthy patients with dipstick positive proteinperemia (MMH) was assessed by flux response to local skin uria [abstract; Lewis DM, XIV International Congress of heating. Macrovascular endothelial function was assessed by Nephrology 3(Suppl 1):S235, 1997] and in patients with flow-associated dilation (FAD) in the brachial artery using nephrotic syndrome [5]. Even otherwise healthy patients ultrasound. von Willebrand factor (vWF) was measured as a with microalbuminuria demonstrate increased transvasmarker of endothelial activation. Low-grade inflammation was cular albumin leakage [6]. Given that increased transvasassessed by measurement of circulating C-reactive protein (CRP) values using a high sensitivity assay. cular leakage, which could allow entry of lipoproteins Results. FAD was impaired in proteinuric subjects (AP) into the vessel wall [7], is an early event in atherogenesis, compared to controls [1.8 (0.2 to 5.3) AP vs. 3.8 (1.5 to 6.2) these demonstrations of an association between protein-C %; P ϭ 0.014]. There was no significant difference between uria and vascular permeability are interesting. groups in MMH or in the response to acetylcholine ionto-The mechanism of this increased vascular permeability phoresis. The AP group had a higher CRP [4.0 (0.5 to 39.0) AP vs. 0.2 (0.1 to 21.3) C mg/L; P Ͻ 0.001] and tendency to in proteinuric subjects is unknown. One possibility is that higher vWF [101.5 (67.0 to 197.0) AP vs. 77.5 (45.0 to 185.0) it is due to abnormal endothelial function. There is now C IU/dL; P ϭ 0.046] compared to controls. In the AP, but not considerable evidence to suggest that contraction of encontrol, group there was an inverse correlation between CRP dothelial cells may change intercellular cleft size [8], that and microvascular function as determined by acetylcholine iontranscellular holes influence fluid and macromolecular tophoresis (r ϭ Ϫ0.509; P ϭ 0.018). movement across the vascular wall [9], and that vesicular Conclusions. In AP subjects there is evidence of macrovascular endothelial dysfunction remote from the kidney and of transport of albumin is controlled by endothelial funclow-grade inflammation that is associated with microvascular tion. Although the role of caveolae in endothelial uptake endothelial dysfunction. and transport is not fully defined, most [10-12] but not all [13] studies suggest that caveolae are important for albumin transport across microvessels. Recent evidence
Journal of Clinical Endocrinology & Metabolism, 1998
Hypertension, 1994
Both insulin resistance and insulin concentrations correlate with blood pressure in nondiabetic s... more Both insulin resistance and insulin concentrations correlate with blood pressure in nondiabetic subjects, but there is no consensus on these relations in subjects with non-insulin-dependent diabetes, perhaps because of the use of nonspecific insulin assays and clinic blood pressure measurement. Therefore, we have investigated the relation between ambulatory blood pressure, insulin sensitivity (measured by an insulin sensitivity test), and levels of insulin and its principal precursors, measured by specific assays, in 24 subjects with non-insulin-dependent diabetes. Insulin sensitivity (glucose metabolic clearance rate) correlated strongly with mean 24-hour ambulatory systolic blood pressure (r = -.650, P < .001). In contrast, there was no relation between this blood pressure index and fasting levels of insulin (r = .096, P = NS) or all insulin-like molecules (r = .077, P = NS). Dichotomized on 24-hour ambulatory systolic blood pressure levels, the hypertensive group was more insu...
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Papers by Vidya Mohamed-Ali