109 results on '"Al Madhoun, Ashraf"'
Search Results
102. The Role of Thymidine Kinases in the Activation of Pyrimidine Nucleoside Analogues
- Author
-
Al-Madhoun, Ashraf, Tjarks, Werner, and Eriksson, Staffan
- Abstract
Deoxynucleoside analogues need activation by deoxynucleoside kinases to serve as antiviral or anticancer agents. Here we review the properties of cellular cytoplasmic thymidine kinase 1, mitochondrial thymidine kinase 2, the multisubstrate deoxynucleoside kinase from Drosophila melanogaster and Herpes virus 1 thymidine kinase. Important substrate activity relationships will be discussed.
- Published
- 2004
103. MicroRNA-630: A potential guardian against inflammation in diabetic kidney disease.
- Author
-
Al Madhoun A
- Abstract
In this editorial, we comment on the article by Wu et al published "MicroRNA-630 alleviates inflammatory reactions in rats with diabetic kidney disease by targeting toll-like receptor 4". Diabetic kidney disease (DKD) stands as a significant complication occurring from diabetes mellitus, which contributes substantially to the morbidity and mortality rates worldwide. Renal tubular epithelial cell da-mage, often accompanied by inflammatory responses and mesenchymal trans-differentiation, plays a pivotal role in the progression of DKD. Despite extensive research, the intricate molecular mechanisms underlying these processes remain to be determined. Wu et al remarkable work identifies microRNA-630 (miR-630) as an emerging potential regulator of cell migration, apoptosis, and autophagy, prompting investigation into its association with DKD pathogenesis. This study endeavors to elucidate the impact of miR-630 on TEC injury and the inflammatory response in DKD rats. The role of miR-630 in human DKD will be of interest for future studies., Competing Interests: Conflict-of-interest statement: The author reports no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
104. Teneligliptin: A potential therapeutic approach for diabetic cardiomyopathy.
- Author
-
Al Madhoun A
- Abstract
In this editorial, we comment on the article by Zhang et al . Diabetes mellitus is a chronic disorder associated with several complications like cardiomyopathy, neuropathy, and retinopathy. Diabetes prevalence is increasing worldwide. Multiple diabetes medications are prescribed based on individual patients' needs. However, the exact mechanisms by which many of these drugs exert their pro-tective effects remain unclear. Zhang et al elucidates molecular mechanisms undelaying cardioprotective effect of the dipeptidyl peptidase-IV inhibitor, teneligliptin. Briefly, teneligliptin alleviates the activation of NOD-like receptor protein 3 inflammasome, a multiprotein complex that plays a pivotal role in regulating the innate immune system and inflammatory signaling. Suppression of NOD-like receptor protein 3 inflammasome activity reduces the expression of cytokines, oxygen radicals and inflammation. These findings highlight teneligliptin as an anti-diabetic cardioprotective reagent., Competing Interests: Conflict-of-interest statement: The author reports no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
105. Effect of Dual Glucagon-Like Peptide 1/Glucose-Dependent Insulinotropic Polypeptide Receptor Agonist (Tirzepatide) versus Bariatric Surgery on Weight Loss and Nonalcoholic Fatty Liver Disease.
- Author
-
Al-Sabah S, Al-Khairi I, Jamal M, Qaddoumi M, Alajmi F, Kumar J, Abukhalaf N, Cherian P, Madhu D, Arefanian H, Dsouza C, Alam-Eldin N, AlSabagh A, Al Madhoun A, Al-Sabah S, Al-Mulla F, Abu-Farha M, and Abubaker J
- Abstract
Objectives: Bariatric surgery is a well-established treatment for obesity and type 2 diabetes. Tirzepatide, a dual GIP/GLP-1 receptor agonist, has emerged as a promising therapy for type 2 diabetes. This study aimed to compare the effects of bariatric surgery, semaglutide (a GLP-1 receptor agonist), and tirzepatide in Sprague-Dawley rats fed a high-fat diet., Methods: Rats were divided into surgery, semaglutide, and tirzepatide treatment groups, along with a control group (sham). Weight, oral glucose tolerance, and levels of metabolic markers were assessed, along with adipose and liver tissue analysis., Results: Surgery led to a 15.5% weight reduction, while rats treated with semaglutide exhibited a 10.7% reduction. Tirzepatide treatment at various concentrations (10, 50, and 100 nmol/kg) resulted in weight reductions of 5.0%, 14.9%, and 17.7%, respectively, compared to the sham group. Metabolic analyte levels decreased in intervention groups compared to the sham group, indicating improved metabolic health and glucose tolerance. Adipose tissue weight and hepatic liver fat droplets decreased in the intervention groups., Conclusion: Bariatric surgery and tirzepatide treatment significantly improved metabolic parameters in obese rats. Tirzepatide, particularly at higher concentrations, showed pronounced improvements compared to surgery and semaglutide. These findings suggest that high doses of tirzepatide could be explored as an alternative to bariatric surgery for the treatment of obesity., (© 2024 The Author(s). Published by S. Karger AG, Basel.)
- Published
- 2024
- Full Text
- View/download PDF
106. Glucokinase regulatory protein rs780094 polymorphism is associated with type 2 diabetes mellitus, dyslipidemia, non-alcoholic fatty liver disease, and nephropathy.
- Author
-
Al Madhoun A
- Abstract
In this editorial, we comment on the article by Liu et al published in the recent issue of the World Journal of Diabetes (Relationship between GCKR gene rs780094 polymorphism and type 2 diabetes with albuminuria). Type 2 diabetes mellitus (T2DM) is a chronic disorder characterized by dysregulated glucose homeostasis. The persistent elevated blood glucose level in T2DM significantly increases the risk of developing severe complications, including cardiovascular disease, re-tinopathy, neuropathy, and nephropathy. T2DM arises from a complex interplay between genetic, epigenetic, and environmental factors. Global genomic studies have identified numerous genetic variations associated with an increased risk of T2DM. Specifically, variations within the glucokinase regulatory protein (GCKR) gene have been linked to heightened susceptibility to T2DM and its associated complications. The clinical trial by Liu et al further elucidates the role of the GCKR rs780094 polymorphism in T2DM and nephropathy development. Their findings demonstrate that individuals carrying the CT or TT genotype at the GCKR rs780094 locus are at a higher risk of developing T2DM with albuminuria compared to those with the CC genotype. These findings highlight the importance of genetic testing and risk assessment in T2DM to develop effective preventive strategies and personalized treatment plans., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
107. Differential effects of fish-oil and cocoa-butter based high-fat/high-sucrose diets on endocrine pancreas morphology and function in mice.
- Author
-
Albeloushi S, Hasan A, Arefanian H, Sindhu S, Al-Rashed F, Kochumon S, Abukhalaf N, Jacob T, Shenouda S, Al Madhoun A, Al-Mulla F, and Ahmad R
- Subjects
- Male, Mice, Animals, Glucagon, Sucrose adverse effects, Fish Oils pharmacology, C-Peptide, Mice, Inbred C57BL, Insulin, Glucose, Glucagon-Like Peptide 1 metabolism, Leptin, Islets of Langerhans metabolism, Dietary Fats
- Abstract
Introduction: A high-fat/high-sucrose diet leads to adverse metabolic changes that affect insulin sensitivity, function, and secretion. The source of fat in the diet might inhibit or increase this adverse effect. Fish oil and cocoa butter are a significant part of our diets. Yet comparisons of these commonly used fat sources with high sucrose on pancreas morphology and function are not made. This study investigated the comparative effects of a fish oil-based high-fat/high-sucrose diet (Fish-HFDS) versus a cocoa butter-based high-fat/high-sucrose diet (Cocoa-HFDS) on endocrine pancreas morphology and function in mice., Methods: C57BL/6 male mice (n=12) were randomly assigned to dietary intervention either Fish-HFDS (n=6) or Cocoa-HFDS (n=6) for 22 weeks. Intraperitoneal glucose and insulin tolerance tests (IP-GTT and IP-ITT) were performed after 20-21 weeks of dietary intervention. Plasma concentrations of c-peptide, insulin, glucagon, GLP-1, and leptin were measured by Milliplex kit. Pancreatic tissues were collected for immunohistochemistry to measure islet number and composition. Tissues were multi-labelled with antibodies against insulin and glucagon, also including expression on Pdx1-positive cells., Results and Discussion: Fish-HFDS-fed mice showed significantly reduced food intake and body weight gain compared to Cocoa-HFDS-fed mice. Fish-HFDS group had lower fasting blood glucose concentration and area under the curve (AUC) for both GTT and ITT. Plasma c-peptide, insulin, glucagon, and GLP-1 concentrations were increased in the Fish-HFDS group. Interestingly, mice fed the Fish-HFDS diet displayed higher plasma leptin concentration. Histochemical analysis revealed a significant increase in endocrine pancreas β-cells and islet numbers in mice fed Fish-HFDS compared to the Cocoa-HFDS group. Taken together, these findings suggest that in a high-fat/high-sucrose dietary setting, the source of the fat, especially fish oil, can ameliorate the effect of sucrose on glucose homeostasis and endocrine pancreas morphology and function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Albeloushi, Hasan, Arefanian, Sindhu, Al-Rashed, Kochumon, Abukhalaf, Jacob, Shenouda, Al Madhoun, Al-Mulla and Ahmad.)
- Published
- 2024
- Full Text
- View/download PDF
108. ACSL1 is a key regulator of inflammatory and macrophage foaming induced by short-term palmitate exposure or acute high-fat feeding.
- Author
-
Al-Rashed F, Haddad D, Al Madhoun A, Sindhu S, Jacob T, Kochumon S, Obeid LM, Al-Mulla F, Hannun YA, and Ahmad R
- Abstract
Foamy and inflammatory macrophages play pathogenic roles in metabolic disorders. However, the mechanisms that promote foamy and inflammatory macrophage phenotypes under acute-high-fat feeding (AHFF) remain elusive. Herein, we investigated the role of acyl-CoA synthetase-1 (ACSL1) in favoring the foamy/inflammatory phenotype of monocytes/macrophages upon short-term exposure to palmitate or AHFF. Palmitate exposure induced a foamy/inflammatory phenotype in macrophages which was associated with increased ACSL1 expression. Inhibition/knockdown of ACSL1 in macrophages suppressed the foamy/inflammatory phenotype through the inhibition of the CD36-FABP4-p38-PPARδ signaling axis. ACSL1 inhibition/knockdown suppressed macrophage foaming/inflammation after palmitate stimulation by downregulating the FABP4 expression. Similar results were obtained using primary human monocytes. As expected, oral administration of ACSL1 inhibitor triacsin-C in mice before AHFF normalized the inflammatory/foamy phenotype of the circulatory monocytes by suppressing FABP4 expression. Our results reveal that targeting ACSL1 leads to the attenuation of the CD36-FABP4-p38-PPARδ signaling axis, providing a therapeutic strategy to prevent the AHFF-induced macrophage foaming and inflammation., Competing Interests: The authors declare that they have no competing interests., (© 2023 The Author(s).)
- Published
- 2023
- Full Text
- View/download PDF
109. MAP kinase phosphatase DUSP1 is overexpressed in obese humans and modulated by physical exercise.
- Author
-
Khadir A, Tiss A, Abubaker J, Abu-Farha M, Al-Khairi I, Cherian P, John J, Kavalakatt S, Warsame S, Al-Madhoun A, Al-Ghimlas F, Elkum N, Behbehani K, Dermime S, and Dehbi M
- Subjects
- Adiposity genetics, Adult, Cohort Studies, Dual Specificity Phosphatase 1 metabolism, Female, Gene Expression Regulation, Enzymologic, Humans, Male, Middle Aged, Obesity metabolism, Thinness genetics, Thinness metabolism, Up-Regulation genetics, Dual Specificity Phosphatase 1 genetics, Exercise physiology, Obesity genetics
- Abstract
Chronic low-grade inflammation and dysregulation of the stress defense system are cardinal features of obesity, a major risk factor for the development of insulin resistance and diabetes. Dual-specificity protein phosphatase 1 (DUSP1), known also as MAP kinase phosphatase 1 (MKP1), is implicated in metabolism and energy expenditure. Mice lacking DUSP1 are resistant to high-fat diet-induced obesity. However, the expression of DUSP1 has not been investigated in human obesity. In the current study, we compared the expression pattern of DUSP1 between lean and obese nondiabetic human subjects using subcutaneous adipose tissue (SAT) and peripheral blood mononuclear cells (PBMCs). The levels of DUSP1 mRNA and protein were significantly increased in obese subjects with concomitant decrease in the phosphorylation of p38 MAPK (p-p38 MAPK) and PGC-1α and an increase in the levels of phospho-JNK (p-JNK) and phospho-ERK (p-ERK). Moreover, obese subjects had higher levels of circulating DUSP1 protein that correlated positively with various obesity indicators, triglycerides, glucagon, insulin, leptin, and PAI-1 (P < 0.05) but negatively with V̇O(2max) and high-density lipoprotein (P < 0.05). The observation that DUSP1 was overexpressed in obese subjects prompted us to investigate whether physical exercise could reduce its expression. In this study, we report for the first time that physical exercise significantly attenuated the expression of DUSP1 in both the SAT and PBMCs, with a parallel increase in the expression of PGC-1α and a reduction in the levels of p-JNK and p-ERK along with attenuated inflammatory response. Collectively, our data suggest that DUSP1 upregulation is strongly linked to adiposity and that physical exercise modulates its expression. This gives further evidence that exercise might be useful as a strategy for managing obesity and preventing its associated complications., (Copyright © 2015 the American Physiological Society.)
- Published
- 2015
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.