Circulating Isthmin-1 Levels and Their Relationship with Diabetes and Metabolic Diseases in Kuwaiti Adults.

Obesity and type 2 diabetes (T2D) are associated with significant alterations in various metabolic biomarkers. Isthmin-1 (Ism1) has recently emerged as a potential marker of metabolic health and was shown in animal studies to associate with metabolic-associated fatty liver disease (MAFLD). In this study, we aimed to investigate the circulatory levels of Ism1 in individuals with obesity compared to non-obese individuals and evaluate their association with insulin resistance, MAFLD, and T2D.

Genetic insights into MIS-C Post-COVID-19 in Kuwaiti children: investigating monogenic factors.

Background: Multisystem inflammatory syndrome in children (MIS-C) is a severe complication arising from SARS-CoV-2 infection, with indications that rare inborn errors of immunity may play a role in its pathogenesis. Recent studies suggest that genetic predispositions, particularly monogenic forms, could significantly influence the immune responses to SARS-CoV-2 in MIS-C.

Methods: We analysed 24 children under 12 years old, all of whom met the criteria provided by the World Health Organization, 2020 for MIS-C diagnosis, from the Paediatric COVID-19 Registry in Kuwait (PCR-Q8).

Complex p53 dynamics regulated by miR-125b in cellular responses to reactive oxidative stress and DNA damage.

In response to distinct cellular stresses, the p53 exhibits distinct dynamics. These p53 dynamics subsequently control cell fate. However, different stresses can generate the same p53 dynamics with different cell fate outcomes, suggesting that the integration of dynamic information from other pathways is important for cell fate regulation.

Targeting mTOR Kinase with Natural Compounds: Potent ATP-Competitive Inhibition Through Enhanced Binding Mechanisms.

: The mammalian target of the rapamycin (mTOR) signaling pathway is a central regulator of cell growth, proliferation, metabolism, and survival. Dysregulation of mTOR signaling contributes to many human diseases, including cancer, diabetes, and obesity. Therefore, inhibitors against mTOR's catalytic kinase domain (KD) have been developed and have shown significant antitumor activities, making it a promising therapeutic target.

Association of mitochondrial haplogroup H with reduced risk of type 2 Diabetes among Gulf Region Arabs.

Background: Numerous studies have linked mitochondrial dysfunction to the development of type 2 diabetes (T2D) by affecting glucose-stimulated insulin secretion in pancreatic beta cells and reducing oxidative phosphorylation in insulin-responsive tissues. Given the strong genetic underpinnings of T2D, research has explored the connection between mitochondrial DNA haplogroups, specific variants, and the risk and comorbidities of T2D. For example, haplogroups F, D, M9, and N9a have been linked to an elevated risk of T2D across various populations.

Adipocyte Angptl8 deletion improves glucose and energy metabolism and obesity associated inflammation in mice.

Angiopoietin-like protein 8 (Angptl8), expressed in the liver and adipocytes, forms a complex with Angptl3 or Angptl4, which regulates lipoprotein lipase and triglyceride metabolism. However, the precise functions of adipocyte Angptl8 remain elusive. Here we report that adipocyte-specific inducible Angptl8-knockout (AT-A8-KO) male mice on normal diet showed minor phenotypic changes, but after a high-fat high fructose (HFHF) diet, exhibited decreased body weight gain and glycemia, elevated rectal temperature and early dark phase energy expenditure compared to the Cre controls.

Impact of Extreme Heat on Cardiovascular Health in Kuwait: Present and Future Projections.

Background: The Middle East, especially Kuwait, is experiencing rapidly rising temperatures due to climate change. Cardiovascular diseases (CVD) are the leading cause of mortality in the country, and extreme heat is expected to exacerbate hospitalizations for cardiovascular diseases. There is limited data quantifying the historical and future impacts of heat on hospitalizations for cardiovascular diseases in Kuwait.

Circulating hsa-miR-320a and its regulatory network in type 1 diabetes mellitus.

Introduction: Increasing evidence from human and animal model studies indicates the significant role of microRNAs (miRNAs) in pancreatic beta cell function, insulin signaling, immune responses, and pathogenesis of type 1 diabetes (T1D).

Methods: We aimed, using next-generation sequencing, to screen miRNAs from peripheral blood mononuclear cells of eight independent Kuwaiti-Arab families with T1D affected siblings, consisting of 18 T1D patients and 18 unaffected members, characterized by no parent-to-child inheritance pattern.

Results: Our analysis revealed 20 miRNAs that are differentially expressed in T1D patients compared with healthy controls.

allele frequencies and implications for pharmacogenetics in the Kuwaiti population.

Unlabelled: This study explores the frequency of human leukocyte antigen (HLA) genes, particularly alleles, within the Kuwaiti population. We aim to identify alleles with known associations to adverse drug reactions (ADRs) based on existing literature. We focus on the gene due to its well-documented associations with severe cutaneous adverse reactions and the extensive pharmacogenetic research supporting its clinical relevance.

IL-6R (trans-signaling) is a key regulator of reverse cholesterol transport in lipid-laden macrophages.

Atherosclerosis is a cardiovascular disease caused by cholesterol-laden arterial plaques. This study evaluated the correlation between interleukin-6 (IL-6), its receptors (IL6R/CD126), and glycoprotein 130 (gp130) alongside atherosclerosis biomarkers in a cohort of 142 subjects, equally divided between lean and obese individuals. Subsequent analyses used THP-1-derived macrophages to assess the biochemical impact of inhibiting IL-6 receptors.

Aryl hydrocarbon receptor: current perspectives on key signaling partners and immunoregulatory role in inflammatory diseases.

The aryl hydrocarbon receptor (AhR) is a versatile environmental sensor and transcription factor found throughout the body, responding to a wide range of small molecules originating from the environment, our diets, host microbiomes, and internal metabolic processes. Increasing evidence highlights AhR's role as a critical regulator of numerous biological functions, such as cellular differentiation, immune response, metabolism, and even tumor formation. Typically located in the cytoplasm, AhR moves to the nucleus upon activation by an agonist where it partners with either the aryl hydrocarbon receptor nuclear translocator (ARNT) or hypoxia-inducible factor 1β (HIF-1β).

Combined impact of heat and dust on diabetes hospitalization in Kuwait.

Introduction: In Kuwait, a severe diabetes and obesity epidemic coexists with intense dust storms and harsh summer heat. While, theoretically, this interplay between dust, heat, and diabetes presents a serious public health problem, the empirical understanding of the actual risks remains limited. We hypothesized that increased exposure to heat and dust, independently and jointly, exacerbates the risk of hospitalization for diabetes patients.

Soybean oil-based HFD induces gut dysbiosis that leads to steatosis, hepatic inflammation and insulin resistance in mice.

High-fat diets (HFDs) shape the gut microbiome and promote obesity, inflammation, and liver steatosis. Fish and soybean are part of a healthy diet; however, the impact of these fats, in the absence of sucrose, on gut microbial dysbiosis and its association with liver steatosis remains unclear. Here, we investigated the effect of sucrose-free soybean oil-and fish oil-based high fat diets (HFDs) (SF-Soy-HFD and SF-Fish-HFD, respectively) on gut dysbiosis, obesity, steatosis, hepatic inflammation, and insulin resistance.

IL-1β-Induced CXCL10 Expression in THP-1 Monocytic Cells Involves the JNK/c-Jun and NF-κB-Mediated Signaling.

CXCL10 (IP-10) plays a key role in leukocyte homing to the inflamed tissues and its increased levels are associated with the pathophysiology of various inflammatory diseases including obesity and type 2 diabetes. IL-1β is a key proinflammatory cytokine that is found upregulated in meta-inflammatory conditions and acts as a potent activator, inducing the expression of cytokines/chemokines by immune cells. However, it is unclear whether IL-1β induces the expression of CXCL10 in monocytic cells.

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.

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.

PPARdelta: A key modulator in the pathogenesis of diabetes mellitus and co-morbidity.

The interplay between lipid metabolism and immune response in macrophages plays a pivotal role in various infectious diseases, notably tuberculosis (TB). Herein, we illuminate the modulatory effect of heat-killed (HKMT) on macrophage lipid metabolism and its implications on the inflammatory cascade. Our findings demonstrate that HKMT potently activates the lipid scavenger receptor, CD36, instigating lipid accumulation.

Dysregulated Urinary Extracellular Vesicle Small RNAs in Diabetic Nephropathy: Implications for Diagnosis and Therapy.

Background: Diabetic nephropathy (DN) represents a major chronic kidney disorder and a leading cause of end-stage renal disease (ESRD). Small RNAs have been showing great promise as diagnostic markers as well as drug targets. Identifying dysregulated micro RNAs (miRNAs) could help in identifying disease biomarkers and investigation of downstream interactions, shedding light on the molecular pathophysiology of DN.

Gut Dysbiosis Shaped by Cocoa Butter-Based Sucrose-Free HFD Leads to Steatohepatitis, and Insulin Resistance in Mice.

Background: High-fat diets cause gut dysbiosis and promote triglyceride accumulation, obesity, gut permeability changes, inflammation, and insulin resistance. Both cocoa butter and fish oil are considered to be a part of healthy diets. However, their differential effects on gut microbiome perturbations in mice fed high concentrations of these fats, in the absence of sucrose, remains to be elucidated.

TNF-α/Stearate Induced H3K9/18 Histone Acetylation Amplifies IL-6 Expression in 3T3-L1 Mouse Adipocytes.

Extensive evidence supports the connection between obesity-induced inflammation and the heightened expression of IL-6 adipose tissues. However, the mechanism underlying the IL-6 exacerbation in the adipose tissue remains unclear. There is general agreement that TNF-α and stearate concentrations are mildly elevated in adipose tissue in the state of obesity.