Prevalence Of Metabolic Disorders Research Articles

Phytochemical compounds for treating hyperuricemia associated with gout: a systematic review.

Gout is a prevalent metabolic disorder characterized by increased uric acid (UA) synthesis or decreased UA clearance from the bloodstream, leading to the formation of urate crystals in joints and surrounding tissues. Hyperuricemia (HUA), the underlying cause of gout, poses a growing challenge for healthcare systems in developed and developing countries. Currently, the most common therapeutic approaches for gouty HUA primarily involve the use of allopathic or modern medicine. However, these treatments are often accompanied by adverse effects and may not be universally effective for all patients. Therefore, this systematic review aims to provide a comprehensive outline of phytochemical compounds that have emerged as alternative treatments for HUA associated with gout and to examine their specific mechanisms of action. A systematic search was conducted to identify phytochemicals that have previously been evaluated for their effectiveness in reducing HUA. From a review of > 800 published articles, 100 studies reporting on 50 phytochemicals associated with the management of HUA and gout were selected for analysis. Experimental models were used to investigate the effects of these phytochemicals, many of which exhibited multiple mechanisms beneficial for managing HUA. This review offers valuable insights for identifying and developing novel compounds that are safer and more effective for treating HUA associated with gout.

Evaluation of Buffalo Health and Prevalence of Metabolic Disorders in Pulivendula: A Urine Analysis Approach

Aim: The study aims to evaluate the health status of buffaloes in selected villages of Pulivendula, detect potential metabolic disorders, and assess the prevalence of common health issues using urine analysis via the dipstick method. Objectives: The main aim of this study is to identify abnormalities, correlates the findings with nutrition and health data and emphasizes student participation in community-based animal health programs. Materials and Methods: A total of 25 buffaloes from five villages in the Pulivendula region were randomly checked as part of the study. The dipstick method was chosen for urine sample collection and analysis because of its ease of use, affordabilitys and speedy findings. Tests were conducted on parameters including Blood, Bilirubin, Nitrite, Leucocytes, Sp. Gravity Glucose, Protein, pH, Urea, RBC and Ketones. Students also completed surveys that yielded information about the diet, living circumstances, and overall health of the buffaloes. Results and Discussion: The investigation found that a less number of buffaloes had aberrant urine parameters, indicating subclinical illnesses. Proteinuria and ketonuria were more common in buffaloes from settlements with limited access to quality feed and water. The study results revealed a link between dietary behaviours and observed urine abnormalities, highlighting the need for better nutritional management and health monitoring in these locations. This study highlights the importance of the dipstick method in routine veterinary health checks, as well as the need for focused interventions to improve buffalo health and productivity in the Pulivendula region.

Diabetes Mellitus: Exploring Biomarkers, Complications, and Therapeutic Strategies with a Spotlight on Cyanobacterial Bioactive Compounds - A Comprehensive Review.

Diabetes, regarded as a prevalent metabolic disorder with multifactorial origins, contributes to a myriad of global complications. These cumulate an elevated susceptibility to kidney failure, nerve impairment, blindness, atherosclerosis, heart ailments, and even strokes. Recent investigations underscore the diverse roles of associated biomarkers in diabetes progression. Among these are biomarkers for diabetes mellitus such as DPP-4, PPAR-ϒ, SGLT-2, α-amylase, and α-glucosidase, which are linked to the onset of diabetes and its related problems. As a result of undesirable adverse consequences linked to extant synthetic antidiabetic medications, research attention is increasingly directed towards formulating natural antidiabetic drugs, aiming for enhanced efficacy and reduced complications. Cyanobacteria stand out as a pivotal repository of natural bioactive metabolites extensively harnessed for pharmaceutical and nutraceutical development. The potent bioactive compounds sourced from cyanobacteria hold substantial promise, kindling high expectations in scientific research and presenting vast prospects for drug discovery and advancement. Some of these bioactive compounds have demonstrated impressive effectiveness, displaying successful applications across various phases of clinical trials. This review strives to provide a more precise understanding of diabetes mellitus, encompassing its clinical manifestation, epidemiological data, complications, and prevailing treatment modalities. The objective of this review is to contribute researchers and readers an enhanced and accurate understanding of diabetes mellitus by covering its clinical manifestation, epidemiological evidence, difficulties, and prevailing therapeutics possibilities.

Modulation of Serum Metabolic Profiles by Bifidobacterium breve BBr60 in Obesity: A Randomized Controlled Trial.

Obesity, a prevalent metabolic disorder in youth, leads to complications and economic strain. Gut dysbiosis significantly contributes to obesity and metabolic issues. Bifidobacterium breve, a probiotic strain, may help regulate gut dysbiosis and benefit obese individuals. However, more research is needed on its effect on serum metabolism. A total of 75 overweight or obese young adults (aged 19-45) participated in the current study, and were randomly divided into probiotic and placebo groups using a random number table. Both groups received dietary guidance and underwent twelve weeks of intervention with either oral Bifidobacterium breve BBr60 (BBr60) or a placebo. After the intervention, collection and analysis of fasting serum samples were conducted using mass spectrometry coupled with liquid chromatography. Analyses of associations were conducted in order to determine the correlations between key serum metabolites and clinical obesity indicators, aiming to understand the influence of BBr60. Due to 10 participants dropping out for personal reasons, the study included 32 and 33 participants in the placebo and the BBr60 groups, respectively. The BBr60 intervention significantly regulated 134 serum metabolites and influenced crucial metabolic pathways in obesity management (p < 0.05), including ascorbate and aldarate metabolism for oxidative stress reduction, cholesterol metabolism for lipid regulation, parathyroid hormone synthesis, secretion and action for the endocrine system, oxidative phosphorylation for enhanced energy efficiency, and glycolysis/gluconeogenesis for glucose metabolism. Analysis showed a positive relationship between fasting blood glucose (FBG), aspartate aminotransferase (AST), total protein (TP), and the content of 5-Methyl DL-glutamate (p < 0.05). Similarly, body mass index (BMI), weight, and body fat percentage (BFP) were positively linked to serum metabolites (1-Hydroxycyclohexyl) acetic acid, and 5-Oxooctanoic acid (p < 0.05). Significant associations of AST levels with key serum metabolites in cholesterol metabolism pathways further suggest BBr60's potential to improve liver function and overall metabolic health in overweight or obese individuals. These findings support BBr60's effectiveness in modulating serum metabolic profiles and suggest it may improve liver function and BMI in overweight or obese individuals by regulating key serum metabolites.

Epidemiology and long-term effects of gestational diabetes mellitus

Background: Gestational diabetes mellitus (GDM) is a prevalent metabolic disorder affecting 2.4%-22.3% of pregnancies, with notable regional variation. While most women with GDM return to normal glucose tolerance in the postpartum period, they remain at an increased risk of subsequent metabolic complications, such as type 2 diabetes mellitus, hypertension, and cardiovascular disease.Current Concept: The prevalence of GDM has been increasing globally, including in Korea. Women diagnosed with GDM have an elevated risk of adverse outcomes during pregnancy, such as hypertensive disorders, cesarean sections, and fetal macrosomia. Additionally, GDM increases the long-term risks for type 2 diabetes mellitus, cardiovascular disease, and potentially liver disorders. The growing prevalence of GDM highlights the need for comprehensive surveillance and targeted interventions. Understanding the risk factors, such as lifestyle, ethnicity, maternal age, and pre-pregnancy obesity, is crucial to develop effective prevention and management strategies.Discussion and Conclusion: Addressing the rising GDM trends requires public health efforts to monitor prevalence and mitigate risk factors through lifestyle modifications, early detection, and careful follow-up. Women with a history of GDM are at high risk for cardiometabolic diseases, necessitating proactive postpartum management including regular glucose monitoring and cardiovascular assessments. Establishing tailored preventive strategies and ensuring long-term follow-up for affected women may help reduce the burden of GDM and its associated complications, ultimately improving maternal health and quality of life.

Adiponectin may play a crucial role in the metabolic effects of GLP-1RAs treatment in patients with Type 2 Diabetes Mellitus: a preliminary longitudinal study.

Type 2 diabetes mellitus (T2DM) stands as the most prevalent metabolic disorder globally. T2DM entails numerous cardiovascular complications, which contribute significantly to morbidity, mortality, and increased public spending worldwide. The real challenge for new diabetes drugs lies not only in reducing blood glucose levels and glycated hemoglobin but also in preventing cardiovascular risk. Emerging receptor agonists for glucagon-like peptide-1 (GLP-1RAs) have demonstrated a pivotal role in diabetes management and mitigating cardiovascular risk. We conducted a 12-month longitudinal investigation evaluating the cardio-metabolic effects of GLP-1RAs on a cohort of 65 Caucasian patients diagnosed with T2DM who were scheduled for treatment with GLP-1RAs. Fifty-four T2DM patients successfully completed the 12-month study period, with 30 receiving dulaglutide and 24 receiving semaglutide. In our study population, GLP-1RAs resulted in several positive changes beyond the observed weight loss: a shift in fat distribution, indicated by a reduction in the percentage of visceral fat (1.21 vs. 1.17, p < 0.05); a significant decrease in LDL cholesterol levels (p < 0.05) and triglycerides (p < 0.01); and a significant increase in serum adiponectin levels (p < 0.05), potentially indicating a reduction in insulin resistance and inflammation. Additionally, we observed a significant decrease in microalbuminuria and media-intimal thickness at the carotid vessel level (p < 0.05). In patients with T2DM 1-year therapy with GLP-1RAs has a positive effect on the main determinants of cardiovascular risk including body weight, visceral fat, dyslipidemia, and atherosclerosis. Moreover, the increase in adiponectin may play a pivotal role in controlling the inflammatory state and the mechanisms of vascular damage.

Incredible Indolinedione Derivatives Nucleus in the Development of Anti‐Diabetic Drugs: Exploring the Mechanistic Studies, Design, and Structure‐Activity Relationship

AbstractDiabetes mellitus, a prevalent metabolic disorder, necessitates continuous exploration for innovative therapeutic agents. Indolinedione has garnered attention for its potential as an antidiabetic scaffold for its structurally diverse nucleus. The search for novel and effective antidiabetic agents has led to the exploration of natural compounds and synthetic derivatives. The review commences with an in‐depth exploration of the biochemical underpinnings of diabetes mellitus, emphasizing rational design strategies employed for modifying the indolinedione nucleus, encompassing various synthetic methodologies aimed at enhancing its pharmacological properties and docking studies. The multifaceted pharmacological properties and diverse synthetic derivatives of indolinedione offer a fertile ground for further exploration in preclinical and clinical studies. As research in this field progresses, indolinedione may emerge as a valuable addition to the arsenal of antidiabetic therapeutics, providing new avenues for the effective management of diabetes mellitus.

ANGPTL3 as a target for treating lipid disorders in type 2 diabetes patients

Type 2 diabetes mellitus (T2DM) is a globally prevalent metabolic disorder, and cardiovascular disease (CVD) is a significant cause of mortality and morbidity in diabetic individuals. In addition to hyperglycemia, lipid abnormalities associated with T2DM play a crucial role in the development of CVD complications. Diabetic dyslipidemia is characterized by elevated levels of triglyceride (TG)-rich lipoproteins and small dense low-density lipoprotein (LDL) particles, reduced high-density lipoprotein (HDL) cholesterol, and impaired HDL function. Angiopoietin protein-like 3 (ANGPTL3) is a liver-derived protein that plays a crucial role in regulating plasma lipoprotein metabolism by inhibiting lipoprotein lipase and influencing lipid levels. Inhibiting ANGPTL3 has shown promising effects in promoting HDL-mediated cholesterol reverse transport and reducing the levels of TG-rich lipoproteins and LDL cholesterol. Here, we explore the potential of ANGPTL3 as a therapeutic target for lipid management in T2DM patients.

New Insights on the potential therapeutic effects of glibenclamide and Obeticholic acid against Alloxan-Induced diabetes mellitus in rat model

Diabetes mellitus (DM) represents a highly prevalent metabolic disorder across the globe. This study aimed to determine the ameliorative efficacy of glibenclamide (Gli) and obeticholic acid (OCA) against biochemical and pathological changes related to alloxan-induced diabetes. Twenty male Wistar rats were allocated into four groups; Control group, Diabetic group: received intraperitoneal injection of alloxan (120 mg/kg) for induction of diabetes, Diabetic + Gli group: Diabetic rats treated daily with oral Gli (5 mg/kg) and Diabetic + OCA group: Diabetic rats treated daily with oral OCA (10 mg/kg). All rats were subjected to 30 days treatments. Our results indicated that Gli successfully ameliorated hyperglycemia and dyslipidemia with a significant decline in serum pancreatic lipase activity and increased insulin level, while OCA had the same effect but without any enhancement in serum insulin levels. Additionally, the disturbances in liver function-related parameters and the evoked oxidative stress, interleukin(IL)-6 and IL-10 in the liver and pancreas were abrogated upon treatment with Gli and OCA. Furthermore, Gli and OCA increased AMP-activated protein kinase (P-AMPK), insulin receptor substrate 1 (IRS1), farnesoid X receptor (FXR), and glucagon-like peptide-1 receptor (GLP-1R) expressions and downregulated sterol regulatory element binding protein-1c mRNA expression. Besides, Gli and OCA have alleviated diabetes-induced histopathological distortions in hepatic and pancreatic tissues and enhanced the immunoexpression of insulin, and proliferating cell nuclear antigen with decreased immune reactivity of glucagon within pancreatic tissues. Gli and OCA decreased the immune reactivity of nuclear factor kappa B and increased the glycogen content of hepatic tissues. In conclusion, OCA is efficacious in the management of dyslipidemia and hyperglycemia of DM and its related oxidative stress.

The relationship between coronary flow reserve and the TyG index in patients with gestational diabetes mellitus

Abstract Gestational diabetes mellitus (GDM) is a prevalent metabolic disorder characterized by glucose intolerance during pregnancy. The triglyceride glucose (TyG) index, a marker of insulin resistance, and coronary flow reserve (CFR), a measure of coronary microvascular function, are emerging as potential indicators of cardiovascular risk. This study aims to investigate the association between CFR and the TyG index in GDM patients. This cross-sectional study of 87 GDM patients and 36 healthy controls was conducted. The participants underwent clinical assessments, blood tests, and echocardiographic evaluations. The TyG index was calculated as ln(triglycerides × fasting glucose/2). CFR was measured using Doppler echocardiography during rest and hyperemia induced by dipyridamole. The study included 87 individuals in the GDM group and 36 individuals in the control group. There was no significant difference in age between the two groups (34.1 ± 5.3 years for GDM vs. 33.1 ± 4.9 years for the control, p = 0.364). The TyG index was significantly higher in the GDM group compared to the controls (p &amp;lt; 0.001) and CFR was lower in the GDM group (p &amp;lt; 0.001) as shown in Figure 1a and 1b. A negative and significant correlation between the TyG index and CFR was observed, which was demonstrated in Figure 2 (r = −0.624, p &amp;lt; 0.001). Linear regression revealed the TyG index as an independent predictor of reduced CFR. The study findings reveal a significant association between the TyG index and CFR in GDM patients, suggesting their potential role in assessing cardiovascular risk.TyG index and CFR of the groupsTyG and CFR correlation analysis

Tirzepatide, GIP(1-42) and GIP(1-30) display unique signaling profiles at two common GIP receptor variants, E354 and Q354.

Type 2 diabetes (T2D) and obesity are prevalent metabolic disorders affecting millions of individuals worldwide. A new effective therapeutic drug called tirzepatide for the treatment of obesity and T2D is a dual agonist of the GIP receptor and GLP-1 receptor. Tirzepatide is clinically more effective than GLP-1 receptor agonists but the reasons why are not well understood. Tirzepatide reportedly stimulates the GIP receptor more potently than the GLP-1 receptor. However, tirzepatide signaling has not been thoroughly investigated at the E354 (wildtype) or Q354 (E354Q) GIP receptor variants. The E354Q variant is associated increased risk of T2D and lower body mass index. To better understand GIP receptor signaling we characterized the activity of endogenous agonists and tirzepatide at both GIP receptor variants. Using Cos7 cells we examined wildtype and E354Q GIP receptor signaling, analyzing cAMP and IP1 accumulation as well as AKT, ERK1/2 and CREB phosphorylation. GIP(1-42) and GIP(1-30)NH2 displayed equipotent effects on these pathways excluding CREB phosphorylation where GIP(1-30)NH2 was more potent than GIP(1-42) at the E354Q GIP receptor. Tirzepatide favored cAMP signaling at both variants. These findings indicate that tirzepatide is a biased agonist towards Gαs signaling and suggests it equally activates the wildtype and E354Q GIP receptor variants. We also observed differences between the pharmacology of the GIP receptor variants with endogenous peptides, which may help to explain differences in phenotype. These findings contribute to a comprehensive understanding of GIP receptor signaling, and will aid development of therapies combating T2D and obesity.

Network Pharmacology Revealing the Therapeutic Potential of Bioactive Components of Triphala and Their Molecular Mechanisms against Obesity.

Obesity, characterized by the excessive accumulation of fat, is a prevalent metabolic disorder that poses a significant global health concern. Triphala, an herbal combination consisting of Phyllanthus emblica Linn, Terminalia chebula Retz, and Terminalia bellerica (Gaertn) Roxb, has emerged as a potential solution for addressing concerns related to obesity. This study aimed to investigate the network pharmacology and molecular docking of Triphala to identify its bioactive ingredients and their interactions with pathways associated with obesity. The bioactive compounds present in Triphala and genes linked to obesity were identified, followed by an analysis of the protein-protein interaction networks. Enrichment analysis, including Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis, was conducted. Prominent genes and compounds were selected for further investigation through molecular docking studies. The study revealed a close correlation between obesity and the AKT1 and PPARG genes. The observed binding energy between beta-sitosterol, 7-dehydrosigmasterol, peraksine, α-amyrin, luteolin, quercetin, kaempferol, ellagic acid, and phyllanthin with AKT1 and PPARG indicated a favorable binding affinity. In conclusion, nine compounds showed promise in regulating these genes for obesity prevention and management. Further research is required to validate their specific effects.

Lactobacillus gasseri BNR17 and Limosilactobacillus fermentum ABF21069 Ameliorate High Sucrose-Induced Obesity and Fatty Liver via Exopolysaccharide Production and β-oxidation.

Obesity and metabolic dysfunction-associated fatty liver disease (MAFLD) are prevalent metabolic disorders with substantial global health implications that are often inadequately addressed by current treatments and may have side effects. Probiotics have emerged as promising therapeutic agents owing to their beneficial effects on gut health and metabolism. This study investigated the synergistic effects of a probiotic combination of BNR17 and ABF21069 on obesity and MAFLD in C57BL/6 mice fed a high-sucrose diet. The probiotic combination significantly reduced body weight and fat accumulation compared with the high-sucrose diet. It also alleviated elevated serum leptin levels induced by a high-sucrose diet. Histological analysis revealed a significant reduction in white adipose tissue and fatty liver in the mice treated with the probiotic combination. Furthermore, increased expression of genes related to β-oxidation, thermogenesis, and lipolysis suggested enhanced metabolic activity. The probiotic groups, particularly the BNR17 group, showed an increase in fecal exopolysaccharides, along with a tendency toward a lower expression of intestinal sugar transport genes, indicating reduced sugar absorption. Additionally, inflammatory markers in the liver tissue exhibited lower expression in the ABF21069 group than in the HSD group. Despite each strain in the combination group having distinct characteristics and functions, their combined effect demonstrated synergy in mitigating obesity and MAFLD, likely through the modulation of fecal exopolysaccharides content and improvement in lipid metabolism. These findings underscore the potential of probiotic supplementation as a promising assistant therapy for managing obesity and MAFLD and provide valuable insights into its therapeutic mechanisms in metabolic disorders.

From millets to medicine: ADMET insights into diabetes management with P. sumatrense compounds

Diabetes mellitus, a prevalent metabolic disorder characterised by impaired blood glucose regulation, has escalated into a global health crisis, exacerbated by high-glycaemic diets and unhealthy eating habits. While therapeutic agents such as acarbose mitigate diabetes by inhibiting alpha-amylase and alpha-glucosidase, their use is marred by adverse side effects, underscoring the need for safer, plant-based alternatives. This study explores the antidiabetic potential of Little Millet, an underutilised cereal grain with a low glycaemic index, rich in bioactive compounds. Unlike common staples such as wheat and rice, Little Millet contains unique compounds, including octodrine, 18,19-secoyohimban-19-oic acid, and phenylephrine, which were investigated for their novel application in diabetes management. Gas chromatography-mass spectrometry (GCMS) analysis identified 120 bioactive compounds, selected for their abundance and potential bioactivity. These compounds span fatty acids, phenols, flavonoids, organic acids, sugar alcohols, and amino acids, all of which were rigorously docked to alpha-amylase and human maltase-glucoamylase receptors. Notably, key ligands such as chlorogenic acid and 18,19-secoyohimban-19-oic acid exhibited superior binding affinities compared to acarbose, with promising drug-likeness and ADMET profiles, suggesting higher absorption and fewer side effects. A 100-ns dynamics simulation further validated the stability of these compounds, positioning them as viable candidates for diabetes treatment. These findings advance drug design and highlight the potential of incorporating Little Millet into diets for diabetes prevention. Further validation through In-vitro, In-vivo, and clinical studies is essential to fully realise their therapeutic potential. This research also opens avenues for exploring Little Millet in managing related conditions and enhancing its health benefits through breeding programmes.

Glycated Hemoglobin as a Predictor of Dyslipidemia and Cardiovascular Risk in Type 2 Diabetes Mellitus

Background: Type 2 Diabetes Mellitus (T2DM) is a globally prevalent metabolic disorder that significantly increases the risk of cardiovascular disease (CVD) through mechanisms such as dyslipidemia, characterized by elevated triglycerides, low high-density lipoprotein (HDL) levels, and small dense low-density lipoprotein (LDL) particles. Glycated hemoglobin (HbA1c) is a key biomarker of glucose control and has been associated with CVD risk. Methods: This cross-sectional study aimed to evaluate the relationship between glycated hemoglobin (HbA1c) levels and lipid profiles, specifically lipid ratios, in a Jordanian population with type 2 diabetes mellitus (T2DM). A total of 140 patients with T2DM and 20 healthy controls participated. Blood samples were analyzed for fasting blood sugar (FBS), HbA1c, total cholesterol, triglycerides, high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C) levels. HbA1c levels were grouped: A (≤7%), B (7–9%), C (9–11%), and D (&gt;11%). Results: The T2DM group showed significantly elevated HbA1c levels compared to controls. Patients with higher HbA1c levels (Groups C and D) exhibited abnormal lipid profiles, including increased total cholesterol and triglycerides and reduced HDL-C. The LDL-C/HDL-C ratio was notably higher in patients with HbA1c &gt;9%, indicating a potential elevated cardiovascular risk. This correlation between HbA1c and lipid profile abnormalities supports the association between poor glycemic control and lipid metabolism dysregulation. Conclusion: HbA1c levels are significantly associated with dyslipidemia, and lipid ratios serve as sensitive indicators for cardiovascular risk in T2DM patients. These findings underscore the clinical importance of monitoring HbA1c and lipid ratios to improve risk assessment and guide intervention strategies in high-risk populations.

Macrophages and T cells in metabolic disorder-associated cancers.

Cancer and metabolic disorders have emerged as major global health challenges, reaching epidemic levels in recent decades. Often viewed as separate issues, metabolic disorders are shown by mounting evidence to heighten cancer risk and incidence. The intricacies underlying this connection are still being unraveled and encompass a complex interplay between metabolites, cancer cells and immune cells within the tumour microenvironment (TME). Here, we outline the interplay between metabolic and immune cell dysfunction in the context of three highly prevalent metabolic disorders, namely obesity; two associated liver diseases, metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH); and type 2 diabetes. We focus primarily on macrophages and T cells, the critical roles of whichin dictating inflammatory response and immune surveillance in metabolic disorder-associated cancers are widely reported. Moreover, considering the ever-increasing number of patients prescribed with metabolism disorder-altering drugs and dietsin recent years, we discuss how these therapies modulate systemic and local immune phenotypes, consequently impacting cancer malignancy. Collectively, unraveling the determinants of metabolic disorder-associated immune landscape and their role in fuelling cancer malignancy will provide a framework essential to therapeutically address these highly prevalent diseases.

Interplay among IL1R1, gut microbiota, and bile acids in metabolic dysfunction-associated steatotic liver disease: a comprehensive review.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent metabolic disorder characterized by hepatic steatosis associated with metabolic abnormalities. Recent research has shed light on the intricate interplay among interleukin-1 receptor 1 (IL1R1), gut microbiota, and bile acids in the pathogenesis of MASLD. This review aims to provide a comprehensive overview of the current understanding of the role of IL1R1, gut microbiota, and bile acids in MASLD, exploring their interrelationships and potential mechanisms. We summarize the evidence supporting the involvement of IL1R1 in inflammation, discuss the influence of gut microbiota on bile acid metabolism and its influence on liver health, and elucidate the bidirectional interactions among IL1R1 signaling, gut microbiota composition, and bile acid homeostasis in MASLD. Furthermore, we highlight emerging therapeutic strategies targeting these interrelated pathways for the management of MASLD.

Empowering probiotics with high xanthine transport for effective hyperuricemia management

ABSTRACT Hyperuricemia, a prevalent metabolic disorder, poses a susceptibility to various complications. The conventional pharmacotherapeutic approaches for hyperuricemia often entail notable adverse effects, posing substantial clinical challenges. Hence, the imperative lies in the development of novel, safe and effective strategies for preventing and treating hyperuricemia. Here, we developed a probiotic Escherichia coli Nissle 1917 strain, designated as YES301, which contains a rationally designed xanthine importer XanQ, enabling efficient uptake of xanthine and hypoxanthine, consequently leading to reduced serum uric acid concentrations and amelioration of renal impairments in a murine model of hyperuricemia. Importantly, YES301 exhibited a therapeutic efficacy comparable to allopurinol, a conventional uric acid-lowering agent, and manifesting fewer adverse effects and enhanced biosafety. These findings highlight the promising potential of engineered probiotics in the management of hyperuricemia through reducing intestinal purine levels.

Discovery of tetrahydro γ-carboline based novel glucose uptake agent for the treatment of diabetes and Alzheimer’s diseases

The emergence of diabetes mellitus (DM), one of the prevalent metabolic disorders, has increased at alarming rates around the globe in the past few decades. The early discovery of insulin paved the way for the broadened non-invasive anti-hyperglycemic drug therapies to manage and treat diabetes. Recently, insulin resistance in brain tissues has been considered a new hallmark of disease progression, leading to neurodegeneration. Tetrahydro γ-carbolines are privileged scaffolds with various activities against obesity, cancer, and central nervous system (CNS) diseases. The failure of Latrepirdine in clinical phase trials as anti-AD, prompted us to explore further the γ-Carboline derivatives with anti-diabetic activity. To address this, we have leveraged our expertise in drug design to develop tetrahydro γ-carboline derivatives and studied their effect on glucose uptake. All the compounds exhibited low cytotoxicity towards the mammalian cell line 3T3-L1. Next, we screened the 10 derivatives to identify the novel anti-diabetic activities using a fluorescent glucose analog 2-NBDG (2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl)-2-deoxy-D-glucose) based on a glucose-uptake assay in differentiated 3T3-L1 adipocytes. Compound 11a has significantly increased glucose uptake at 100 µM compared to rH-Insulin. The dose optimization (1 nM-100 nM) of lead compounds for 2-NBDG-glucose uptake clearly indicated that 11a is superior compared to Insulin. The 11a is the close analog of Latrepirdine, an anti-histamine drug, reported for Alzheimer disease (AD). Further, to understand its anti-AD potential we carried out in silico docking studies with its probable targets, Acetylcholinesterase (AChE), 5-hydroxytryptamine (5HT6) receptor, Butyrylcholinesterase (BChE), and N-methyl-D-aspartate (NMDA) receptor. The docking studies revealed that 11a had stronger binding to these targets than Latrepirdine, correlating with the glucose uptake assay. Thus, 11a is a potential lead disease-modifying agent and could be considered for the management and treatment of type 2 DM and AD.

MTOR gene variant rs2295080 might be a risk factor for atherosclerosis in Iranian women with type 2 diabetes mellitus

BackgroundType 2 diabetes mellitus, one of the most prevalent metabolic disorders worldwide, is closely linked with an enhanced risk of atherosclerosis. However, the molecular mechanism of this linkage is not still clear. Genetic variations in the mTOR gene may increase the susceptibility of individuals to these diseases.MethodsOne hundred nine diabetic patients and 375 healthy subjects participated in this study. mTOR Single Nucleotide Polymorphism (SNP) rs2295080 was determined using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP).ResultsComparison of genotypic, allelic, and genotypic combination frequencies between cases and controls revealed no significant result. Nevertheless, the frequency of rs2295080 GT + TT genotype was significantly more in diabetic women with atherosclerosis compared with those without atherosclerosis (p = 0.047). Besides, the rs2295080 G allele was more frequently detected in diabetic women without atherosclerosis compared to those with atherosclerosis (p = 0.046).ConclusionThe rs2295080 GT + TT genotype predisposes Iranian diabetic women to atherosclerosis, while the rs2295080 G allele protects them against atherosclerosis. However, additional experiments using larger sample sizes are needed to verify this result.