Diabetes Liver Research Articles

A predicted epithelial-to-mesenchymal transition-associated mRNA/miRNA axis contributes to the progression of diabetic liver disease.

Despite public health measures, type 2 diabetes (T2D) is still a significant concern worldwide, given its associated complications, including hepatic alterations. The role of epithelial-to-mesenchymal transition (EMT) in liver fibrosis is well established. However, its effects on the progression of diabetic liver diseases are not well understood. Therefore, this study aims to investigate the mRNA/miRNA axes involved in this process. Bioinformatic analysis revealed new EMT-associated genes (CDH2, ITGB1, COL4A1, COL1A1, TNC, CCN2, and JUN), which showed higher expression in obese T2D and hepatocellular carcinoma (HCC) patients. In addition, six miRNAs (miR-21-5p, miR-26a-5p, miR-34a-5p, miR-106a-5p, miR-320a-3p and miR-424-5p) have been found as potential targets. Among them, miR-26a-5p and miR-424-5p were significantly downregulated in nonalcoholic steatohepatitis (NASH) and HCC (p < 0.05), being considered potential negative regulators of the EMT process. In our hepatic mesenchymal culture model, miR-26a-5p negatively regulated cadherin 2 (also known as N-cadherin, CDH2) and promoted the cadherin 1 (also known as E-cadherin, CDH1) expression. Our results reveal potential molecules involved in liver tumor development. Moreover, we observe that miR-26a-5p impairs EMT in the initial stages of diabetic liver disease by inhibiting CDH2 and could be a valuable target in this pathology.

Increased risk of vascular complications in patients with type 2 diabetes and fatty liver disease

BackgroundThe prevalence of steatotic liver disease (SLD) in patients with type 2 diabetes (T2DM) exceeds 50%. This study aimed to investigate the clinical characteristics of SLD and liver fibrosis in Chinese patients with T2DM.MethodsInpatients from 2021 to 2023 were included in the study. Fatty liver index (FLI) and fibrosis-4 (FIB-4) were calculated to assess hepatic steatosis and fibrosis respectively. Statistical analysis was completed by SPSS v25 and GraphPad Prism v8.0.1.ResultsOf the 1466 participants, about one-third of the patients in T2DM-SLD group were diagnosed with liver fibrosis (LF), and the percentage of patients over 50 years old was 85.9%. Patients with SLD had higher levels of BMI, blood pressure, liver enzymes, fasting blood glucose (FBG), HbA1c, C-peptide, total cholesterol (TC) and triglyceride (TG) (P<0.05 for all). Patients with liver fibrosis had lower TC, TG, hemoglobin (Hb), erythrocyte count (RBC), leukocyte count (WBC) and platelet (PLT) levels (P<0.05 for all). Compared with simple T2DM and SLD-NLF (non-liver fibrosis) groups, for patients over 50 years old, the prevalence of coronary heart disease, stroke, tumor, and diabetic nephropathy was higher in patients with liver fibrosis. Liver fibrosis might be the risk factor of arterial stiffness, stroke, coronary heart disease and numbness based on multivariable logistic regression analysis.ConclusionHepatic steatosis and fibrosis were common in patients with T2DM. Liver fibrosis was relevant to many macrovascular and microvascular diabetic complications.

Primary Prevention Strategy for Non-Communicable Diseases (NCDs) and Their Risk Factors: The Role of Intestinal Microbiota

Non-communicable diseases (NCDs) are the leading cause of morbidity and mortality worldwide. These conditions have numerous health consequences and significantly impact patients’ lifestyles. Effective long-term treatment is essential since NCDs are irreversible. Therefore, primary healthcare must be both exclusive and of the highest quality, ensuring comprehensive care. The primary goal should be to improve quality of life with a focus on patients, families, and communities, as most of these diseases can be prevented and controlled, although not cured. Several factors have been linked to individual health, including social, cultural, and economic aspects, lifestyle, and certain environmental factors, including work, that can have positive or negative effects. More of these variables may contribute to the onset of NCDs, which are defined by their chronic nature, propensity for prolongation, and generally slow rate of progression. Examples of NCDs include hypertension, type 2 diabetes (T2D), dyslipidemia, and fatty liver disease linked to metabolic dysfunction. The onset of these diseases has been associated with an imbalance in certain microbial niches, such as the gut, which hosts billions of microorganisms performing multiple metabolic functions, such as the production of metabolites like bile acids (BAs), short-chain fatty acids (SCFAs), and trimethylamine N-oxide (TMAO). Therefore, lifestyle changes and personal habits can significantly impact the gut microbiota (GM), potentially preventing chronic diseases associated with metabolism. NCDs are highly prevalent worldwide, prompting increased attention to strategies for modifying the intestinal microbiota (IM). Approaches such as probiotics, prebiotics, synbiotics, and fecal transplantation (FMT) have demonstrated improvements in the quality of life for individuals with these conditions. Additionally, lifestyle changes and the adoption of healthy habits can significantly impact IM and may help prevent chronic diseases related to metabolism. Therefore, the main aim of this review is to analyze and understand the importance of microbiota intervention in the prevention of non-communicable diseases. R3:A1

Clinical care guidance in patients with diabetes and metabolic dysfunction-associated steatotic liver disease: A joint consensus.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide, affecting >30% of the global population. Metabolic dysregulation, particularly insulin resistance and its subsequent manifestation as type 2 diabetes mellitus, serves as the fundamental pathogenesis of metabolic liver disease. Clinical evidence of the recent nomenclature evolution is accumulating. The interaction and impacts are bidirectional between MASLD and diabetes in terms of disease course, risk, and prognosis. Therefore, there is an urgent need to highlight the multifaceted links between MASLD and diabetes for both hepatologists and diabetologists. The surveillance strategy, risk stratification of management, and current therapeutic achievements of metabolic liver disease remain the major pillars in a clinical care setting. Therefore, the Taiwan Association for the Study of the Liver (TASL), Taiwanese Association of Diabetes Educators, and Diabetes Association of the Republic of China (Taiwan) collaboratively completed the first guidance in patients with diabetes and MASLD, which provides practical recommendations for patient care.

Microplastics in the Human Body: Exposure, Detection, and Risk of Carcinogenesis: A State-of-the-Art Review.

Background: Humans cannot avoid plastic exposure due to its ubiquitous presence in the natural environment. The waste generated is poorly biodegradable and exists in the form of MPs, which can enter the human body primarily through the digestive tract, respiratory tract, or damaged skin and accumulate in various tissues by crossing biological membrane barriers. There is an increasing amount of research on the health effects of MPs. Most literature reports focus on the impact of plastics on the respiratory, digestive, reproductive, hormonal, nervous, and immune systems, as well as the metabolic effects of MPs accumulation leading to epidemics of obesity, diabetes, hypertension, and non-alcoholic fatty liver disease. MPs, as xenobiotics, undergo ADMET processes in the body, i.e., absorption, distribution, metabolism, and excretion, which are not fully understood. Of particular concern are the carcinogenic chemicals added to plastics during manufacturing or adsorbed from the environment, such as chlorinated paraffins, phthalates, phenols, and bisphenols, which can be released when absorbed by the body. The continuous increase in NMP exposure has accelerated during the SARS-CoV-2 pandemic when there was a need to use single-use plastic products in daily life. Therefore, there is an urgent need to diagnose problems related to the health effects of MP exposure and detection. Methods: We collected eligible publications mainly from PubMed published between 2017 and 2024. Results: In this review, we summarize the current knowledge on potential sources and routes of exposure, translocation pathways, identification methods, and carcinogenic potential confirmed by in vitro and in vivo studies. Additionally, we discuss the limitations of studies such as contamination during sample preparation and instrumental limitations constraints affecting imaging quality and MPs detection sensitivity. Conclusions: The assessment of MP content in samples should be performed according to the appropriate procedure and analytical technique to ensure Quality and Control (QA/QC). It was confirmed that MPs can be absorbed and accumulated in distant tissues, leading to an inflammatory response and initiation of signaling pathways responsible for malignant transformation.

Inhibition of ketohexokinase prevents fructose-induced insulin resistance and endothelial dysfunction in high fat and sucrose-fed mice via enhancing energy expenditure

Abstract Introduction Cardiovascular disease linked to fatty liver poses a significant threat to health. Consumption of high-fat diets (HFD) is known to trigger a cascade of health issues including obesity, diabetes and non-alcoholic fatty liver disease (NAFLD). These conditions are exacerbated, with the addition of dietary sugar to high-fat diets (HFSD), resulting in non-alcoholic steatohepatitis (NASH). Studies have shown that fructokinase (ketohexokinase or KHK) knockdown protects mice from HFSD-induced NASH. Purpose This study focused on examining the temporal changes of metabolic perturbations, triggered by sugar consumption, particularly in the transition from fatty liver to cardiovascular disease. Methods C57/BL6 wild type (WT) and KHK-knockout mice were fed with HFD or HFSD for different durations between 6 to 20 weeks, to induce NAFLD and NASH. Western blotting and quantitative-PCR were carried out on tissues and isolated endothelial cells for protein and mRNA expressions, respectively. Glucose and insulin tolerance tests and whole-body energy measurements were performed at different time-points. Combined Laboratory Animal Monitoring System was used to monitor various parameters of energy expenditure. Functional interactions between endothelial cells and adipose tissues were carried out using an in-house Organ-On-a-chip technology. Endothelial function was studied by measuring isometric tensions in organ bath. Results KHK-deficient mice had significantly lower weight compared to WT littermates. Wild-type mice fed HFD and HFSD exhibited significant glucose intolerance, insulin resistance, and endothelial dysfunction compared to KHK-knockout mice. However, HFSD led to more severe outcomes compared to HFD, demonstrating differing temporal effects on glucose intolerance and insulin resistance. Interestingly, KHK-knockout mice were significantly protected from the effects induced by HFSD, as well as, such as increased body weight, fasting hyperglycemia, hyperinsulinemia and endothelial function. KHK-knockout mice exhibited significant increase in oxygen consumption and energy expenditure, both in HFD and HFSD-fed conditions. These data suggest that high energy-expenditure is one of the primary mechanisms, in reducing adiposity and body weight in HFSD-fed knockout mice. Notably, KHK-deficient mice were protected against sugar-induced fat accumulation, random hyperinsulinemia and significant impairment of endothelial function. Conclusions A novel finding in this study is that KHK ablation protects not only against HFSD-induced, but also HFD-induced pathologies via significantly enhancing energy expenditure. The results suggest that targeting KHK could potentially mitigate the development of fatty liver and cardiovascular diseases, induced by high calorie diets.

Use of cholesterol-lowering medications in relation to risk of primary liver cancer in the Clinical Practice Research Datalink.

Although the relation between statin use and liver cancer risk has been extensively examined, few studies have examined other cholesterol-lowering medications in relation to liver cancer risk. The authors examined five classes of nonstatin medications and liver cancer risk. A nested case-control including 3719 cases and 14,876 matched controls was conducted within the Clinical Practice Research Datalink. Additional matches on type 2 diabetes and chronic liver disease were also implemented. The medications examined included cholesterol absorption inhibitors, bile acid sequestrants, fibrates, niacin, and omega-3 fatty acids. Conditional logistic regression estimated odds ratios and 95% confidence intervals. Cholesterol absorption inhibitor use was associated with reduced liver cancer risk in the overall analysis (odds ratio, 0.69; 95% confidence interval, 0.50-0.96) and in analyses based on type 2 diabetes and chronic liver disease status. Although bile acid sequestrant use was associated with increased liver cancer risk in the overall analysis (odds ratio, 5.31; 95% confidence interval, 3.53-7.97), the results of the analyses based on type 2 diabetes and chronic liver disease status were inconsistent. [Correction added on 19 August 2024, after first online publication: In the preceding sentence, the value '3.534' has been changed to '3.54'.]. No associations were observed for the other medications. Cholesterol absorption inhibitors may be associated with reduced liver cancer risk. Whether bile acid sequestrant use was associated with increased risk was only partially supported in the current study.

Entamoeba muris mitigates metabolic consequences of high-fat diet in mice

ABSTRACT Metabolic syndrome (MetS) is a cluster of several human conditions including abdominal obesity, hypertension, dyslipidemia, and hyperglycemia, all of which are risk factors of type 2 diabetes, cardiovascular disease, and metabolic dysfunction-associated steatotic liver disease (MASLD). Dietary pattern is a well-recognized MetS risk factor, but additional changes related to the modern Western life-style may also contribute to MetS. Here we hypothesize that the disappearance of amoebas in the gut plays a role in the emergence of MetS in association with dietary changes. Four groups of C57B/6J mice fed with a high-fat diet (HFD) or a normal diet (ND) were colonized or not with Entamoeba muris, a commensal amoeba. Seventy days after inoculation, cecal microbiota, and bile acid compositions were analyzed by high-throughput sequencing of 16S rDNA and mass spectrometry, respectively. Cytokine concentrations were measured in the gut, liver, and mesenteric fat looking for low-grade inflammation. The impact of HFD on liver metabolic dysfunction was explored by Oil Red O staining, triglycerides, cholesterol concentrations, and the expression of genes involved in β-oxidation and lipogenesis. Colonization with E. muris had a beneficial impact, with a reduction in dysbiosis, lower levels of fecal secondary bile acids, and an improvement in hepatic steatosis, arguing for a protective role of commensal amoebas in MetS and more specifically HFD-associated MASLD.

Coffee Bioactive N-Methylpyridinium: Unveiling Its Antilipogenic Effects by Targeting De Novo Lipogenesis in Human Hepatocytes.

Type 2 diabetes and nonalcoholic fatty liver diseases (NAFLDs) are promoted by insulin resistance (IR), which alters lipid homeostasis in the liver. This study aims to investigate the effect of N-methylpyridinium (NMP), a bioactive alkaloid of coffee brew, on lipid metabolism in hepatocytes. The effect of NMP in modulating lipid metabolism is evaluated at physiological concentrations in a diabetes cell model represented by HepG2 cells cultured in a high-glucose medium. Hyperglycemia triggers lipid droplet accumulation in cells and enhances the lipogenic gene expression, which is transactivated by sterol regulatory element binding protein-1 (SREBP-1). Lipid droplet accumulation alters the redox status and endoplasmic reticulum (ER) stress, leading to the activation of the unfolded protein response and antioxidative pathways by X-Box Binding Protein 1(XBP-1)/eukaryotic Initiation Factor 2 alpha (eIF2α) Protein Kinase RNA-Like ER Kinase and nuclear factor erythroid 2-related factor 2 (NRF2), respectively. NMP induces the phosphorylation of AMP-dependent protein kinase (AMPK) and acetyl-CoA carboxylase α (ACACA), and improves the redox status and ER homeostasis, essential steps to reduce lipogenesis and lipid droplet accumulation. These results suggest that NMP may be beneficial for the management of T2D and NAFLD by ameliorating the cell oxidative and ER homeostasis and lipid metabolism.

7184 Type 2 Diabetes As An Independent Risk Factor For Increased Incidence Of Cardiovascular Events In Patient With Nonalcoholic Fatty Liver Disease

Abstract Disclosure: E. Roh: None. K. Son: None. H. Jung: None. J. Huh: None. S. Lee: None. S. Ihm: None. K. Han: None. J. Kang: None. Background: Although coexistence of type 2 diabetes (T2DM) and non-alcoholic fatty liver disease (NAFLD) has been linked to unfavorable metabolic profile and an increasing cardiovascular risk, the impact of T2DM on the risk of developing CVD within the context of NAFLD remains unclear. This study aimed to investigate long-term CVD outcomes in patients with NAFLD according to glycemic status using nationwide cohort of Korean adults. Methods: This retrospective, longitudinal study included 1,057,775 patients with NAFLD, who had participated in the national health screening in 2009 and were followed up until 2020. The baseline glycemic status was divided into three categories [normal fasting glucose (NFG), impaired fasting glucose (IFG) and T2DM]. Cox proportional hazards models were used to assess the association of glycemic status with incident CVD. Results: During a median follow-up period of 10.3 years, 26,491 cases of MI, 55,791 cases of stroke, and 11,147 cases of CV death were identified. After adjusting for possible covariates, participants with T2DM had a higher risk of CVD, with hazard ratios of 1.394 (95% CI 1.351−1.439) for MI and 1.391 (95% CI 1.362−1.420) for stroke, and 1.457 (95% CI 1.392−1.524) for CV mortality, compared to those with NFG. The increased risk of CVD attributable to T2DM was more profound among individuals with fewer conventional CVD risk factos, including younger age, not obese, and the absence of hypertension. Conclusions: These results suggest that the identification of T2DM in individuals of NAFLD may help the prediction of future progression of CVD. Presentation: 6/3/2024

Gallic Acid Alleviates Glucolipotoxicity-Induced Nephropathy by miR-709-NFE2L2 Pathway in db/db Mice on a High-Fat Diet.

Type 2 diabetes mellitus (T2DM) has become a major global issue, with diabetic nephropathy (DN) ranking as one of its most serious complications. The involvement of microRNAs (miRNAs) in the progression of T2DM and DN is an area of active research, yet the molecular mechanisms remain only partially elucidated. Gallic acid (GA), a naturally occurring polyphenolic compound found in various plants such as bearberry leaves, pomegranate root bark, tea leaves, and oak bark, has demonstrated antioxidant properties that may offer therapeutic benefits in DN. The study aimed to investigate the therapeutic potential of GA in mitigating kidney fibrosis, oxidative stress and inflammation, within a glucolipotoxicity-induced diabetic model using db/db mice. The mice were subjected to a high-fat diet to induce glucolipotoxicity, a condition that mimics the metabolic stress experienced in T2DM. Through microarray data analysis, we identified a significant upregulation of renal miR-709a-5p in the diabetic mice, linking this miRNA to the pathological processes underlying DN. GA treatment was shown to boost the activity of including catalase, essential antioxidant enzymes, glutathione peroxidase and superoxide dismutase, while also reducing lipid accumulation in the kidneys, indicating a protective effect against HFD-induced steatosis. In vitro experiments further revealed that silencing miR-709a-5p in MES-13 renal cells led to a reduction in oxidative stress markers, notably lowering lipid peroxidation markers, and significantly boosting the activity of antioxidant defenses. Additionally, NFE2L2, a crucial transcription factor involved in the antioxidant response, was identified as a direct target of miR-709a-5p. The downregulation of miR-709a-5p by GA suggests that this polyphenol mitigates glucolipotoxicity-induced lipogenesis and oxidative stress, potentially offering a novel therapeutic avenue for managing diabetic fatty liver disease and DN. Our findings indicate that GA exerts a protective effect in DN by downregulating miR-709a-5p, thereby alleviating oxidative stress through the suppression of NFE2L2. The results highlight the potential of GA and NFE2L2-activating agents as promising therapeutic strategies in the treatment of DN.

Outcomes of kidney transplantation in recipients with SARS-cov-2 infection: a 282-case single-center experience in Japan.

The coronavirus disease 2019, caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has become a global epidemic. There are concerns regarding the severity of SARS-CoV-2 infections in kidney transplant (KTx) recipients. However, there is limited data on how the epidemic has affected the treatment and prognosis of these patients. Therefore, we aimed to report the changes in the treatment and outcomes of KTx recipients infected with SARS-CoV-2 during each wave at our institution. A total of 282 KTx recipients who were infected with SARS-CoV-2 during the study period were followed up at Tokyo Women's Medical University between March 2020 and August 2022. We investigated the outcomes and treatments of infected KTx recipients. Nineteen (6.7%) patients showed severe outcomes, including eight SARS-CoV-2 infection-related deaths. Risk factors associated with severe outcomes included underlying conditions, such as diabetes mellitus, heart disease, and liver disease (odds ratios, 2.09, 2.88, and 5.52, respectively). Treatment strategies changed throughout the epidemic in response to changes in the SARS-CoV-2 variants. Antiviral drugs were gradually administered as soon as they were approved for use. Treatment strategies for KTx recipients were gradually established over the course of the epidemic. Although the proportion of infected KTx recipients decreased compared to that of the general population throughout the epidemic, many patients still followed a severe course.

Glycaemic sugar metabolism and the gut microbiota: past, present and future.

Non-communicable diseases (NCDs), such as type 2 diabetes (T2D) and metabolic dysfunction-associated fatty liver disease, have reached epidemic proportions worldwide. The global increase in dietary sugar consumption, which is largely attributed to the production and widespread use of cheap alternatives such as high-fructose corn syrup, is a major driving factor of NCDs. Therefore, a comprehensive understanding of sugar metabolism and its impact on host health is imperative to rise to the challenge of reducing NCDs. Notably, fructose appears to exert more pronounced deleterious effects than glucose, as hepatic fructose metabolism induces de novo lipogenesis and insulin resistance through distinct mechanisms. Furthermore, recent studies have demonstrated an intricate relationship between sugar metabolism and the small intestinal microbiota (SIM). In contrast to the beneficial role of colonic microbiota in complex carbohydrate metabolism, sugar metabolism by the SIM appears to be less beneficial to the host as it can generate toxic metabolites. These fermentation products can serve as a substrate for fatty acid synthesis, imposing negative health effects on the host. Nevertheless, due to the challenging accessibility of the small intestine, our knowledge of the SIM and its involvement in sugar metabolism remains limited. This review presents an overview of the current knowledge in this field along with implications for future research, ultimately offering potential therapeutic avenues for addressing NCDs.

Non-alcoholic fatty liver and periodontal disease in the adult population: Overview of systematic reviews

Introduction: Periodontal disease is a chronic inflammatory condition affecting the periodontal supporting tissues. In addition to dental loss, it has been associated with various metabolic disorders, including obesity, diabetes, dyslipidemia, and non-alcoholic fatty liver disease (NAFLD). This study aimed to analyze the effects of periodontal disease on the prevention and treatment of NAFLD in the adult population. Method: An electronic search of systematic reviews published between 2019 and 2024 was conducted in the Medline, Scopus, and Web of Science databases, as well as in the Epistemonikos meta-search engine. The search strategy was "Non-alcoholic Fatty Liver Disease AND Periodontitis". A total of 47 articles were identified, of which three systematic reviews with meta-analyses were analyzed. Results: The results indicated a potential association between periodontal disease and NAFLD, with an odds ratio (OR) of 1.48 (95% CI: 1.15 to 1.89; I² = 92%) and 1.91 (95% CI: 1.21 to 3.02; I² = 95%). However, this link has not been definitively proven, as heterogeneity decreases and the number of patients increases, resulting in an OR of 1.04 (95% CI: 0.97 to 1.12; I² = 58%). Conclusion: It is suggested that systemic inflammation and pro-inflammatory markers may play a significant role in the pathophysiology of both conditions. Nonetheless, further studies are needed to clarify this relationship and explore the common metabolic parameters.

Evaluation of the Hypoglycemic and Hypolipidemic Potential of Extract Fraction of Quercus baloot Griff Seeds in Alloxan-induced Diabetic Mice.

The discovery and development of new phytomedicines can be greatly aided by plants because of their tremendous therapeutic benefits, efficiency, cost-effectiveness, lack of side effects, and cheaper therapies. In this regard, Quercus baloot, generally known as oak, is used in folkloric medicine for treating and preventing various human disorders, including diabetes. For this purpose, the present study aimed to evaluate crude methanolic extract and various fractions of Quercus baloot for antihyperlipidemic and antihyperglycemic potential followed by the analysis of active compounds. The hypoglycemic and hypolipidemic activity was evaluated in Swiss male Albino mice by administering an oral dose of 150-300 mg/kg of Q. baloot extracts in alloxan induced diabetic mice for 14 days. The results revealed that crude methanolic extract at a dose of 300 mg/kg exhibited a significant reduction in the blood glucose level (198.50 ± 1.99 mg/dl) at day 14 and the same treatment significantly increased the body weight (31.26 ± 0.27 g) at day 14 in comparison to the control group. Moreover, the biochemical parameters were investigated which presented an increase in high-density lipids (HDL) (30.33 ± 0.33 mg/dl), whereas low-density lipids (LDL) showed a significant decrease (105.66 ± 0.26 mg/dl). Additionally, triglyceride levels 104.83 ± 0.70 mg/dl, and total cholesterol 185.50 ± 0.76 mg/dl are significantly decreased. In serum biochemical analysis creatinine and hepatic enzyme markers, like serum glutamate pyruvate transaminase (32.00 ± 0.36 U/mg), serum glutamate oxaloacetate transaminase (34.33 ± 0.61 U/mg), and alkaline phosphatase (157.00 ± 0.73 U/mg), were significantly reduced by the crude methanolic extract at a dose of 300 mg/kg as compared to the control group. The antioxidant enzymes like Superoxide dismutase (4.57 ± 0.011), peroxidases dismutase (6.53 ± 0.014, and catalase (8.38 ± 0.014) at a dosage of 300 mg/kg of methanolic extract exhibited a significant increase. The histopathological study of the diabetic heart, liver, and pancreas showed substantial restoration of damaged tissues in the methanolic extract 150 and 300 mg/kg treated group, which supports the effectiveness of Q. baloot seeds. The gas chromatography-mass spectrometry analysis of methanolic extract identified 10 antidiabetic active compounds in the Q. baloot seeds, validating the antihyperglycemic activity. Thus, methanolic crude extract at the doses 150 and 300 mg/kg of Q. baloot showed significant antihyperlipidemic and antihyperglycemic activities, which validate the folkloric utilization of Q. baloot as a remedy in diabetes. In conclusion, the 300 mg/kg methanolic extract of Q. baloot has notable hypoglycemic and hypolipidemic potential, supporting the plant's traditional medicinal usage in the treatment of diabetes and its complications. Further studies are needed for the purification, characterization, and structural clarification of bioactive compounds.

Protein posttranslational modifications in metabolic diseases: basic concepts and targeted therapies.

Metabolism-related diseases, including diabetes mellitus, obesity, hyperlipidemia, and nonalcoholic fatty liver disease, are becoming increasingly prevalent, thereby posing significant threats to human health and longevity. Proteins, as the primary mediators of biological activities, undergo various posttranslational modifications (PTMs), including phosphorylation, ubiquitination, acetylation, methylation, and SUMOylation, among others, which substantially diversify their functions. These modifications are crucial in the physiological and pathological processes associated with metabolic disorders. Despite advancements in the field, there remains a deficiency in contemporary summaries addressing how these modifications influence processes of metabolic disease. This review aims to systematically elucidate the mechanisms through which PTM of proteins impact the progression of metabolic diseases, including diabetes, obesity, hyperlipidemia, and nonalcoholic fatty liver disease. Additionally, the limitations of the current body of research are critically assessed. Leveraging PTMs of proteins provides novel insights and therapeutic targets for the prevention and treatment of metabolic disorders. Numerous drugs designed to target these modifications are currently in preclinical or clinical trials. This review also provides a comprehensive summary. By elucidating the intricate interplay between PTMs and metabolic pathways, this study advances understanding of the molecular mechanisms underlying metabolic dysfunction, thereby facilitating the development of more precise and effective disease management strategies.

Integrative bioinformatic and experimental analysis of benzoylbenzodioxol derivatives: hypoglycemic potential in diabetic mice.

We investigated the hypoglycemic activity and pharmacokinetic study of two synthesized benzoyl benzodioxol derivatives, compound I (methyl 2-(6-(2-bromobenzoyl)benzo[d][1,3]dioxol-5-yl)acetate), and compound II, 2-(6-benzoylbenzo[d][1,3]dioxol-5-yl)acetic acid, which showed very strong α-amylase inhibiting activity in our previous study. Then, diabetes was induced by the injection of streptozotocin to mice. The molecular docking simulations and analyses of density functional theory analyses were conducted to study the binding interactions with human pancreatic alpha-amylase, and their pharmacokinetic properties were further evaluated by ADMET profiling. Compound I showed the most important hypoglycemic effect, decreasing the blood glucose by 32.4%, higher than that of compound II by 14.8% and even the positive control acarbose by 22.9%. Histopathological examination revealed that diabetic livers showed portal inflammation with some apoptotic hepatocytes due to streptozotocin treatment, whereas controls without any treatment maintained normal liver architecture. Molecular docking studies gave results for the best binding affinity of the compound I, through its strong water bridges and π-π interactions, and also through analysis with density functional theory, was more stable and reactive when compared to compound II. Further ADMET analysis showed that both compounds shared a promising pharmacokinetic profile, and compound I had the potential for CNS penetration. Thus, compound I was selected as the best candidate for developing new hypoglycemic agents with potent efficacy, good binding interactions, and excellent pharmacokinetic properties.

A Case of Acute Pericardial Abscess Due to Klebsiella Pneumoniae

Klebsiella pneumoniae (KPn) is a gram-negative bacterium, which is an opportunistic pathogen commonly found in the natural environment, and the infection rate of Klebsiella pneumoniae is increased in patients with underlying diseases such as diabetes mellitus, malignant tumors, liver and gallbladder diseases, and those who have received glucocorticoid therapy for a long period of time [1]-[4], which can cause urinary, respiratory, digestive, hematological, neurological and other multi-system infections with high morbidity and mortality rates [5]. Klebsiella pneumoniae infection involving the heart leading to purulent pericardial effusion has a lower incidence, and the literature in this regard reported extremely rare [6], mostly secondary to other parts of the infection, once suspected of pericardial abscess should be immediately performed pericardiocentesis to drain adequately, the application of saline to flush the pericardial cavity, can be thrombolysis of pericardial cavity with antibiotics or urokinase to speed up the process of treatment, to avoid the formation of constrictive pericarditis [7]-[9]. In order to improve clinicians' understanding of this disease, this article reports the diagnosis and treatment of a case of pericardial abscess caused by Klebsiella pneumoniae, with the aim of providing more case references for the clinic.

Black rice bran extract exerts hepatoprotection via attenuating inflammation and apoptosis in obese-insulin-resistant rats

Global pandemic of obesity contributes to increasing the risk of diabetes and non-alcoholic fatty liver disease (NAFLD). To find an alternative approach to lower the risk caused by obesity. AimsWe investigated the antidiabetic and hepatoprotective activity of black rice bran extract (BRE) in obese, insulin-resistant rats induced by a high-fat diet (HFD). Main methodsAfter HFD feeding, the parameters related to glucose, lipid profiles, and liver injury were determined. Key findingsRats on a HFD exhibited significantly elevated plasma glucose and lipid levels, as well as increased liver enzyme activities (aspartate transaminase and alanine transaminase), relative to the control group. Interestingly, those parameters in the BRE-treated group were significantly decreased. We investigated the liver histological study, and the BRE-treated group showed to ameliorate the liver injury accompanied by lower inflammatory and apoptotic markers. SignificanceOur findings suggest that BRE has the potential to be used as a dietary supplement to lessen metabolic dysregulation and prevent liver impairment.

Sex differences in pathogenesis and treatment of dyslipidemia in patients with type 2 diabetes and steatotic liver disease.

Previously published studies have shown that women with type 2 diabetes have a higher risk of atherosclerotic cardiovascular disease than men with type 2 diabetes. The exact reason for this is not yet known. The association between metabolic dysfunction-associated steatotic liver disease and type 2 diabetes appears to be bidirectional, meaning that the onset of one may increase the risk of the onset and progression of the other. Dyslipidemia is common in both diseases. Our aim was therefore to investigate whether there is a sex difference in the pathogenesis and management of dyslipidemia in patients with type 2 diabetes and steatotic liver disease with metabolic dysfunction. While the majority of published studies to date have found no difference between men and women in statin treatment, some studies have shown reduced effectiveness in women compared to men. Statin treatment is under-prescribed for both type 2 diabetics and patients with dysfunction-associated steatotic liver disease. No sex differences were found for ezetimibe treatment. However, to the best of our knowledge, no such study was found for fibrate treatment. Conflicting results on the efficacy of newer cholesterol-lowering PCSK9 inhibitors have been reported in women and men. Results from two real-world studies suggest that up-titration of statin dose improves the efficacy of PCSK9 inhibitors in women. Bempedoic acid treatment has been shown to be effective and safe in patients with type 2 diabetes and more effective in lipid lowering in women compared to men, based on phase 3 results published to date. Further research is needed to clarify whether the sex difference in dyslipidemia management shown in some studies plays a role in the risk of ASCVD in patients with type 2 diabetes and steatotic liver disease with metabolic dysfunction.