Secreted Frizzled-Related Protein 5 Mediates Wnt5a Expression in Microcystin-Leucine-Arginine-Induced Liver Lipid Metabolism Disorder in Mice

Objective Microcystin-leucine-arginine(MC-LR)exposure induces lipid metabolism disorders in the liver.Secreted frizzled-related protein 5(SFRP5)is a natural antagonist of winglesstype MMTV integration site family,member 5A(Wnt5a)and an anti-inflammatory adipocytokine.In this study,we aimed to investigate whether MC-LR can induce lipid metabolism disorders in hepatocytes and whether SFRP5,which has anti-inflammatory effects,can alleviate the effects of hepatic lipid metabolism by inhibiting the Wnt5a/Jun N-terminal kinase(JNK)pathway.Methods We exposed mice to MC-LR in vivo to induce liver lipid metabolism disorders.Subsequently,mouse hepatocytes that overexpressed SFRP5 or did not express SFRP5 were exposed to MC-LR,and the effects of SFRP5 overexpression on inflammation and Wnt5a/JNK activation by MC-LR were observed.Results MC-LR exposure induced liver lipid metabolism disorders in mice and significantly decreased SFRP5 mRNA and protein levels in a concentration-dependent manner.SFRP5 overexpression in AML12cells suppressed MC-LR-induced inflammation.Overexpression of SFRP5 also inhibited Wnt5a and phosphorylation of JNK.Conclusion MC-LR can induce lipid metabolism disorders in mice,and SFRP5 can attenuate lipid metabolism disorders in the mouse liver by inhibiting Wnt5a/JNK signaling.

Mechanistic study of lipid metabolism disorders in diabetic kidney disease treated with GLQMP based on network pharmacology,molecular docking and in vitro experiments

Background:In this study,we used network pharmacology and molecular docking combined with vitro experiments to explore the potential mechanism of action of Gualou Qumai pill(GLQMP)against DKD.Methods:We screened effective compounds and drug targets using Chinese medicine systemic pharmacology database and analysis platform and Chinese medicine molecular mechanism bioinformatics analysis tools;and searched for DKD targets using human online Mendelian genetics and gene cards.The potential targets of GLQMP for DKD were obtained through the intersection of drug targets and disease targets.Cytoscape software was applied to build herbal medicine-active compound-target-disease networks and analyze them;protein-protein interaction networks were analyzed using the STRING database platform;gene ontology and Kyoto Encyclopedia of Genes and Genomes were used for gene ontology and gene and genome encyclopedia to enrich potential targets using the DAVID database;and the AutoDock Vina 1.1.2 software for molecular docking of key targets with corresponding key components.In vitro experiments were validated by CCK8,oil red O staining,TC,TG,RT-qPCR,and Western blot.Results:Through network pharmacology analysis,a total of 99 potential therapeutic targets of GLQMP for DKD and the corresponding 38 active compounds were obtained,and 5 core compounds were identified.By constructing the protein-protein interaction network and performing network topology analysis,we found that PPARA and PPARG were the key targets,and then we molecularly docked these two key targets with the 38 active compounds,especially the 5 core compounds,and found that PPARA and PPARG had good binding ability with a variety of compounds.In vitro experiments showed that GLQMP was able to ameliorate HK-2 cell injury under high glucose stress,improve cell viability,reduce TC and TG levels as well as decrease the accumulation of lipid droplets,and RT-qPCR and Western blot confirmed that GLQMP was able to promote the expression levels of PPARA and PPARG.Conclusion:Overall,this study revealed the active compounds,important targets and possible mechanisms of GLQMP treatment for DKD,and conducted preliminary verification experiments on its correctness,provided novel insights into the treatment of DKD by GLQMP.

The Role of Adipose Tissue-derived Exosomes in Chronic Metabolic Disorders

Excessive fat deposition in obese subjects promotes the occurrence of metabolic diseases,such as type 2 diabetes mellitus(T2DM),cardiovascular diseases,and non-alcoholic fatty liver disease(NAFLD).Adipose tissue is not only the main form of energy storage but also an endocrine organ that not only secretes adipocytokines but also releases many extracellular vesicles(EVs)that play a role in the regulation of whole-body metabolism.Exosomes are a subtype of EVs,and accumulating evidence indicates that adipose tissue exosomes(AT Exos)mediate crosstalk between adipose tissue and multiple organs by being transferred to targeted cells or tissues through paracrine or endocrine mechanisms.However,the roles of AT Exos in crosstalk with metabolic organs remain to be fully elucidated.In this review,we summarize the latest research progress on the role of AT Exos in the regulation of metabolic disorders.Moreover,we discuss the potential role of AT Exos as biomarkers in metabolic diseases and their clinical application.

Huangqin decoction alleviates lipid metabolism disorders and insulin resistance in nonalcoholic fatty liver disease by triggering Sirt1/NF-κB pathway

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is a clinicopathological entity characterized by intrahepatic ectopic steatosis.As a consequence of increased consumption of high-calorie diet and adoption of a sedentary lifestyle,the incidence of NAFLD has surpassed that of viral hepatitis,making it the most common cause of chronic liver disease globally.Huangqin decoction(HQD),a Chinese medicinal formulation that has been used clinically for thousands of years,has beneficial outcomes in patients with liver diseases,including NAFLD.However,the role and mechanism of action of HQD in lipid metabolism disorders and insulin resistance in NAFLD remain poorly understood.AIM To evaluate the ameliorative effects of HQD in NAFLD,with a focus on lipid metabolism and insulin resistance,and to elucidate the underlying mechanism of action.METHODS High-fat diet-induced NAFLD rats and palmitic acid(PA)-stimulated HepG2 cells were used to investigate the effects of HQD and identify its potential mechanism of action.Phytochemicals in HQD were analyzed by highperformance liquid chromatography(HPLC)to identify the key components.RESULTS Ten primary chemical components of HQD were identified by HPLC analysis.In vivo,HQD effectively prevented rats from gaining body and liver weight,improved the liver index,ameliorated hepatic histological aberrations,decreased transaminase and lipid profile disorders,and reduced the levels of pro-inflammatory factors and insulin resistance.In vitro studies revealed that HQD effectively alleviated PA-induced lipid accumulation,inflammation,and insulin resistance in HepG2 cells.In-depth investigation revealed that HQD triggers Sirt1/NF-κB pathwaymodulated lipogenesis and inflammation,contributing to its beneficial actions,which was further corroborated by the addition of the Sirt1 antagonist EX-527 that compromised the favorable effects of HQD.CONCLUSION In summary,our study confirmed that HQD mitigates lipid metabolism disorders and insulin resistance in NAFLD by triggering the Sirt1/NF-κB pathway.

Exploiting fly models to investigate rare human neurological disorders

Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological symptoms.Often attributed to genetic mutations that disrupt protein function or structure,understanding their genetic basis is crucial for accurate diagnosis and targeted therapies.To investigate the underlying pathogenesis of these conditions,researchers often use non-mammalian model organisms,such as Drosophila(fruit flies),which is valued for their genetic manipulability,cost-efficiency,and preservation of genes and biological functions across evolutionary time.Genetic tools available in Drosophila,including CRISPR-Cas9,offer a means to manipulate gene expression,allowing for a deep exploration of the genetic underpinnings of rare neurological diseases.Drosophila boasts a versatile genetic toolkit,rapid generation turnover,and ease of large-scale experimentation,making it an invaluable resource for identifying potential drug candidates.Researchers can expose flies carrying disease-associated mutations to various compounds,rapidly pinpointing promising therapeutic agents for further investigation in mammalian models and,ultimately,clinical trials.In this comprehensive review,we explore rare neurological diseases where fly research has significantly contributed to our understanding of their genetic basis,pathophysiology,and potential therapeutic implications.We discuss rare diseases associated with both neuron-expressed and glial-expressed genes.Specific cases include mutations in CDK19 resulting in epilepsy and developmental delay,mutations in TIAM1 leading to a neurodevelopmental disorder with seizures and language delay,and mutations in IRF2BPL causing seizures,a neurodevelopmental disorder with regression,loss of speech,and abnormal movements.And we explore mutations in EMC1 related to cerebellar atrophy,visual impairment,psychomotor retardation,and gain-of-function mutations in ACOX1 causing Mitchell syndrome.Loss-of-function mutations in ACOX1 result in ACOX1 deficiency,characterized by very-long-chain fatty acid accumulation and glial degeneration.Notably,this review highlights how modeling these diseases in Drosophila has provided valuable insights into their pathophysiology,offering a platform for the rapid identification of potential therapeutic interventions.Rare neurological diseases involve a wide range of expression systems,and sometimes common phenotypes can be found among different genes that cause abnormalities in neurons or glia.Furthermore,mutations within the same gene may result in varying functional outcomes,such as complete loss of function,partial loss of function,or gain-of-function mutations.The phenotypes observed in patients can differ significantly,underscoring the complexity of these conditions.In conclusion,Drosophila represents an indispensable and cost-effective tool for investigating rare neurological diseases.By facilitating the modeling of these conditions,Drosophila contributes to a deeper understanding of their genetic basis,pathophysiology,and potential therapies.This approach accelerates the discovery of promising drug candidates,ultimately benefiting patients affected by these complex and understudied diseases.

Biochemical Changes in the Brain and Metabolism as Risk Factors of Neurological Disorders

This paper aims to examine theories that attempt to explain biochemical changes in the brain as well as the metabolism of individuals who experience symptoms and conditions related to neurological disorders like depression. A systematic literature search was performed on NCBI and PubMed. The search included the keywords neurological disorders, monoamine hypothesis, metabolic syndrome, oxytocin receptor, dietary health, and magnesium intake. Twenty-five research articles met the criteria for the literature review of this examination. In particular, this paper will review multiple studies that investigate the monoamine (MAO) hypothesis of depression and metabolic syndrome (MetS) as a risk factor for neurological disorders. While studies that evaluate additional risk factors for neurological disorders, such as autoimmunity and rheumatic diseases, oxytocin receptor (OXTR) DNA methylation in postpartum depression, dietary health in children and their psychological health, and dietary magnesium and cardiovascular disease, will be reviewed as well.

The effect of iron metabolism on anxiety disorder

Anxiety disorder is one of the most common emotional disorders,but its pathogenesis re-mains unclear.Research has shown that iron deficiency is more common in people with emotional disorders and that these disorders can improve after taking iron supple-ments.Many factors can cause anxiety disorders,includ-ing external stress,genetic factors,impaired neurodevel-opment,and abnormal monoamine metabolism.Studies have shown that abnormal monoamine metabolism and impaired neurodevelopment can contribute to the severity of emotional disorders.The synthesis of serotonin(5-HT)and dopamine(DA)require iron as a cofactor in the syn-thesis of monoamine metabolism,and the release of epi-nephrine(E)was potentially associated with labile iron in plasma.At the same time,iron is also directly involved in myelin synthesis as a cofactor in neural development.Therefore,iron maybe involved some of the main causes of the onset of anxiety disorders.

A review of methylenetetrahydrofolate reductase in one-carbon metabolism and psychiatric disorders

Methylenetetrahydrofolate reductase(MTHFR)is a key enzyme for the critical process of one-carbon circulation,which convert5,10-methylenetetrahydrofolate to5-methyltetrahydrofolate and participate in folate and homocysteine conversion correlated to methyl group supply.The enzyme activity decline depends on the gene polymorphism.MTHFR impacts on the methylation process which is related to psychiatric diseases.Studies have shown association between MTHFR gene polymorphisms and mental disorders,some of which stratified by folate and cobalamin levels.In this review,we will summarize the testimony on the relationship between methylation and MTHFR polymorphism as well as the implication on psychiatric diseases by MTHFR mutation.

Study on mechanism and genetic analysis of lipid metabolism disorder in pregnant rats

Objective: To analyze the characteristics and possible mechanism of lipid metabolism in pregnant rats with intestinal flora imbalance. Methods: A total of 129 sexually mature female SD rats were divided into three groups: non-pregnant group (untreated healthy rats), healthy pregnant group (natural insemination pregnant rats), and pregnant microflora disorder group (pregnant rats were given mixed antibiotics by gavage to build the modeling), with 43 rats in each group. The contents of TG, LDL, HDL and TC were detected by automatic biochemical analyzer, and the contents of SCD1, PGC-1 alpha, PEPCK, ApoE and MTTP genes were detected by fluorescence quantitative PCR technology. Regression analysis was used to explore the comprehensive influence of each gene on total cholesterol expression in rats. Principal component analysis was used to explore the internal mechanism of lipid metabolism in pregnant rats with intestinal flora disorder. Results: The contents of TG, TC, LDL and HDL were compared among the three groups of rats and the differences were statistically significant (P<0.05) . The expression levels of related genes (SCD1, PGC-1, PEPCK, ApoE, MTTP) in the three groups were statistically significant (P<0.05) . SCD1 content in the non-pregnant group, healthy pregnancy group, and disordered pregnancy group was (0.92±0.12) μg/mL, (1.20±0.15)μg/mL, and (1.53±0.20) μg/mL, respectively. PGC-1 alpha content in the non-pregnant group, healthy pregnancy group, and disordered pregnancy group was (1.34±0.21) μg/mL, (0.93±0.12) micron /mL, and (0.41±0.08) μg/mL, respectively. PEPCK content in the non-pregnant group, healthy pregnancy group, and disordered pregnancy group was (0.48±0.06) μg/mL, (0.35±0.09)μg/mL, and (0.22±0.05) μg/mL, and the differences were statistically significant (P<0.05) . Multivariate linear regression analysis showed that the influence of gene content on The effect of each gene content on TC content was in order from large to small: SCD1 (OR=4.572) , PGC-1 (OR=3.387) , PEPCK (OR=3.935) , ApoE (OR=3.597) , MTTP (OR=3.096) . The principal component analysis showed that three principal components could be extracted from five related genes of lipid metabolism in pregnant rats with intestinal dysbiosis: SCD1/PEPCK pathway (contribution rate: 36.28%) , PGC-1 /ApoE pathway (contribution rate: 30.42%) , and MTTP pathway (contribution rate: 15.37%) . Conclusion: After pregnancy, blood lipids in rats are significantly increased while the imbalance of intestinal flora will lead to decreased blood lipids. The disorder of lipid metabolism in pregnant rats with intestinal flora imbalance is mainly related to the disorder of gene expression, which further affects the functions of SCD1/PEPCK, PGC-1 /ApoE and MTTP pathways.

Mechanism and recent updates on insulin-related disorders

Insulin,a small protein with 51 amino acids synthesized by pancreatic β-cells,is crucial to sustain glucose homeostasis at biochemical and molecular levels.Numerous metabolic dysfunctions are related to insulin-mediated altered glucose homeostasis.One of the significant pathophysiological conditions linked to the insulin associated disorder is diabetes mellitus(DM)(type 1,type 2,and gestational).Insulin resistance(IR)is one of the major underlying causes of metabolic disorders despite its association with several physiological conditions.Metabolic syndrome(MS)is another pathophysiological condition that is associated with IR,hypertension,and obesity.Further,several other pathophysiological disorders/diseases are associated with the insulin malfunctioning,which include polycystic ovary syndrome,neuronal disorders,and cancer.Insulinomas are an uncommon type of pancreatic β-cell-derived neuroendocrine tumor that makes up 2% of all pancreatic neoplasms.Literature revealed that different biochemical events,molecular signaling pathways,microRNAs,and microbiota act as connecting links between insulin disorder and associated pathophysiology such as DM,insuloma,neurological disorder,MS,and cancer.In this review,we focus on the insulin-related disorders and the underlying mechanisms associated with the pathophysiology.

Prevalence of Metabolic Syndrome and Its Associations with Other Metabolic Disorders and Cardiovascular Changes in Health Examination Population in Beijing

Objective To investigate the prevalence of metabolic syndrome(MS) and its associations with other metabolic disorders and cardiovascular changes in health examination population in Beijing.Methods Totally,10 916 individuals who received health examination in Health Examination Center of Peking Union Medical College Hospital were enrolled.The height,weight,blood pressure,serum levels of triglyceride,high-density lipoprotein cholesterol(HDL-C),and fasting blood glucose were recorded.MS was diagnosed based on the working criteria of Chinese Diabetes Society 2004(CDS2004).Meanwhile,other metabolic disorders,including fatty liver and hyperuricemia,were recorded.The cardiovascular changes were reflected by the reports of electrocardiogram(ECG) ST-T changes and atherosclerosis of retinal arteries.Results The overall prevalence rate of MS was 6.1%(666/10 916) in the population.The prevalence rate of MS in male was much higher than that in female(9.0% vs.2.7%,P=0.000).For individuals with MS,the prevalence rates of fatty liver and hyperuricemia were significantly higher than those without MS,respectively(70.4% vs.35.4%,P=0.000;29.9% vs.17.7%,P=0.000).As for cardiovascular changes,the prevalence rates of ECG ST-T changes and atherosclerosis of retinal arteries were significantly higher in individuals with MS than those without MS,respectively(13.8% vs.11.7%,P=0.012;12.0% vs.6.8%,P=0.000).Conclusions The prevalence of MS in Beijing population is high.The individuals with MS have a higher risk for other metabolic disorders and cardiovascular changes.

Lean-non-alcoholic fatty liver disease increases risk for metabolic disorders in a normal weight Chinese population

AIM:To study the prevalence and clinical biochemical,blood cell and metabolic features of lean-non-alcoholic fatty liver disease(lean-NAFLD)and its association with other diseases.METHODS:Demographic,biochemical and blood examinations were conducted in all the subjects in this study.We classified the subjects into four groups according to their weight and NAFLD status:lean-control,lean-NAFLD[body mass index(BMI)<24 kg/m2],overweight-obese control and overweight-obese NAFLD.One-way analysis of variance(ANOVA)was used to compare the means of continuous variables(age,BMI,blood pressure,glucose,lipid,insulin,liver enzymes and blood cell counts)and theχ2 test was used to compare the differences in frequency of categorical variables(sex,education,physical activity,smoking,alcohol consumption and prevalence of hypertension,hyperlipidemia,diabetes,metabolic syndrome central obesity and obesity).Both univariate and multivariate logistic regression models were adopted to calculate odds ratios(ORs)and predict hyperlipidemia,hypertension,diabetes and metabolic syndrome when we respectively set all controls,lean-control and overweightobese-control as references.In multivariate logistic regression models,we adjusted potential confounding factors,including age,sex,smoking,alcohol consumption and physical activity.RESULTS:The prevalence of NAFLD was very high in China.NAFLD patients were older,had a higher BMI,waist circumference,blood pressure,fasting blood glucose,insulin,blood lipid,liver enzymes and uric acid than the controls.Although lean-NAFLD patients had lower BMI and waist circumstance,they had significantly higher visceral adiposity index than overweightobese controls.Lean-NAFLD patients had comparable triglyceride,cholesterin and low-density lipoprotein cholesterin to overweight-obese NAFLD patients.In blood cell examination,both lean and overweightobese NAFLD was companied by higher white blood cell count,red blood cell count,hemoglobin and hematocrit value.All NAFLD patients were at risk of hyperlipidemia,hypertension,diabetes and metabolic syndrome(Met S).Lean-NAFLD was more strongly associated with diabetes(OR=2.47,95%CI:1.14-5.35),hypertension(OR=1.72,95%CI:1.00-2.96)and Met S(OR=3.19,95%CI:1.17-4.05)than overweight-obese-NAFLD(only OR for Met S was meaningful:OR=1.89,95%CI:1.29-2.77).NAFLD patients were more likely to have central obesity(OR=1.97,95%CI:1.38-2.80),especially in lean groups(OR=2.17,95%CI:1.17-4.05).CONCLUSION:Lean-NAFLD has unique results in demographic,biochemical and blood examinations,and adds significant risk for diabetes,hypertension and Met S in lean individuals.

Gastric xanthelasma and metabolic disorders: A large retrospective study among Chinese population

AIM To gain knowledge of xanthelasma,a large populationbased study was conducted. METHODS Patients who underwent upper gastrointestinal endoscopy at the First Affiliated Hospital,College of Medicine,Zhejiang University,Hangzhou,China during Jan 2009 to Nov 2016 were included. General characteristics as well as clinical data were collected,including blood routine,serum biochemical analysis,endoscopic findinds,histological evaluation and comorbiditie. Statistical analyses was performed using SPSS 20.0 software for Windows(IBM Inc.,Chicago,IL,United States) using Student's t-test,Mann-Whitney U test,χ2 test,univariable and multivariable logistic analysis. 2-tailed P value less than 0.05 was considered to be statistically significant. RESULTS A total of 176006 endoscopies were retrieved and we included 1370 xanthelasma participants(703 men,667 women) in this study. Prevalence of xanthelasma was 0.78% with average age of 56.6 ± 11.2 years. Chief complaint of xanthelasma consisted abdominal pain (24.2%),up-abdominal discomfort(14.1%),abdominal distention(10.1%),dyspepsia(9.1%),et al. Most xanthelasma occurred as single lesion in gastric antrum. Xanthelasma patients witnessed higher Helicobacter pylori(H. pylori) infection rate,more of other gastric lesions including atrophy,intestinal metaplasia and dysplasia(P < 0.01). In xanthelasma patients,serum carcinoembryonic antigen,triglyceride,fasting glucose,neutrophil,neutrophil-to-lymphocyte ratio were significantly higher,and high density lipoprotein-cholesterol,lymphocyte was lower(P < 0.05). Xanthelasma accompanied with more fatty liver disease and hepatic cyst,but fewer gallbladder polyp(P < 0.05). In logistic regression,it revealed that fasting plasma glucose(OR = 3.347,1.170-9.575,P < 0.05),neutrophil(OR = 1.617,1.003-2.605,P < 0.05),and carcinoembryonic antigen(OR = 2.011,1.236-3.271,P < 0.01) were all independent risk factors in xanthelasma. CONCLUSION Current study described a large xanthelasma cohort in Chinese population,revealed its relationship with H. pylori infection,carcinogenesis,metabolic dysfunction and inflammation as well.

Impact of the adherence to medical treatment on the main urinary metabolic disorders in patients with kidney stones

Objective:To assess the effect of the adherence to medical treatment on urinary parameters in the 24-h metabolic study of patients with kidney stones.Methods:A retrospective,longitudinal,descriptive,and observational study was carried out by reviewing the hospital electronic medical record from 2014 to 2018.The adherence to drug treatment was measured 6 months after its initiation,and the numerical values of the metabolic studies were compared.Wilcoxon tests were performed to compare the difference before and after treatment.Results:Ninety patients were evaluated,with 73.3% of adherence.The 180-day overall adherence rate was 61.2% in patients treated with a single drug and 85.4% in patients treated with multiple drugs.There is a statistically significant increase in citrate levels in patients with good adherence in comparison with non-adherent patients(p=0.031 vs.p=0.528).Conclusions:Medical treatment and dietary measures in patients with kidney stones have an initial impact at 6 months on the values of the main urinary metabolic alterations that predispose to calculi formation;the most significant is seen in those patients with adherence to medical treatment for hypocitraturia.

Endocrine disrupting chemicals in mixture and obesity,diabetes and related metabolic disorders

Obesity and associated metabolic disorders represent a major societal challenge in health and quality of life with large psychological consequences in addition to physical disabilities. They are also one of the leading causes of morbidity and mortality. Although, different etiologic factors including excessive food intake and reduced physical activity have been well identified, they cannot explain the kinetics of epidemic evolution of obesity and diabetes with prevalence rates reaching pandemic proportions. Interestingly, convincing data have shown that environmental pollutants, specifically those endowed with endocrine disrupting activities, could contribute to the etiology of these multifactorial metabolic disorders. Within this review, we will recapitulate characteristics of endocrine disruption. We will demonstrate that metabolic disorders could originate from endocrine disruption with a particular focus on convincing data from the literature. Eventually, we will present how handling an original mouse model of chronic exposition to a mixture of pollutants allowed demonstrating that a mixture of pollutants each at doses beyond their active dose could induce substantial deleterious effects on several metabolic end-points. This proof-of-concept study, as well as other studies on mixtures of pollutants, stresses the needs for revisiting the current threshold model used in risk assessment which does not take into account potential effects of mixtures containing pollutants at environmental doses, e.g., the real life exposure. Certainly, more studies are necessary to better determine the nature of the chemicals to which humans are exposed and at which level, and their health impact. As well, research studies on substitute products are essential to identify harmless molecules.

Cardiac energy metabolism disorder mediated by energy substrate imbalance and mitochondrial damage upon tebuconazole exposure

Tebuconazole exposure has been described as an increasing hazard to human health.An increasing number of recent studies have shown a positive association between tebuconazole exposure and cardiovascular disease risk,which is characterized by the reduction of adenosine triphosphate(ATP)synthesis.However,researches on the damage of tebuconazole exposure to energy metabolism and the related molecular mechanisms are limited.In the present study,male C57BL/6 mice were treated with tebuconazole at different low concentrations for 4 weeks.The results indicated that tebuconazole could accumulate in the heart and further induce the decrease of ATP content in the mouse heart.Importantly,tebuconazole induced an obvious shift in substrate utilization of fatty acid and glucose by disrupting their corresponding transporters(GLUT1,GLUT4,CD36,FABP3 and FATP1)expression,and significantly repressed the expression of mitochondrial biogenesis(Gabpa and Tfam)and oxidative phosphorylation(CS,Ndufa4,Sdhb,Cox5a and Atp5b)related genes in a dosedependent manner.Further investigation revealed that these alterations were related to the IRS1/AKT and PPARγ/RXRαpathways.These findings contribute to a better understanding of triazole fungicide-induced cardiovascular disease by revealing the key indicators associated with this phenomenon.

Epidemiological and Hemato-Biochemical Profiles of Diabetic Patients at the Diabetology, Endocrinology, and Metabolic Diseases Department of the Alpha Oumar Diallo Regional Hospital, Kindia (Republic of Guinea)

This study aims to enhance the healthcare services for diabetic patients in the administrative region of Kindia by suggesting dietary interventions to assist diabetics in better managing their condition. Conducted over a period of six months, from February 18 to July 18, 2021, this prospective and descriptive cross-sectional study involved 220 diabetic patients. Among these, 48 patients (22%) maintained balanced glucose levels (2 g/l). Positive glycosuria was observed in 54% of the patients, whereas 46% demonstrated normal glycosuria. An analysis of urinary parameters revealed that 15% of the patients had abnormal Ketone Bodies. Normal HbA1c levels (9%) HbA1c levels. Hematological assessments indicated significant variation: 56% of the patients had low hemoglobin levels, 4% suffered from hyper-eosinophilia, and 1% each from hyper-basophilia and hyper-hemoglobinemia. The anemic profile was characterized as mild anemia in 75%, moderate anemia in 20%, and severe anemia in 5%. Furthermore, 25% of patients were affected by Microcytic anemia and 75% by Normocytic anemia. Demographically, women constituted 65% of the study group compared to 35% of men. The most represented age bracket was 41 to 60 years, accounting for 52% of the patients, while those between 61 and 80 years comprised 36%. Every district in Kindia was impacted by diabetes.

Lipid droplets in the nervous system:involvement in cell metabolic homeostasis

Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous system.Lipid droplet formation begins with the synthesis of neutral lipids in the endoplasmic reticulum.Previously,lipid droplets were recognized for their role in maintaining lipid metabolism and energy homeostasis;however,recent research has shown that lipid droplets are highly adaptive organelles with diverse functions in the nervous system.In addition to their role in regulating cell metabolism,lipid droplets play a protective role in various cellular stress responses.Furthermore,lipid droplets exhibit specific functions in neurons and glial cells.Dysregulation of lipid droplet formation leads to cellular dysfunction,metabolic abnormalities,and nervous system diseases.This review aims to provide an overview of the role of lipid droplets in the nervous system,covering topics such as biogenesis,cellular specificity,and functions.Additionally,it will explore the association between lipid droplets and neurodegenerative disorders.Understanding the involvement of lipid droplets in cell metabolic homeostasis related to the nervous system is crucial to determine the underlying causes and in exploring potential therapeutic approaches for these diseases.

Comparative Efficacy of Lifestyle Modifications versus Pharmacotherapy on Weight Loss and Metabolic Health Outcomes: A Comprehensive Review

Background: Obesity has become a serious global public health challenge, given that it leads to various adverse health outcomes that include cardiovascular illnesses, diabetes, and certain types of cancer. The World Health Organization (WHO) has estimated that, at the end of 2022, 1 out of every 8 individuals were obese, and that the global adult obesity rates have over doubled since 1990, even as the adolescent obesity rates have quadrupled. Thus, as of 2022, nearly 2.5 billion adults, aged 18 years and above, were overweight, with 890 million being obese. Obesity and overweight incidence rate has been gradually increasing over the years, presenting significant challenges to the healthcare systems throughout the globe. In this regard, the objective of this systematic review was to evaluate the effectiveness and safety of lifestyle modifications (diet and physical activity) and pharmacotherapy in promoting weight loss and improving metabolic health in overweight adults. Methodology: To attain the above stated study objective, a systematic evaluation of previous studies was carried out, particularly studies that assessed the effectiveness and safety of lifestyle modifications (diet and physical activity) and pharmacotherapy in promoting weight loss and improving metabolic health in overweight adults. The authors have used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) in the selection of eligible studies for inclusion in the study. Results: The findings indicate that lifestyle interventions resulted in 5% - 10% weight reduction and significant improvements in metabolic indicators, while pharmacotherapy (GLP-1 receptor agonists) achieved up to 15% weight reduction and considerable metabolic health benefits. Further, comparative studies show lifestyle modifications provide overall health benefits, while medication is necessary for non-responders. Conclusion: Individualized treatment strategies are crucial, and further research is needed on long-term consequences and combination therapies.

Study on the Correlation between Metabolic Syndrome and Colorectal

Metabolic syndrome has been widely recognized in various studies as being intricately linked to the initiation and progression of colorectal adenoma. The potential pathways through which metabolic syndrome influences colorectal adenoma encompass chronic inflammation, insulin resistance, oxidative stress, and dysbiosis of the intestinal flora. This review aims to consolidate the understanding of the association between metabolic syndrome and colorectal adenoma, elucidating the interconnected mechanisms between different metabolic syndrome-related disorders and colorectal adenoma. By shedding light on these connections, this review offers valuable insights for the preventive strategies targeting colorectal adenoma.