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.

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.

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.

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.

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.

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.

Impact of the Association of a High Fructose Diet and Chronic Mild Stress on Metabolic and Affective Disorders in Male Rat

An early unbalanced nutritional diet can induce affective disorders in adulthood. As well as stress in adolescence can accentuate these disorders. Both human and rat structural changes have been demonstrated in the hippocampus, likewise, oxidative stress may be involved in these disturbances. The objective of this study is to see the impact of a high-fructose diet (PN21) associated with chronic mild stress (CMS) at the end of adolescence (PN55) on metabolic and affective disorders in rats Wistar. This study was performed on four groups of male rats: control group, CMS for five weeks (PN55), fructose for ten weeks (PN21) and fructose for ten weeks (PN21) associated with CMS for five weeks (PN55). These animals underwent behavioral tests to evaluate their affective states (open field test, Sucrose preference test). After sacrifice, the dosage of glucose, triglycerides and total cholesterol was performed at the prefrontal cortex (CPF) and also at the hippocampus;the dosage of nitric oxide (NO) was performed, too. The bulk of our results show that fructose induces metabolic disturbances;the CMS induces a state of depression-like, while the association potentiated metabolic disturbances, depression-like state and also inducing anxiety. This study has shown that fructose and CMS can disrupt the various functions of the body and their association can potentiate these disturbances.

High Sugar-Fat Diet Induces Metabolic-Inflammatory Disorders Independent of Obesity Development

Background: The modern dietary habit, which is rich in refined carbohydrates and saturated fats, increases the risk of chronic diseases due to the proinflammatory effect of these nutrients. Aim: To evaluate the impact of high sugar-fat diet in the development of metabolic-inflammatory disorders in non-obese animals. Methods: Male Wistar rats were distributed into two groups according to the diet: control and high sugar-fat for 30 weeks. It was analyzed: dietary efficiency;chow, water and caloric intake;metabolic and hormonal profile in plasma and inflammatory cytokines in epididymal adipose tissue. Data were compared by Student’s t test or by Mann-Whitney U test with p Results: HSF presented lower chow intake, higher water consumption and dietary efficiency with no difference in the caloric intake. The final body weight (FBW) and weight gain (WG) were lower in the HSF group and there was no difference in the adiposity index (AI). HSF diet-induced hyperglycemia and hyperinsulinemia with no difference for Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). Triglycerides, uric acid, adiponectin and leptin levels were higher in the HSF group. The HSF group showed increased interleukin-6 (IL-6) and tumoral necrosis factor-alpha (TNF-α) levels in epidydimal adipose tissue. The urinary protein-creatinine ratio and albuminuria were higher in the HSF group. Conclusion: HSF diet intake is directly involved in the development of metabolic-inflammatory disorders independent of obesity, dissociating the view that increased adiposity is the major risk factor for complications commonly found in obese individuals.

Liujunzi decoction ameliorats cisplatin-induced anorexia via adjusting metabolic disorders in rats

OBJECTIVE Cisplatin is a formidable chemotherapy agent widely applying in antineoplastic treatments,but its side effects often limit the clinical usage.Metabolic disorders are one of the side effects induced by cisplatin,which closely relate to the onset of chemotherapy-induced anorexia(CIA)in cancer patients but lacks effective controls.Liujunzi decoction(LJZD)is a traditional Chinese formula that has a promising effect in treating CIA.However,whether LJZD ameliorates CIA through adjusting cisplatin-induced metabolic disorders remain unknow.The present study evaluated the mechanism of cisplatin-induced metabolic disorders,and the effect of LJZD in ameliorating these disturbances.METHODS 42 male Sprague-Dawley(SD)rats(180-220 g)were randomly divided into 3 groups:normal control group(distilled water+saline),model group(distilled water+cisplatin),LJZD group(4.8 g·kg^(-1)Liujunzi decoction ingredients+cisplatin).Intragastrical administered each drug twice a day(7∶00-19∶00)since day 0 for 4 d,animals were intraperitoneal injected with cisplatin 6 mg·kg^(-1)1 h after administration while normal control groups were injected with same volume of saline.On day 3,each group was anesthetized with pentobarbital sodium 45 mg·kg^(-1)(ip),and blood samples were collected from aorta abdominalis.Then the samples were analyzed using an LC-ESI-MS/MS system.Significantly regulated metabolites between groups were determined by VIP≥1 and absolute Log2FC(fold change)≥1.Identified metabolites were mapped to Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway database using Metaboanalyst 5.0(https://www.metaboanalyst.ca/).RESULTS A total of 133,77 and 32 differential metabolites were filtrated in control vs model,control vs LJZD and model vs LJZD groups respectively.Comparing to control,the levels of hexadecanoic acid(Log2FC=6.3153),linoleic acid(Log2FC=5.3478),and 8,11-icosadienoic acid(Log2FC=5.2342)significantly increased,and the levels of N-acetyl-L-tyrosine(Log2FC=-2.6283),cinnamic acid(Log2FC=-2.3381),N-acetylphenylalanine(Log2FC=-2.2501)significantly decreased in model group.The KEGG pathway enrichments of these metabolites indicated that,cisplatin-induced metabolic disorders by disturbing metabolism pathways such as linoleic acid metabolism,biosynthesis of unsaturated fatty acids,and phenylalanine metabolism,which suggested that the onset of CIA was partly associated with the metabolic disorders of linoleic acid,unsaturated fatty acids,and phenylalanine.Compared to control,treatment of LJZD significantly increased the levels of 4-hydroxytryptamine(Log2FC=12.0186),hexadecanoic acid(Log2FC=5.7412),linoleic acid(Log2FC=5.1877)and significantly decreased the levels of N-acetylmethionine(Log2FC=-1.7317),2-aminoethanesulfinic acid(Log2FC=-1.6578),N-acetyl-L-tyrosine(Log2FC=-1.5355).And comparing to the model group,4-hydroxytryptamine(Log2FC=12.0186),7,12-diketocholic acid(Log2FC=2.0998),N-acetylneuraminic acid(Log2FC=2.0560)markedly increased,and 3-hydroxy-3-methylpentane-1(Log2FC=-1.9202),5-dioic acid(Log2FC=-1.7166),N-isovaleroylglycine,hexanoyl glycine(Log2FC=-1.4958)markedly decreased in LJZD group.It was worth noting that,there were 23 differential metabolites filtrated both in control vs model and model vs LJZD groups,which were the key metabolites of LJZD in treating CIA.Among these 23 common metabolites,there were 16 metabolites excluding the control vs LJZD group,that was,LJZD had no effect in normal rats while being able to ameliorated cisplatin-induced metabolic disorders by regulating these 16 metabolites.Cisplatin-induced downregulation of 11 metabolites such as hydrocinnamic acid,(±)12(13)epoxy-9Z-octadecenoic acid,cinnamic acid were upregulated after LJZD treatment,and cisplatin-induced upregulation of imidazoleacetic acid,2′-deoxycytidine-5′-monophosphate and other 5 metabolites were downregulated by LJZD.The KEGG pathway analysis indicated that the linoleic acid metabolism,histidine metabolism,and pyrimidine metabolism were the most enriched metabolic pathway.Thus,cisplatin-induced metabolic disturbances mainly by disturbing linoleic acid metabolism,histidine metabolism,and pyrimidine metabolism,and LJZD interacted with these metabolic pathways to reduce metabolic disorders and thus ameliorated CIA.CONCLUSION Cisplatin-induced anorexia was closely related to the metabolic disorders of linoleic acid metabolism,biosynthesis of unsaturated fatty acids,and phenylalanine metabolism.The mechanism of LJZD in ameliorating CIA was in concerned with the metabolic adjustments,relating to the regulation of linoleic acid metabolism,histidine metabolism,and pyrimidine metabolism.

Relationship between Binge Eating Disorder (BED) and Development of Metabolic Syndrome (METs): A Systematic Review

Binge Eating Disorder (BED) or uncontrolled food consumption is strongly associated with metabolic syndrome as a significant risk factor for health. Metabolic Syndrome (MetS) is characterized by central adiposity, high-density lipoprotein (HDL) cholesterol, hypertriglyceridemia, hypertension, and increased fasting blood glucose. Approximately 9% of the general population suffer from Binge eating disorder (BED), a significant risk factor for Metabolic Syndrome (MetS). This study evaluates the association between Binge Eating disorder (BED) and Metabolic Syndrome (MetS) development through a systematic review. Through analysis of previous studies, we discovered that 93 percent of those with BED had metabolic syndrome parameters in a series of investigations on BED conducted in general care. This systematic review aims to connect the frequency of binge-eating episodes and the development of metabolic syndrome. We have extracted five major studies (n = 5) through screening following systematic review standards.

Influence of Metabolic Syndrome versus Musculoskeletal Disorders on Saudi Health-Related Quality of Life

Aim: This work aimed to study the influence of two chronic health conditions, metabolic syndrome (MetS) and musculoskeletal disorders (MSDs), on the health-related quality of life (HRQoL) of Saudis. Method: The Medical Outcomes Study Short Form-36 (SF-36) health status questionnaire was used to measure the HRQoL and compare the mean scores of the questionnaire subscales and physical and mental component summaries (PCS and MCS) of 33 patients with MetS, 18 patients with MSDs, and 30 apparently healthy (AH) subjects. Regression analysis was used to measure the prediction power of the study group, age and gender of the participants in estimating the HRQoL. Results: Results showed that the mean scores of the physical subscales, the PCS, the mental subscales and MCS were arranged in descending order from AH subjects, patients with MetS, to patients with MSDs. The mean scores difference among the 3 study groups were statistically significant with the only exception for the general mental health (GMH) subscale (P = 0.404). The study group and age accounted for 41.8% of the variability of PCS while the study group accounted for 19.6% of the variability in the MCS. The resulted equation to estimate the PCS score was as follows: PCS = 113.18 - 12.85 (Group: 0 for AH, 1 for MetS, and 2 for MSDs) - 0.67 age. On the other hand the resulted equation to estimate the MCS score was as follows: MCS = 76.203 - 10.426 (Group: 0 for AH, 1 for MetS, and 2 for MSDs). Conclusion: Patients with MetS and patients with MSDs had lower HRQoL than AH subjects. All the physical and mental dimensions of HRQoL are negatively influenced with MetS and with MSDs with the only exception for the GMH subscale. The physical and mental burden of MSDs is more dominant. The study group and age can be used to predict the PCS while the study group can be used to predict the MCS.

Metabolic Emergencies in Newborns in a Subsaharian Neonatology Department: Evaluation of Glucose, Sodium and Potassium Disorders

Introduction: Metabolic neonatal adaptation is a complex phenomenon and metabolic disorders can be frequent in immature newborns or in life-threatening situations. In Low and Middle income countries (LMIC) the difficult access to some diagnostic tests makes the management of the metabolic emergencies challenging. The main objectives of this study were to assess the frequency and circumstances of occurrence and to describe the clinical picture associated with glucose, sodium and potassium disorders in neonates. Patients and Methods: Our study was a retrospective and descriptive study conducted in the neonatology unit of National Children Hospital Albert Royer in Dakar (Senegal) from January 1 to December 31, 2014. Results: The prevalence of the studied metabolic disorders was 46.7%. The most common metabolic disorder noted was Hyperglycemia followed by Hyponatremia. Thermoregulation disturbances were found particularly in newborns with serum sodium disorders (hyponatremia 33.5% and hypernatremia 59.7%). Neurological signs were noted in case of blood sugar abnormalities (hypoglycemia 26.1% and hyperglycemia 29.8%). Half of the newborns with hyperglycemia (82 cases/50%) had blood sugar levels greater than or equal to 2 g/l. Hypernatremia was severe (Serum sodium> 180 mmol/l) in 12 neonates (16.7%). The main diagnoses retained were sepsis (159 cases/45.4%), prematurity (96 cases/27.4%), intrauterine growth retardation (66 cases/18.9%), malformations (63 cases/18%), perinatal asphyxia (44 cases/12.6%) and malnutrition (36 cases/10.3%). For most metabolic disorders, the correction was late and was done beyond 48 hours. On average, the correction time varied between 3 hours and 6 days. The most frequent complications were cerebral edema (12 cases), brain death (8 cases) and increased intracranial pressure (3 cases). The most lethal disorders were Hyperkalemia followed by Hyperglycemia. Conclusion: Metabolic disorders especially glucose, sodium and potassium disorders are common in newborns. They are medical emergencies that can lead to vital instability and death. Their management is challenging in low-income countries due to the lack of adapted facilities and means to diagnose them. It is therefore important to improve the availability of technical methods and means of biological analysis in hospital laboratories and to monitor closely all newborns for early diagnosis of these disorders.

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.

Advanced glycation end product signaling and metabolic complications:Dietary approach

Advanced glycation end products(AGEs)are a heterogeneous collection of compounds formed during industrial processing and home cooking through a sequence of nonenzymatic glycation reactions.The modern western diet is full of heat-treated foods that contribute to AGE intake.Foods high in AGEs in the contemporary diet include processed cereal products.Due to industrialization and marketing strategies,restaurant meals are modified rather than being traditionally or conventionally cooked.Fried,grilled,baked,and boiled foods have the greatest AGE levels.Higher AGE-content foods include dry nuts,roasted walnuts,sunflower seeds,fried chicken,bacon,and beef.Animal proteins and processed plant foods contain furosine,acrylamide,heterocyclic amines,and 5-hydroxymethylfurfural.Furosine(2-furoil-methyl-lysine)is an amino acid found in cooked meat products and other processed foods.High concentrations of carboxymethyl-lysine,carboxyethyl-lysine,and methylglyoxal-O are found in heat-treated nonvegetarian foods,peanut butter,and cereal items.Increased plasma levels of AGEs,which are harmful chemicals that lead to age-related diseases and physiological aging,diabetes,and autoimmune/inflammatory rheumatic diseases such as systemic lupus erythematosus and rheumatoid arthritis.AGEs in the pathophysiology of metabolic diseases have been linked to individuals with diabetes mellitus who have peripheral nerves with high amounts of AGEs and diabetes has been linked to increased myelin glycation.Insulin resistance and hyperglycemia can impact numerous human tissues and organs,leading to long-term difficulties in a number of systems and organs,including the cardiovascular system.Plasma AGE levels are linked to all-cause mortality in individuals with diabetes who have fatal or nonfatal coronary artery disease,such as ventricular dysfunction.High levels of tissue AGEs are independently associated with cardiac systolic dysfunction in diabetic patients with heart failure compared with diabetic patients without heart failure.It is widely recognized that AGEs and oxidative stress play a key role in the cardiovascular complications of diabetes because they both influence and are impacted by oxidative stress.All chronic illnesses involve protein,lipid,or nucleic acid modifications including crosslinked and nondegradable aggregates known as AGEs.Endogenous AGE formation or dietary AGE uptake can result in additional protein modifications and stimulation of several inflammatory signaling pathways.Many of these systems,however,require additional explanation because they are not entirely obvious.This review summarizes the current evidence regarding dietary sources of AGEs and metabolism-related complications associated with AGEs.