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.

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.

Inonotus obliquus(Chaga)against HFD/STZ-induced glucolipid metabolism disorders and abnormal renal functions by regulating NOS-cGMP-PDE5 signaling pathway

Our prior investigations have established that Inonotus obliquus(Chaga)possesses hypoglycemic effects.Persistent hyperglycemia is known to precipitate renal function abnormalities.The functionality of the kidneys is intricately linked to the levels of cyclic guanosine-3',5'-monophosphate(cGMP),which are influenced by the activities of nitric oxide synthase(NOS)and phosphodiesterase(PDE).Enhanced cGMP levels can be achieved either through the upregulation of NOS activity or the downregulation of PDE activity.The objective of the current study is to elucidate the effects of Chaga on disorders of glucolipid metabolism and renal abnormalities in rats with type 2 diabetes mellitus(T2DM),while concurrently examining the NOS-cGMP-PDE5 signaling pathway.A model of T2DM was developed in rats using a high-fat diet(HFD)combined with streptozotocin(STZ)administration,followed by treatment with Chaga extracts at doses of 50 and 100 mg·kg^(−1)for eight weeks.The findings revealed that Chaga not only mitigated metabolic dysfunctions,evidenced by improvements in fasting blood glucose,total cholesterol,triglycerides,and insulin resistance,but also ameliorated renal function markers,including serum creatinine,urine creatinine(UCr),blood urea nitrogen,24-h urinary protein,and estimated creatinine clearance.Additionally,enhancements in glomerular volume,GBM thickness,podocyte foot process width(FPW),and the mRNA and protein expressions of podocyte markers,such as nephrin and wilms tumor-1,were observed.Chaga was found to elevate cGMP levels in both serum and kidney tissues by increasing mRNA and protein expressions of renal endothelial NOS and neural NOS,while simultaneously reducing the expressions of renal inducible NOS and PDE5.In summary,Chaga counteracts HFD/STZ-induced glucolipid metabolism and renal function disturbances by modulating the NOS-cGMP-PDE5 signaling pathway.This research supports the potential application of Chaga in the clinical prevention and treatment of T2DM and diabetic nephropathy(DN),with cGMP serving as a potential therapeutic target.

Transcriptome reveals overview of Ca^(2+) dose-dependent metabolism disorders in zebrafish larvae after Cd^(2+) exposure

Cadmium (Cd),a ubiquitous environmental hazardous heavy metal,poses a significant threat to the health of aquatic organisms,including teleosts.Although the toxic profile of Cd is well recognized,little is known regarding the overall view of toxic responses to varying aquatic environmental parameters (e.g.,water hardness) at an individual level.Herein,differences in water hardness were partially mimicked by adjusting Ca^(2+)levels in E3 medium.As an in vivo model,zebrafish embryos were exposed to variable Ca^(2+)levels (NV,normal Ca^(2+);LV,low Ca^(2+);HV,high Ca^(2+)) alone or combined with 30.7μg/L Cd^(2+)(NC,LC,and HC,respectively) until 144 hr post-fertilization.The genome-wide transcriptome revealed differentially expressed genes between groups.Functional enrichment analysis found that biological processes related to metabolism,particularly lipid metabolism,were significantly disrupted in NC and LC treatments,while a remission was observed in the HC group.Biochemical assays confirmed that the decrease in Ca^(2+)enhanced synthesis,inhibited mobilization and increased the storage of lipids in Cd^(2+)treatments.This study suggests that the toxic effect of Cd on biological pathways will be influenced by Ca^(2+),which will improve the toxicological understanding and facilitate accurate assessment of Cd.

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.

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.

Asiaticoside ameliorates type 2 diabetes mellitus in rats by modulating carbohydrate metabolism and regulating insulin signaling

Objective:To evaluate the effect of asiaticoside on streptozotocin(STZ)and nicotinamide(NAD)-induced carbohydrate metabolism abnormalities and deregulated insulin signaling pathways in rats.Methods:Asiaticoside(50 and 100 mg/kg body weight)was administered to STZ-NAD-induced diabetic rats for 45 days,and its effects on hyperglycaemic,carbohydrate metabolic,and insulin signaling pathway markers were examined.Results:Asiaticoside increased insulin production,lowered blood glucose levels,and enhanced glycolysis by improving hexokinase activity and suppressing glucose-6-phosphatase and fructose-1,6-bisphosphatase activities.Abnormalities in glycogen metabolism were mitigated by increasing glycogen synthase activity and gluconeogenesis was decreased by decreasing glycogen phosphorylase activity.Furthermore,asiaticoside upregulated the mRNA expressions of IRS-1,IRS-2,and GLUT4 in STZ-NAD-induced diabetic rats and restored the beta cell morphology to normal.Conclusions:Asiaticoside has the potential to ameliorate type 2 diabetes by improving glycolysis,gluconeogenesis,and insulin signaling pathways.

Targeting uridine diphosphate glucuronosyltransferase 1A1 in liver disease:Current research and future directions

The current letter to the editor pertains to the manuscript entitled'Uridine diphosphate glucuronosyltransferase 1A1 prevents the progression of liver injury'.Increased levels of uridine diphosphate glucuronosyltransferase 1A1 during liver injury could mitigate damage by reducing endoplasmic reticulum stress,oxidative stress,and dysregulated lipid metabolism,impeding hepatocyte apoptosis and necroptosis.

Uridine diphosphate glucuronosyltransferase 1A1 prevents the progression of liver injury

BACKGROUND Uridine diphosphate glucuronosyltransferase 1A1(UGT1A1)plays a crucial role in metabolizing and detoxifying endogenous and exogenous substances.However,its contribution to the progression of liver damage remains unclear.AIM To determine the role and mechanism of UGT1A1 in liver damage progression.METHODS We investigated the relationship between UGT1A1 expression and liver injury through clinical research.Additionally,the impact and mechanism of UGT1A1 on the progression of liver injury was analyzed through a mouse model study.RESULTS Patients with UGT1A1 gene mutations showed varying degrees of liver damage,while patients with acute-onchronic liver failure(ACLF)exhibited relatively reduced levels of UGT1A1 protein in the liver as compared to patients with chronic hepatitis.This suggests that low UGT1A1 levels may be associated with the progression of liver damage.In mouse models of liver injury induced by carbon tetrachloride(CCl_(4))and concanavalin A(ConA),the hepatic levels of UGT1A1 protein were found to be increased.In mice with lipopolysaccharide or liver steatosis-mediated liver-injury progression,the hepatic protein levels of UGT1A1 were decreased,which is consistent with the observations in patients with ACLF.UGT1A1 knockout exacerbated CCl_(4)-and ConA-induced liver injury,hepatocyte apoptosis and necroptosis in mice,intensified hepatocyte endoplasmic reticulum(ER)stress and oxidative stress,and disrupted lipid metabolism.CONCLUSION UGT1A1 is upregulated as a compensatory response during liver injury,and interference with this upregulation process may worsen liver injury.UGT1A1 reduces ER stress,oxidative stress,and lipid metabolism disorder,thereby mitigating hepatocyte apoptosis and necroptosis.

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.

Roles of fibroblast growth factors in the treatment of diabetes

Diabetes affects about 422 million people worldwide,causing 1.5 million deaths each year.However,the incidence of diabetes is increasing,including several types of diabetes.Type 1 diabetes(5%-10%of diabetic cases)and type 2 diabetes(90%-95%of diabetic cases)are the main types of diabetes in the clinic.Accumulating evidence shows that the fibroblast growth factor(FGF)family plays important roles in many metabolic disorders,including type 1 and type 2 diabetes.FGF consists of 23 family members(FGF-1-23)in humans.Here,we review current findings of FGFs in the treatment of diabetes and management of diabetic complications.Some FGFs(e.g.,FGF-15,FGF-19,and FGF-21)have been broadly investigated in preclinical studies for the diagnosis and treatment of diabetes,and their therapeutic roles in diabetes are currently under investigation in clinical trials.Overall,the roles of FGFs in diabetes and diabetic complications are involved in numerous processes.First,FGF intervention can prevent high-fat diet-induced obesity and insulin resistance and reduce the levels of fasting blood glucose and triglycerides by regulating lipolysis in adipose tissues and hepatic glucose production.Second,modulation of FGF expression can inhibit renal and cardiac fibrosis by regulating the expression of extracellular matrix components,promote diabetic wound healing process and bone repair,and inhibit cancer cell proliferation and migration.Finally,FGFs can regulate the activation of glucoseexcited neurons and the expression of thermogenic genes.

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.

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.

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.

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.

Infant with cardiomyopathy: When to suspect inborn errors of metabolism?

Inborn errors of metabolism are identified in 5%-26% of infants and children with cardiomyopathy. Although fatty acid oxidation disorders, lysosomal and glycogen storage disorders and organic acidurias are well-known to be associated with cardiomyopathies, emerging reports suggest that mitochondrial dysfunction and congenital disorders of glycosylation may also account for a proportion of cardiomyopathies. This review article clarifies when primary care physicians and cardiologists should suspect inborn errors of metabolism in a patient with cardiomyopathy, and refer the patient to a metabolic specialist for a further metabolic work up, with specific discussions of "red flags" which should prompt additional evaluation.

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.

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.

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.