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 ...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.展开更多
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 leadin...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.展开更多
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 cispla...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.展开更多
Polyhalogenated carbazoles(PHCZs)have been widely accepted as emerging pollutants,whereas their ecological and health risks remain uncertain.Herein,female and male Sprague-Dawley(SD)mice were treated with four typical...Polyhalogenated carbazoles(PHCZs)have been widely accepted as emerging pollutants,whereas their ecological and health risks remain uncertain.Herein,female and male Sprague-Dawley(SD)mice were treated with four typical PHCZs to investigate their negative consequences,along with alternations in gutmicrobiota to indicate underlyingmechanisms.In female mice,the relative liver weight ratio increased after four PHCZs exposure;2-bromocarbazole(2-BCZ)increased urine glucose level;3-bromocarbazole(3-BCZ)decreased the glucose and total cholesterol levels;3,6-dichlorocarbazole(3,6-DCCZ)decreased glucose level.The only disturbed biochemical index in male mice was the promoted alkaline phosphatase(ALP)level by 3,6-DCCZ.We also found that the differential blood biochemical indices were correlated with gut microbiota.3-BCZ and 3,6-DCCZ altered Bacteroidetes and Proteobacteria phyla in female and male mice,which were correlated with metabolic disorders.Our findings demonstrated the correlation between PHCZs induced potential hepatotoxicity andmetabolic disordersmay be due to their dioxin-like potentials and endocrine disrupting activities,and the gender differences might result from their estrogenic activities.Overall,data presented here can help to evaluate the ecological and health risks of PHCZs and reveal the underlying mechanisms.展开更多
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 effec...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.展开更多
A metabolically healthy status,whether obese or not,is a transient stage with the potential to develop into metabolic disor-ders during the course of life.We investigated the incidence of metabolic disorders in 1078 m...A metabolically healthy status,whether obese or not,is a transient stage with the potential to develop into metabolic disor-ders during the course of life.We investigated the incidence of metabolic disorders in 1078 metabolically healthy Chinese adults from the Shanghai Changfeng Study and looked for metabolites that discriminated the participants who would develop metabolic disorders in the future.Participants were divided into metabolically healthy overweight/obesity(MHO)and meta-bolically healthy normal weight(MHNW)groups according to their body mass index(BMI)and metabolic status.Their serum metabolomic profile was measured using a ^(1)H nuclear magnetic resonance spectrometer(^(1)H-NMR).The prevalence of diabetes,hypertriglyceridemia,hypercholesterolemia and metabolic syndrome was similar between the MHNW and MHO participants at baseline.After a median of 4.2 years of follow-up,more MHO participants became metabolically unhealthy than MHNW participants.However,a subgroup of MHO participants who remained metabolically healthy(MHO→MHO)had a similar prevalence of metabolic disorders as the MHNW participants at the follow-up examination,despite a signifi-cant reduction in their serum concentrations of high-density lipoprotein(HDL)and an elevation in valine,leucine,alanine and tyrosine.Further correlation analysis indicated that serum intermediate-density lipoprotein(IDL)and very low-density lipoprotein cholesterol(VLDL-CH)might be involved in the transition from metabolically healthy to unhealthy status and could be valuable to identify the MHNW and MHO with increased metabolic risks.展开更多
Metabolic disorders are public health problems that require prevention and new efficient drugs for treatment.Cellular repressor of E1A-stimulated genes(CREG)is ubiquitously expressed in mature tissues and cells in mam...Metabolic disorders are public health problems that require prevention and new efficient drugs for treatment.Cellular repressor of E1A-stimulated genes(CREG)is ubiquitously expressed in mature tissues and cells in mammals and plays a critical role in keeping cells or tissues in a mature,homeostatic state.Recently,CREG turns to be an important mediator in the development of metabolic disorders.Here in this review,we briefly discuss the structure and molecular regulation of CREG along with the therapeutic strategy to combat the metabolic disorders.展开更多
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 difficu...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.展开更多
Background: Weight gain during chemotherapy in patients with breast cancer contributes to their poor prognosis. However, a growing number of studies have found that metabolic disorders seem to play a more important ro...Background: Weight gain during chemotherapy in patients with breast cancer contributes to their poor prognosis. However, a growing number of studies have found that metabolic disorders seem to play a more important role in breast cancer prognosis than weight gain. This study aimed to explore the prognostic effects of body mass index (BMI), weight gain, and metabolic disorders on the overall survival (OS) and prognosis of patients with breast cancer who underwent chemotherapy.Methods: Data from the inpatient medical records of patients with breast cancer who underwent chemotherapy at the Beijing Cancer Hospital Breast Cancer Center from January to December 2010 were retrospectively collected, and the patients were followed up until August 2020.Results: A total of 438 patients with stages I to III breast cancer met the inclusion and exclusion criteria. Forty-nine (11.19%) patients died, while 82 (18.72%) patients had tumor recurrence and metastasis at the last follow-up (August 2020). From the time of diagnosis until after chemotherapy, no significant differences were observed in the body weight (t=4.694,P<0.001), BMI categories (χ^(2)=19.215,P=0.001), and incidence of metabolic disorders (χ^(2)=24.841,P<0.001);the BMI categories and weight change had no effect on the OS. Both univariate (χ^(2)=6.771,P=0.009) and multivariate survival analyses (hazard ratio=2.775, 95% confidence interval [CI]: 1.326-5.807,P=0.007) showed that low high-density lipoprotein cholesterol (HDL-C) levels at diagnosis had a negative impact on the OS. The multivariate logistic regression analysis showed that the HDL-C level at diagnosis (odds ratio [OR]=2.200, 95% CI: 0.996-4.859,P=0.051) and metabolic disorders after chemotherapy (OR=1.514, 95% CI: 1.047-2.189,P=0.028) are risk factors for poor prognosis in patients with breast cancer.Conclusions: Chemotherapy led to weight gain and aggravated the metabolic disorders in patients with breast cancer. Low HDL-C levels at diagnosis and metabolic disorders after chemotherapy may have negative effects on the OS and prognosis of patients with breast cancer.展开更多
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 sedent...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.展开更多
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 f...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.展开更多
Metabolic associated fatty liver disorder(MAFLD)characterizes the contributing etiologies(i.e.,type 2 diabetes mellitus,metabolic syndrome,overweight)of individuals with fatty liver disease that affects 1/3rd of the w...Metabolic associated fatty liver disorder(MAFLD)characterizes the contributing etiologies(i.e.,type 2 diabetes mellitus,metabolic syndrome,overweight)of individuals with fatty liver disease that affects 1/3rd of the world population.In 2020,the coronavirus disease 2019(COVID-19)crisis was unprecedented,and people with different comorbidities became more susceptible to the infection caused by severe acute respiratory syndrome coronavirus 2.MAFLD patients are frequently obese with added metabolic menace like diabetes,hypertension,and dyslipidemia leading to greater jeopardy of COVID-19.MAFLD patients are 4 to 6-fold more prone towards infections.COVID-19 induces liver injury with elevated levels of aspartate aminotransferase and alanine aminotransferase and insignificantly elevated bilirubin.Hence,MAFLD in COVID-19 patients worsens the condition significantly.The evidence highlighting the interaction between MAFLD and altered liver functioning in COVID-19 suggested that COVID-19 patients with pre-existing MAFLD are at greater risk of morbidity or intensive care unit admission.Direct hepatic injury,enhanced levels of inflammatory cytokines,declined hepatic mitochondrial activity,and compromised immunity are considered as some underlying mechanisms.The main focus of this review is to discuss the implications of metabolic dysfunction associated with fatty liver disease in COVID-19 patients.The review systematically analyzes the effect of striking two worldwide pandemics(MAFLD and COVID-19)together in the present era.展开更多
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 ...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.展开更多
Liver transplantation(LT)remains the gold standard treatment for end stage liver disease in the pediatric population.For liver based metabolic disorders(LBMDs),the decision for LT is predicated on a different set of p...Liver transplantation(LT)remains the gold standard treatment for end stage liver disease in the pediatric population.For liver based metabolic disorders(LBMDs),the decision for LT is predicated on a different set of paradigms.With improved outcomes post-transplantation,LT is no longer merely life saving,but has the potential to also significantly improve quality of life.This review summarizes the clinical presentation,medical treatment and indications for LT for some of the common LBMDs.We also provide a practical update on the dilemmas and controversies surrounding the indications for transplantation,surgical considerations and prognosis and long terms outcomes for pediatric LT in LBMDs.Important progress has been made in understanding these diseases in recent years and with that we outline some of the new therapies that have emerged.展开更多
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 re...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.展开更多
There is a recent increase in the worldwide prevalence of both obesity and diabetes.In this review we assessed insulin signaling,genetics,environment,lipid metabolism dysfunction and mitochondria as the major determin...There is a recent increase in the worldwide prevalence of both obesity and diabetes.In this review we assessed insulin signaling,genetics,environment,lipid metabolism dysfunction and mitochondria as the major determinants in diabetes and to identify the potential mechanism of gut microbiota in diabetes diseases.We searched relevant articles,which have key information from laboratory experiments,epidemiological evidence,clinical trials,experimental models,metaanalysis and review articles,in PubMed,MEDLINE,EMBASE,Google scholars and Cochrane Controlled Trial Database.We selected 144 full-length articles that met our inclusion and exclusion criteria for complete assessment.We have briefly discussed these associations,challenges,and the need for further research to manage and treat diabetes more efficiently.Diabetes involves the complex network of physiological dysfunction that can be attributed to insulin signaling,genetics,environment,obesity,mitochondria and stress.In recent years,there are intriguing findings regarding gut microbiome as the important regulator of diabetes.Valid approaches are necessary for speeding medical advances but we should find a solution sooner given the burden of the metabolic disorder―What we need is a collaborative venture that may involve laboratories both in academia and industries for the scientific progress and its application for the diabetes control.展开更多
With the increasing incidence of obesity and metabolic syndrome worldwide,concomitant nonalcoholic fatty liver disease(NAFLD)in patients with chronic hepatitis B(CHB)has become highly prevalent.The risk of dual etiolo...With the increasing incidence of obesity and metabolic syndrome worldwide,concomitant nonalcoholic fatty liver disease(NAFLD)in patients with chronic hepatitis B(CHB)has become highly prevalent.The risk of dual etiologies,outcome,and mechanism of CHB with concomitant NAFLD have not been fully characterized.In this review,we assessed the overlapping prevalence of metabolic disorders and CHB,assessed the risk of advanced fibrosis/hepatocellular carcinoma in CHB patients concomitant with NAFLD,and discussed the remaining clinical issues to be addressed in the outcome of such patients.We also explored the possible roles of hepatitis B virus in the development of steatosis and discussed difficultiesof histological evaluation.For CHB patients,it is important to address concomitant NAFLD through lifestyle management and disease screening to achieve better prognoses.The assessment of progressive changes and novel therapies for CHB patients concomitant with NAFLD deserve further research.展开更多
Background:Metabolic diseases pose considerable burden on the healthcare system worldwide,indicating the significance of prevention and treatment.In constitution theory of traditional Chinese medicine,phlegm-dampness ...Background:Metabolic diseases pose considerable burden on the healthcare system worldwide,indicating the significance of prevention and treatment.In constitution theory of traditional Chinese medicine,phlegm-dampness constitution(PDC)is the common basis of metabolic diseases.In clinical practice,Huatan Qushi(HTQS)decoction targeting on PDC can effectively improve metabolic indicators.However,its underlying biochemical mechanism still remains unclear.Methods:Eight PDC participants received HTQS decoction for three months.Their blood was collected at baseline and 1 and 3 months after intervention started.Related biomedical indicators were detected.High-throughput sequencing and RT-qPCR were used for validation.Due to the missing data,repeated measures with missing values in mixed models were used.Results:After 3-month treatment,HDL-C level increased(P<.001)and FBG,FINS,and HbA1c all showed decreasing trend at different time points(all P<.05).After miRNA high-throughput sequencing,compared with the baseline,differential miRNAs at 1 and 3 months were screened,and target gene prediction and KEGG pathway enrichment analysis were performed.The results displayed that metabolic disease-related pathways mainly included pathways in cancer,PI3K-Akt signaling pathway,etc.Further,RT-qPCR showed that hsa-miR-1237e3p differed statistically(P=.008).Then we validated the target genes of hsa-miR-1237e3p in the“Pathways in Cancer”pathway including SDF1,AC,CRK,and HGF,also known as upstream target genes of PI3K/AKT pathway.The results showed that two indicators of CRK and HGF were in statistical significance(P=.045 and P=.036,respectively).Conclusion:PDC serves as a common basis for various metabolic diseases.Through adjusting PDC,HTQS decoction can improve biomedical indicators including blood glucose,HbA1c,insulin,and HDL-C.The target pathway is“Pathways in cancer”.Specifically,HTQS decoction acts on targets of CRK and HGF by regulating hsa-miR-1237e3p,and probably exerts effects on their downstream PI3K/AKT pathway.展开更多
Amplified inflammatory reaction has been observed to be involved in cardiometabolic diseases such as obesity,insulin resistance,diabetes,dyslipidemia,and atherosclerosis.The complement system was originally viewed as ...Amplified inflammatory reaction has been observed to be involved in cardiometabolic diseases such as obesity,insulin resistance,diabetes,dyslipidemia,and atherosclerosis.The complement system was originally viewed as a supportive first line of defense against microbial invaders,and research over the past decade has come to appreciate that the functions of the complement system extend beyond the defense and elimination of microbes,involving in such diverse processes as clearance of the immune complexes,complementing T and B cell immune functions,tissue regeneration,and metabolism.The focus of this review is to summarize the role of the activation of complement system and the initiation and progression of metabolic disorders including obesity,insulin resistance and diabetes mellitus.In addition,we briefly describe the interaction of the activation of the complement system with diabetic complications such as diabetic retinopathy,nephropathy and neuropathy,highlighting that targeting complement system therapeutics could be one of possible routes to slow down those aforementioned diabetic complications.展开更多
The gastrointestinal tract is the key interface between the ingesta and the human body.There is wide recognition that the gastrointestinal response to nutrients or bioactive compounds,particularly the secretion of num...The gastrointestinal tract is the key interface between the ingesta and the human body.There is wide recognition that the gastrointestinal response to nutrients or bioactive compounds,particularly the secretion of numerous hormones,is critical to the regulation of appetite,body weight and blood glucose.This concept has led to an increasing focus on“gut-based”strategies for the management of metabolic disorders,including type 2 diabetes and obesity.Understanding the underlying mechanisms and downstream effects of nutrient-gut interactions is fundamental to effective translation of this knowledge to clinical practice.To this end,an array of research tools and platforms have been developed to better understand the mechanisms of gut hormone secretion from enteroendocrine cells.This review discusses the evolution of in vitro and in vivo models and the integration of innovative techniques that will ultimately enable the development of novel therapies for metabolic diseases.展开更多
文摘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.
基金INSERM to Inserm U1060“Région Rh?ne-Alpes”,No.ARC 2013-ARC1 SANTE-13-018955-01(to Labaronne E)
文摘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.
基金National Natural Science Foundation of China(82174143)and Scientific Research Foundation of Guangdong Pharmaceutical University(51348136)。
文摘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.
基金supported by Joint Innovation Fund for Regional Development of National Natural Science Foundation of China(No.U20A20134)Leading Talent of Technological Innovation of Ten-Thousands Talents Program of Zhejiang Province(No.2020R52012).
文摘Polyhalogenated carbazoles(PHCZs)have been widely accepted as emerging pollutants,whereas their ecological and health risks remain uncertain.Herein,female and male Sprague-Dawley(SD)mice were treated with four typical PHCZs to investigate their negative consequences,along with alternations in gutmicrobiota to indicate underlyingmechanisms.In female mice,the relative liver weight ratio increased after four PHCZs exposure;2-bromocarbazole(2-BCZ)increased urine glucose level;3-bromocarbazole(3-BCZ)decreased the glucose and total cholesterol levels;3,6-dichlorocarbazole(3,6-DCCZ)decreased glucose level.The only disturbed biochemical index in male mice was the promoted alkaline phosphatase(ALP)level by 3,6-DCCZ.We also found that the differential blood biochemical indices were correlated with gut microbiota.3-BCZ and 3,6-DCCZ altered Bacteroidetes and Proteobacteria phyla in female and male mice,which were correlated with metabolic disorders.Our findings demonstrated the correlation between PHCZs induced potential hepatotoxicity andmetabolic disordersmay be due to their dioxin-like potentials and endocrine disrupting activities,and the gender differences might result from their estrogenic activities.Overall,data presented here can help to evaluate the ecological and health risks of PHCZs and reveal the underlying mechanisms.
基金supported by the grants from National Natural Science Foundation of China(No.82174334)Hainan Provincial Key Laboratory of Tropical Brain Science Research and Transformation Research Project(JCKF2021001)Innovative Research Projects for Graduate Students(HYYS2021B01).
文摘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.
基金supported by the Shanghai Municipal Science and Technology Major Project(2017SHZDZX01)the Science and Technology Commission of Shanghai Municipality(16JC1400500).
文摘A metabolically healthy status,whether obese or not,is a transient stage with the potential to develop into metabolic disor-ders during the course of life.We investigated the incidence of metabolic disorders in 1078 metabolically healthy Chinese adults from the Shanghai Changfeng Study and looked for metabolites that discriminated the participants who would develop metabolic disorders in the future.Participants were divided into metabolically healthy overweight/obesity(MHO)and meta-bolically healthy normal weight(MHNW)groups according to their body mass index(BMI)and metabolic status.Their serum metabolomic profile was measured using a ^(1)H nuclear magnetic resonance spectrometer(^(1)H-NMR).The prevalence of diabetes,hypertriglyceridemia,hypercholesterolemia and metabolic syndrome was similar between the MHNW and MHO participants at baseline.After a median of 4.2 years of follow-up,more MHO participants became metabolically unhealthy than MHNW participants.However,a subgroup of MHO participants who remained metabolically healthy(MHO→MHO)had a similar prevalence of metabolic disorders as the MHNW participants at the follow-up examination,despite a signifi-cant reduction in their serum concentrations of high-density lipoprotein(HDL)and an elevation in valine,leucine,alanine and tyrosine.Further correlation analysis indicated that serum intermediate-density lipoprotein(IDL)and very low-density lipoprotein cholesterol(VLDL-CH)might be involved in the transition from metabolically healthy to unhealthy status and could be valuable to identify the MHNW and MHO with increased metabolic risks.
基金supported by Key R&D Program of Liaoning Province of China(2020JH 2/10300167)Cardiacare Sponsored Optimizing Antithrombotic Research Fund of China(BJUHFCSOARF201901-06).
文摘Metabolic disorders are public health problems that require prevention and new efficient drugs for treatment.Cellular repressor of E1A-stimulated genes(CREG)is ubiquitously expressed in mature tissues and cells in mammals and plays a critical role in keeping cells or tissues in a mature,homeostatic state.Recently,CREG turns to be an important mediator in the development of metabolic disorders.Here in this review,we briefly discuss the structure and molecular regulation of CREG along with the therapeutic strategy to combat the metabolic disorders.
文摘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.
文摘Background: Weight gain during chemotherapy in patients with breast cancer contributes to their poor prognosis. However, a growing number of studies have found that metabolic disorders seem to play a more important role in breast cancer prognosis than weight gain. This study aimed to explore the prognostic effects of body mass index (BMI), weight gain, and metabolic disorders on the overall survival (OS) and prognosis of patients with breast cancer who underwent chemotherapy.Methods: Data from the inpatient medical records of patients with breast cancer who underwent chemotherapy at the Beijing Cancer Hospital Breast Cancer Center from January to December 2010 were retrospectively collected, and the patients were followed up until August 2020.Results: A total of 438 patients with stages I to III breast cancer met the inclusion and exclusion criteria. Forty-nine (11.19%) patients died, while 82 (18.72%) patients had tumor recurrence and metastasis at the last follow-up (August 2020). From the time of diagnosis until after chemotherapy, no significant differences were observed in the body weight (t=4.694,P<0.001), BMI categories (χ^(2)=19.215,P=0.001), and incidence of metabolic disorders (χ^(2)=24.841,P<0.001);the BMI categories and weight change had no effect on the OS. Both univariate (χ^(2)=6.771,P=0.009) and multivariate survival analyses (hazard ratio=2.775, 95% confidence interval [CI]: 1.326-5.807,P=0.007) showed that low high-density lipoprotein cholesterol (HDL-C) levels at diagnosis had a negative impact on the OS. The multivariate logistic regression analysis showed that the HDL-C level at diagnosis (odds ratio [OR]=2.200, 95% CI: 0.996-4.859,P=0.051) and metabolic disorders after chemotherapy (OR=1.514, 95% CI: 1.047-2.189,P=0.028) are risk factors for poor prognosis in patients with breast cancer.Conclusions: Chemotherapy led to weight gain and aggravated the metabolic disorders in patients with breast cancer. Low HDL-C levels at diagnosis and metabolic disorders after chemotherapy may have negative effects on the OS and prognosis of patients with breast cancer.
基金the Scientific Research Project of Jiangsu Health Commission,No.Z2022078the Natural Science Foundation of Jiangsu Province,No.BK20220299.
文摘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.
基金Supported by the Deputyship for Research and Innovation,Ministry of Education and Qassim University,Saudi Arabia(Project No.QUIF-2-2-1-27012).
文摘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.
文摘Metabolic associated fatty liver disorder(MAFLD)characterizes the contributing etiologies(i.e.,type 2 diabetes mellitus,metabolic syndrome,overweight)of individuals with fatty liver disease that affects 1/3rd of the world population.In 2020,the coronavirus disease 2019(COVID-19)crisis was unprecedented,and people with different comorbidities became more susceptible to the infection caused by severe acute respiratory syndrome coronavirus 2.MAFLD patients are frequently obese with added metabolic menace like diabetes,hypertension,and dyslipidemia leading to greater jeopardy of COVID-19.MAFLD patients are 4 to 6-fold more prone towards infections.COVID-19 induces liver injury with elevated levels of aspartate aminotransferase and alanine aminotransferase and insignificantly elevated bilirubin.Hence,MAFLD in COVID-19 patients worsens the condition significantly.The evidence highlighting the interaction between MAFLD and altered liver functioning in COVID-19 suggested that COVID-19 patients with pre-existing MAFLD are at greater risk of morbidity or intensive care unit admission.Direct hepatic injury,enhanced levels of inflammatory cytokines,declined hepatic mitochondrial activity,and compromised immunity are considered as some underlying mechanisms.The main focus of this review is to discuss the implications of metabolic dysfunction associated with fatty liver disease in COVID-19 patients.The review systematically analyzes the effect of striking two worldwide pandemics(MAFLD and COVID-19)together in the present era.
文摘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.
文摘Liver transplantation(LT)remains the gold standard treatment for end stage liver disease in the pediatric population.For liver based metabolic disorders(LBMDs),the decision for LT is predicated on a different set of paradigms.With improved outcomes post-transplantation,LT is no longer merely life saving,but has the potential to also significantly improve quality of life.This review summarizes the clinical presentation,medical treatment and indications for LT for some of the common LBMDs.We also provide a practical update on the dilemmas and controversies surrounding the indications for transplantation,surgical considerations and prognosis and long terms outcomes for pediatric LT in LBMDs.Important progress has been made in understanding these diseases in recent years and with that we outline some of the new therapies that have emerged.
基金the Science and Technology Research Foundations of Guizhou Province,No.QKHJC-ZK(2022)YB642Zunyi Science and Technology Plan Project,No.ZSKHHZ(2022)344,No.ZSKHHZ(2022)360,and No.ZYK160+2 种基金Hubei Province Central Leading Local Science and Technology Development Special Project,No.2022BCE030Changzhou Science and Technology Projects,No.CE20225054Bijie City Science and Planning Bureau,No.BKH(2022)8.
文摘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.
文摘There is a recent increase in the worldwide prevalence of both obesity and diabetes.In this review we assessed insulin signaling,genetics,environment,lipid metabolism dysfunction and mitochondria as the major determinants in diabetes and to identify the potential mechanism of gut microbiota in diabetes diseases.We searched relevant articles,which have key information from laboratory experiments,epidemiological evidence,clinical trials,experimental models,metaanalysis and review articles,in PubMed,MEDLINE,EMBASE,Google scholars and Cochrane Controlled Trial Database.We selected 144 full-length articles that met our inclusion and exclusion criteria for complete assessment.We have briefly discussed these associations,challenges,and the need for further research to manage and treat diabetes more efficiently.Diabetes involves the complex network of physiological dysfunction that can be attributed to insulin signaling,genetics,environment,obesity,mitochondria and stress.In recent years,there are intriguing findings regarding gut microbiome as the important regulator of diabetes.Valid approaches are necessary for speeding medical advances but we should find a solution sooner given the burden of the metabolic disorder―What we need is a collaborative venture that may involve laboratories both in academia and industries for the scientific progress and its application for the diabetes control.
基金Supported by National Key Research and Development Program of China,No.2017YFC0908903National Natural Science Foundation of China,No.81873565 and No.81900507.
文摘With the increasing incidence of obesity and metabolic syndrome worldwide,concomitant nonalcoholic fatty liver disease(NAFLD)in patients with chronic hepatitis B(CHB)has become highly prevalent.The risk of dual etiologies,outcome,and mechanism of CHB with concomitant NAFLD have not been fully characterized.In this review,we assessed the overlapping prevalence of metabolic disorders and CHB,assessed the risk of advanced fibrosis/hepatocellular carcinoma in CHB patients concomitant with NAFLD,and discussed the remaining clinical issues to be addressed in the outcome of such patients.We also explored the possible roles of hepatitis B virus in the development of steatosis and discussed difficultiesof histological evaluation.For CHB patients,it is important to address concomitant NAFLD through lifestyle management and disease screening to achieve better prognoses.The assessment of progressive changes and novel therapies for CHB patients concomitant with NAFLD deserve further research.
基金This work was supported by the National Natural Science Foundation of China(81730112&81874413)Scientific Research and Innovation Team of Beijing University of Chinese Medicine(2019-JYB-TD010).
文摘Background:Metabolic diseases pose considerable burden on the healthcare system worldwide,indicating the significance of prevention and treatment.In constitution theory of traditional Chinese medicine,phlegm-dampness constitution(PDC)is the common basis of metabolic diseases.In clinical practice,Huatan Qushi(HTQS)decoction targeting on PDC can effectively improve metabolic indicators.However,its underlying biochemical mechanism still remains unclear.Methods:Eight PDC participants received HTQS decoction for three months.Their blood was collected at baseline and 1 and 3 months after intervention started.Related biomedical indicators were detected.High-throughput sequencing and RT-qPCR were used for validation.Due to the missing data,repeated measures with missing values in mixed models were used.Results:After 3-month treatment,HDL-C level increased(P<.001)and FBG,FINS,and HbA1c all showed decreasing trend at different time points(all P<.05).After miRNA high-throughput sequencing,compared with the baseline,differential miRNAs at 1 and 3 months were screened,and target gene prediction and KEGG pathway enrichment analysis were performed.The results displayed that metabolic disease-related pathways mainly included pathways in cancer,PI3K-Akt signaling pathway,etc.Further,RT-qPCR showed that hsa-miR-1237e3p differed statistically(P=.008).Then we validated the target genes of hsa-miR-1237e3p in the“Pathways in Cancer”pathway including SDF1,AC,CRK,and HGF,also known as upstream target genes of PI3K/AKT pathway.The results showed that two indicators of CRK and HGF were in statistical significance(P=.045 and P=.036,respectively).Conclusion:PDC serves as a common basis for various metabolic diseases.Through adjusting PDC,HTQS decoction can improve biomedical indicators including blood glucose,HbA1c,insulin,and HDL-C.The target pathway is“Pathways in cancer”.Specifically,HTQS decoction acts on targets of CRK and HGF by regulating hsa-miR-1237e3p,and probably exerts effects on their downstream PI3K/AKT pathway.
文摘Amplified inflammatory reaction has been observed to be involved in cardiometabolic diseases such as obesity,insulin resistance,diabetes,dyslipidemia,and atherosclerosis.The complement system was originally viewed as a supportive first line of defense against microbial invaders,and research over the past decade has come to appreciate that the functions of the complement system extend beyond the defense and elimination of microbes,involving in such diverse processes as clearance of the immune complexes,complementing T and B cell immune functions,tissue regeneration,and metabolism.The focus of this review is to summarize the role of the activation of complement system and the initiation and progression of metabolic disorders including obesity,insulin resistance and diabetes mellitus.In addition,we briefly describe the interaction of the activation of the complement system with diabetic complications such as diabetic retinopathy,nephropathy and neuropathy,highlighting that targeting complement system therapeutics could be one of possible routes to slow down those aforementioned diabetic complications.
基金Supported by the National Health and Medical Research Council(NHMRC)of Australia,No.APP1147333the National Nature Science Foundation of China,No.81870561+1 种基金the Hospital Research Foundation of Australiathe Australian Research Council Centre of Excellence for Nanoscale BioPhotonics,No.CE140100003.
文摘The gastrointestinal tract is the key interface between the ingesta and the human body.There is wide recognition that the gastrointestinal response to nutrients or bioactive compounds,particularly the secretion of numerous hormones,is critical to the regulation of appetite,body weight and blood glucose.This concept has led to an increasing focus on“gut-based”strategies for the management of metabolic disorders,including type 2 diabetes and obesity.Understanding the underlying mechanisms and downstream effects of nutrient-gut interactions is fundamental to effective translation of this knowledge to clinical practice.To this end,an array of research tools and platforms have been developed to better understand the mechanisms of gut hormone secretion from enteroendocrine cells.This review discusses the evolution of in vitro and in vivo models and the integration of innovative techniques that will ultimately enable the development of novel therapies for metabolic diseases.
