Effect of Maternal DEHP Exposure on Lipid Metabolism in Adult Male Rats and the Antagonistic Effect of Genistein

Lipid metabolism refers to the biochemical processes involved in synthesising,storing,utilising,and breaking down lipids in living organisms.Lipids are essential for various physiological functions,including energy storage,insulation,protection of organs,and the formation of cell membranes.Aberrations in lipid metabolism can lead to a number of health issues,such as atherosclerosis,obesity,and type 2 diabetes,etc.[1].Environmental factors,genetics,and lifestyle factors are some of the factors that can contribute to the development of dyslipidemia.Currently,there is a growing academic interest in the impact of environmental factors.

Soy Isoflavone and Its Effect to Regulate Hypothalamus and Peripheral Orexigenic Gene Expression in Ovariectomized Rats Fed on A High-Fat Diet

Objective To explore the effect of soy isoflavone on obesity in the light of hypothalamus and peripheral orexigenic gene regulation. Methods Fifty-four female rats were randomly assigned to 6 groups： one sham-operated group （SHAM）, one ovariectomized （OVX） control group, three OVX groups fed with 400 ppm （L-SI）, 1 200 ppm （M-SI） and 3 600 ppm （H-SI） isoflavone respectively, and one OVX group receiving 0.45 ppm diethylstilbestrol （EC）. All rats were allowed to take high-fat diet for 4 weeks. Some neuropeptides were measured by RT-PCR. These neuropeptides included NPY, pro-opiomelanocortin （POMC）, cocaine and amphetamine regulated transcript （CART）, orexin, melanin-concentrating hormone （MCH）, ting hormone precursor （P-MCH）, ghrelin, and leptin. Results Compared with the OVX control group, the body weight and food intake in the H-S1 group were reduced significantly and there was a significant dose-dependent manner in the 3 isoflavone groups. The results of RT-PCR showed that the NPY level in the 3 isoflavone groups was significantly increased and the POMC/CART gene expression decreased significantly in rats＇ hypothalamus compared with that in the OVX control group. However, the expression of orexin, MCH and P-MCH had no change. The peripheral grelin mRNA expression was higher in the 3 isoflavone groups, while leptin gene expression in the fat was not consistent. Conclusions This research showed that isoflavone could prevent obesity induced by high-fat diet and ovariectomy through regulating hypothalamus and peripheral orexigenic gene expressions associated with food intake.

Effect of Soy Isoflavone Crude Extract Supplementation on High Fat Diet-induced Insulin Resistance in Ovariectomized Rats

Female Wister rats aged 8 weeks were randomly divided into sham operation group, ovariectomized （OVX） control group, and 20VX groups fed with soy isoflavone crude extract supplementation. The rats had free access to high fat diet and water for 9 weeks. No significant difference was found in body weight （BW）, total abdominal fat, food intake and food utilization rate between OVX control group and 20VX groups. However, the fasting blood glucose and blood lipid levels were significantly higher in 20VX groups than in OVX control group （P〈0.05）. Intraperitoneal glucose tolerance test （IGTI＂） showed that the area under AUC was smaller in 20VX groups than in OVX control group （P〈0.05）. These findings showed that soy isoflavone crude extract supplementation can improve glucose tolerance and prevent high fat diet-induced insulin resistance in ovariectomized rats.

Maternal Genistein Intake Can Reduce Body Weight in Male Offspring

The study objectives were to investigate the relationship between early exposure to genistein and obesity in young adulthood and to evaluate changes in reproductive health during puberty and adulthood following in utero exposure to genistein.

Significant Polymorphisms of Vitamin D Receptor Gene(rs2189480 and rs3847987) Related to the Risk of Type 2 Diabetes in Henan Rural Area

Type 2 diabetes mellitus (T2DM) accounts for 90% of all diabetes cases and results in severe complications. It is a multifactorial metabolic disorder that results from a combination of resistance to insulin action and an inadequate compensatory insulin secretory response. The interaction between multiple genetic and environmental determinants has been considered to contribute to the pathogenesis of T2DM[1].

Influence of Soy Isoflavone on Lindane Cumulant in Sprague-Dawley Rats

Female Sprague-Dawley rats weighing 60-80 t were given different dosages of soy isoflavone! and/or lindane for four weeks. Soy isoflavones wa! added in feed and lindane was given by oral gavag（ We found that soy isoflavones could reduce the level of lindane in rat＇s serum and brain, but might cause the uterus hyperplasia. Lindane could inhibit the effect of soy isoflavones on uterus and significantly decrease the level of estradiol and testosterone in serum. This study indicated that soy isoflavones could reduce the level of lindane in rat＇s body. Lindane could reduce the level of hormones and decreased the effect of soy isoflavones on rat＇s uterus.

Urine Metabonomic Analysis of Interventions Effect of Soy Isoflavones on Rats Exposed to Di-(2-ethylhexyl) Phthalate

Objective Di-(2-ethylhexyl) phthalate(DEHP) is a ubiquitous environmental contaminant.As an endocrine disruptor,it seriously threatens human health and ecological environmental safety.This study examines the impact of intervention with soybean isoflavones(SIF) on DEHP-induced toxicity using a metabonomics approach.Methods Rats were randomly divided into control(H),SIF-treated(A,86 mg/kg body weight),DEHP-treated(B,68 mg/kg),and SIF plus DEHP-treated(D) groups.Rats were given SIF and DEHP daily through diet and gavage,respectively.After 30 d of treatment,rat urine was tested using UPLC/MS with multivariate analysis.Metabolic changes were also evaluated using biochemical assays.Results Metabolomics analyses revealed that p-cresol glucuronide,methyl hippuric acid,N1-methyl-2-pyridone-5-carboxamide,lysophosphatidycholine [18:2(9 Z,12 Z)] {lyso PC [18:2(9 Z,12 Z)]},lyso PC(16:0),xanthosine,undecanedioic acid,and N6-acetyl-l-lysine were present at significantly different levels in control and treatment groups.Conclusion SIF supplementation partially protects rats from DEHP-induced metabolic abnormalities by regulating fatty acid metabolism,antioxidant defense system,amino acid metabolism,and is also involved in the protection of mitochondria.

Long-term Di-(2-ethylhexyl) phthalate Exposure Disturbs the Lipid Metabolism Profiles and Hepatic Enzymes in Male Rats:A UPLC-MS-based Serum Metabolomics Analysis

In recent years,many investigations have indicated that environmental endocrine disruptors(EEDs)may accelerate the development of obesity[1].One kind of EEDs,di-(2-ethylhexyl)phthalate(DEHP),is ubiquitous in natural environments due to its role in the manufacture and use of plastic products[2].

Combined Effects of Dibutyl Phthalate (DBP) and Benzo(a)Pyrene on Fertility in Male Rats

Our previous studies revealed the polycyclic aromatic hydrocarbon and phthalic acid esters were the major organic pollutants in the Jialing River and Yangtze River in the Three Gorges area, and they might cause the toxicity in male fertility when combined. Thus we used di-n-butyl phthalate (DBP) and Benzo(a)pyrene (Bap) as their representatives respectively to explore their effects on the spermatogenesis in male rats. Male Sprague Dawley rats were randomly divided into 4 groups and respectively exposed to corn oil, Bap (5 mg/kg/d), DBP (250 mg/kg/d), and combined doses of Bap (5 mg/kg/d) and DBP (250 mg/kg/d) for 90 days. We observed a significant increase in the stillbirth rate after Bap and combined treatments, while the mean area of seminiferous tubules was reduced after Bap, DBP and combined treatments. Bap and combined treatment had a sup- pressing effect on meiosis in germ cells, which reduced the haploid contents and the ratio between haploid and diploid but increased the tetraploid and diploid contents and the ratio between hap- loid and tetraploid. These effects were more obvious in the combined group. Furthermore, the ex- pression of a number of proteins was changed, of which was associated with the oxidative stress and cAMP/PKA signaling pathway. Our results suggest that Bap has significant toxic effects on male fertility, while the combined treatment of Bap and DBP has more toxic effects.

The effects of cold stimulation and exercise on human health

Cold stimulation and exercise are two independent stimulus variables,each yielding unique impacts on human health.However,in many cases,individuals often encounter both factors simultaneously,particularly in colder regions where outdoor physical activity is prevalent.Despite numerous studies exploring the effects of cold exposure and exercise independently,only a limited number of comprehensive reviews have evaluated their combined influence on health.This review aims to bridge this gap by meticulously examining the potential benefits and detriments of both cold stimulation and exercise on human health.Specifically,the review focuses on their impacts on cardiovascular,respiratory,and immune function,as well as the favorable effects of moderate exercise on the human body.While evidence suggests that cold exposure can enhance health outcomes in certain disease contexts,it also poses risks,particularly for vulnerable populations.Furthermore,while moderate exercise is generally beneficial,engaging in physical activity in cold weather conditions can increase the risk of hypothermia,frostbite,and other cold-related injuries.Consequently,there is an urgent need to develop safe and effective guidelines for exercising in cold weather,particularly for individuals living in colder regions.This review emphasizes the necessity for further research on the combined effects of cold stimulation and exercise,with the goal of informing public health policies and guidelines for physical activity in cold weather conditions.

The link between dietary nutrients intake and cardiovascular diseases in cold regions

Background:The cold winter weather in northern China influences the dietary habits of its residents,contributing to a heightened risk of cardiovascular disorders,such as hypertension and coronary heart disease.Key factors include low vegetable consumption and high salt and fat intakes.This study aims to investigate the relationships between northern dietary nutrient intake in northern China and cardiovascular disorders during the winter season.Methods:A food frequency questionnaire tailored to the actual eating habits in northern China was designed.Retrospective data from 955 Chinese adults were collected from November to March between 2014 to 2023.Logistic regression was employed to analyze the relationship between dietary nutrients and cardiovascular diseases,with model performance assessed using receiver operating characteristic(ROC)curves.Results:Adjusted for gender,age,and body mass index(BMI),an inverse association was observed between vitamin A(OR=0.706,95%CI:0.550,0.907),nicotinic acid(OR=0.584,95%CI:0.447,0.762),phosphorus(OR=0.777,95%CI:0.608,0.994),selenium(OR=0.719,95%CI:0.560,0.923),zinc(OR=0.683,95%CI:0.531,0.880),methionine(OR=0.730,95%CI:0.569,0.936),arginine(OR=0.753,95%CI:0.588,0.964),lysine(OR=0.706,95%CI:0.550,0.907),aspartic acid(OR=0.730,95%CI:0.569,0.936)and hypertension.Additionally,a negative association was found between niacin(OR=0.752,95%CI:0.597,0.946)and coronary heart disease.Conversely,a positive association was identified between iodine and hypertension(OR=1.305,95%CI:1.020,1.669)and coronary heart disease(OR=1.301,95%CI:1.037,1.634).Conclusion:Our study suggests that maintaining a balanced dietary intake of vitamin A,niacin,phosphorus,selenium,zinc,methionine,arginine,lysine,and aspartic acid can be beneficial in preventing hypertension.Adequate niacin intake is associated with a lower risk of coronary heart disease.However,excessive iodine intake may contribute to hypertension and coronary heart disease.

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.

Polymorphisms in CYP2R1 Gene Associated with Serum Vitamin D Levels and Status in a Chinese Rural Population

Vitamin D, a fat-soluble vitamin and endocrine horm one, and it impacts various bone and extra-bone health, such as osteoporosis, diabetes, and cancer. The main circulating form of vitamin D is 25-hydroxyvitamin D [25(OH)D] and it is a useful clinical biomarker of vitamin D status. The Institute of Medicine (IOM) defines as vitamin D deficiency (VDD) when serum 25(OH)D concentration is less than 20 ng/mL⑴.Worldwide, VDD is recognized as a severe public health problem. In 2007, Holick estimated that globally over one billion people suffered from VDD or vitamin D insufficiency (VDI). In China, it has bee n reported that the prevale nee of VDD ranged from 38.8% to 91.2% in different regions.

X-ray repair cross-complementing gene 1 Arg399Gln polymorphism and glioma risk among Asians A meta-analysis based on 2 326 cases and 3 610 controls

OBJECTIVE： Previous reports have demonstrated that X-ray repair cross-complementing gene 1 （XRCCl） Arg399GIn polymorphism is a possible risk factor for several cancers. Published data on the association of XRCCl Arg399GIn polymorphism with glioma susceptibility have generated conflicting results. This study is designed to precisely estimate the relationship. DATA RETRIEVAL： A computer-based online retrieval of Medline, EMBASE, OVID, Sciencedirect, and Chinese National Knowledge Infrastructure was performed to search papers regarding association of XRCC1 Arg399GIn polymorphisms with glioma published up to April 2012. SELECTION CRITERIA： Two investigators selected data independently. Meta analysis was then performed for the selected studies using STATA 11.0 software after strict selection. Heterogeneity test, sensitivity analysis and publication bias assessments were then conducted. MAIN OUTCOME MEASURES： Association of XRCCl Arg399GIn polymorphism with glioma risk. RESULTS： A total of nine case-controlled studies comprising 2 326 cases and 3 610 controls were selected for final analysis. The overall data failed to indicate a significant association of XRCCl Arg399GIn polymorphism with glioma risk （Gin/Gin vs. Arg/Arg： odds ratio （OR） = 1.11; 95% confidence interval （Cl） = 0.94-1.31; dominant model： OR = 1.06; 95%C/= 0.95-1.18; recessive model： OR = 1.04; 95%C/= 0.81-1.34）. However, subgroup analysis regarding ethnicity showed an increased risk among Asians （Gin/Gin vs. Arg/Arg OR = 1.40; 95%C/= 1.10-1.78; recessive model： Caucasians or mixed ethnicities. OR = 1.70; 95%Cl = 1.17-2.46; dominant mode OR = 1.46; 95%C/= 1.04-2.05） but not CONCLUSION： XRCCl Arg399GIn polymorphism might modify the susceptibility to glioma among Asians but not Caucasians. Further large and well-designed studies are needed to confirm this conclusion.

Gastrointestinal toxicity induced by microcystins

Microcystins(MCs) are produced by certain bloomforming cyanobacteria that can induce toxicity in various organs, including renal toxicity, reproductive toxicity, cardiotoxicity, and immunosuppressive effects. It has been a significant global environmental issue due to its harm to the aquatic environment and human health. Numerous investigators have demonstrated that MC exposure can induce a widespread epidemic of enterogastritis with symptoms similar to food poisoning in areas close to lakes. Both in vivo and in vitro studies have provided evidence of positive associations between MC exposure and gastrointestinal toxicity. The toxicity of MCs on the gastrointestinal tract is multidimensional. MCs can affect gastrointestinal barrier function and shift the structure of gut microbiota in different gut regions. Furthermore, MCs can inhibit the secretion of gastrointestinal digestive enzymes and the release of inflammatory cytokines, which affects the expression of immune-related genes in the intestine. The damage of the intestine is closely correlated to MC exposure because the intestine is the main site for the digestion and absorption of nutrients. The damage to the gastrointestinal tract due to MCs was summarized from different aspects, which can be used as a foundation for further exploration of molecular damage mechanisms.

Quality Problems in Waters Used for Drinking Purposes in Italy

With a grant from the Italian Ministry of the Environment, the National Institute of Health (Istituto Superiore di Sanita) promoted and coordinated some activities aimed at determining the extent and the intensity of contamination of waters used for human consumption by some chemical agents, and describing causes and modalities of contamination and human health implications. The chemical agents examined were herbicides, nitrates, trihalomethanes, asbestos, manganese and fluoride. In this paper a first nationwide picture of these problems is reported.

Occurrence and infection risk of waterborne pathogens in Wanzhou watershed of the Three Gorges Reservoir, China

The Three Gorges Reservoir （TGR）, formed by China＇s Yangtze Three Gorges Project, is the largest lake in the world, but there is too little information available about fecal contamination and waterborne pathogen impacts on this aquatic ecosystem. During two successive 1-year study periods （July 2009 to July 2011）, the water quality in Wanzhou watershed of the TGR was tested with regard to the presence of fecal indicators and pathogens. According to Chinese and World Health Organization water quality standards, water quality in the mainstream was good but poor in backwater areas. Salmonella, Enterohemorrhagic Escherichia coli （EHEC）, Giardia and Cryptosporidium were detected in the watershed. Prevalence and concentrations of the pathogens in the mainstream were lower than those in backwater areas. The estimated risk of infection with Salmonella, EHEC, Cryptosporidium, and Giardia per exposure event ranged from 2.9 × 10 -7 to 1.68 × 10-5 , 7.04 × 10-10 to 2.36 × 10-7 , 5.39 × 10-6 to 1.25 × 10-4 and 0 to 1.2 × 10-3 , respectively, for occupational divers and recreational swimmers exposed to the waters. The estimated risk of infection at exposure to the 95% upper confidence limit concentrations of Salmonella, Cryptosporidium and Giardia may be up to 2.62 × 10-5 , 2.55 × 10-4 and 2.86 × 10-3 , respectively. This study provides useful information for the residents, health care workers and managers to improve the safety of surface water and reduce the risk of fecal contamination in the TGR.

Seasonal variation in dietary intake and its association with obesity-related chronic diseases in northeast China

Objective:The objective of this study was to assess seasonal changes in dietary and nutrient intake of residents(18-75 years old)in Northeast China during summer and winter,and to explore the associations between fatty acids,phytosterols,and the prevalence of obesity-related chronic diseases,particularly obesity,hyperlipidemia,and NAFLD.Methods:A total of 4773 participants from the Internet-based Dietary Questionnaire for Chinese(IDQC)were included in this study.Dietary intake information was collected using a validated food frequency questionnaire.Student's t-test or Mann-Whitney U-test was used to analyze continuous variables,while Chi-squared tests were used to compare categorical variables.Multivariable logistic regression was employed to assess the relationship between fatty acids,phytosterols,and obesity-related chronic diseases.Results:The mean consumption of legumes,vegetables,fruits,nuts,dairy products,fish,condiments,energy,protein,fat,and carbohydrate differed significantly between summer and winter(P<0.05).Significant inverse associations were found between both fatty acids and phytosterols and obesity-related chronic diseases in multivariate adjusted models.Summer polyunsaturated fatty acid(PUFA)intake was negatively associated with the prevalence of hyperlipidemia(Q4,OR,0.515;95%CI,0.283-0.921;P<0.05)and non-alcoholic fatty liver disease(NAFLD)(Q4,OR,0.331;95%CI,0.176-0.599;P<0.001).Phytosterols intake was negatively associated with the prevalence of obesity(Q4,OR,0.603;95%CI,0.414-0.873;P<0.05),hyperlipidemia(Q4,OR,0.420;95%CI,0.233-0.731;P<0.001),and NAFLD(Q4,OR,0.206;95%CI,0.111-0.360;P<0.001)during the summer.Conclusions:Higher PUFA intake was associated with a lower prevalence of obesity,hyperlipidemia,and NAFLD.Phytosterol intake was inversely associated with the prevalence of hyperlipidemia and NAFLD.These findings suggest that the associations between PUFA and phytosterols and the prevalence of obesity-related chronic diseases may be influenced by seasonal differences in food intake.

Zoonotic sources and the spread of antimicrobial resistance from the perspective of low and middle-income countries

Background Antimicrobial resistance is an increasing challenge in low and middle-income countries as it is wide-spread in these countries and is linked to an increased mortality.Apart from human and environmental factors,animal-related drivers of antimicrobial resistance in low-and middle-income countries have special features that differ from high-income countries.The aim of this narrative review is to address the zoonotic sources and the spread of antimicrobial resistance from the perspective of low-and middle-income countries.Main body Contamination with extended-spectrum beta-lactamase(ESBL)-producingEscherichia coli is highest in poultry(Africa:8.9–60%,Asia:53–93%)and there is a risk to import ESBL-producingE.coli through poultry meat in Africa.In aquacultures,the proportion of ESBL-producers amongE.coli can be high(27%)but the overall low quality of published studies limit the general conclusion on the impact of aquacultures on human health.ESBL-producingE.coli colonization of wildlife is 1–9%in bats or 2.5–63%birds.Since most of them are migratory animals,they can disperse antimicrobial resistant bacteria over large distances.So-called‘filth flies’are a relevant vector not only of enteric pathogens but also of antimicrobial resistant bacteria in settings where sanitary systems are poor.In Africa,up to 72.5%of‘filth flies’are colonized with ESBL-producingE.coli,mostly conferred by CTX-M(24.4–100%).While methicillin-resistantStaphylococcus aureus plays a minor role in livestock in Africa,it is frequently found in South America in poultry(27%)or pork(37.5–56.5%)but less common in Asia(poultry:3%,pork:1–16%).Conclusions Interventions to contain the spread of AMR should be tailored to the needs of low-and middle-income countries.These comprise capacity building of diagnostic facilities,surveillance,infection prevention and control in small-scale farming.

Interaction of Hepatitis B Virus X Protein with the Pregnane X Receptor Enhances the Synergistic Effects of Aflatoxin B1 and Hepatitis B Virus on Promoting Hepatocarcinogenesis

Background and Aims:Hepatitis B virus(HBV)infection has been found to increase hepatocellular sensitivity to carcinogenic xenobiotics,by unknown mechanisms,in the generation of hepatocellular carcinoma.The pregnane X receptor(PXR)is a key regulator of the body’s defense against xenobiotics,including xenobiotic carcinogens and clinical drugs.In this study,we aimed to investigate the molecular mechanisms of HBV X protein(HBx)-PXR signaling in the synergistic effects of chemical carcinogens in HBV-associated hepatocarcinogenesis.Methods:The expression profile of PXR-cytochrome p4503A4(CYP3A4)signaling was determined by PCR,western blotting,and tissue microarray.Cell viability and aflatoxin B1(AFB1)cytotoxicity were measured using the cell counting kit-8 assay.Target gene expression was evaluated using transient transfection and real time-PCR.The genotoxicity of AFB1 was assessed in newborn mice with a single dose of AFB1.Results:HBx enhanced the hepatotoxicity of AFB1 by activating CYP3A4 and reducing glutathione Stransferase Mu 1(GSTM1)in cell lines.Activation of PXR by pregnenolone 16α-carbonitrile increased AFB1-induced liver tumor incidence by up-regulating oncogenic KRAS to enhance interleukin(IL)-11:IL-11 receptor subunit alpha-1(IL11RA-1)-mediated inflammation in an HBx transgenic model.Conclusions:Our finding regarding AFB1 toxicity enhancement by an HBx-PXR-CYP3A4/GSTM1-KRASIL11:IL11RA signaling axis provides a rational explanation for the synergistic effects of chemical carcinogens in HBV infection-associated hepatocarcinogenesis.