Polymorphisms of DNA repair genes XRCC1 and XRCC3, interaction with environmental exposure and risk of chronic gastritis and gastric cancer

AIM： TO evaluate the association between poly- morphisms XRCC1 Arg194Trp and Arg399GIn and XRCC3 Thr241Met and the risk for chronic gastritis and gastric cancer, in a Southeastern Brazilian population. METHODS： Genotyping by PCR-RFLP was carried out on 202 patients with chronic gastritis （CG） and 160 patients with gastric cancer （GC）, matched to 202 （Cl） and 150 （C2） controls, respectively. RESULTS： No differences were observed among the studied groups with regard to the genotype distribution of XRCC1 codons 194 and 399 and of XRCC3 codon 241. However, the combined analyses of the three variant alleles （194Trp, 399Gin and 241Met） showed an increased risk for chronic gastritis when compared to the GC group. Moreover, an interaction between the polymorphic alleles and demographic and environmental factors was observed in the CG and GC groups. XRCC1 194Trp was associated with smoking in the CG group, while the variant alleles XRCC1 399Gin and XRCC3 241Met were related with gender, smoking, drinking and Hpylori infection in the CG and GC groups. CONCLUSION： Our results showed no evidence of a rela-tionship between the polymorphisms XRCC1 Arg194Trp and Arg399Gln and XRCC3 Thr241Met and the risk of chronic gastritis and gastric cancer in the Brazilianpopulation, but the combined effect of these variants may interact to increase the risk for chronic gastritis, considered a premalignant lesion. Our data also indicate a gene-environment interaction in the susceptibility to chronic gastritis and gastric cancer.

Evaluation of laboratory and environmental exposure systems for protein modification upon gas pollutants and environmental factors

Chemical modifications of proteins induced by ambient ozone(O_(3))and nitrogen oxides(NOx)are of public health concerns due to their potential to trigger respiratory diseases.The laboratory and environmental exposure systems have been widely used to investigate their relevant mechanism in the atmosphere.Using bovine serum albumin(BSA)as a model protein,we evaluated the two systems and aimed to reduce the uncertainties of both the reactants and products in the corresponding kinetic study.In the laboratory simulation system,the generated gaseous pollutants showed negligible losses.Ten layers of BSA were coated on the flow tube with protein extraction recovery of 87.4%.For environmental exposure experiment,quartz fiber filter was selected as the upper filter with low gaseous O_(3)(8.0%)and NO_(2)(1.7%)losses,and cellulose acetate filter was appropriate for the lower filter with protein extraction efficiency of 95.2%.The protein degradation process was observed without the exposure to atmospheric oxidants and contributed to the loss of protein monomer mass fractions,while environmental factors(e.g.,molecular oxygen and ultraviolet)may cause greater protein monomer losses.Based on the evaluation,the study exemplarily applied the two systems to protein modification and both showed that O_(3) promotes the protein oligomerization and nitration,while increased temperature can accelerate the oligomerization and increased relative humidity can inhibit the nitration in the environmental exposure samples.The developed laboratory and environmental systems are suitable for studying protein modifications formed under different atmospheric conditions.A combination of the two will further reveal the actual mechanism of protein modifications.

Environmental exposure and flux of thallium by industrial activities utilizing thallium-bearing pyrite

Thallium(Tl) is a typical toxic heavy metal,with higher toxicity to mammals than Hg,Cd,and Pb.Accurate assessments of its environmental exposure and flux are central to effective management and control of Tl pollution.This paper first presents in detail the environmental exposure and flux of Tl by typical industrial activities utilizing Tl-bearing pyrite minerals to produce sulfuric acid.For this purpose,sequential extraction and Inductively Coupled Plasma Mass Spectrometry(ICP-MS) were used to investigate total content and geo-chemical partitioning of Tl in raw pyrite ores and solid roasting wastes,thereby uncovering Tl distribution and transformation during the production process.Results showed that some portions of Tl bearing in the minerals went into vapor,which transferred Tl into different processes;and some portions of Tl went into water during the gas washing procedure,leaving some other portions remained in the solid slags.More importantly,detailed investigation revealed that 40% of Tl in the pyrite minerals was active,among which 25% of Tl originally in the pyrite minerals was washed into water during gas cleaning process and 15% of active Tl retained in the slags.The latter portion of active Tl could be possibly transferred to the soil or water with the slag deposal or being reused;and 60% of Tl remained relatively stable in the residual phase.

Environmental mercury exposure, semen quality and reproductive hormones in Greenlandic Inuit and European men： a cross-sectional study

Several animal studies indicate that mercury is a male reproductive toxicant, but human studies are few and contradictory. We examined semen characteristics and serum levels of reproductive hormones in relation to environmental exposure to mercury. Blood and semen samples were collected from 529 male partners of pregnant women living in Greenland, Poland and Ukraine between May 2002 and February 2004. The median concentration of the total content of mercury in whole blood was 9.2 ng ml-1 in Greenland （0.2- 385.8 ng ml-1）, 1.0 ng m1-1 in Poland （0.2-6.4 ng ml-z） and 1.0 ng ml-I in Ukraine （0.2-4.9 ng ml-1）. We found a significantly positive association between the blood levels of mercury and serum concentration of inhibin B in men from Greenland （p=0.074, 95% confidence interval （CI）=0.021 to 0.126） and in an analysis including men from all three regions （p=0.067, 95% C1=0.024 to O. 110）. The association may be due to beneficial effects of polyunsaturated fatty acids （PUFAs）, which are contained in seafood and fish. No significant association （P〉O.05） was found between blood concentrations of mercury and any of the other measured semen characteristics （semen volume, total sperm count, sperm concentration, morphology and motility） and reproductive hormones （free androgen index {FAI）, follicle-stimulating hormone （FSH）, luteinizing hormone （LH）, testosterone and LH xtestosterone） in any region. In conclusion, the findings do not provide evidence that environmental mercury exposure in Greenlandic and European men with median whole blood concentration up to 10 ng m1^-1 has adverse effects on biomarkers of male reproductive health.

Exposure to Environmental Hexachlorocyclohexane(HCH)and Dichlorodiphenyltrichloroethane(DDT)among Rural Children in North Eastern China

Objective To assess HCH and DDT exposure levels and associated risk factors among 262 children aged 6-10 years in a northeastern rural area of China between April and May of 2008. Methods Eight HCH and DDT metabolites in serum samples were monitored by gas chromatography. A questionnaire was administered to identify the sources of pesticides in children＇ serum samples. Results At least one pesticide metabolite was detected in 81.7% of the tested children. Higher amounts of pp＇DDD were detected in 50% of them. Children＇s age and their father＇s occupation as farmers, together with not changing work clothes after work, were the main risk factors for HCH and DDT exposure among them. Conclusion Children living in rural areas are experiencing multiple sources of organochlorine pesticide exposure. These pesticides may have been retained in the environment for a long period of time.

A Judgment of Attribution of Increase in Urine β_2-Microglobulin after Environmental Cadmium Exposure

Urineβ_2-microglobulin (β_2-m) was measured in 433 persons with low-level, long-term environmental exposure to Cd, and in 124 control persons from unpolluted area. In 152 of the exposed persons, and some of the controls, the urine β-m exceeded the limit. Of the 433 exposed persons, 74 cases with both urine Cd and β_2-m exceeding the limit were matched by the control. This study suggests that after the stratification of the degrees of renal tubular injury according to the fractional β_2-m excretion (FE β_2-m) and coordination of clinical examination, FE β_2-m could contribute to identifying renal tubular dysfunction due to Cd exposure and kidney lesion when both Cd exposure and original nephropathy exist.

Epigenetics and environmental health

Epigenetic modifications including DNA methylation,histone modifications,chromatin remodeling,and RNA modifications complicate gene regulation and heredity and profoundly impact various physiological and pathological processes.In recent years,accumulating evidence indicates that epigenetics is vulnerable to environmental changes and regulates the growth,development,and diseases of individuals by affecting chromatin activity and regulating gene expression.Environmental exposure or induced epigenetic changes can regulate the state of development and lead to developmental disorders,aging,cardiovascular disease,Alzheimer's disease,cancers,and so on.However,epigenetic modifications are reversible.The use of specific epigenetic inhibitors targeting epigenetic changes in response to environmental exposure is useful in disease therapy.Here,we provide an overview of the role of epigenetics in various diseases.Furthermore,we summarize the mechanism of epigenetic alterations induced by different environmental exposures,the influence of different environmental exposures,and the crosstalk between environmental variation epigenetics,and genes that are implicated in the body's health.However,the interaction of multiple factors and epigenetics in regulating the initiation and progression of various diseases complicates clinical treatments.We discuss some commonly used epigenetic drugs targeting epigenetic modifications and methods to prevent or relieve various diseases regulated by environmental exposure and epigenetics through diet.

A census tract-level assessment of social determinants of health,traffic exposure,and asthma exacerbations in New York State's Medicaid Population(2005–2015)

This study aims to evaluate the association between social determinants,environmental exposure metrics,and the risk of asthma emergency department(ED)visits in the New York State(NYS)Medicaid population using smallarea analysis.Traffic densities for each census tract in NYS were calculated using the length of road segments within each tract and total area of the tract to produce a measure of average number of vehicles per square meter per day.Data on social determinants of health including internal and external environments and other demographic factors were obtained from various sources.Poisson regression analyses were conducted to identify significant factors associated with asthma ED visits in Medicaid claim and encounter data for years 2005–2015.High traffic density in NYS excluding New York City(NYC)correlated with increased risk of asthma ED visits(RR 1.69;95%CI:1.42,2.00),mitigated by adjusting for environmental and social determinants(RR 1.00;95%CI:0.85,1.19).Similar trends were observed in NYC only(RR 1.19;95%CI:1.00,1.41),with the adjusted risk remaining elevated(RR 1.14;95%CI:0.98,1.33)albeit not statistically significant.Living in census tracts with high concentrated disadvantage index,high proportions of minorities,and less green space predicted higher asthma ED visits.We mapped predicted rates and model residuals to identify areas of high risk.Our results support previous findings that environmental and social risk factors in poor and urban areas contribute to asthma exacerbations in the NYS Medicaid population,even if they may not necessarily contribute to its development.

Canine on the Couch:The New Canary in the Coal Mine for Environmental Health Research

Human health is intimately connected and tied to the health of our environment and ecosystem,with only a very small fraction of the risk for chronic diseases explained by genetics alone.Companion animals are prone to disease types that are shared with people,including cancers and endocrine disorders,reinforcing the thought that environmental factors contribute to the risks for chronic diseases.These factors include air and water pollution and the built environment.As such,there is increasing interest in pursuing research with companion animals,and specifically dogs,as sentinel species to inform comparative health assessments and identify risk factors for disease.Of the canine diseases for which environmental exposure research has been published,cancers have received the most attention.This review summarizes two main aspects of this comparative approach:(1)cancers that occur in dogs and which are similar to humans and(2)research investigating environmental exposures and health outcomes in dogs.The goal of this review is to highlight the diverse conditions in which pet dogs may provide unique perspectives and advantages to examine relationships between environmental exposures and health outcomes,with an emphasis on chemical pollution and cancer.Furthermore,this review seeks to raise awareness and stimulate discussion around the best practices for the use of companion animals as environmental health sentinels.

Early-onset colorectal cancer:Current insights and future directions

Early-onset colorectal cancer(EOCRC)has seen an alarming rise worldwide over the past two decades.The reason for this global trend is poorly understood.EOCRC appears to have its own unique clinical and molecular features when compared with late-onset colorectal cancer.Younger patients appear to have more distal or rectal disease,a more advanced stage of disease at presentation,and more unfavorable histological features.Identifying risk factors for EOCRC is the first step in mitigating the rising burden of this disease.Here we summarize several noteworthy biological factors and environmental exposures that are postulated to be responsible culprits.This can hopefully translate in clinical practice to the development of better risk stratification tool for identifying highrisk individuals for early colorectal cancer screening,and identifying areas needed for further research to curb this rising trend.

Sick Neighborhood Syndrome: Population with Multiple Chemical Sensitivity Adjacent to Bioethanol Distillery

The population of a neighborhood in the city of Córdoba presents general irritant symptoms since a bioethanol distillery began to operate there, from which formaldehyde, toluene, xylene mainly emanate. At the request of the community, collective environmental health was evaluated with a cross-sectional study of prevalence of these conditions. 53% of the residents reported respiratory disorders, conjunctivitis 31%, headaches 27%, dermatitis 23% and dyspepsia 22%. 57% of children aged 6 - 7 use bronchodilators (an indicator of asthma). 66% of the population has one of these conditions, 46% has two and 26% has three;children are the most affected. The results coincide with the Consensus on Multiple Chemical Sensitivity Syndrome in that it is reproducible by repeated chemical exposure, is chronic and does not improve without eliminating exposure, affecting multiple organs and systems. 14.8% of newborns feature malformations, while in the rest of the city, only 1.7% did. Similar to the Sick Building Syndrome, the collective health picture found suggests a “Sick Neighborhood Syndrome”.

A systematic review of the impacts of exposure to micro-and nano-plastics on human tissue accumulation and health

Micro-and nano-plastics(MNPs)pollution has become a pressing global environmental issue,with growing concerns regarding its impact on human health.However,evidence on the effects of MNPs on human health remains limited.This paper reviews the three routes of human exposure to MNPs,which include ingestion,inhalation,and dermal contact.It further discusses the potential routes of translocation of MNPs in human lungs,intestines,and skin,analyses the potential impact of MNPs on the homeostasis of human organ systems,and provides an outlook on future research priorities for MNPs in human health.There is growing evidence that MNPs are present in human tissues or fluids.Lab studies,including in vivo animal models and in vitro human-derived cell cultures,revealed that MNPs exposure could negatively affect human health.MNPs exposure could cause oxidative stress,cytotoxicity,disruption of internal barriers like the intestinal,the air–blood and the placental barrier,tissue damage,as well as immune homeostasis imbalance,endocrine disruption,and reproductive and developmental toxicity.Limitedly available epidemiological studies suggest that disorders like lung nodules,asthma,and blood thrombus might be caused or exacerbated by MNPs exposure.However,direct evidence for the effects of MNPs on human health is still scarce,and future research in this area is needed to provide quantitative support for assessing the risk of MNPs to human health.

"Smoke Detector"of Human Diseases for Environmental Aerosol Exposure

Air consists of various different pollutants(both biological and non-biological).COVID-19 pandemic further threatens the air safety.Aerosol exposure causes many diseases including asthma,respiratory infections and death.Using protein bi-omarker for early diagnosis often fails due to its lower level at the very beginning of a disease.On another front,different technologies were attempted for realtime monitoring of air toxicity.Nonetheless,many aerosol exposures occur silently without any knowledge due to limitation of available analytical methods.Exhaled breath has emerged as a promising non-invasive sample for disease diagnosis,in-cluding cancer and diabetes.Most recently,it was shown that rats emitted distinc-tive profile of volatile organic compounds(VOCs)within minutes when exposed to different air pollutants including ozone and endotoxin.During the pandemic times,breath-borne VOC was also used to rapidly screen COVID-19.Pollutant exposure could result in changes in metabolism,thus releasing different pat-terns of VOCs via breath within very short time.Close monitoring of exhaled biomarker profile could spot the early signs of a disease,thus offering an earlier warning.Sensor array and machine learning together can lend a great hand toward such an objective.This mini review is undertaken to share such endeavors and inspire further innovations.

Repeated exposure to moxa-burning smoke: its acute and chronic toxicities in rats

OBJECTIVE： To assess toxicities of the air in Chinese medicine clinics polluted by moxa-burning smoke due to moxibustion-derived burning products （MBP）. METHODS： Both acute and chronic toxicity studies were conducted. For the acute toxicity study, five groups of Wistar rats （n = 16/group, male： female = 1 ： 1） were exposed to five different concentrations （95%, 90%, 85%, 80% and 75%, respectively） of MBP for 2 h. For the chronic toxicity study, another three groups of male rats （n = 21/group） were ex- posed to MBP in three concentrations （10%, 40% and 70%, respectively） and one control group ex- posed to clean air 20 min/d for 144 d. Routine ex- aminations were performed and analyzed by analy- sis of variance and dose-response relationship. RESULTS： In the acute toxicity study, the number of dead rats in the 95%, 90%, 85%, 80% and 75% groups were 16, 13, 7, 6 LDS0 of 86.274% after or and 3, respectively, with during the 2 h exposure. In the chronic toxicity study, MBP exposure induced a decline in activity of the rats. Rats in the 10% group showed no signs of toxicity, while those in the 40% MBP group showed toxicity effects on the body weights （P 〈 0.05） and lung. Rats in the 70% MBP group also presented with reversible damage in the blood coagulation system （P 〈 0.05）. CONCLUSION： Exposure to 10% MBP, which is equivalent to 27.45 mg/m^3 was under the critical threshold for male rats＇safety. Exposure to MBP above that limit induced lung damage. MBP in clinics need to be reduced to a safe level with enhanced ventilation.

Role of genetic and environmental factors in DNA methylation of lipid metabolism

A number of recent studies revealed that DNA methylation plays a central role in the regulation of lipid metabolism.DNA methylation modifications are important regulators of transcriptional networks that do not affect the DNA sequence and can translate genetic variants and environmental factors into phenotypic traits.Therefore,elucidating the factors that underlie inter-individual DNA methylation variations gives us an opportunity to predict diseases and interfere with the establishment of aberrant DNA methylation early.In this review,we summarize the findings of DNA methylation-related studies focused on unravelling the potential role of genetic and environmental factors in DNA methylation and the regulatory effect of DNA methylation on gene expression in lipid metabolism.

Does exposure to poultry and wild fowl confer immunity to H5N1 ？

Human outbreaks of highly pathogenic avian influenza （HPAI） such as H5N1 and novel avian strains such as H7N9 have provoked significant public health concern. An outbreak of H5N1 in humans was first reported in Hong Kong （HK）, China in 1997. This event was curtailed by a variety of public health measures including the culling of over 1.5 million chickens in the city.1 HSN1 has since re-emerged in multiple countries with over 600 reported infections and, since 2003, a case fatality of about 59% （World Health Organization （WHO） report, as of January 24, 2014）.

Environmentally Induced Paternal Epigenetic Inheritance and Its Effects on Offspring Health

Increasing evidences indicate that chronic diseases in offspring may be the result of ancestral environmental exposures. Exposures to environmental compounds in windows of epigenetic susceptibility have been shown to promote epigenetic alterations that can be inherited between generations. DNA methylation, histone modifications, and noncoding RNAs are sound mechanistic candidates for the delivery of environmental information from gametes to zygotes. This review focuses mainly on paternal exposures and assesses the risk of epigenetic alterations in the development of diseases, providing insights into relationships between aberrant sperm epigenetic patterns and offspring health. Elucidation of the mechanisms underlying environmental epigenetic information that survive from epigenetic reprogramming and its transmission to future generations may hold a great promise for providing therapeutic targets for epigenetic diseases associated with environmental exposures.

Genetic architecture, epigenetic influence and environment exposure in the pathogenesis of Autism

Autism spectrum disorder(ASD) is a spectral neurodevelopment disorder affecting approximately 1% of the population. ASD is characterized by impairments in reciprocal social interaction, communication deficits and restricted patterns of behavior. Multiple factors, including genetic/genomic, epigenetic/epigenomic and environmental, are thought to be necessary for autism development. Recent reviews have provided further insight into the genetic/genomic basis of ASD. It has long been suspected that epigenetic mechanisms, including DNA methylation, chromatin structures and long non-coding RNAs may play important roles in the pathology of ASD. In addition to genetic/genomic alterations and epigenetic/epigenomic influences, environmental exposures have been widely accepted as an important role in autism etiology, among which immune dysregulation and gastrointestinal microbiota are two prominent ones.

Etiology and early pathogenesis of malignant testicular germ cell tumors： towards possibilities for preinvasive diagnosis

Malignant testicular germ cell tumors （TGCT） are the most frequent cancers in Caucasian males （20-40 years） with an 70% increasing incidence the last 20 years, probably due to combined action of （epi）genetic and （micro）environmental factors. It is expected that TGCT have carcinoma in situ （CIS） as their common precursor, originating from an embryonic germ cell blocked in its maturation process. The overall cure rate of TGCT is more than 90%, however, men surviving TGCT can present long-term side effects of systemic cancer treatment. In contrast, men diagnosed and treated for CIS only continue to live without these long-term side effects. Therefore, early detection of CIS has great health benefits, which will require an informative screening method. This review described the etiology and early pathogenesis of TGCT, as well as the possibilities of early detection and future potential of screening men at risk for TGCT. For screening, a well-defined risk profile based on both genetic and environmental risk factors is needed. Since 2009, several genome wide association studies （GWAS） have been published, reporting on single-nucleotide polymorphisms （SNPs） with significant associations in or near the genes KITLG, SPRY4, BAK1, DMRT1, TERT, ATF71P, HPGDS, MAD1L1, RFWD3, TEX14, and PPMIE, likely to be related to TGCT development. Prenatal, perinatal, and postnatal environmental factors also influence the onset of CIS. A noninvasive early detection method for CIS would be highly beneficial in a clinical setting, for which specific miRNA detection in semen seems to be very promising. Further research is needed to develop a well-defined TGCT risk profile, based on gene-environment interactions, combined with noninvasive detection method for CIS.

Relationship between urinary cadmium and mortality in habitants of a cadmium-polluted area： a 22-year follow-up study in Japan

Background Several studies have suggested that the exposure to cadmium （Cd） increased mortalities from renal diseases, cardiovascular diseases and malignant neoplasm, including lung cancer and prostate cancer among inhabitants living in Cd-polluted areas and factory workers. This study aimed to assess the influence of environmental exposure to Cd on long term outcome of inhabitants living in an area polluted by Cd. Methods A 22-year follow-up study was conducted with 3119 inhabitants （1403 men and 1716 women） living in the Cd polluted Kakehashi River basin in Japan. The subjects were divided into 4 groups according to the amount of urinary Cd level （〈3.0 μg/g creatinine （Cr）, 3.0-4.9 μg/g Cr, 5.0-9.9 μg/g Cr, and -〉10.0 μg/g Cr）. Mortality was calculated by the person-years method. Hazards ratios （HR） and 95% confidence intervals （CI） were assessed by the Cox＇s proportional hazard model. Results Compared with urinary Cd 〈3.0 μg/g Cr group, the HR of 5.0-9.9μg/g Cr and 〉10.0 μg/g Cr groups were significantly increased after adjustment for age in both sexes： 1.24 （95% Cl 1.01-1.51） and 1.48 （95% CI 1.17-1.90） for men; 1.64 （95% CI 1.17-2.28） and 1.78 （95% Cl 1.27-2.50） for women. The most frequent cause of death was malignant neoplasm in men and cardiovascular diseases in women. The significant increase in mortality risk for cardiovascular diseases was observed in the subjects with 〉10 μg/g Cr in both sexes： 1.79 for men （95% Cl 1.02-3.12） and 2.38 for women （95% Cl 1.11-5.07）. When the subjects were divided into 2 categories （〈20μg/g Cr and 〉20 μg/g Cr）, the HR of the urinary Cd 〉20 μg/g Cr group for nephritis and nephrosis were 4.82 （95% Cl 1.07-21.61） in men and 7.92 （95% Cl 1.77-35.33） in women, respectively. The significant increase was not observed for malignant neoplasm. Conclusion These results suggest a dose-response relationship between Cd body burden and mortality for cardiovascular diseases, cerebrovascular diseases and nephritis and nephrosis.