The exposome is defined as the cumulative lifetime exposure to exogenous environmental factors and their corresponding biological responses,thereby providing a holistic framework for elucidating the complex interplay ...The exposome is defined as the cumulative lifetime exposure to exogenous environmental factors and their corresponding biological responses,thereby providing a holistic framework for elucidating the complex interplay between environmental determinants and human health outcomes.Understanding these complex interactions is important for identifying the causes of diseases and associated risk factors.Recent advances in analytical methodologies employed in exposomics,including mass spectrometry and sensor-based platforms,have significantly expanded our capacity to identify and quantify both external exposures and internal biological responses.This review explores recent advancements and practical applications of these techniques in environmental health studies,with a focus on their role in detecting and characterizing complex exposure patterns.Additionally,we discuss the challenges in exposome research and propose strategies to improve its application,thereby reinforcing the potential of the exposome paradigm in advancing precision public health.展开更多
Genomic medicine has evolved significantly,merging centuries of scientific progress with modern molecular biology and clinical care.It utilizes knowledge of the human genome to enhance disease prevention,diagnosis,tre...Genomic medicine has evolved significantly,merging centuries of scientific progress with modern molecular biology and clinical care.It utilizes knowledge of the human genome to enhance disease prevention,diagnosis,treatment,and potential reversal.Genomic medicine in hepatology is particularly promising due to the crucial role of the liver in several metabolic processes and its association with diseases such as metabolic dysfunction-associated steatotic liver disease,type 2 diabetes mellitus,liver cirrhosis,and cardiovascular conditions.The mid-20th century witnessed a paradigm shift in medicine,marked by the emergence of molecular biology,which enabled a deeper understanding of gene expression and regulation.This connection between basic science and clinical practice has enhanced our knowledge of the role of gene-environment interactions in the onset and progression of liver diseases.In Latin America,including Mexico,with its genetically diverse and admixed populations,genomic medicine provides a foundation for personalized and culturally relevant health strategies.This review highlights the need for genomic medicine,examining its historical evolution,integration into hepatology in Mexico,and its potential applications in the prevention of chronic diseases.It emphasizes the importance of training in genomic literacy and interdisciplinary education in medical training,particularly in the field of hepatology,with a focus on genomic medicine expertise.展开更多
AIM: To advances in genetics and immunology have contributed to the current understanding of the pathogenesis of inflammatory bowel diseases(IBD). METHODS: The current opinion on the pathogenesis of IBD suggests that ...AIM: To advances in genetics and immunology have contributed to the current understanding of the pathogenesis of inflammatory bowel diseases(IBD). METHODS: The current opinion on the pathogenesis of IBD suggests that genetically susceptible individuals develop intolerance to dysregulated gut microflora(dysbiosis) and chronic inflammation develops as a result of environmental insults. Environmental exposures are innumerable with varying effects during the life course of individuals with IBD. Studying the relationship between environmental factors and IBD may provide the missing link to increasing our understanding of the etiology and increased incidence of IBD in recent years with implications for prevention, diagnosis, and treatment. Environmental factors are heterogeneous and genetic predisposition, immune dysregulation, or dysbiosis do not lead to the development of IBD in isolation. RESULTS: Current challenges in the study of environmental factors and IBD are how to effectively translate promising results from experimental studies to humans in order to develop models that incorporate the complex interactions between the environment, genetics, immunology, and gut microbiota, and limited high quality interventional studies assessing the effect of modifying environmental factors on the natural history and patient outcomes in IBD.CONCLUSION: This article critically reviews the current evidence on environmental risk factors for IBD and proposes directions for future research.展开更多
Amyotrophic lateral sclerosis(ALS) is a rapidly progressing neurodegenerative disease that leads to death. No effective treatments are currently available. Based on data from epidemiological, etiological, laboratory, ...Amyotrophic lateral sclerosis(ALS) is a rapidly progressing neurodegenerative disease that leads to death. No effective treatments are currently available. Based on data from epidemiological, etiological, laboratory, and clinical studies, I offer a new way of thinking about ALS and its treatment. This paper describes a host of extrinsic factors, including the exposome, that disrupt the extracellular matrix and protein function such that a spreading, prionlike disease leads to neurodegeneration in the motor tracts. A treatment regimen is described using the stem cell released molecules from a number of types of adult stem cells to provide tissue dependent molecules that restore homeostasis, including proteostasis, in the ALS patient. Because stem cells themselves as a therapeutic are cumbersome and expensive, and when implanted in a host cause aging of the host tissue and often fail to engraft or remain viable, only the S2 RM molecules are used. Rebuilding of the extracellular matrix and repair of the dysfunctional proteins in the ALS patient ensues.展开更多
The intestinal tract(i.e.,the gut),is where the body’s nutrients are absorbed,and is simultaneously inhabited by numerous microbes.An increasing body of literature suggests a crucial role for the gut microbiome in mo...The intestinal tract(i.e.,the gut),is where the body’s nutrients are absorbed,and is simultaneously inhabited by numerous microbes.An increasing body of literature suggests a crucial role for the gut microbiome in modulating systemic inflammatory disease.Psoriasis is a chronic systemic inflammatory disease and its pathogenesis is related to the interaction between genetic susceptibility,immune response and environmental triggers.The omics era has allowed physicians to assess different aspects of psoriasis pathogenesis such as the microbiome,infectome,and autoinfectome.Furthermore,diet appears to play an important role in modulating disease activity,perhaps by influencing gut microbes.Given these observations,we aimed to summarize the current knowledge regarding skin-microbiome-gut-nutrients and psoriasis.展开更多
Background: The skin is the outer shell of the mammalian body and it is continuously exposed to a large spectrum of external stimuli including sun irradiation and atmospheric pollutants. These factors present deleteri...Background: The skin is the outer shell of the mammalian body and it is continuously exposed to a large spectrum of external stimuli including sun irradiation and atmospheric pollutants. These factors present deleterious effects on the cutaneous compartment by altering the skin barrier functions and accelerating the aging of the skin. Objectives: The goal of this study was to investigate the activity of Seaberry and Water Lily extracts, here called Dermina complex, against different external stresses. Methods: Human skin explants were exposed to different stimuli including delipidation by organic solvents, blue light, atmospheric pollutants and UV-A. The activity of the Seaberry and Water Lily extracts was assessed by immunohistochemistry and by biochemical assays. Results: We showed that Dermina complex prevents the delipidation-induced filaggrin decrease, suggesting that these plant extracts exhibited barrier function protecting properties. Also, we observed that Dermina complex showed an antioxidant and DNA protection activity by decreasing the activated form of Nrf2, the oxidized proteins and the formation of γ-H2AX induced upon stress conditions. The Dermina complex also decreased the pro-inflammatory cytokine IL-1 alpha released in the culture medium following atmospheric pollutants and UV-A exposure confirming its anti-inflammatory activity. Moreover, Dermina complex reduced the blue light-induced overexpression of opsin 3, indicating that its skin protection activities may be due, in part, to filter property against environmental stresses. Conclusions: Dermina complex shows a protective activity of the skin against different environmental stresses and these extracts may be able to slow down the aging process of the cutaneous compartment.展开更多
Cardiovascular diseases (CVD) are one of the leading causes of death worldwide. The knowledge andunderstanding of CVD are based on the study of vascular physiology and how the smooth muscle cells and tissuesperform th...Cardiovascular diseases (CVD) are one of the leading causes of death worldwide. The knowledge andunderstanding of CVD are based on the study of vascular physiology and how the smooth muscle cells and tissuesperform their different functions. Exposure to endocrine disruptors (EDCs), such as phytoestrogens, polycyclicaromatic hydrocarbons, flame retardants, plasticizers, pesticides, and cosmetics, is an integral and fundamental part ofhuman exposure. Humans are exposed to EDCs by multiple pathways including air, food, water, and consumerproducts. However, this exposure can lead to several adverse effects on human health, including on the cardiovascular(CV) system. The negative impact that EDC toxicity has on human CV health is a serious problem that must not beoverlooked. In this point of view, we proposed the use of the human umbilical artery as a human model to study thedirect effects of EDCs on the vascular level. Several works where these cells were directly exposed to EDC’s werepresented to highlight this well-established model as a great strategy to be used. In the future, we emphasize the needto continue to carry out different investigations using HUA to unveil and understand the vascular toxicity of EDCsand improve human CV health.展开更多
Some geographic regions induce beneficial effects on health status. The world health organization is interested in analyzing this type of climate area in order to establish a network health status. Understanding the p...Some geographic regions induce beneficial effects on health status. The world health organization is interested in analyzing this type of climate area in order to establish a network health status. Understanding the parameters of this type of climate creates the prerequisites for further research to define their influence on humans, as an external determining factor of the exposome. Supported by historic and medical epidemioiogy data, the Cacica area, Roman has beneficial effects on human health. This climatic natural are, a will be characterized by monitoring their parameters. Thus, they will be rigorously defined and considered of major influence in the exposome. Air quality measurements were made and the local meteorological parameters were monitored. These were correlated with LIDAR data. The atmospheric layers have been evidenced and a possible scenario for the elimination of the pollutant ~erosols has been created, in case, the area suffers contamination during a certain season. The analyzed area shows as climatic characteristics both the absence of pollutant factors and the natural structure of the geo-system. The characterization of this area associated with the special terrain （the through）, involves the introduction of new local development directions： education, ecology and economy.展开更多
Over a century ago,the first clinical and neuropathological insights into major neurodegenerative diseases began to emerge:the description of Alzheimer’s disease(AD)by Alois Alzheimer in 1906,frontotemporal dementia ...Over a century ago,the first clinical and neuropathological insights into major neurodegenerative diseases began to emerge:the description of Alzheimer’s disease(AD)by Alois Alzheimer in 1906,frontotemporal dementia by Arnold Pick in the same years,and Lewy bodies by Friedrich Lewy in 1912.These foundational studies laid the groundwork for the classification of what we now recognize as distinct neurodegenerative entities(Allali,2024).展开更多
Precision medicine, often termed “personalized medicine,” aims to enhance the categorization and timing of healthcare interventions by leveraging biological data and biomarkers at the molecular level, including dise...Precision medicine, often termed “personalized medicine,” aims to enhance the categorization and timing of healthcare interventions by leveraging biological data and biomarkers at the molecular level, including disease pathways, genet-ics, proteomics, and metabolomics (Schleidgen et al. 2013). Over the past decades, with the continuous advancement of omics technologies, numerous studies have utilized vari-ous methods such as genomics, transcriptomics, proteom-ics, and others to investigate personalized biomarkers and therapeutic targets for a variety of diseases including cancer, diabetes, asthma, and so on. In addition to genetics, environ-mental exposures profoundly affect human health, exhibiting significant intra-individual variability and influencing the success of interventions (Goetz and Schork 2018). Conse-quently, conducting comprehensive investigations into indi-vidual-level precise environmental exposures is valuable for understanding individual health and interactions with the environment.展开更多
Background:Exposures to benzene,toluene,ethylbenzene and xylenes(BTEX)have been associated with impairment of the hematopoietic system,often leading to leukemogenesis.A prospective panel study:i)characterized the effe...Background:Exposures to benzene,toluene,ethylbenzene and xylenes(BTEX)have been associated with impairment of the hematopoietic system,often leading to leukemogenesis.A prospective panel study:i)characterized the effect of night shift work(NSW)(12-hr night shift vs.12-hr day shift)on urinary BTEX and metabolites in gasoline station workers in Plovdiv,Bulgaria,ii)evaluated the NSW effect on chrono-based BTEX genotoxic effects(as measured by 8-OHdG,a nonspecific biomarker of genotoxicity)including the influence of the downstream urinary metabolome.Methods:During a week’s working period,workers(n=71)followed both day shift and night shift work schedules(12-h long each shift)collecting four urine samples per worker(pre and end of shift).Airborne BTEX exposures were evaluated over 12-h shift periods using wearable passive samplers.Urinary BTEX and the metabolome were measured using mass spectrometry.8-OHdG was measured using an ELISA immunoassay.Associations were examined using mixed-effect regression models and corrected for false-discovery rates of 0.05.Results:Median personal airborne benzene levels were 3.05(IQR:2.89),and 2.92(IQR:1.86)𝜇g/m^(3) for day and night work shifts,respectively,suggestive of a low-level BTEX study.Results supported a consistent trend of lower urinary BTEX levels in NSW than those observed in day shift,after adjusting for airborne BTEX and confounders.Metabolomic signatures revealed a few significant metabolites associated with NSW or 8-OHdG with 4-hydroxybenzeneacetic acid(level I)being associated with both NSW and 8-OHdG.The biological pathway with high metabolic pathway impact were glycine,serine and threonine metabolism.Conclusion:Larger NSW studies with longer and more frequent follow-up times are warranted to better delineate the possible influence of NSW chrono-modulated working activities in leukemogenic processes.展开更多
Characterizing the chemical composition of semen can provide valuable insights into the exposome and environmental factors that directly affect seminal and overall health.In this study,we compared molecular profiles o...Characterizing the chemical composition of semen can provide valuable insights into the exposome and environmental factors that directly affect seminal and overall health.In this study,we compared molecular profiles of 45 donated semen samples from general population New York City participants and examined the correlation between the chemical profiles in semen and fertility parameters,i.e.,sperm concentration,sperm motility,sperm morphology,and semen volume.Samples were prepared using a protein precipitation procedure and analyzed using liquid chromatography(LC)coupled to high-resolution mass spectrometry(HRMS).Non-targeted analysis(NTA)revealed 18 chemicals not previously reported in human exposome studies,with 3-hydroxyoctanedioic acid,a cosmetic additive,emerging as a plausible candidate found to be at higher levels in cases vs controls(p<0.01)and associated with adverse sperm motility and morphology.Four level 1 identified compounds were found to have associations with semen health parameters;dibutyl phthalate and 2-aminophenol negatively impacted motility,4-nitrophenol was associated with low morphology,while palmitic acid was found to be associated with both low morphology and low volume.This study aims to utilize NTA to understand the association of contaminants of emerging concern(CECs)along with a full chemical profile to find trends separating poor and normal semen health parameters from each other chemically.Our results suggest that the collective effects of many CECs could adversely affect semen quality.展开更多
As environmental exposomes are changing with time,so are liver diseases around the globe.Due to an increasing prevalence of overnutrition and sedentary lifestyle in the global population,metabolic dysfunction-associat...As environmental exposomes are changing with time,so are liver diseases around the globe.Due to an increasing prevalence of overnutrition and sedentary lifestyle in the global population,metabolic dysfunction-associated steatotic liver disease(MASLD)and steatohepatitis have been increasing steadily in the past decades.Alcohol consumption is another common risk factor for liver diseases such as alcohol-associated liver disease or hepatitis.For both alcohol-associated and metabolic dysfunction-associated liver diseases,hepatocyte injuries are among the early events during the development of steatotic liver disease(SLD).Hepatic inflammation and fibrosis ensue with recurring hepatic damages owing to immune responses from multiple immune cell types,particularly neutrophils,Kupffer cells and monocyte-derived macrophages in response to damage-associated and pathogen-associated molecular patterns,and extracellular matrix production predominantly from hepatic stellate cells.Both environmental and genetic factors contribute to the SLD pathogenesis.Common environmental risk factors include obesity,type 2 diabetes mellitus,unhealthy diets,sedentary lifestyle and excessive alcohol consumption.Numerous genome-wide association studies have identified multiple genetic variants associated with key traits of SLD,including patatin-like phospholipase domain containing 3 rs738409,transmembrane 6 superfamily member 2 rs58542926,membrane bound O-acyltransferase domain containing 7 rs641738 and hydroxysteroid 17 beta-dehydrogenase 13 rs72613567.Cirrhosis and liver cancer are common late-stage developments of various chronic liver diseases;however,there are pathological differences according to disease aetiologies.Therefore,preventive and therapeutic intervention strategies should align with the underlying causal and modifiable factors.Currently,multiple therapeutics have been developed or approved for treatment of SLD,including thyroid hormone receptorβagonists,glucagon-like peptide 1 receptor agonists and fibroblast growth factor 21 analogues.The concept of this review was motivated and inspired by the Seventh Annual Symposium of Chinese American Liver Society held in San Diego,California,USA on 13-14 November 2024.展开更多
Liver diseases are considered to predominantly possess an inherited or xenobiotic etiology.However,inheritance drives the ability to appropriately adapt to environmental stressors,and disease is the culmination of a m...Liver diseases are considered to predominantly possess an inherited or xenobiotic etiology.However,inheritance drives the ability to appropriately adapt to environmental stressors,and disease is the culmination of a maladaptive response.Thus "pure" genetic and "pure" xenobiotic liver diseases are modified by each other and other factors,identified or unknown.The purpose of this review is to highlight the knowledgebase of environmental exposure as a potential risk modifying agent for the development of liver disease by other causes.This exercise is not to argue that all liver diseases have an environmental component,but to challenge the assumption that the current state of our knowledge is sufficient in all cases to conclusively dismiss this as a possibility.This review also discusses key new tools and approaches that will likely be critical to address this question in the future.Taken together,identifying the key gaps in our understanding is critical for the field to move forward,or at the very least to "know what we don't know."展开更多
Mycotoxin exposure during pregnancy has been associated with adverse birth outcomes and poor infant growth in low-and middle-income countries.We assessed multiple biomarkers and metabolites of exposure to mycotoxins d...Mycotoxin exposure during pregnancy has been associated with adverse birth outcomes and poor infant growth in low-and middle-income countries.We assessed multiple biomarkers and metabolites of exposure to mycotoxins during pregnancy and their associations with birth outcomes and infant growth in 305 pregnant participants,between 30 and 34 completed weeks of gestation,in rural Burkina Faso.In this study,whole blood microsamples were analyzed for mycotoxin concentrations using ultra-performance liquid chromatography coupled to tandem mass spectrometry.Unadjusted and adjusted associations between mycotoxin exposure,and birth outcomes and infant growth at 6 months were estimated using linear regression models for continuous outcomes and linear probability models with robust variance estimation for binary outcomes.Infant growth trajectories from birth to 6 months were compared by exposure status using mixed-effects models with random intercept for the individual infant and random slope for the infant's age.Ochratoxin A(OTA)exposure was detected in 50.8%of the study participants,with aflatoxin G1,aflatoxin M1,cyclopiazonic acid,deoxynivalenol and T-2-toxin being detected in the range of 0.33%and 2.31%of the population.We found no statistically significant(p≥0.05)associations between OTA exposure,and birth outcomes and infant growth.Despite this,the findings indicate a significant presence of ochratoxin A among pregnant participants.Public health policies and nutrition-sensitive interventions must ensure that OTA exposure is reduced in Burkina Faso.展开更多
Alterations to the gut microbiome and exposure to metals during pregnancy have been suggested to impact inflammatory bowel disease.Nonetheless,how prenatal exposure to metals eventually results in long-term effects on...Alterations to the gut microbiome and exposure to metals during pregnancy have been suggested to impact inflammatory bowel disease.Nonetheless,how prenatal exposure to metals eventually results in long-term effects on the gut microbiome,leading to subclinical intestinal inflammation,particularly during late childhood,has not been studied.It is also unknown whether such an interactive effect drives a specific subgroup of children toward elevated susceptibility to intestinal inflammation.We used an amalgamation of machine-learning techniques with a regression-based framework to explore if children with distinct sets of gut microbes and certain patterns of exposure to metals during pregnancy(metal−microbial clique signature)had a higher likelihood of intestinal inflammation,measured based on fecal calprotectin(FC)in late childhood.We obtained samples from a well-characterized longitudinal birth cohort from Mexico City(n=108),Mexico.In the second and third trimesters of pregnancy,11 metals were measured in whole blood.Gut microbial abundances and FC were measured in stool samples from children 9−11 years of age.Elevated FC was defined as having FC above 100μg/g of stool.We identified subgroups of children in whom microbial and metal−microbial clique signatures were associated with elevated FC(false discovery rate(FDR)<0.05).In particular,we found two metal−microbial clique signatures significantly associated with elevated FC:(1)low cesium(Cs)and copper(Cu)in the third trimester and low relative abundance of Eubacterium ventriosum(OR[95%CI]:10.27[3.57,29.52],FDR<0.001)and(2)low Cu in the third trimester and high relative abundances of Roseburia inulinivorans and Ruminococcus torques(OR[95%CI]:7.21[1.81,28.77],FDR<0.05).This exploratory study demonstrates that children with specific gut microbes and specific exposure patterns to metals during pregnancy may have higher fecal calprotectin levels in late childhood,denoting an elevated risk of intestinal inflammation.展开更多
A healthy lifestyle has been associated with decreased risk of developing breast cancer.Using untargeted metabolomics profiling,which provides unbiased information regarding lifestyle choices such as diet and exercise...A healthy lifestyle has been associated with decreased risk of developing breast cancer.Using untargeted metabolomics profiling,which provides unbiased information regarding lifestyle choices such as diet and exercise,we aim to identify the molecular mechanisms connecting lifestyle and breast cancer through network analysis.A total of 100 postmenopausal women,50 with breast cancer and 50 cancer-free controls,were selected from the Long Island Breast Cancer Study Project(LIBCSP).We measured untargeted plasma metabolomics using liquid chromatography-high-resolution mass spectrometry(LCHRMS).Using the“enet”package,we retained highly correlated metabolites representing active molecular network(AMN)clusters for analysis.LASSO was used to examine associations between cancer status and AMN metabolites and covariates such as BMI,age,and reproductive factors.LASSO was then repeated to examine associations between AMN metabolites and 10 lifestyle-related variables including smoking,physical activity,alcohol consumption,meat consumption,fruit and vegetable consumption,and supplemental vitamin use.Results were displayed as a network to uncover biological pathways linking lifestyle factors to breast cancer status.After filtering,851“active”metabolites out of 1797 metabolomics were retained in 197 correlation AMN clusters.Using LASSO,breast cancer status was associated with 71“active”metabolites.Several of these metabolites were associated with lifestyle variables including meat consumption,alcohol consumption,and supplementalβ-carotene,B12,and folate use.Those metabolites could potentially serve as molecular-level biological intermediaries connecting healthy lifestyle factors to breast cancer,even though direct associations between breast cancer and the investigated lifestyles at the phenotype level are not evident.In particular,DiHODE,a metabolite linked with inflammation,was associated with breast cancer status and connected toβ-carotene supplement usage through an AMN.We found several plasma metabolites associated with lifestyle factors and breast cancer status.Future studies investigating the mechanistic role of inflammation in linking supplement usage to breast cancer status are warranted.展开更多
Exposure to complex environmental mixtures leads to dynamic and evolving exposomes under different environ-mental conditions,presenting significant challenges to humans and other organisms.Therefore,on the demand of r...Exposure to complex environmental mixtures leads to dynamic and evolving exposomes under different environ-mental conditions,presenting significant challenges to humans and other organisms.Therefore,on the demand of risk management of complex mixture exposure,the determination of the overall toxicity and the key components that drive the observed toxic effects is the prerequisite.展开更多
基金supported by the National Natural Science Foundation of China(22425041,22188102,22193050)the Chinese Academy of Sciences Project for Young Scientists in Basic Research(YSBR-086)+1 种基金the National Key R&D Program of China(2023YFC3708302)the Major Project of Guangzhou National Laboratory(GZNL2024A01028)。
文摘The exposome is defined as the cumulative lifetime exposure to exogenous environmental factors and their corresponding biological responses,thereby providing a holistic framework for elucidating the complex interplay between environmental determinants and human health outcomes.Understanding these complex interactions is important for identifying the causes of diseases and associated risk factors.Recent advances in analytical methodologies employed in exposomics,including mass spectrometry and sensor-based platforms,have significantly expanded our capacity to identify and quantify both external exposures and internal biological responses.This review explores recent advancements and practical applications of these techniques in environmental health studies,with a focus on their role in detecting and characterizing complex exposure patterns.Additionally,we discuss the challenges in exposome research and propose strategies to improve its application,thereby reinforcing the potential of the exposome paradigm in advancing precision public health.
文摘Genomic medicine has evolved significantly,merging centuries of scientific progress with modern molecular biology and clinical care.It utilizes knowledge of the human genome to enhance disease prevention,diagnosis,treatment,and potential reversal.Genomic medicine in hepatology is particularly promising due to the crucial role of the liver in several metabolic processes and its association with diseases such as metabolic dysfunction-associated steatotic liver disease,type 2 diabetes mellitus,liver cirrhosis,and cardiovascular conditions.The mid-20th century witnessed a paradigm shift in medicine,marked by the emergence of molecular biology,which enabled a deeper understanding of gene expression and regulation.This connection between basic science and clinical practice has enhanced our knowledge of the role of gene-environment interactions in the onset and progression of liver diseases.In Latin America,including Mexico,with its genetically diverse and admixed populations,genomic medicine provides a foundation for personalized and culturally relevant health strategies.This review highlights the need for genomic medicine,examining its historical evolution,integration into hepatology in Mexico,and its potential applications in the prevention of chronic diseases.It emphasizes the importance of training in genomic literacy and interdisciplinary education in medical training,particularly in the field of hepatology,with a focus on genomic medicine expertise.
文摘AIM: To advances in genetics and immunology have contributed to the current understanding of the pathogenesis of inflammatory bowel diseases(IBD). METHODS: The current opinion on the pathogenesis of IBD suggests that genetically susceptible individuals develop intolerance to dysregulated gut microflora(dysbiosis) and chronic inflammation develops as a result of environmental insults. Environmental exposures are innumerable with varying effects during the life course of individuals with IBD. Studying the relationship between environmental factors and IBD may provide the missing link to increasing our understanding of the etiology and increased incidence of IBD in recent years with implications for prevention, diagnosis, and treatment. Environmental factors are heterogeneous and genetic predisposition, immune dysregulation, or dysbiosis do not lead to the development of IBD in isolation. RESULTS: Current challenges in the study of environmental factors and IBD are how to effectively translate promising results from experimental studies to humans in order to develop models that incorporate the complex interactions between the environment, genetics, immunology, and gut microbiota, and limited high quality interventional studies assessing the effect of modifying environmental factors on the natural history and patient outcomes in IBD.CONCLUSION: This article critically reviews the current evidence on environmental risk factors for IBD and proposes directions for future research.
文摘Amyotrophic lateral sclerosis(ALS) is a rapidly progressing neurodegenerative disease that leads to death. No effective treatments are currently available. Based on data from epidemiological, etiological, laboratory, and clinical studies, I offer a new way of thinking about ALS and its treatment. This paper describes a host of extrinsic factors, including the exposome, that disrupt the extracellular matrix and protein function such that a spreading, prionlike disease leads to neurodegeneration in the motor tracts. A treatment regimen is described using the stem cell released molecules from a number of types of adult stem cells to provide tissue dependent molecules that restore homeostasis, including proteostasis, in the ALS patient. Because stem cells themselves as a therapeutic are cumbersome and expensive, and when implanted in a host cause aging of the host tissue and often fail to engraft or remain viable, only the S2 RM molecules are used. Rebuilding of the extracellular matrix and repair of the dysfunctional proteins in the ALS patient ensues.
文摘The intestinal tract(i.e.,the gut),is where the body’s nutrients are absorbed,and is simultaneously inhabited by numerous microbes.An increasing body of literature suggests a crucial role for the gut microbiome in modulating systemic inflammatory disease.Psoriasis is a chronic systemic inflammatory disease and its pathogenesis is related to the interaction between genetic susceptibility,immune response and environmental triggers.The omics era has allowed physicians to assess different aspects of psoriasis pathogenesis such as the microbiome,infectome,and autoinfectome.Furthermore,diet appears to play an important role in modulating disease activity,perhaps by influencing gut microbes.Given these observations,we aimed to summarize the current knowledge regarding skin-microbiome-gut-nutrients and psoriasis.
文摘Background: The skin is the outer shell of the mammalian body and it is continuously exposed to a large spectrum of external stimuli including sun irradiation and atmospheric pollutants. These factors present deleterious effects on the cutaneous compartment by altering the skin barrier functions and accelerating the aging of the skin. Objectives: The goal of this study was to investigate the activity of Seaberry and Water Lily extracts, here called Dermina complex, against different external stresses. Methods: Human skin explants were exposed to different stimuli including delipidation by organic solvents, blue light, atmospheric pollutants and UV-A. The activity of the Seaberry and Water Lily extracts was assessed by immunohistochemistry and by biochemical assays. Results: We showed that Dermina complex prevents the delipidation-induced filaggrin decrease, suggesting that these plant extracts exhibited barrier function protecting properties. Also, we observed that Dermina complex showed an antioxidant and DNA protection activity by decreasing the activated form of Nrf2, the oxidized proteins and the formation of γ-H2AX induced upon stress conditions. The Dermina complex also decreased the pro-inflammatory cytokine IL-1 alpha released in the culture medium following atmospheric pollutants and UV-A exposure confirming its anti-inflammatory activity. Moreover, Dermina complex reduced the blue light-induced overexpression of opsin 3, indicating that its skin protection activities may be due, in part, to filter property against environmental stresses. Conclusions: Dermina complex shows a protective activity of the skin against different environmental stresses and these extracts may be able to slow down the aging process of the cutaneous compartment.
基金This work was financed by the Foundation for Science and Technology(FCT)through funds from the State Budget,and by the European Regional Development Fund(ERDF),under the Portugal 2020 Program+2 种基金through the Regional Operational Program of the Center(Centro2020)through the Project with the reference UIDB/00709/2020M.L.acknowledges the Ph.D.fellowship from FCT(Reference:2020.06616.BD).
文摘Cardiovascular diseases (CVD) are one of the leading causes of death worldwide. The knowledge andunderstanding of CVD are based on the study of vascular physiology and how the smooth muscle cells and tissuesperform their different functions. Exposure to endocrine disruptors (EDCs), such as phytoestrogens, polycyclicaromatic hydrocarbons, flame retardants, plasticizers, pesticides, and cosmetics, is an integral and fundamental part ofhuman exposure. Humans are exposed to EDCs by multiple pathways including air, food, water, and consumerproducts. However, this exposure can lead to several adverse effects on human health, including on the cardiovascular(CV) system. The negative impact that EDC toxicity has on human CV health is a serious problem that must not beoverlooked. In this point of view, we proposed the use of the human umbilical artery as a human model to study thedirect effects of EDCs on the vascular level. Several works where these cells were directly exposed to EDC’s werepresented to highlight this well-established model as a great strategy to be used. In the future, we emphasize the needto continue to carry out different investigations using HUA to unveil and understand the vascular toxicity of EDCsand improve human CV health.
文摘Some geographic regions induce beneficial effects on health status. The world health organization is interested in analyzing this type of climate area in order to establish a network health status. Understanding the parameters of this type of climate creates the prerequisites for further research to define their influence on humans, as an external determining factor of the exposome. Supported by historic and medical epidemioiogy data, the Cacica area, Roman has beneficial effects on human health. This climatic natural are, a will be characterized by monitoring their parameters. Thus, they will be rigorously defined and considered of major influence in the exposome. Air quality measurements were made and the local meteorological parameters were monitored. These were correlated with LIDAR data. The atmospheric layers have been evidenced and a possible scenario for the elimination of the pollutant ~erosols has been created, in case, the area suffers contamination during a certain season. The analyzed area shows as climatic characteristics both the absence of pollutant factors and the natural structure of the geo-system. The characterization of this area associated with the special terrain （the through）, involves the introduction of new local development directions： education, ecology and economy.
文摘Over a century ago,the first clinical and neuropathological insights into major neurodegenerative diseases began to emerge:the description of Alzheimer’s disease(AD)by Alois Alzheimer in 1906,frontotemporal dementia by Arnold Pick in the same years,and Lewy bodies by Friedrich Lewy in 1912.These foundational studies laid the groundwork for the classification of what we now recognize as distinct neurodegenerative entities(Allali,2024).
基金National Natural Science Foundation of China(82404365,82404278)Noncommunicable Chronic Diseases-National Science and Technology Major Project(2023ZD0513200)+8 种基金the Fundamental Research Funds for the Central Universities(No.3332023042)Peking Union Medical College Graduate Innovation Fund(No.2019-1004-02)the China Postdoctoral Science Foundation(Nos.2023M730317,and 2023T160066)the Open Project of Hebei Key Laboratory of Environment and Human Health(No.202301)The special fund of State Environmental Protection Key Laboratory of Environmental Health Impact Assessment of Emerging Contaminants(SEPKL-EHIAEC-202205)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2022-JKCS-11)CAMS Innovation Fund for Medical Sciences(No.2022-I2M-JB-003)China Medical Board(Grant No.15-230)China Prospective cohort study of Air pollution and health effects in Typical areas(C-PAT)(Grant No.MEE-EH-20190802).
文摘Precision medicine, often termed “personalized medicine,” aims to enhance the categorization and timing of healthcare interventions by leveraging biological data and biomarkers at the molecular level, including disease pathways, genet-ics, proteomics, and metabolomics (Schleidgen et al. 2013). Over the past decades, with the continuous advancement of omics technologies, numerous studies have utilized vari-ous methods such as genomics, transcriptomics, proteom-ics, and others to investigate personalized biomarkers and therapeutic targets for a variety of diseases including cancer, diabetes, asthma, and so on. In addition to genetics, environ-mental exposures profoundly affect human health, exhibiting significant intra-individual variability and influencing the success of interventions (Goetz and Schork 2018). Conse-quently, conducting comprehensive investigations into indi-vidual-level precise environmental exposures is valuable for understanding individual health and interactions with the environment.
基金funding support by the EX-POSOWORK project(OPPORTUNITY/0916/MSCA/0077)co-financed by the European Regional Development Fund and the Republic of Cyprus through the Research and Innovation Foundation,and the Nor-wegian Cancer Society(grant no:222387).
文摘Background:Exposures to benzene,toluene,ethylbenzene and xylenes(BTEX)have been associated with impairment of the hematopoietic system,often leading to leukemogenesis.A prospective panel study:i)characterized the effect of night shift work(NSW)(12-hr night shift vs.12-hr day shift)on urinary BTEX and metabolites in gasoline station workers in Plovdiv,Bulgaria,ii)evaluated the NSW effect on chrono-based BTEX genotoxic effects(as measured by 8-OHdG,a nonspecific biomarker of genotoxicity)including the influence of the downstream urinary metabolome.Methods:During a week’s working period,workers(n=71)followed both day shift and night shift work schedules(12-h long each shift)collecting four urine samples per worker(pre and end of shift).Airborne BTEX exposures were evaluated over 12-h shift periods using wearable passive samplers.Urinary BTEX and the metabolome were measured using mass spectrometry.8-OHdG was measured using an ELISA immunoassay.Associations were examined using mixed-effect regression models and corrected for false-discovery rates of 0.05.Results:Median personal airborne benzene levels were 3.05(IQR:2.89),and 2.92(IQR:1.86)𝜇g/m^(3) for day and night work shifts,respectively,suggestive of a low-level BTEX study.Results supported a consistent trend of lower urinary BTEX levels in NSW than those observed in day shift,after adjusting for airborne BTEX and confounders.Metabolomic signatures revealed a few significant metabolites associated with NSW or 8-OHdG with 4-hydroxybenzeneacetic acid(level I)being associated with both NSW and 8-OHdG.The biological pathway with high metabolic pathway impact were glycine,serine and threonine metabolism.Conclusion:Larger NSW studies with longer and more frequent follow-up times are warranted to better delineate the possible influence of NSW chrono-modulated working activities in leukemogenic processes.
基金funded by the National Institutes of Health-National Institute of Environmental Health Sciences(NIHNIEHS)(R00ES032892,K99ES032892,R00ES030403,K99ES030403,P30ES030284)by NYU Langone.
文摘Characterizing the chemical composition of semen can provide valuable insights into the exposome and environmental factors that directly affect seminal and overall health.In this study,we compared molecular profiles of 45 donated semen samples from general population New York City participants and examined the correlation between the chemical profiles in semen and fertility parameters,i.e.,sperm concentration,sperm motility,sperm morphology,and semen volume.Samples were prepared using a protein precipitation procedure and analyzed using liquid chromatography(LC)coupled to high-resolution mass spectrometry(HRMS).Non-targeted analysis(NTA)revealed 18 chemicals not previously reported in human exposome studies,with 3-hydroxyoctanedioic acid,a cosmetic additive,emerging as a plausible candidate found to be at higher levels in cases vs controls(p<0.01)and associated with adverse sperm motility and morphology.Four level 1 identified compounds were found to have associations with semen health parameters;dibutyl phthalate and 2-aminophenol negatively impacted motility,4-nitrophenol was associated with low morphology,while palmitic acid was found to be associated with both low morphology and low volume.This study aims to utilize NTA to understand the association of contaminants of emerging concern(CECs)along with a full chemical profile to find trends separating poor and normal semen health parameters from each other chemically.Our results suggest that the collective effects of many CECs could adversely affect semen quality.
基金supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases awards R01DK120689(XCD),R01DK121925(XCD)and R01DK124612(WL)the National Institute on Alcohol Abuse and Alcoholism awards R01AA028506(XCD and WL),UT2AA031151(WL and XCD),K01AA26385(ZY)R01AA030993(ZY),and the National Institute on Aging award R21AG072288(XCD).
文摘As environmental exposomes are changing with time,so are liver diseases around the globe.Due to an increasing prevalence of overnutrition and sedentary lifestyle in the global population,metabolic dysfunction-associated steatotic liver disease(MASLD)and steatohepatitis have been increasing steadily in the past decades.Alcohol consumption is another common risk factor for liver diseases such as alcohol-associated liver disease or hepatitis.For both alcohol-associated and metabolic dysfunction-associated liver diseases,hepatocyte injuries are among the early events during the development of steatotic liver disease(SLD).Hepatic inflammation and fibrosis ensue with recurring hepatic damages owing to immune responses from multiple immune cell types,particularly neutrophils,Kupffer cells and monocyte-derived macrophages in response to damage-associated and pathogen-associated molecular patterns,and extracellular matrix production predominantly from hepatic stellate cells.Both environmental and genetic factors contribute to the SLD pathogenesis.Common environmental risk factors include obesity,type 2 diabetes mellitus,unhealthy diets,sedentary lifestyle and excessive alcohol consumption.Numerous genome-wide association studies have identified multiple genetic variants associated with key traits of SLD,including patatin-like phospholipase domain containing 3 rs738409,transmembrane 6 superfamily member 2 rs58542926,membrane bound O-acyltransferase domain containing 7 rs641738 and hydroxysteroid 17 beta-dehydrogenase 13 rs72613567.Cirrhosis and liver cancer are common late-stage developments of various chronic liver diseases;however,there are pathological differences according to disease aetiologies.Therefore,preventive and therapeutic intervention strategies should align with the underlying causal and modifiable factors.Currently,multiple therapeutics have been developed or approved for treatment of SLD,including thyroid hormone receptorβagonists,glucagon-like peptide 1 receptor agonists and fibroblast growth factor 21 analogues.The concept of this review was motivated and inspired by the Seventh Annual Symposium of Chinese American Liver Society held in San Diego,California,USA on 13-14 November 2024.
基金Supported, in part, by grants from NIH (R01 AA021978, P30 DK120531, and R21 ES031531, USA)。
文摘Liver diseases are considered to predominantly possess an inherited or xenobiotic etiology.However,inheritance drives the ability to appropriately adapt to environmental stressors,and disease is the culmination of a maladaptive response.Thus "pure" genetic and "pure" xenobiotic liver diseases are modified by each other and other factors,identified or unknown.The purpose of this review is to highlight the knowledgebase of environmental exposure as a potential risk modifying agent for the development of liver disease by other causes.This exercise is not to argue that all liver diseases have an environmental component,but to challenge the assumption that the current state of our knowledge is sufficient in all cases to conclusively dismiss this as a possibility.This review also discusses key new tools and approaches that will likely be critical to address this question in the future.Taken together,identifying the key gaps in our understanding is critical for the field to move forward,or at the very least to "know what we don't know."
基金supported by Fonds Wetenschappelijk Onderzoek(project No G085921 N).
文摘Mycotoxin exposure during pregnancy has been associated with adverse birth outcomes and poor infant growth in low-and middle-income countries.We assessed multiple biomarkers and metabolites of exposure to mycotoxins during pregnancy and their associations with birth outcomes and infant growth in 305 pregnant participants,between 30 and 34 completed weeks of gestation,in rural Burkina Faso.In this study,whole blood microsamples were analyzed for mycotoxin concentrations using ultra-performance liquid chromatography coupled to tandem mass spectrometry.Unadjusted and adjusted associations between mycotoxin exposure,and birth outcomes and infant growth at 6 months were estimated using linear regression models for continuous outcomes and linear probability models with robust variance estimation for binary outcomes.Infant growth trajectories from birth to 6 months were compared by exposure status using mixed-effects models with random intercept for the individual infant and random slope for the infant's age.Ochratoxin A(OTA)exposure was detected in 50.8%of the study participants,with aflatoxin G1,aflatoxin M1,cyclopiazonic acid,deoxynivalenol and T-2-toxin being detected in the range of 0.33%and 2.31%of the population.We found no statistically significant(p≥0.05)associations between OTA exposure,and birth outcomes and infant growth.Despite this,the findings indicate a significant presence of ochratoxin A among pregnant participants.Public health policies and nutrition-sensitive interventions must ensure that OTA exposure is reduced in Burkina Faso.
基金supported by the National Institute of Environmental Health Sciences(P30ES023515)M.Agrawal is supported by the National Institute of Diabetes and Digestive and Kidney Diseases(K23DK129762-03)+3 种基金the National Institute of General Medical Sciences(R25GM143298)S.E.is supported by the National Institute of Environmental Health Sciences(R00ES032884)R.O.W.,L.A.T.-O.,and M.M.T.-R.are supported by the National Institute of Environmental Health Sciences(P30ES023515 and R01ES013744)M.Arora and V.M.are supported by the National Institute of Environmental Health Sciences(U2CES030859 and R35ES030435).
文摘Alterations to the gut microbiome and exposure to metals during pregnancy have been suggested to impact inflammatory bowel disease.Nonetheless,how prenatal exposure to metals eventually results in long-term effects on the gut microbiome,leading to subclinical intestinal inflammation,particularly during late childhood,has not been studied.It is also unknown whether such an interactive effect drives a specific subgroup of children toward elevated susceptibility to intestinal inflammation.We used an amalgamation of machine-learning techniques with a regression-based framework to explore if children with distinct sets of gut microbes and certain patterns of exposure to metals during pregnancy(metal−microbial clique signature)had a higher likelihood of intestinal inflammation,measured based on fecal calprotectin(FC)in late childhood.We obtained samples from a well-characterized longitudinal birth cohort from Mexico City(n=108),Mexico.In the second and third trimesters of pregnancy,11 metals were measured in whole blood.Gut microbial abundances and FC were measured in stool samples from children 9−11 years of age.Elevated FC was defined as having FC above 100μg/g of stool.We identified subgroups of children in whom microbial and metal−microbial clique signatures were associated with elevated FC(false discovery rate(FDR)<0.05).In particular,we found two metal−microbial clique signatures significantly associated with elevated FC:(1)low cesium(Cs)and copper(Cu)in the third trimester and low relative abundance of Eubacterium ventriosum(OR[95%CI]:10.27[3.57,29.52],FDR<0.001)and(2)low Cu in the third trimester and high relative abundances of Roseburia inulinivorans and Ruminococcus torques(OR[95%CI]:7.21[1.81,28.77],FDR<0.05).This exploratory study demonstrates that children with specific gut microbes and specific exposure patterns to metals during pregnancy may have higher fecal calprotectin levels in late childhood,denoting an elevated risk of intestinal inflammation.
基金the National Institutes of Health(grants P30ES023515,U2CES030859,U2CES026561,U2CES026555,R21ES030882,R01ES031117,UH2CA248974,and U01CA066572).
文摘A healthy lifestyle has been associated with decreased risk of developing breast cancer.Using untargeted metabolomics profiling,which provides unbiased information regarding lifestyle choices such as diet and exercise,we aim to identify the molecular mechanisms connecting lifestyle and breast cancer through network analysis.A total of 100 postmenopausal women,50 with breast cancer and 50 cancer-free controls,were selected from the Long Island Breast Cancer Study Project(LIBCSP).We measured untargeted plasma metabolomics using liquid chromatography-high-resolution mass spectrometry(LCHRMS).Using the“enet”package,we retained highly correlated metabolites representing active molecular network(AMN)clusters for analysis.LASSO was used to examine associations between cancer status and AMN metabolites and covariates such as BMI,age,and reproductive factors.LASSO was then repeated to examine associations between AMN metabolites and 10 lifestyle-related variables including smoking,physical activity,alcohol consumption,meat consumption,fruit and vegetable consumption,and supplemental vitamin use.Results were displayed as a network to uncover biological pathways linking lifestyle factors to breast cancer status.After filtering,851“active”metabolites out of 1797 metabolomics were retained in 197 correlation AMN clusters.Using LASSO,breast cancer status was associated with 71“active”metabolites.Several of these metabolites were associated with lifestyle variables including meat consumption,alcohol consumption,and supplementalβ-carotene,B12,and folate use.Those metabolites could potentially serve as molecular-level biological intermediaries connecting healthy lifestyle factors to breast cancer,even though direct associations between breast cancer and the investigated lifestyles at the phenotype level are not evident.In particular,DiHODE,a metabolite linked with inflammation,was associated with breast cancer status and connected toβ-carotene supplement usage through an AMN.We found several plasma metabolites associated with lifestyle factors and breast cancer status.Future studies investigating the mechanistic role of inflammation in linking supplement usage to breast cancer status are warranted.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB0750300)the National Natural Science Foundation of China(22325606,22241604,52170106).
文摘Exposure to complex environmental mixtures leads to dynamic and evolving exposomes under different environ-mental conditions,presenting significant challenges to humans and other organisms.Therefore,on the demand of risk management of complex mixture exposure,the determination of the overall toxicity and the key components that drive the observed toxic effects is the prerequisite.
