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
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 assoc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
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
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
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.
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 assoc
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.
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.
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.
