Dataset Information

Modulation of Intestinal Epithelial Permeability in Differentiated Caco-2 Cells Exposed to Aflatoxin M1 and Ochratoxin A Individually or Collectively.

ABSTRACT: Aflatoxin M1 (AFM1) and ochratoxin A (OTA) are mycotoxins commonly found in milk; however, their effects on intestinal epithelial cells have not been reported. In the present study, we show that AFM1 (0.12 and 12 ?M) and OTA (0.2 and 20 ?M) individually or collectively increased the paracellular flux of lucifer yellow and fluorescein isothiocyanate (FITC)-dextrans (4 and 40 kDa) and decreased transepithelial electrical resistance values in differentiated Caco-2 cells after 48 h of exposure, indicating increased epithelial permeability. Immunoblotting and immunofluorescent analysis revealed that AFM1, OTA, and their combination decreased the expression levels of tight junction (TJ) proteins and disrupted their structures, namely, claudin-3, claudin-4, occludin, and zonula occludens-1 (ZO-1), and p44/42 mitogen-activated protein kinase (MAPK) partially involved in the mycotoxins-induced disruption of intestinal barrier. The effects of a combination of AFM1 and OTA on intestinal barrier function were more significant (p < 0.05) than those of AFM1 and OTA alone, yielding additive or synergistic effects. The additive or synergistic effects of AFM1 and OTA on intestinal barrier function might affect human health, especially in children, and toxin risks should be considered.

SUBMITTER: Gao Y

PROVIDER: S-EPMC5793100 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Modulation of Intestinal Epithelial Permeability in Differentiated Caco-2 Cells Exposed to Aflatoxin M1 and Ochratoxin A Individually or Collectively.

Gao Yanan Y Li Songli S Wang Jiaqi J Luo Chaochao C Zhao Shengguo S Zheng Nan N

Toxins 20171227 1

Aflatoxin M1 (AFM1) and ochratoxin A (OTA) are mycotoxins commonly found in milk; however, their effects on intestinal epithelial cells have not been reported. In the present study, we show that AFM1 (0.12 and 12 μM) and OTA (0.2 and 20 μM) individually or collectively increased the paracellular flux of lucifer yellow and fluorescein isothiocyanate (FITC)-dextrans (4 and 40 kDa) and decreased transepithelial electrical resistance values in differentiated Caco-2 cells after 48 h of exposure, indi ...[more]

PMID: 29280945

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Project description:BackgroundThe word 'pandemic' conjures dystopian images of bodies stacked in the streets and societies on the brink of collapse. Despite this frightening picture, denialism and noncompliance with public health measures are common in the historical record, for example during the 1918 Influenza pandemic or the 2015 Ebola epidemic. The unique characteristics of SARS-CoV-2-its high basic reproduction number (R0), time-limited natural immunity and considerable potential for asymptomatic spread-exacerbate the public health repercussions of noncompliance with interventions (such as vaccines and masks) to limit disease transmission. Our work explores the rationality and impact of noncompliance with measures aimed at limiting the spread of SARS-CoV-2.MethodsIn this work, we used game theory to explore when noncompliance confers a perceived benefit to individuals. We then used epidemiological modeling to predict the impact of noncompliance on control of SARS-CoV-2, demonstrating that the presence of a noncompliant subpopulation prevents suppression of disease spread.ResultsOur modeling demonstrates that noncompliance is a Nash equilibrium under a broad set of conditions and that the existence of a noncompliant population can result in extensive endemic disease in the long-term after a return to pre-pandemic social and economic activity. Endemic disease poses a threat for both compliant and noncompliant individuals; all community members are protected if complete suppression is achieved, which is only possible with a high degree of compliance. For interventions that are highly effective at preventing disease spread, however, the consequences of noncompliance are borne disproportionately by noncompliant individuals.ConclusionsIn sum, our work demonstrates the limits of free-market approaches to compliance with disease control measures during a pandemic. The act of noncompliance with disease intervention measures creates a negative externality, rendering suppression of SARS-CoV-2 spread ineffective. Our work underscores the importance of developing effective strategies for prophylaxis through public health measures aimed at complete suppression and the need to focus on compliance at a population level.

Project description:ImportanceOccupational exposure to carcinogens has been shown to pose a serious disease burden at the global, regional, and national levels. Based on epidemiologic studies and clinical observations, working environment appears to have important effects on the occurrence of human malignant tumors; however, to date, no systematic articles have been published that specifically investigated cancer burden due to occupational exposure in an individual and collective manner.ObjectiveTo estimate the degree of exposure and evaluate the cancer burden attributable to occupational carcinogens (OCs) individually and collectively by sex, age, year, and location.Design, setting, and participantsCross-sectional study including data on 195 countries from the Global Burden of Diseases, Injuries, and Risk Factors Study from January 1, 1990, to December 31, 2017. Data were analyzed from June 24, 2020, to July 20, 2020.ExposuresThirteen OCs (ie, arsenic, asbestos, benzene, beryllium, cadmium, chromium, diesel engine exhaust, formaldehyde, nickel, polycyclic aromatic hydrocarbons, silica, sulfuric acid, and trichloroethylene).Main outcomes and measuresThe degree and change patterns of exposure as well as the attributable cancer burden, including deaths and disability-adjusted life years (DALYs), by sex, age, year, and location for 13 OCs. The calculation of the population-attributable fraction was based on past exposure in the population and relative risks.ResultsBased on the GBD 2017 study, 13 OCs attributable to 7 cancer types were included. Most summary exposure values for the 13 OCs, particularly those of diesel engine exhaust (35.6% increase; 95% uncertainty interval [UI], 32.4%-38.5%) and trichloroethylene (30.3% increase; 95% UI, 27.3%-33.5%), increased from 1990 to 2017. Only exposure to asbestos decreased by 13.8% (95% UI, -26.7% to 2.2%). In 2017, 319 000 (95% UI, 256 000-382 000) cancer deaths and 6.42 million (95% UI, 5.15 million to 7.76 million) DALYs were associated with OCs combined, accounting for 61.0% (95% UI, 59.6%-62.4%) of the total cancer deaths and 48.3% (46.3% to 50.2%) of the DALYs. Among the 13 OCs, the 3 leading risk factors for cancer burden were asbestos (71.8%), silica (15.4%), and diesel engine exhaust (5.6%). For most OCs, the attributed cancer outcome was tracheal, bronchial, and lung cancer, which accounted for 89.0% of attributable cancer deaths. China (61 644 cancer deaths), the US (42 848), and Japan (20 748) accounted for the largest number of attributable cancer deaths in 2017; for DALYs, China (1.47 million), the US (0.71 million), and India (0.37 million) were the 3 leading countries.Conclusions and relevanceResults of this study suggest that although OC exposure levels have decreased, the overall cancer burden is continuously increasing.

Dataset Information

Modulation of Intestinal Epithelial Permeability in Differentiated Caco-2 Cells Exposed to Aflatoxin M1 and Ochratoxin A Individually or Collectively.

Publications

Modulation of Intestinal Epithelial Permeability in Differentiated Caco-2 Cells Exposed to Aflatoxin M1 and Ochratoxin A Individually or Collectively.

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