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Postepy Dermatologii I Alergologii Feb 2024The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that has gained increasing attention in the field of dermatology due to its multifaceted... (Review)
Review
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that has gained increasing attention in the field of dermatology due to its multifaceted role in skin health and disease. This review provides a comprehensive overview of the current state of knowledge regarding the AHR and its implications in dermatological conditions. The AHR is well known for its involvement in xenobiotic metabolism, particularly in response to polycyclic aromatic hydrocarbons and dioxins. However, recent research has unveiled its pivotal role in the skin immune response, barrier function, and homeostasis. The AHR signalling pathway is intricately linked to various dermatological disorders, including psoriasis, atopic dermatitis, acne and hidradenitis suppurativa. In this review, we delve into the molecular mechanisms through which AHR activation influences skin physiology and highlight how dysregulation can lead to pathological conditions. Moreover, we discuss the emerging therapeutic potential of AHR modulators in the treatment of skin diseases. In conclusion, the AHR is a pivotal player in dermatology, with a multifaceted role in skin physiology and pathology. Understanding the intricacies of AHR signalling in the skin offers promising avenues for the development of novel therapies and preventive strategies for various dermatological conditions. Further research is warranted to elucidate the full scope of AHR's contributions to dermatology and its potential as a therapeutic target.
PubMed: 38533374
DOI: 10.5114/ada.2023.135617 -
Food Chemistry: X Jun 2024The occurrence of persistent organic pollutants like polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) in food represents a public health...
The occurrence of persistent organic pollutants like polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) in food represents a public health concern. The BfR MEAL Study was initiated to generate a comprehensive data base of occurrence data for chemicals in the most consumed foods in Germany. Non-dioxin-like PCBs (NDL-PCBs) and PBDEs were analysed in 300 foods, purchased and prepared representatively for the eating behaviour of the population in Germany. Highest levels of NDL-PCBs and PBDEs were detected in spiny dogfish, cod liver, herring, and eel. High NDL-PCB and PBDE levels were observed in other oily fish, wild boar meat, sheep liver, and high-fat dairy products. The comparison of food from conventional and organic production revealed higher NDL-PCB values in the food group 'meat and meat products' if produced organically. Occurrence data of this study will improve future dietary exposure and risk assessments in Germany.
PubMed: 38524778
DOI: 10.1016/j.fochx.2024.101274 -
Environmental Science & Technology Apr 2024Human exposure to toxic chemicals presents a huge health burden. Key to understanding chemical toxicity is knowledge of the molecular target(s) of the chemicals. Because...
Human exposure to toxic chemicals presents a huge health burden. Key to understanding chemical toxicity is knowledge of the molecular target(s) of the chemicals. Because a comprehensive safety assessment for all chemicals is infeasible due to limited resources, a robust computational method for discovering targets of environmental exposures is a promising direction for public health research. In this study, we implemented a novel matrix completion algorithm named coupled matrix-matrix completion (CMMC) for predicting direct and indirect exposome-target interactions, which exploits the vast amount of accumulated data regarding chemical exposures and their molecular targets. Our approach achieved an AUC of 0.89 on a benchmark data set generated using data from the Comparative Toxicogenomics Database. Our case studies with bisphenol A and its analogues, PFAS, dioxins, PCBs, and VOCs show that CMMC can be used to accurately predict molecular targets of novel chemicals without any prior bioactivity knowledge. Our results demonstrate the feasibility and promise of computationally predicting environmental chemical-target interactions to efficiently prioritize chemicals in hazard identification and risk assessment.
Topics: Humans; Environmental Exposure; Polychlorinated Biphenyls; Dioxins; Risk Assessment; Public Health
PubMed: 38501580
DOI: 10.1021/acs.est.4c00458 -
The Journal of Biological Chemistry Apr 2024The aryl hydrocarbon receptor (AhR)-interacting protein (AIP) is a ubiquitously expressed, immunophilin-like protein best known for its role as a co-chaperone in the... (Review)
Review
The aryl hydrocarbon receptor (AhR)-interacting protein (AIP) is a ubiquitously expressed, immunophilin-like protein best known for its role as a co-chaperone in the AhR-AIP-Hsp90 cytoplasmic complex. In addition to regulating AhR and the xenobiotic response, AIP has been linked to various aspects of cancer and immunity that will be the focus of this review article. Loss-of-function AIP mutations are associated with pituitary adenomas, suggesting that AIP acts as a tumor suppressor in the pituitary gland. However, the tumor suppressor mechanisms of AIP remain unclear, and AIP can exert oncogenic functions in other tissues. While global deletion of AIP in mice yields embryonically lethal cardiac malformations, heterozygote, and tissue-specific conditional AIP knockout mice have revealed various physiological roles of AIP. Emerging studies have established the regulatory roles of AIP in both innate and adaptive immunity. AIP interacts with and inhibits the nuclear translocation of the transcription factor IRF7 to inhibit type I interferon production. AIP also interacts with the CARMA1-BCL10-MALT1 complex in T cells to enhance IKK/NF-κB signaling and T cell activation. Taken together, AIP has diverse functions that vary considerably depending on the client protein, the tissue, and the species.
Topics: Animals; Humans; Neoplasms; Receptors, Aryl Hydrocarbon; Intracellular Signaling Peptides and Proteins; Mice; Molecular Chaperones; Immunity, Innate
PubMed: 38479600
DOI: 10.1016/j.jbc.2024.107157 -
Ecotoxicology and Environmental Safety Apr 2024PCDD/Fs are dioxins produced by waste incineration and pose risks to human health. We aimed to detail the health risks of airborne and soil PCDD/Fs near a municipal...
PCDD/Fs are dioxins produced by waste incineration and pose risks to human health. We aimed to detail the health risks of airborne and soil PCDD/Fs near a municipal solid-waste incinerator (MSWI) for the surrounding population and develop a new model that improves upon existing methods. Thus, we conducted field sampling and then investigated a MSWI in the Pearl River Delta (2016-2018). Our results showed that the carcinogenic and non-carcinogenic risk values of PCDD/Fs exposed to residents in nearby areas were acceptable, with hazard index (HI) values lower than 1.0 and a total carcinogenic risk lower than 1.0E-6. Notably, the results raised concerns regarding higher non-carcinogenic risks in children than in adults. Comparative analysis of the frequency accumulation diagram, accumulated probability risk, and the absolute value of error (δ) between the 95% confidence interval (CI) and the 90% CI of the Monte Carlo stochastic simulation-triangular fuzzy number (MCSS-TFN) and the MCSS model, respectively, demonstrated that the MCSS-TFN exhibited less uncertainty than the MCSS model, regardless of the health risk value of PCDD/Fs in ambient air or in soil. This observation underscores the superiority of the MCSS-TFN model over other models in assessing the health risks associated with PCDD/Fs in situations with limited data. Our new method overcomes the limited dataset size and high uncertainty in assessing the health risks of dioxin substances, providing a more comprehensive understanding of their associated health risks than MCSS models.
Topics: Adult; Child; Humans; Solid Waste; Environmental Monitoring; Polychlorinated Dibenzodioxins; Dibenzofurans; Air Pollutants; Incineration; Dioxins; Risk Assessment; Dibenzofurans, Polychlorinated; Soil
PubMed: 38479313
DOI: 10.1016/j.ecoenv.2024.116203 -
Ecotoxicology and Environmental Safety Apr 2024Copper plays a crucial role in the heterogenous dissociation of chlorothiophenols (CTPs) to form chlorothiophenoxy radicals (CTPRs), which is the initial and critical...
Copper plays a crucial role in the heterogenous dissociation of chlorothiophenols (CTPs) to form chlorothiophenoxy radicals (CTPRs), which is the initial and critical step in the formation of polychlorinated thianthrenes/dibenzothiophenes (PCTA/DTs). Here, first-principles calculations were performed to investigate the activity of Cu(111) surface towards the formation of adsorbed 2-CTPR from 2-CTP. The interaction between 2-CTP and Cu(111) surface was explored to find stable adsorption configurations. Besides, the decomposition routes of 2-CTP on the Cu(111) surface were further explored. Moreover, the effects of water on the formation of absorbed 2-CTPR on the Cu(111) surface were examined. Our results demonstrate that the flat adsorption of 2-CTP on the surface with adsorption energy in the range of -33.21 kcal/mol to -28.37 kcal/mol is more stable than the vertical adsorption with adsorption energy ranging from -23.53 kcal/mol to -13.38 kcal/mol. The Cu(111) surface catalyzes the conversion of 2-CTP into the adsorbed 2-CTPR with a modest energy barrier of 9.46 kcal/mol. Furthermore, water molecules exhibit stronger catalytic activity in this process with a decreased energy barrier of 5.87 kcal/mol through "water bridge" and hydrogen bonding. Specifically, the water accepts the hydrogen atom from 2-CTP and donates another hydrogen to the surface via "water bridge". This research provides a molecular-level understanding of the heterogeneous formation of PCTA/DTs by fly ash, suggesting novel approaches for control strategy and legislation of dioxin analogues.
Topics: Coal Ash; Copper; Density Functional Theory; Hydrogen; Water; Thiophenes
PubMed: 38471341
DOI: 10.1016/j.ecoenv.2024.116186 -
BMC Microbiology Mar 2024Although the pathology of multiple chemical sensitivity (MCS) is unknown, the central nervous system is reportedly involved. The gut microbiota is important in modifying...
BACKGROUND
Although the pathology of multiple chemical sensitivity (MCS) is unknown, the central nervous system is reportedly involved. The gut microbiota is important in modifying central nervous system diseases. However, the relationship between the gut microbiota and MCS remains unclear. This study aimed to identify gut microbiota variations associated with MCS using shotgun metagenomic sequencing of fecal samples.
METHODS
We prospectively recruited 30 consecutive Japanese female patients with MCS and analyzed their gut microbiomes using shotgun metagenomic sequencing. The data were compared with metagenomic data obtained from 24 age- and sex-matched Japanese healthy controls (HC).
RESULTS
We observed no significant difference in alpha and beta diversity of the gut microbiota between the MCS patients and HC. Focusing on the important changes in the literatures, at the genus level, Streptococcus, Veillonella, and Akkermansia were significantly more abundant in MCS patients than in HC (p < 0.01, p < 0.01, p = 0.01, respectively, fold change = 4.03, 1.53, 2.86, respectively). At the species level, Akkermansia muciniphila was significantly more abundant (p = 0.02, fold change = 3.3) and Faecalibacterium prausnitzii significantly less abundant in MCS patients than in HC (p = 0.03, fold change = 0.53). Functional analysis revealed that xylene and dioxin degradation pathways were significantly enriched (p < 0.01, p = 0.01, respectively, fold change = 1.54, 1.46, respectively), whereas pathways involved in amino acid metabolism and synthesis were significantly depleted in MCS (p < 0.01, fold change = 0.96). Pathways related to antimicrobial resistance, including the two-component system and cationic antimicrobial peptide resistance, were also significantly enriched in MCS (p < 0.01, p < 0.01, respectively, fold change = 1.1, 1.2, respectively).
CONCLUSIONS
The gut microbiota of patients with MCS shows dysbiosis and alterations in bacterial functions related to exogenous chemicals and amino acid metabolism and synthesis. These findings may contribute to the further development of treatment for MCS.
TRIAL REGISTRATION
This study was registered with the University Hospital Medical Information Clinical Trials Registry as UMIN000031031. The date of first trial registration: 28/01/2018.
Topics: Humans; Female; Gastrointestinal Microbiome; Multiple Chemical Sensitivity; Japan; Feces; Amino Acids
PubMed: 38468206
DOI: 10.1186/s12866-024-03239-y -
Annals of Work Exposures and Health Apr 2024The dermal exposure route is expected to become increasingly significant relative to total worker exposure as inhalational exposure limits continue to decrease. However,... (Review)
Review
OBJECTIVES
The dermal exposure route is expected to become increasingly significant relative to total worker exposure as inhalational exposure limits continue to decrease. However, standardization of occupational exposure assessment methods and scientific consensus are needed. This is the first scoping review mapping the literature across all dermal exposure assessment methods and their targeted substances/chemicals in occupational settings.
METHODS
Eligibility criteria broadly included studies reporting any noninvasive dermal exposure assessment method in an occupational setting. The literature search (Web of Science and MEDLINE) was restricted to peer-reviewed, primary literature published in the last 20 years (2002-2022). Titles/abstracts were dual independently screened. Data charting was performed by a single reviewer using standard template. All stages were pilot tested. The JBI (formerly, the Joanna Briggs Institute) scoping review methods and PRISMA-ScR checklist (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) were used.
RESULTS
In total, 493 articles were data charted and categorized by 4 study types: methods development (22%), exposure assessment (51%), health outcomes (21%), and controls assessment (6%). Fourteen types of dermal exposure assessment methods were charted with biomarkers (51%), dosimeters (21%), and qualitative assessments such as questionnaires or surveys (17%) most common. Seventeen different chemicals/substances were charted; pesticides (28%) and polycyclic aromatic hydrocarbons (PAHs) (22%) associated with crude oil products and combustion were most common. Mapping between substances and exposure assessment method categories, pesticide dosimeters (11%), and PAH biomarker studies (14%) were most reported. Literature gaps were identified for cleaning agents, hair dyes, glycol ether, N,N-dimethylformamide/N-methyl-2-pyrrolidone, dioxins, and bisphenol A.
CONCLUSIONS
To foster scientific consensus, standardization across study reporting is needed for describing: (i) exposure assessment methods used, (ii) worker tasking/conditions, (iii) targeted substances and substance state, and (iv) targeted exposure routes. Overall, this review categorizes, maps, and defines the scope of literature for occupational dermal exposure assessment methods.
Topics: Humans; Air Pollutants, Occupational; Environmental Monitoring; Occupational Exposure; Skin
PubMed: 38466914
DOI: 10.1093/annweh/wxae015 -
Ecotoxicology and Environmental Safety Mar 2024The toxicity of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is generally believed to be mediated by aryl hydrocarbon receptor (AhR), but some evidence suggests that the...
The toxicity of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is generally believed to be mediated by aryl hydrocarbon receptor (AhR), but some evidence suggests that the effects of TCDD can also be produced through AhR-independent mechanisms. In previous experiments, we found that mainly AhR-dependent mechanism was involved in the migration inhibition of glioblastoma U87 cells by TCDD. Due to the heterogeneity of glioblastomas, not all tumor cells have significant AhR expression. The effects and mechanisms of TCDD on the migration of glioblastomas with low AhR expression are still unclear. We employed a glioblastoma cell line A172 with low AhR expression as a model, using wound healing and Transwell® assay to detect the effect of TCDD on cell migration. We found that TCDD can inhibit the migration of A172 cells without activating AhR signaling pathway. Further, after being pre-treated with AhR antagonist CH223191, the inhibition of TCDD on A172 cells migration was not changed, indicating that the effect of TCDD on A172 cells is not dependent on AhR activation. By transcriptome sequencing analysis, we propose dysregulation of the expression of certain migration-related genes, such as IL6, IL1B, CXCL8, FOS, SYK, and PTGS2 involved in cytokines, MAPK, NF-κB, and IL-17 signaling pathways, as potential AhR-independent mechanisms that mediate the inhibition of TCDD migration in A172 cells.
Topics: Humans; Polychlorinated Dibenzodioxins; Receptors, Aryl Hydrocarbon; Glioblastoma; Signal Transduction; Cell Movement
PubMed: 38458072
DOI: 10.1016/j.ecoenv.2024.116172 -
Heliyon Mar 2024Tuberculosis has been a challenge to the world since prehistoric times, and with the advent of drug-resistant strains, it has become more challenging to treat this...
Tuberculosis has been a challenge to the world since prehistoric times, and with the advent of drug-resistant strains, it has become more challenging to treat this infection. Ethionamide (ETH), a second-line drug, acts as a prodrug and targets mycolic acid synthesis by targeting the enoyl-acyl carrier protein reductase (InhA) enzyme. (Mtb) EthR is an ethA gene repressor required to activate prodrug ETH. Recent studies suggest targeting the EthR could lead to newer drug molecules that would help better activate the ETH or complement this process. In this report, we have attempted and successfully identified three new molecules from the drug repurposing library that can target EthR protein and function as ETH boosters. These molecules were obtained after rigorous filtering of the database for their physicochemical, toxicological properties and safety. The molecular docking, molecular dynamics simulations and binding energy studies yielded three compounds, Ethyl (2-amino-4-((4-fluorobenzyl)amino)phenyl)carbamate) (L1), 2-((2,2-Difluorobenzo [d] [1,3]dioxol-5-yl)amino)-2-oxoethyl (E)-3-(5-bromofuran-2-yl)acrylate (L2), and N-(2,3-Dihydrobenzo [b] [1,4]dioxin-6-yl)-4-(2-((4-fluorophenyl)amino)-2-oxoethoxy)-3-methoxy benzamide (L3) are potential EthR inhibitors. We applied machine learning methods to evaluate these molecules for toxicity and synthesisability, suggesting safety and ease of synthesis for these molecules. These molecules are known for other pharmacological activities and can be repurposed faster as adjuvant therapy for tuberculosis.
PubMed: 38434349
DOI: 10.1016/j.heliyon.2024.e26802