Characterizing the effects of triclosan and triclocarban on the intestinal epithelial homeostasis using small intestinal organoids.

Intestinal epithelium has the largest surface of human body, contributes dramatically to defense of toxicant-associated intestinal injury. Triclosan (TCS) and triclocarban (TCC), extensively employed as antibacterial agents in personal care products (PCPs) and healthcare facilities, caused serious damage to human intestine. However, the role of the intestinal epithelium in TCS/TCC-induced intestinal toxicity and its underlying toxic mechanisms remain incompletely understood. In this study, a novel 3D intestinal organoid model was utilized to investigate that exposure to TCS/TCC led to a compromised self-renewal and differentiation of intestinal stem cells (ISCs). Consequently, this disrupted intestinal epithelial homeostasis ultimately caused a reduction in nutrient absorption and deficient of epithelial defense to exogenous and endogenous pathogens stimulation. The inhibition of the Wnt signaling pathway in intestinal stem cell was contributed to the intestinal toxicity of TCS/TCC. These results were further confirmed in vivo with mice exposed to TCS/TCC. The findings of this study provide evidence that TCS/TCC possess the capacity to disturb the homeostasis of the intestinal epithelium, and emphasize the credibility of organoids as a valuable model for toxicological studies, as they could faithfully recapitulate in vivo phenomena.

Integrated multi-omics approaches reveal the neurotoxicity of triclocarban in mouse brain.

Triclocarban (TCC) is an antimicrobial ingredient that commonly incorporated in many household and personal care products, raising public concerns about its potential health risks. Previous research has showed that TCC could cross the blood-brain barrier, but to date our understanding of its potential neurotoxicity at human-relevant concentrations remains lacking. In this study, we observed anxiety-like behaviors in mice with continuous percutaneous exposure to TCC. Subsequently, we combined lipidomic, proteomic, and metabolic landscapes to investigate the underlying mechanisms of TCC-related neurotoxicity. The results showed that TCC exposure dysregulated the proteins involved in endocytosis and neurodegenerative disorders in mouse cerebrum. Brain energy homeostasis was also altered, as evidenced by the perturbation of pyruvate metabolism, TCA cycle, and oxidative phosphorylation, which in turn caused mitochondrial dysfunction. Meanwhile, the changing trends of sphingolipid signaling pathway and overproduction of mitochondrial reactive oxygen species (mROS) could enhance the neural apoptosis. The in vitro approach further demonstrated that TCC exposure promoted apoptosis, accompanied by the overproduction of mROS and alteration in the mitochondrial membrane potential in N2A cells. Together, dysregulated endocytosis, mROS-related mitochondrial dysfunction and neural cell apoptosis are considered to be crucial factors for TCC-induced neurotoxicity, which may contribute to the occurrence and development of neurodegenerative disorders. Our findings provide novel perspectives for the mechanisms of TCC-triggered neurotoxicity.

Fluorine-functionalized covalent organic framework coated solid-phase microextraction probe coupled with electrospray ionization mass spectrometry for monitoring triclosan, triclocarban, and chlorophenols in mice.

Triclosan (TCS), triclocarban (TCC), and chlorophenols (CPs) are broad-spectrum antibacterials widely used in dermatological and oral hygiene products, which could induce severe liver and intestine injuries. Hence, it is essential to establish a rapid and sensitive method to monitor TCS, TCC, and CPs in various organisms. In this work, fluorine-functionalized covalent organic framework (COF-F) was prepared by using 4,4',4''-(1,3,5-triazine-2,4,6-triyl)tri-aniline and 2,3,5,6-tetrafluoroterephthalaldehyde as two building units and employed as a solid phase microextraction (SPME) probe for the extraction of TCS, TCC and CPs. The COF-F possessed excellent hydrophobicity, a large specific surface area (1354.3 m2 g-1) and high uniform porosity (3.2 nm), which facilitated high selectivity and adsorption properties towards TCS, TCC, and CPs. Therefore, the as-prepared COF-F-SPME in combination with electrospray ionization mass spectrometry has been developed to provide fast and ultrasensitive detection of TCS, TCC, and CPs in biological samples. The established method demonstrated satisfactory linear ranges (0.01-100.00 µg L-1) and low limits of detection (0.003-0.040 µg L-1) for TCS, TCC and CPs. The developed method could be successfully applied to detect TCS, TCC and CPs in the liver and kidney tissues of mice, demonstrating the potential for the detection of chlorinated aromatic pollutants in the biological samples.

Single-/Co-Driving of Tetracycline, Triclocarban and Zinc on Microbial Community, Resistome and Function in the Cyanobacteria-Blooming Freshwater Ecosystem.

Environmental concentrations of antimicrobials can inhibit Cyanobacteria, but little is known about their effects on Cyanobacteria-blooming freshwater ecosystem. Here, a 21 days' outdoor freshwater mesocosm experiment was established to study effects of single and combined tetracycline, triclocarban and zinc at environmental concentrations on microbial community, microbial function and antimicrobial resistance using amplicon- and metagenomic-based methods. Results showed that three chemicals reshaped the microbial community with magnified effects by chemical combinations. Relative abundance of Cyanobacteria was decreased in all chemical groups, especially from 74.5 to 0.9% in combination of three chemicals. Microbial community networks were more simplified after exposure. Proteobacteria and Bacteroidetes predominated in Cyanobacteria-degraded ecosystems, and their relative abundances were significantly correlated with antibiotic resistome, suggesting that they might host antibiotic resistance genes. Notably, relative abundance (copy per 16 S rRNA gene) of total antibiotic resistome reached five to nine folds higher than the initial abundance in chemical-combined groups. The affected antibiotic resistance genes referred to a wide range of antibiotic classes. However, weak effects were detected on biocide/metal resistance and microbial virulence. Three chemicals posed complicated effects on microbial function, some of which had consistent variations across the groups, while some varied greatly in chemical groups. The findings highlight sensitivity of Cyanobacteria-blooming ecosystem to antimicrobials.

Co-exposure of parabens, benzophenones, triclosan, and triclocarban in human urine from children and adults in South China.

Endocrine-disrupting chemicals (EDCs) are pervasive in the environment, prompting significant public concern regarding human exposure to these pollutants. In this study, we analyzed the levels of various endocrine-disrupting compounds, including parabens (PBs), benzophenones (BzPs), triclocarban (TCC) and triclosan (TCS), across 565 urine samples collected from residents of South China. All 11 target chemicals were detected at relatively high frequencies (41-100%), with the most prevalent ones being 3,4-dihydroxybenzoic acid (5.39 ng/mL), methyl-paraben (5.12 ng/mL), ethyl-paraben (3.11 ng/mL) and triclosan (0.978 ng/mL). PBs emerged as the most predominant group with a median concentration of 32.2 ng/mL, followed by TCs (sum of TCC and TCS, 0.998 ng/mL) and BzPs (0.211 ng/mL). Notably, urinary concentrations of PBs in adults were significantly higher (p < 0.01) compared to children, while BzPs and TCs were elevated in children (p < 0.001). The increased presence of BzPs and TCs in children is a cause for concern, given their heightened sensitivity and vulnerability to chemicals. Significant correlations were found between urinary target compounds and demographic factors, including gender, age and body mass index. Specifically, females, younger adults (18 ≤ age ≤ 35) and individuals with under/normal weight (16 ≤ BMI ≤ 23.9) were found to have higher exposure levels to EDCs, as indicated by the median values of their estimated daily intakes. Despite these higher levels still being lower than the acceptable daily intake thresholds, the health risks stemming from simultaneous exposure to these EDCs must not be overlooked.

Mechanisms linking triclocarban biotransformation to functional response and antimicrobial resistome evolution in wastewater treatment systems.

Evaluating the role of antimicrobials biotransformation in the regulation of metabolic functions and antimicrobial resistance evolution in wastewater biotreatment systems is crucial to ensuring water security. However, the associated mechanisms remain poorly understood. Here, we investigate triclocarban (TCC, one of the typical antimicrobials) biotransformation mechanisms and the dynamic evolution of systemic function disturbance and antimicrobial resistance risk in a complex anaerobic hydrolytic acidification (HA)-anoxic (ANO)/oxic (O) process. We mined key functional genes involved in the TCC upstream (reductive dechlorination and amide bonds hydrolysis) and downstream (chloroanilines catabolism) biotransformation pathways by metagenomic sequencing. Acute and chronic stress of TCC inhibit the production of volatile fatty acids (VFAs), NH4+ assimilation, and nitrification. The biotransformation of TCC via a single pathway cannot effectively relieve the inhibition of metabolic functions (e.g., carbon and nitrogen transformation and cycling) and enrichment of antimicrobial resistance genes (ARGs). Importantly, the coexistence of TCC reductive dechlorination and hydrolysis pathways and subsequent ring-opening catabolism play a critical role for stabilization of systemic metabolic functions and partial control of antimicrobial resistance risk. This study provides new insights into the mechanisms linking TCC biotransformation to the dynamic evolution of systemic functions and risks, and highlights critical regulatory information for enhanced control of TCC risks in complex biotreatment systems.

Enhancement of triclocarban biodegradation: Metabolic division of labor in co-culture of Rhodococcus sp. BX2 and Pseudomonas sp. LY-1.

Triclocarban (TCC) and its metabolite, 3,4-dichloroaniline (DCA), are classified as emerging organic contaminants (EOCs). Significant concerns arise from water and soil contamination with TCC and its metabolites. These concerns are especially pronounced at high concentrations of up to approximately 20 mg/kg dry weight, as observed in wastewater treatment plants (WWTPs). Here, a TCC-degrading co-culture system comprising Rhodococcus rhodochrous BX2 and Pseudomonas sp. LY-1 was utilized to degrade TCC (14.5 mg/L) by 85.9% in 7 days, showing improved degradation efficiency compared with monocultures. A combination of high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), genome sequencing, transcriptomic analysis, and quantitative reverse transcription-PCR (qRT-PCR) was performed. Meanwhile, through the combination of further experiments involving heterologous expression and gene knockout, we proposed three TCC metabolic pathways and identified four key genes (tccG, tccS, phB, phL) involved in the TCC degradation process. Moreover, we revealed the internal labor division patterns and connections in the co-culture system, indicating that TCC hydrolysis products were exchanged between co-cultured strains. Additionally, mutualistic cooperation between BX2 and LY-1 enhances TCC degradation efficiency. Finally, phytotoxicity assays confirmed a significant reduction in the plant toxicity of TCC following synergistic degradation by two strains. The in-depth understanding of the TCC biotransformation mechanisms and microbial interactions provides useful information for elucidating the mechanism of the collaborative biodegradation of various contaminants.

Integrated remediation and detoxification of triclocarban-contaminated water using waste-derived biochar-immobilized cells by long-term column experiments.

Triclocarban (TCC), an antibacterial agent commonly used in personal care products, is one of the top ten contaminants of emerging concern in various environmental media, including soil and contaminated water in vadose zone. This study aimed to investigate TCC-contaminated water remediation using biochar-immobilized bacterial cells. Pseudomonas fluorescens strain MC46 (MC46), an efficient TCC-degrading isolate, was chosen, whereas agro-industrial carbonized waste as biochar was directly used as a sustainable cell immobilization carrier. According to the long-term TCC removal performance results (160 d), the biochar-immobilized cells consistently exhibited high TCC removal efficiencies (84-97%), whereas the free MC46 removed TCC for 76-94%. At 100 days, the detachment of the MC46 cells from the immobilized cell column was observed. The micro-Fourier-transform infrared spectroscopy results indicated that extracellular polymeric substance (EPS) was produced, but polysaccharide and protein fractions were washed out of the column. The lipid fraction of EPS adhered to the biochar, promoting TCC sorption for long-term treatment. The shortening of MC46 cells improved the tolerance of TCC toxicity. The TCC-contaminated water was successfully detoxified by the biochar-immobilized MC46 cells. Overall, the waste-derived biochar-immobilized cell system proposed in this study for the removal of emerging contaminants, including TCC, is efficient, economical, and aligned with the sustainable development concept of value-added utilization of waste.

Recent use of consumer and personal care products and exposures to select endocrine disrupting chemicals among urban children with asthma.

BACKGROUND: Emerging studies suggest that endocrine disrupting chemicals (EDCs) in personal care and other consumer products are linked with various adverse health effects, including respiratory and reproductive effects. Despite Black persons using more personal care products than other demographic groups and having a high asthma burden, little is known regarding their consumer product use patterns and associated EDC exposures. OBJECTIVE: To examine the association between recent exposure to select EDCs with specific consumer products and behaviors in a cohort of 110 predominantly Black children with asthma, ages 8-17 years, living in Baltimore City, Maryland. METHODS: We quantified concentrations of bisphenol A (BPA), bisphenol S (BPS), bisphenol F, two dichlorophenols, four parabens, triclosan, benzophenone-3, and triclocarban in spot urine samples. Questionnaires were used to capture recent (last 24-h) consumer product use and behaviors. Associations between EDCs and consumer product uses/behaviors were assessed using multivariable linear regression, adjusting for age, gender, race/ethnicity, and caregiver income level. Effect estimates were expressed as geometric mean ratios of biomarker concentrations of product-users vs non-users. RESULTS: Increased concentrations to select EDCs were associated with recent use of air freshener (ratios; BPA: 1.9, 95%CI 1.4-2; BPS 1.7, 95%CI 1-2.97; propyl paraben: 3.0, 95%CI 1.6-5.6), scented candles (methyl paraben: 2.6, 95%CI 1.1-6.1), and scented carpet powder (2,5-dichlorophenol: 2.8, 95%CI 1.2-6.3). Additionally, consuming canned food was associated with some increased biomarker concentrations (ratios: BPA: 1.7, 95%CI 1.2-2.4; BPS: 2.1, 95% CI: 1.2-3.6). SIGNIFICANCE: These findings add to the body of evidence suggesting that recent use of select consumer products in Black children contributes to exposure of chemicals of concern and could potentially inform exposure mitigation interventions. Findings have broad potential health implications for pediatric populations and Black children who may face exposure and health disparities. IMPACT: Little is known about how children's personal care product use and consumer behaviors affect their exposures to endocrine disrupting chemicals (EDCs). This is particularly true for Black children who often experience a disparate exposure burden to many EDCs. This is a significant knowledge gap among children that are uniquely vulnerable to EDCs as they undergo critical windows of growth and development. Our findings show associations between consumer products and EDC exposures in predominantly Black children in low-income settings. Identifying EDC exposure determinants has broad health implications as many of these chemicals have been associated with adverse health risks.

Short-term exposure to triclocarban alters microbial community composition and metabolite profiles in freshwater biofilms.

Triclocarban (TCC), an emerging contaminant in water environments, its effects on freshwater biofilms remain insufficiently understood. This study investigates the effects of TCC exposure (at concentrations of 10 µg L-1 and 10 mg L-1) on mature freshwater biofilms. TCC was found to inhibit biofilm activity as evidenced by changes in surface morphology and the ratio of live/dead cells. Moreover, both concentrations of TCC were observed to modify the structure of the biofilm community. Metabolomics analysis revealed an overlap in the toxicity mechanisms and detoxification strategies triggered by various concentrations of TCC in biofilms. However, the higher toxicity induced by 10 mg L-1 TCC resulted from the downregulation of proline betaine, disrupting the homeostasis of cellular osmotic pressure regulation in biofilms. Notably, lipid and lipid-like molecules showed high sensitivity to different concentrations of TCC, indicating their potential as biomarkers for TCC exposure. Annotation of the differential metabolites by KEGG revealed that alterations in amino acid and carbon metabolism constituted the primary response mechanisms of biofilms to TCC. Moreover, the biofilm demonstrated enhanced nucleic acid metabolism, which bolstered resistance against TCC stress and heightened tolerance. Furthermore, elevated TCC concentrations prompted more robust detoxification processes for self-defense. Overall, short-term exposure to TCC induced acute toxicity in biofilms, yet they managed to regulate their community structure and metabolic levels to uphold oxidative homeostasis and activity. This research contributes to a deeper comprehension of TCC risk assessment and policy control in aquatic environments.

Mitigation of Triclocarban Inhibition in Microbial Electrolysis Cell-Assisted Anaerobic Digestion.

Triclocarban (TCC), as a widely used antimicrobial agent, is accumulated in waste activated sludge at a high level and inhibits the subsequent anaerobic digestion of sludge. This study, for the first time, investigated the effectiveness of microbial electrolysis cell-assisted anaerobic digestion (MEC-AD) in mitigating the inhibition of TCC to methane production. Experimental results showed that 20 mg/L TCC inhibited sludge disintegration, hydrolysis, acidogenesis, and methanogenesis processes and finally reduced methane production from traditional sludge anaerobic digestion by 19.1%. Molecular docking revealed the potential inactivation of binding of TCC to key enzymes in these processes. However, MEC-AD with 0.6 and 0.8 V external voltages achieved much higher methane production and controlled the TCC inhibition to less than 5.8%. TCC in the MEC-AD systems was adsorbed by humic substances and degraded to dichlorocarbanilide, leading to a certain detoxification effect. Methanogenic activities were increased in MEC-AD systems, accompanied by complete VFA consumption. Moreover, the applied voltage promoted cell apoptosis and sludge disintegration to release biodegradable organics. Metagenomic analysis revealed that the applied voltage increased the resistance of electrode biofilms to TCC by enriching functional microorganisms (syntrophic VFA-oxidizing and electroactive bacteria and hydrogenotrophic methanogens), acidification and methanogenesis pathways, multidrug efflux pumps, and SOS response.

Novel pentafluorosulfanyl-containing triclocarban analogs selectively kill Gram-positive bacteria.

Novel antimicrobial agents are needed to combat antimicrobial resistance. This study tested novel pentafluorosulfanyl-containing triclocarban analogs for their potential antibacterial efficacy. Standard procedures were used to produce pentafluorosulfanyl-containing triclocarban analogs. Twenty new compounds were tested against seven Gram-positive and Gram-negative indicator strains as well as 10 clinical isolates for their antibacterial and antibiofilm activity. Mechanistic investigations focused on damage to cell membrane, oxidizing reduced thiols, iron-sulfur clusters, and oxidative stress to explain the compounds' activity. Safety profiles were assessed using cytotoxicity experiments in eukaryotic cell lines. Following screening, selected components had significantly better antibacterial and antibiofilm activity against Gram-positive bacteria in lower concentrations in comparison to ciprofloxacin and gentamycin. For instance, one compound had a minimum inhibitory concentration of <0.0003 mM, but ciprofloxacin had 0.08 mM. Mechanistic studies show that these novel compounds do not affect reduced thiol content, iron-sulfur clusters, or hydrogen peroxide pathways. Their impact comes from Gram-positive bacterial cell membrane damage. Tests on cell culture toxicity and host component safety showed promise. Novel diarylurea compounds show promise as Gram-positive antimicrobials. These compounds offer prospects for study and optimization. IMPORTANCE: The rise of antibiotic resistance among bacterial pathogens poses a significant threat to global health, underscoring the urgent need for novel antimicrobial agents. This study presents research on a promising class of novel compounds with potent antibacterial properties against Gram-positive bacteria, notably Staphylococcus aureus and MRSA. What sets these novel analogs apart is their superior efficacy at substantially lower concentrations compared with commonly used antibiotics like ciprofloxacin and gentamycin. Importantly, these compounds act by disrupting the bacterial cell membrane, offering a unique mechanism that could potentially circumvent existing resistance mechanisms. Preliminary safety assessments also highlight their potential for therapeutic use. This study not only opens new avenues for combating antibiotic-resistant infections but also underscores the importance of innovative chemical approaches in addressing the global antimicrobial resistance crisis.

Temporal trends in exposure to parabens, benzophenones, triclosan, and triclocarban in adult females in Kyoto, Japan, from 1993 to 2016.

Products used in daily life can contain chemicals such as parabens, benzophenones, triclosan, and triclocarban that have potential endocrine-disrupting effects. Little is known about the temporal trends of exposure levels to some of these chemicals in Japan. Our study assessed the intake and risk associated with exposure to commonly used chemicals. We measured the concentrations of five parabens, four benzophenones, and triclosan and triclocarban in 133 single spot urine samples. The urine samples were collected in 1993, 2000, 2003, 2009, 2011, and 2016 from healthy female residents in Kyoto, Japan. With the exception of methylparaben, ethylparaben, and butylparaben, there were no significant fluctuations in the concentrations of target chemicals over the study period; however, methylparaben, ethylparaben, and butylparaben showed temporal changes in concentrations. Methylparaben concentrations peaked in 2003 with a median value of 309 µg/g creatinine, ethylparaben concentrations peaked in 1993 with a median value of 17.3 µg/g creatinine, and butylparaben showed a decline, with the median values becoming non-detectable in 2009 and 2016. We calculated estimated daily intakes and hazard quotients for each chemical. In the analysis of total samples, 2.3% (3 samples) for butylparaben and 0.8% (1 sample) for propylparaben were found to surpass a hazard quotient of 1. Overall, 3% (n = 4) of the study participants exceeded a hazard index of 1. The potential health risks associated with exposure to butylparaben and propylparaben emphasize the need for further monitoring and research.

Triclocarban and triclosan promote breast cancer progression in vitro and in vivo via activating G protein-coupled estrogen receptor signaling pathways.

Triclocarban (TCC) and triclosan (TCS) have been detected ubiquitously in human body and evoked increasing concerns. This study aimed to reveal the induction risks of TCC and TCS on triple negative breast cancer through non-genomic GPER-mediated signaling pathways. Molecular simulation indicated that TCC exhibited higher GPER binding affinity than TCS theoretically. Calcium mobilization assay displayed that TCC/TCS activated GPER signaling pathway with the lowest observed effective concentrations (LOEC) of 10 nM/100 nM. TCC and TCS also upregulated MMP-2/9, EGFR, MAPK3 but downregulated MAPK8 via GPER-mediated signaling pathway. Proliferation assay showed that TCC/TCS induced 4 T1 breast cancer cells proliferation with the LOEC of 100 nM/1000 nM. Wound-healing and transwell assays showed that TCC/TCS promoted 4 T1 cells migration in a concentration-dependent manner with the LOEC of 10 nM. The effects of TCC on breast cancer cells proliferation and migration were stronger than TCS and both were regulated by GPER. TCC/TCS induced migratory effects were more significantly than proliferative effect. Mechanism study showed that TCC/TCS downregulated the expression of epithelial marker (E-cadherin) but upregulated mesenchymal markers (snail and N-cadherin), which was reversed by GPER inhibitor G15. These biomarkers results indicated that TCC/TCS-induced 4 T1 cells migration was a classic epithelial to mesenchymal transition mechanism regulated by GPER signaling pathway. Orthotopic tumor model verified that TCC promoted breast cancer in-situ tumor growth and distal tissue metastasis via GPER-mediated signaling pathway at human-exposure level of 10 mg/kg/d. TCC-induced tissue metastasis of breast cancer was more significantly than in-situ tumor growth. Overall, we demonstrated for the first time that TCC/TCS could activate the GPER signaling pathways to induce breast cancer progression.

Influence of microplastic contamination on the dissipation of endocrine disrupting chemicals in soil environment.

Microplastic (MP) contamination is in the spotlight today, yet knowledge of their interaction with other organic contaminants in the soil environment is limited. Concerns extend to endocrine disrupting chemicals (EDCs), known for their potential to interfere with the hormonal systems of organisms and for their persistence and widespread presence in the environment. In this study, the most frequently occurring EDCs were monitored both in alluvial soil and in soil contaminated with different MPs commonly found in soil media, polyethylene, polyamide, and polystyrene. Bisphenol A and parabens were the most rapidly dissipating compounds, followed by triclosan and triclocarban, with the latter showing poor degradation. Per- and polyfluoroalkyl substances (PFAS) showed high persistence as concentrations remained nearly constant throughout the experiment. Although they fitted well with first-order dissipation kinetics, most showed biphasic behavior. The co-occurrence of MPs in the soil influenced the kinetic behavior in most cases although the differences were not very marked. MPs could impact sorption-desorption processes, affecting contaminant mobility and bioavailability to organisms in soil. These findings strengthen evidence for the influence of MPs on the behavior of soil contaminants such as EDCs, not only as vectors or sources of contaminants but by affecting dissipation kinetics.

Triclocarban induces lipid droplet accumulation and oxidative stress responses by inhibiting mitochondrial fatty acid oxidation in HepaRG cells.

Mitochondrial fatty acid oxidation (mtFAO) plays an important role in hepatic energy metabolism. Severe mtFAO injury leads to nonalcoholic fatty liver disease (NAFLD) and liver failure. Several drugs have been withdrawn owing to safety issues, such as induction of fatty liver disease through mtFAO disruption. For instance, the antimicrobial triclocarban (TCC), an environmental contaminant that was removed from the market due to its unknown safety in humans, induces NAFLD in rats and promotes hepatic FAO in mice. Therefore, there are no consistent conclusions regarding the effects of TCC on FAO and lipid droplet accumulation. We hypothesized that TCC induces lipid droplet accumulation by inhibiting mtFAO in human hepatocytes. Here, we evaluated mitochondrial respiration in HepaRG cells to investigate the effects of TCC on fatty acid-driven oxidation in cells, electron transport chain parameters, lipid droplet accumulation, and antioxidant genes. The results suggest that TCC increases oxidative stress gene expression (GCLM, p62, HO-1, and NRF2) through lipid droplet accumulation via mtFAO inhibition in HepaRG cells. The results of the present study provide further insights into the effect of TCC on human NAFLD through mtFAO inhibition, and further in vivo studies could be used to validate the mechanisms.

Non-persistent endocrine disrupting chemical mixtures and uterine leiomyomata in the study of environment, lifestyle and fibroids (SELF).

BACKGROUND: Results of studies investigating associations between individual endocrine-disrupting chemicals (EDCs) and incidence of uterine leiomyomata (UL), a hormone-dependent gynecological condition, have been inconsistent. However, few studies have evaluated simultaneous exposure to a mixture of EDCs with UL incidence. METHODS: We conducted a case-cohort analysis (n = 708) of data from the Study of the Environment, Lifestyle and Fibroids (SELF), a prospective cohort study. Participants were aged 23-35 years at enrollment, had an intact uterus, and identified as Black or African American. We measured biomarker concentrations of 21 non-persistent EDCs, including phthalates, phenols, parabens, and triclocarban, in urine collected at baseline, 20-month, and 40-month clinic visits. We ascertained UL incidence and characteristics using ultrasounds at baseline and approximately every 20 months through 60 months. We used probit Bayesian Kernel Machine Regression (BKMR-P) to evaluate joint associations between EDC mixtures with cumulative UL incidence. We estimated the mean difference in the probit of UL incidence over the study period, adjusting for baseline age, education, years since last birth, parity, smoking status and body mass index. We converted probit estimates to odds ratios for ease of interpretation. RESULTS: We observed that urinary concentrations of the overall EDC mixture were inversely associated with UL incidence in the overall mixtures model, with the strongest inverse associations at the 70th percentile of all biomarkers compared with their 50th percentile (odds ratio = 0.59; 95% confidence interval: 0.36, 0.96). Strongest contributors to the joint association for the mixture were bisphenol S (BPS), ethyl paraben (EPB), bisphenol F (BPF) and mono (2-ethyl-5-carboxypentyl) phthalate (MECPP), which each demonstrated inverse associations except for MECPP. There was suggestive evidence of an interaction between MECPP and EPB. CONCLUSION: In this prospective ultrasound study, we observed evidence of an inverse association between the overall mixture of urinary biomarker concentrations of non-persistent EDCs with UL incidence.

The fate of pharmaceuticals and personal care products (PPCPs) in sewer sediments:Adsorption triggering resistance gene proliferation.

In recent years, large quantities of pharmaceuticals and personal care products (PPCPs) have been discharged into sewers, while the mechanisms of PPCPs enrichment in sewer sediments have rarely been revealed. In this study, three PPCPs (tetracycline, sulfamethoxazole, and triclocarban) were added consecutively over a 90-day experimental period to reveal the mechanisms of PPCPs enrichment and the transmission of resistance genes in sewer sediments. The results showed that tetracycline (TC) and triclocarban (TCC) have higher adsorption concentration in sediments compared to sulfamethoxazole (SMX). The absolute abundance of Tets and suls genes increased in sediments under PPCPs pressure. The increase in secretion of extracellular polymeric substances (EPS) and the loosening of the structure exposed a large number of hydrophobic functional groups, which promoted the adsorption of PPCPs. The absolute abundance of antibiotic resistance genes (ARGs), EPS and the content of PPCPs in sediments exhibited significant correlations. The enrichment of PPCPs in sediments was attributed to the accumulation of EPS, which led to the proliferation of ARGs. These findings contributed to further understanding of the fate of PPCPs in sewer sediments and opened a new perspective for consideration of controlling the proliferation of resistance genes.

Synergistic detoxification efficiency and mechanism of triclocarban degradation by a bacterial consortium in the liver-gut-microbiota axis of zebrafish (Danio rerio).

Triclocarban (TCC), an emerging organic contaminant, poses a potential threat to human health with long-term exposure. Here, Rhodococcus rhodochrous BX2 and Pseudomonas sp. LY-1 were utilized to degrade TCC at environmental related concentrations for enhancing TCC biodegradation and investigating whether the toxicity of intermediate metabolites is lower than that of the parent compound. The results demonstrated that the bacterial consortium could degrade TCC by 82.0% within 7 days. The calculated 96 h LC50 for TCC, as well as its main degradation product 3,4-Dichloroaniline (DCA) were 0.134 mg/L and 1.318 mg/L respectively. Biodegradation also alleviated histopathological lesions induced by TCC in zebrafish liver and gut tissues. Liver transcriptome analysis revealed that biodegradation weakened differential expression of genes involved in disrupted immune regulation and lipid metabolism caused by TCC, verified through RT-qPCR analysis and measurement of related enzyme activities and protein contents. 16 S rRNA sequencing indicated that exposure to TCC led to gut microbial dysbiosis, which was efficiently improved through TCC biodegradation, resulting in decreased relative abundances of major pathogens. Overall, this study evaluated potential environmental risks associated with biodegradation of TCC and explored possible biodetoxification mechanisms, providing a theoretical foundation for efficient and harmless bioremediation of environmental pollutants.

Cloflucarban Illuminates Specificity and Context-Dependent Activation of the PINK1-Parkin Pathway by Mitochondrial Complex Inhibition.

The PTEN-induced kinase 1 (PINK1)-Parkin pathway plays a vital role in maintaining a healthy pool of mitochondria in higher eukaryotic cells. While the downstream components of this pathway are well understood, the upstream triggers remain less explored. In this study, we conducted an extensive analysis of inhibitors targeting various mitochondrial electron transport chain (ETC) complexes to investigate their potential as activators of the PINK1-Parkin pathway. We identified cloflucarban, an antibacterial compound, as a novel pathway activator that simultaneously inhibits mitochondrial complexes III and V, and V. RNA interference (RNAi) confirmed that the dual inhibition of these complexes activates the PINK1-Parkin pathway. Intriguingly, we discovered that albumin, specifically bovine serum albumin (BSA) and human serum albumin (HSA) commonly present in culture media, can hinder carbonyl cyanide m-chlorophenyl hydrazone (CCCP)-induced pathway activation. However, cloflucarban's efficacy remains unaffected by albumin, highlighting its reliability for studying the PINK1-Parkin pathway. This study provides insights into the activation of the upstream PINK1-Parkin pathway and underscores the influence of culture conditions on research outcomes. Cloflucarban emerges as a promising tool for investigating mitochondrial quality control and neurodegenerative diseases.