Exposure to endocrine disrupting chemicals (bisphenols, parabens, and triclosan) and their associations with preterm birth in humans.

Preterm birth in humans (PTB), defined as birth prior to 37 weeks of gestation, is one of the most important causes of neonatal morbidity and mortality and is associated with adverse health outcomes later in life. Attributed to many different etiological factors, estimated 15.1 million or 11.1% of births each year are preterm, which is more than 1 per 10 livebirths globally. Environmental pollution is a well-established risk factor that could influence the pathogenesis of PTB. Increasing evidence has shown an association between maternal exposure to endocrine disrupting chemicals (EDCs) and PTB. This scoping review aims to summarize current research on the association between EDC exposure and PTB in humans. Database PubMed was used to identify articles discussing the effect of selected EDCs, namely bisphenol A, bisphenol S, bisphenol F, parabens, and triclosan, found in plastics, cosmetics and other personal care products, on PTB occurrence. Regardless of some inconsistences in the findings across studies, the reviewed studies suggest a potential association between involuntary exposure to reviewed EDCs and the risk of PTB. However, further studies are needed to delineate exact correlations and mechanisms through which EDC exposure causes PTB so that efficient preventative measures could be implemented. Until then, health care providers should inform women about possible EDC exposure thus empowering them to make healthy choices and at the same time decrease the EDC negative effects.

Dynamic alterations in physiological and biochemical indicators of Cirrhinus mrigala hatchlings: A sublethal exposure of triclosan.

Triclosan (TCS), a biocide used in various day-to-day products, has been associated with several toxic effects in aquatic organisms. In the present study, biochemical and hematological alterations were evaluated after 14 d (sublethal) exposure of tap water (control), acetone (solvent control), 5, 10, 20, and 50 µg/L (environmentally relevant concentrations) TCS to the embryos/hatchlings of Cirrhinus mrigala, a major freshwater carp distributed in tropic and sub-tropical areas of Asia. A concentration-dependent increase in the content of urea and protein carbonyl, while a decrease in the total protein, glucose, cholesterol, triglycerides, uric acid, and bilirubin was observed after the exposure. Hematological analysis revealed a decrease in the total erythrocyte count, hemoglobin, and partial pressure of oxygen, while there was an increase in the total leucocyte count, carbon dioxide, and partial pressure of carbon dioxide and serum electrolytes. Comet assay demonstrates a concentration-dependent increase in tail length, tail moment, olive tail moment, and percent tail DNA. An amino acid analyzer showed a TCS-dose-dependent increase in various amino acids. Sodium dodecyl sulphate polyacrylamide gel electrophoresis analysis revealed different proteins ranging from 6.5 to 200 kDa, demonstrating TCS-induced upregulation. Fourier transform infrared spectra analysis exhibited a decline in peak area percents with an increase in the concentration of TCS in water. Curve fitting of amide I (1,700-1600 cm-1) showed a decline in α-helix and turns and an increase in ß-sheets. Nuclear magnetic resonance study also revealed concentration-dependent alterations in the metabolites after 14 d exposure. TCS caused alterations in the biomolecules and heamatological parameters of fish, raising the possibility that small amounts of TCS may change the species richness in natural aquatic habitats. In addition, consuming TCS-contaminated fish may have detrimental effects on human health. Consequently, there is a need for the proper utilisation and disposal of this hazardous compound in legitimate quantities.

Uptake, tissue distribution, and biotransformation pattern of triclosan in tilapia exposed to environmentally-relevant concentrations.

Although triclosan has been ubiquitously detected in aquatic environment and is known to have various adverse effects to fish, details on its uptake, bioconcentration, and elimination in fish tissues are still limited. This study investigated the uptake and elimination toxicokinetics, bioconcentration, and biotransformation potential of triclosan in Nile tilapia (Oreochromis niloticus) exposed to environmentally-relevant concentrations under semi-static regimes for 7 days. For toxicokinetics, triclosan reached a plateau concentration within 5-days of exposure, and decreased to stable concentration within 5 days of elimination. Approximately 50 % of triclosan was excreted by fish through feces, and up to 29 % of triclosan was excreted through the biliary excretion. For fish exposed to 200 ng·L-1, 2000 ng·L-1, and 20,000 ng·L-1, the bioconcentration factors (log BCFs) of triclosan in fish tissues obeyed similar order: bile ≈ intestine > gonad ≈ stomach > liver > kidney ≈ gill > skin ≈ plasma > brain > muscle. The log BCFs of triclosan in fish tissues are approximately maintained constants, no matter what triclosan concentrations in exposure water. Seven biotransformation products of triclosan, involved in both phase I and phase II metabolism, were identified in this study, which were produced through hydroxylation, bond cleavages, dichlorination, and sulfation pathways. Metabolite of triclosan-O-sulfate was detected in all tissues of tilapia, and more toxic product of 2,4-dichlorophenol was also found in intestine, gonad, and bile of tilapia. Meanwhile, two metabolites of 2,4-dichlorophenol-O-sulfate and monohydroxy-triclosan-O-sulfate were firstly discovered in the skin, liver, gill, intestine, gonad, and bile of tilapia in this study. These findings highlight the importance of considering triclosan biotransformation products in ecological assessment. They also provide a scientific basis for health risk evaluation of triclosan to humans, who are associated with dietary exposure through ingesting fish.

The effect of triclosan on intergeneric horizontal transmission of plasmid-mediated tigecycline resistance gene tet(X4) from Citrobacter freundii isolated from grass carp gut.

The transmission of antibiotic resistance genes (ARGs) in pathogenic bacteria affects culture animal health, endangers food safety, and thus gravely threatens public health. However, information about the effect of disinfectants - triclosan (TCS) on ARGs dissemination of bacterial pathogens in aquatic animals is still limited. One Citrobacter freundii (C. freundii) strain harboring tet(X4)-resistant plasmid was isolated from farmed grass carp guts, and subsequently conjugative transfer frequency from C. freundii to Escherichia coli C600 (E. coli C600) was analyzed under different mating time, temperature, and ratio. The effect of different concentrations of TCS (0.02, 0.2, 2, 20, 200 and 2000 µg/L) on the conjugative transfer was detected. The optimum conditions for conjugative transfer were at 37 °C for 8h with mating ratio of 2:1 or 1:1 (C. freundii: E. coli C600). The conjugative transfer frequency was significantly promoted under TCS treatment and reached the maximum value under 2.00 µg/L TCS with 18.39 times that of the control group. Reactive oxygen species (ROS), superoxide dismutase (SOD) and catalase (CAT) activities, cell membrane permeability of C. freundii and E. coli C600 were obviously increased under TCS stress. Scanning electron microscope showed that the cell membrane surface of the conjugative strains was wrinkled and pitted, even broken at 2.00 µg/L TCS, while lysed or even ruptured at 200.00 µg/L TCS. In addition, TCS up-regulated expression levels of oxidative stress genes (katE, hemF, bcp, hemA, katG, ahpF, and ahpC) and cell membrane-related genes (fimC, bamE and ompA) of donor and recipient bacteria. Gene Ontology (GO) enrichment demonstrated significant changes in categories relevant to pilus, porin activity, transmembrane transporter activity, transferase activity, hydrolase activity, material transport and metabolism. Taken together, a tet(X4)-resistant plasmid could horizontal transmission among different pathogens, while TCS can promote the propagation of the resistant plasmid.

The pharmaceutical triclosan induced oxidative stress and physiological disorder in marine organism and nanoparticles as a potential mitigating tool.

Environmental research plays a crucial role in formulating novel approaches to pollution management and preservation of biodiversity. This study aims to assess the potential harm of pharmaceutical triclosan (TCS) to non-target aquatic organism, the mussel Mytilus galloprovincialis. Furthermore, our study investigates the potential effectiveness of TiO2 and ZnO nanomaterials (TiO2 NPs and ZnO NPs) in degrading TCS. To ascertain the morphology, structure, and stability of the nanomaterials, several chemical techniques were employed. To evaluate the impact of TCS, TiO2 NPs, and ZnO NPs, both physiological (filtration rate (FR) and respiration rate (RR)), antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST)) activities and malondialdehyde (MDA) contents were measured in M. galloprovincialis gills and digestive gland. The mussel's responses varied depending on the contaminant, concentration, and organ, underscoring the significance of compiling these factors in ecotoxicity tests. The main toxic mechanisms of TCS and ZnO NPs at a concentration of 100 µg/L were likely to be a decrease in FR and RR, an increase in oxidative stress, and increased lipid peroxidation. Our findings indicate that a mixture of TCS and NPs has an antagonist effect on the gills and digestive gland. This effect is particularly notable in the case of TCS2 = 100 µg/L combined with TiO2 NP2 = 100 µg/L, which warrants further investigation to determine the underlying mechanism. Additionally, our results suggest that TiO2 NPs are more effective than ZnO NPs at degrading TCS, which may have practical implications for pharmaceutical control in marine ecosystems and in water purification plants. In summary, our study provides valuable information on the impact of pharmaceuticals on non-target organisms and sheds light on potential solutions for their removal from aqueous environments.

Toxic effects of triclosan on hepatic and intestinal lipid accumulation in zebrafish via regulation of m6A-RNA methylation.

Triclosan (TCS), recognized as an endocrine disruptor, has raised significant concerns due to its widespread use and potential health risks. To explore the impact of TCS on lipid metabolism, both larval and adult zebrafish were subjected to acute and chronic exposure to TCS. Through analyzes of biochemical and physiological markers, as well as Oil Red O (ORO) and hematoxylin and eosin (H&E) staining, our investigation revealed that TCS exposure induced hepatic and intestinal lipid accumulation in larval and adult zebrafish, leading to structural damage and inflammatory responses in these tissues. The strong affinity of TCS with PPARγ and subsequent pathway activation indicate that PPARγ pathway plays a crucial role in TCS-induced lipid buildup. Furthermore, we observed a decrease in m6A-RNA methylation levels in the TCS-treated group, which attributed to the increased activity of the demethylase FTO and concurrent suppression of the methyltransferase METTL3 gene expression by TCS. The alteration in methylation dynamics is identified as a potential underlying mechanism behind TCS-induced lipid accumulation. To address this concern, we explored the impact of folic acid-a methyl donor for m6A-RNA methylation-on lipid accumulation in zebrafish. Remarkably, folic acid administration partially alleviated lipid accumulation by restoring m6A-RNA methylation. This restoration, in turn, contributed to a reduction in inflammatory damage observed in both the liver and intestines. Additionally, folic acid partially mitigates the up-regulation of PPARγ and related genes induced by TCS. These findings carry substantial implications for understanding the adverse effects of environmental pollutants such as TCS. They also emphasize the promising potential of folic acid as a therapeutic intervention to alleviate disturbances in lipid metabolism induced by environmental pollutants.

[Contamination Characteristics and Ecological Risk Assessment of Pharmaceuticals and Personal Care Products in Drains Flowing into the Yellow River of Ningxia].

Pharmaceuticals and personal care products (PPCPs) are a group of emerging contaminants causing detrimental effects on aquatic living organisms even at low doses. To investigate the contamination characteristics and ecological risks of PPCPs in drains flowing into the Yellow River of Ningxia, 21 PPCPs were detected and analyzed using solid phase extraction and ultra-high performance liquid chromatography-mass spectrometry in this study. All 21 targeted compounds were detected in the drains, with total concentrations ranging from 47.52 to 1 700.96 ng·L-1. Ciprofloxacin, acetaminophen, benzophenone-3, and diethyltoluamide were the more commonly detected compounds, with detection frequencies exceeding 80%. The five highest-concentration PPCPs were acetaminophen, diethyltoluamide, caffeine, benzophenone-3, and levofloxacin, with the maximum concentrations of 597.21, 563.23, 559.00, 477.28, and 473.07 ng·L-1, respectively. Spatial analysis showed that the pollution levels of PPCPs in the drains of the four cities were different, with average concentrations of ∑PPCPs in the order of Yinchuan>Shizuishan>Wuzhong>Zhongwei. The total concentration of PPCPs before flowing into the Yellow River ranged from 124.82 to 1 046.61 ng·L-1. Source analysis showed that livestock and poultry breeding wastewater was the primary source for sulfadiazine and oxytetracycline, whereas medical wastewater was the primary source for levofloxacin and ciprofloxacin. The primary sources of triclocarban and triclosan were domestic sewage and industrial wastewater, whereas the primary source of caffeine and diethyltoluamide was domestic sewage. The pollution of diciofenac, cimetidine, triclocarban, and triclosan in the drains was positively correlated with the regional population and economic development level. The ecological risk assessment indicated that levofloxacin, diclofenac, gemfibrozil, benzophenone-3, and triclocarban posed high risks to aquatic organisms in drains flowing into the Yellow River. It is worthwhile to consider the mixture risk of the PPCPs that exhibited high risk at most sampling sites.

Reproductive endocrine disruption effect and mechanism in male zebrafish after life cycle exposure to environmental relevant triclosan.

Triclosan (TCS) is a wide-spectrum antibacterial agent that is found in various water environments. It has been reported to have estrogenic effects. However, the impact of TCS exposure on the reproductive system of zebrafish (Danio rerio) throughout their life cycle is not well understood. In this study, zebrafish fertilized eggs were exposed to 0, 10, and 50 µg/L TCS for 120 days. The study investigated the effects of TCS exposure on brain and testis coefficients, the expression of genes related to the hypothalamus-pituitary-gonadal (HPG) axis, hormone levels, vitellogenin (VTG) content, histopathological sections, and performed RNA sequencing of male zebrafish. The results revealed that life cycle TCS exposure had significant effects on zebrafish reproductive parameters. It increased the testis coefficient, while decreasing the brain coefficient. TCS exposure also led to a decrease in mature spermatozoa and altered the expression of genes related to the HPG axis. Furthermore, TCS disrupted the balance of sex hormone levels and increased VTG content of male zebrafish. Transcriptome sequencing analysis indicated that TCS affected reproductive endocrine related pathways, including PPAR signaling pathway, cell cycle, GnRH signaling pathway, steroid biosynthesis, cytokine-cytokine receptor interaction, and steroid hormone biosynthesis. Protein-protein interaction (PPI) network analysis confirmed the enrichment of hub genes in these pathways, including bub1bb, ccnb1, cdc20, cdk1, mcm2, mcm5, mcm6, plk1, and ttk in the brain, as well as fabp1b.1, fabp2, fabp6, ccr7, cxcl11.8, hsd11b2, and hsd3b1 in the testis. This study sheds light on the reproductive endocrine-disrupting mechanisms of life cycle exposure to TCS.

Triclosan, an antimicrobial drug, induced reproductive impairment in the freshwater fish, Anabas testudineus (Bloch, 1792).

Triclosan (TCS), an antimicrobial drug, is known to occupy different compartments in aquatic ecosystems. The present study focused to evaluate the reproductive toxicity of triclosan, at environmentally relevant (0.009 and 9 µg L-1) and sublethal (176.7 µg L-1) concentrations for 90 days in the pre-spawning phase of the fish, Anabas testudineus. The reproductive biomarkers, namely, gonadal steroidogenic enzymes, expression of aromatic genes, levels of serum gonadotropins, sex hormones, and histology of gonads were analyzed. The weight of the animal, brain weights along with gonadosomatic index decreased while mucus deposition increased significantly at all concentrations of triclosan as the primary defensive mechanism to prevent the entry of toxicants. Triclosan disrupted gonadal steroidogenesis as evidenced by a reduction in the activities of gonadal steroidogenic enzymes. The expressions of cyp19a1a and cyp19a1b genes were up-regulated in the brain of both sexes and testis, while down-regulated in the ovary indicating estrogenic effects of the compound. The endocrine-disrupting effects of triclosan were confirmed. The current results suggest that chronic exposure to triclosan altered reproductive endpoints thereby impairing normal reproductive functions in fish.

Assessing silver nanoparticle and antimicrobial combinations for antibacterial activity and biofilm prevention on surgical sutures.

AIMS: To evaluate the effect of silver nanoparticles alone and in combination with Triclosan, and trans-cinnamaldehyde against Staphylococcus aureus and Escherichia coli biofilms on sutures to improve patients' outcomes. METHODS AND RESULTS: Silver nanoparticles were prepared by chemical method and characterized by UV-visible spectrophotometer and dynamic light scattering. The minimum inhibitory concentration was assessed by the Microdilution assay. The antibiofilm activity was determined using crystal violet assay. A checkerboard assay using the fractional inhibitory concentration index and time-kill curve was used to investigate the synergistic effect of silver nanoparticle combinations. The hemolytic activity was determined using an erythrocyte hemolytic assay. Our results revealed that silver nanoparticles, Triclosan, and trans-cinnamaldehyde (TCA) inhibited S.aureus and E.coli biofilms. Silver nanoparticles with TCA showed a synergistic effect (FICI values 0.35 and 0.45 against S. aureus and E. coli biofilms, respectively), and silver nanoparticles with Triclosan showed complete inhibition of S. aureus biofilm. The hemolytic activity was <2.50% for the combinations.

Toxic effects of triclosan in aquatic organisms: A review focusing on single and combined exposure of environmental conditions and pollutants.

Triclosan (TCS) is an antibacterial agent commonly used in personal care products. Due to its widespread use and improper disposal, it is also a pervasive contaminant, particularly in aquatic environments. When released into water bodies, TCS can induce deleterious effects on developmental and physiological aspects of aquatic organisms and also interact with environmental stressors such as weather, metals, pharmaceuticals, and microplastics. Multiple studies have described the adverse effects of TCS on aquatic organisms, but few have reported on the interactions between TCS and other environmental conditions and pollutants. Because aquatic environments include a mix of contaminants and natural factors can correlate with contaminants, it is important to understand the toxicological outcomes of combinations of substances. Due to its lipophilic characteristics, TCS can interact with a wide range of substances and environmental stressors in aquatic environments. Here, we identify a need for caution when using TCS by describing not only the effects of exposure to TCS alone on aquatic organisms but also how toxicity changes when it acts in combination with multiple environmental stressors.

A Unique Monitoring Method for Fecal and Sewage-Derived Chemical Pollution Utilizing International Pellet Watch Approach.

This study established a unique approach to assess fecal contamination by measuring fecal sterols, especially coprostanol (5ß-cholestanol-3ß-ol, 5ß) and cholestanol (5α-cholestan-3ß-ol, 5α) and their ratio 5ß/(5ß + 5α) alongside triclosan (TCS) and methyl-triclosan (MTC) in beached plastic pellets across 40 countries. Coprostanol concentrations ranged from 3.6 to 8190 ng/g pellet with extremely high levels in densely populated areas in African countries. The 5ß/(5ß + 5α) ratio was not affected by the difference in residence time of pellets in aquatic environments, and their spatial pattern showed a positive correlation with that of sedimentary sterols, demonstrating its reliability as an indicator of fecal contamination. Pellets from populated areas of economically developing countries, i.e., Africa and Asia, with lower coverage of wastewater treatment exhibited higher 5ß/(5ß + 5α) ratios (∼0.7) corresponding to ∼1% sewage in seawater, while pellets from developed countries, i.e., the USA, Canada, Japan, and Europe, with higher coverage of modern wastewater treatment displayed lower ratios (∼0.5), corresponding to the first contact limit. Triclosan levels were higher in developing countries (0.4-1298 ng/g pellet), whereas developed countries showed higher methyl-triclosan levels (0.5-70 ng/g pellet) due to TCS conversion during secondary treatment. However, some samples from Japan and Europe displayed higher TCS levels, suggesting contributions from combined sewage overflow (CSO). Combination of 5ß/(5ß + 5α) and MTC/TCS ratios revealed extreme fecal contamination from direct input of raw sewage due to inadequate treatment facilities in some African and South and Southeast Asian countries.

Multiresidue determination and predicted risk assessment of emerging contaminants in sediments from Kongsfjorden, Svalbard.

The present work provides the first data on the occurrence of different classes of pharmaceuticals and personal care products (PPCPs) in surface marine sediments from an Arctic fjord (Kongsfjorden, Svalbard Islands, Norway). The target compounds included: ciprofloxacin; enrofloxacin; amoxicillin; erythromycin; sulfamethoxazole; carbamazepine; diclofenac; ibuprofen; acetylsalicylic acid; paracetamol; caffeine; triclosan; N,N-diethyl-meta-toluamide; 17ß-estradiol; 17α-ethinyl estradiol and estrone. Sampling was performed in the late summer, when high sedimentation rates occur, and over 5 years (2018-2022). Based on the environmental concentrations (MECs) found of emerging contaminants and the relative predicted no-effect concentrations (PNECs), an environmental risk assessment (ERA) for sediments was performed, including the estimation of the Risk Quotients (RQs) of selection and propagation of antimicrobial resistance (AMR) in this Arctic marine ecosystem. Sediments were extracted by Pressurized Liquid Extraction (PLE) and the extracts were purified by Solid Phase Extraction (SPE). Analytical determination was conducted with liquid chromatography-high-resolution mass spectrometry (HPLC-HRMS). PPCPs were detected in the sediments along the fjord in all the years investigated, with overall concentrations similar in most cases to those reported in urbanized areas of the planet and ranging from a minimum of 6.85 ng/g for triclosan to a maximum of 684.5 ng/g for ciprofloxacin. This latter was the only antibiotic detected but was the most abundant compound (32 %) followed by antipyretics (16 %), hormones (14 %), anti-inflammatories (13 %), insect repellents (11 %), stimulants (9 %), and disinfectants (5 %). Highest concentrations of all PPCPs detected were found close to the Ny-Ålesund research village, where human activities and the lack of appropriate wastewater treatment technologies were recognized as primary causes of local contamination. Finally, due to the presence in the sediments of the PPCPs investigated, the ERA highlights a medium (0.1 < RQ < 1) to high risk (RQ > 1) for organisms living in this Arctic marine ecosystem, including high risk of the spread of AMR.

Triclosan induces liver injury in long-life exposed mice via activation of TLR4/NF-κB/NLRP3 pathway.

Triclosan (TCS) is a widely used synthetic, with broad-spectrum antibacterial properties found in both pharmaceuticals and personal care products. More specifically, it is hepatotoxic in rodents and exhibits differential effects in mice and humans. However, the mechanisms underlying TCS-induced liver toxicity have not been elucidated. This study examined the role of the toll-like receptor 4 (TLR4)/ nuclear factor kappa B (NF-κB)/ nod-like receptor protein 3 (NLRP3) pathway in TCS-exposed liver toxicity by established a long-life TCS-exposed mice liver injury model. The 24 C57BL/6 pregnant mice exposed to TCS (0, 50 and 100 mg/kg) every day during the gestation and nursing period. After weaning, the male mice were left to continue administrate with TCS until 8 weeks of age. Then, mice in each group were sacrificed for investigation. Long-life exposure to TCS resulted in a reduction of body weight in growth mice. TCS exposure caused the increase of serum ALT, AST and ALP. The situation of inflammatory cell infiltration, macrophage recruitment and collagen fiber deposition in TCS-exposed mice liver tissues were performed by histological analysis including hematoxylin-eosin, Masson, Sirius red, and immunohistochemistry staining. Protein expression levels in TLR4/NF-κB/NLRP3 pathway was measured through Western blot, and the NLRP3 inflammasome activation was measured using real-time quantitative PCR (RT-qPCR). The results showed that exposure to TCS elevated TLR4, myeloid differentiation factor 88 (Myd88), TNF receptor associated factor 6 (TRAF6), enhanced NF-κB activation, and affected NLRP3 inflammasome activation in mice liver. Collectively, these findings indicate that long-life exposure to TCS-induced mice by upregulating the TLR4-Myd88-TRAF6 pathway, activating the NF-κB signaling cascade, initiating the NLRP3 inflammasome pathway, and ultimately leading to liver injury, including inflammation, hepatocyte pyroptosis and hepatofibrosis. Henceforth, the TLR4/NF-κB/NLRP3 pathway may now provide a theoretical basis and valuable therapeutic targets for overcoming TCS-induced liver toxicity.

Co-exposure to polystyrene nanoplastics and triclosan induces synergistic cytotoxicity in human KGN granulosa cells by promoting reactive oxygen species accumulation.

In recent years, nanoplastics (NPs) and triclosan (TCS, a pharmaceutical and personal care product) have emerged as environmental pollution issues, and their combined presence has raised widespread concern regarding potential risks to organisms. However, the combined toxicity and mechanisms of NPs and TCS remain unclear. In this study, we investigated the toxic effects of polystyrene NPs and TCS and their mechanisms on KGN cells, a human ovarian granulosa cell line. We exposed KGN cells to NPs (150 µg/mL) and TCS (15 µM) alone or together for 24 hours. Co-exposure significantly reduced cell viability. Compared with exposure to NPs or TCS alone, co-exposure increased reactive oxygen species (ROS) production. Interestingly, co-exposure to NPs and TCS produced synergistic effects. We examined the activity of superoxide dismutase (SOD) and catalase (CAT), two antioxidant enzymes; it was significantly decreased after co-exposure. We also noted an increase in the lipid oxidation product malondialdehyde (MDA) after co-exposure. Furthermore, co-exposure to NPs and TCS had a more detrimental effect on mitochondrial function than the individual treatments. Co-exposure activated the NRF2-KEAP1-HO-1 antioxidant stress pathway. Surprisingly, the expression of SESTRIN2, an antioxidant protein, was inhibited by co-exposure treatments. Co-exposure to NPs and TCS significantly increased the autophagy-related proteins LC3B-II and LC3B-Ⅰ and decreased P62. Moreover, co-exposure enhanced CASPASE-3 expression and inhibited the BCL-2/BAX ratio. In summary, our study revealed the synergistic toxic effects of NPs and TCS in vitro exposure. Our findings provide insight into the toxic mechanisms associated with co-exposure to NPs and TCS to KGN cells by inducing oxidative stress, activations of the NRF2-KEAP1-HO-1 pathway, autophagy, and apoptosis.

The first-in-class pyrazole-based dual InhA-VEGFR inhibitors towards integrated antitubercular host-directed therapy.

Several facets of the host response to tuberculosis have been tapped for clinical investigation, especially targeting angiogenesis mediated by VEGF signaling from infected macrophages. Herein, we rationalized combining the antiangiogenic effects of VEGFR-2 blockade with direct antitubercular InhA inhibition in single hybrid dual inhibitors as advantageous alternatives to the multidrug regimens. Inspired by expanded triclosans, the ether ligation of triclosan was replaced by rationalized linkers to assemble the VEGFR-2 inhibitors thematic scaffold. Accordingly, new series of 3-(p-chlorophenyl)-1-phenylpyrazole derivatives tethered to substituted ureas and their isosteres were synthesized, evaluated against Mycobacterium tuberculosis virulent cell line H37Rv, and assessed for their InhA inhibitory activities. The urea derivatives 8d and 8g exhibited the most promising antitubercular activity (MIC = 6.25 µg/mL) surpassing triclosan (MIC = 20 µg/mL) with potential InhA inhibition, thus identified as the study hits. Interestingly, both compounds inhibited VEGFR-2 at nanomolar IC50 (15.27 and 24.12 nM, respectively). Docking and molecular dynamics simulations presumed that 8d and 8g could bind to their molecular targets InhA and VEGFR-2 posing essential stable interactions shared by the reference inhibitors triclosan and sorafenib. Finally, practical LogP, Lipinski's parameters and in silico ADMET calculations highlighted their drug-likeness as novel leads in the arsenal against TB.

[Determination of triclocarban and triclosan in urine by QuEChERS extraction and ultra-performance liquid chromatography-tandem mass spectrometry].

Objective: To establish a method for the determination of triclocarban (TCC) and triclosan (TCS) in urine by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) after purification by QuEChERS. Methods: In May 2022, urine samples were extracted by acetonitrile, purified by QuEChERS, separated by Waters Acquity UPLC BEH C18 column (100 mm×2.1 mm, 1.7 µm), and eluated with water-acetonitrile as mobile phase gradient at a flow rate of 0.3 ml/min. The detection was conducted in negative ion mode (ESI(-)) and multiple reaction monitoring (MRM) scanning, it was quantified with a internal standard method, and the methodology was verified. Results: The linear ranges of TCC and TCS were 0.5-100.0 µg/L and 1.0-100.0 µg/L, and the correlation coefficients were 0.9997 and 0.9991, respectively. The limits of detection and quantitation of TCC and TCS were 0.17 and 0.33 µg/L, and 0.5 and 1.0 µg/L, respectively. The recoveries of TCC and TCS were 100.1%-102.8% and 96.7%-108.6%, and the relative standard deviations were 4.9%-6.7% and 4.1%-8.3%, respectively, at 2.0, 10.0 and 80.0 µg/L. Conclusion: QuEChERS-UPLC-MS/MS method is simple, rapid, sensitive and reproducible, and can be used for rapid and accurate simultaneous detection of TCC and TCS exposure levels in occupational population.

Degradation of triclosan by peroxydisulfate/peroxomonosulfate binary oxidants activation under thermal conditions: Efficiency and mechanism.

Peroxydisulfate (PDS) and peroxymonosulfate (PMS) could be efficiently activated by heat to generate reactive oxygen species (ROS) for the degradation of organic contaminants. However, defects including the inefficiency treatment and pH dependence of monooxidant process are prominent. In this study, synergy of heat and the PDS-PMS binary oxidant was studied for efficient triclosan (TCS) degradation and apply in rubber wastewater. Under different pH values, the degradation of TCS followed pseudo-first-order kinetics, the reaction rate constant (kobs) value of TCS in heat/PDS/PMS system increased from 1.8 to 4.4 fold and 6.8-49.1 fold when compared to heat/PDS system and heat/PMS system, respectively. Hydroxyl radicals (·OH), sulfate radicals (SO4·-) and singlet oxygen (1O2) were the major ROS for the degradation of TCS in heat/PDS/PMS system. In addition, the steady-state concentrations of ·OH/1O2 and SO4·-/·OH/1O2 increased under acidic conditions and alkaline conditions, respectively. It was concluded that the pH regulated the ROS for degradation of TCS in heat/PDS/PMS system significantly. Based on the analysis of degradation byproducts, it was inferred that the dechlorination, hydroxylation and ether bond breaking reactions occurred during the degradation of TCS. Moreover, the biological toxicity of the ten byproducts was lower than that of TCS was determined. Furthermore, the heat/PDS/PMS system is resistant to the influence of water substrates and can effectively improve the water quality of rubber wastewater. This study provides a novel perspective for efficient degradation of TCS independent of pH in the heat/PDS/PMS system and its application of rubber wastewater.

Acute/chronic triclosan exposure induces downregulation of m6A-RNA methylation modification via mettl3 suppression and elicits developmental and immune toxicity to zebrafish.

Triclosan (TCS), a prevalent contaminant in aquatic ecosystems, has been identified as a potential threat to both aquatic biota and human health. Despite its widespread presence, research into the immunotoxic effects of TCS on aquatic organisms is limited, and the underlying mechanisms driving these effects remain largely unexplored. Herein, we investigated the developmental and immune toxicities of environmentally relevant concentrations of TCS in zebrafish, characterized by morphological anomalies, histopathological impairments, and fluctuations in cytological differentiation and biomarkers following both acute (from 6 to 72/120 hpf) and chronic exposure periods (from 30 to 100 dpf). Specifically, acute exposure to TCS resulted in a significant increase in innate immune cells, contrasted by a marked decrease in T cells. Furthermore, we observed that TCS exposure elicited oxidative stress and a reduction in global m6A levels, alongside abnormal expressions within the m6A modification enzyme system in zebrafish larvae. Molecular docking studies suggested that mettl3 might be a target molecule for TCS interaction. Intriguingly, the knock-down of mettl3 mirrored the effects of TCS exposure, adversely impacting the growth and development of zebrafish, as well as the differentiation of innate immune cells. These results provide insights into the molecular basis of TCS-induced immunotoxicity through m6A-RNA epigenetic modification and aid in assessing its ecological risks, informing strategies for disease prevention linked to environmental contaminants.

Multifunctional Suture Coating for Combating Surgical Site Infections and Mitigating Associated Complications.

Despite advancements in preventive measures and hospital protocols, surgical site infections (SSIs) remain a significant concern following surgeries. Sutures, commonly used for wound closure, can serve as a platform for microbial adherence and contamination, leading to extensive debridement and recurrent antibiotic therapy. The emergence of drug resistance and the formation of biofilms on sutures have further complicated the management of SSIs. Drug-eluting sutures incorporating biocides like triclosan have limitations due to uncontrolled release and associated toxicity. Therefore, there is a need for alternative approaches to impart antimicrobial properties to sutures. In this study, we present a one-step covalent cross-linking method to coat surgical sutures with an antimicrobial small molecule, quaternary benzophenone-based antimicrobial (QSM). Additionally, the sutures are dip-coated with ibuprofen, a nonsteroidal anti-inflammatory drug with analgesic properties. The coated sutures maintained their morphological and tensile properties after in vivo implantation. The antimicrobial coating demonstrated efficacy against a broad-spectrum pathogens, including drug-resistant bacteria and fungi. The optimized formulation retained its biodegradability in vivo. Furthermore, the coated sutures exhibited ∼3 log reduction in methicillin-resistant Staphylococcus aureus (MRSA) burden in a subcutaneous implantation mouse model. Overall, this multifunctional coating provides antimicrobial properties to surgical sutures while preserving their mechanical integrity and biodegradability. These coated sutures have the potential to address the challenge of SSIs and contribute to improved surgical outcomes.