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.
OBJECTIVE: 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.

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.
CONCLUSIONS: 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 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.

Freshwater organisms are suitable models to study the fate of environmental pollutants. Due to their versatile and everyday use, many environmental pollutants such as triclocarban (TCC) or multi-walled carbon nanotubes (MWCNTs) enter environmental compartments very easily. TCC is known as a disinfectant and is declared as a highly aquatic toxicant. Multi-walled carbon nanotubes are used, e.g., in the automotive industry to improve plastic properties. Both TCCs and MWCNTs can pose major pollution hazards to various organisms. In addition, these substances can bind to each other due to their tendency to interact via strong hydrophobic interactions. Therefore, a short-term test was conducted to investigate the effects of the individual chemicals TCC and weathered MWCNTs (wMWCNTs) on a benthic biofilm and a grazing organism, Lymnaea stagnalis. Furthermore, the two compounds were coupled by an adsorption experiment resulting in a coupled complex formation (TCC + wMWCNTs). L. stagnalis showed no effects in terms of mortality. For benthic biofilm, the coupling test (TCC + wMWCNTs) showed a decrease of 58% in chlorophyll a (Chl-a) concentration. The main effect could be attributed to the wMWCNTs\' exposure alone (decrease of 82%), but not to presence of TCC. The concentration range of Chl-a upon TCC exposure alone was comparable to that in the control group (32 and 37 µg/cm2). With respect to the particulate organic carbon (POC) concentration, very similar results were found for the solvent control, the TCC, and also for the TCC + wMWCNTs group (3, 2.9, and 2.9 mg/cm2). In contrast to the control, a significant increase in POC concentration (100%) was observed for wMWCNTs, but no synergistic effect of TCC + wMWCNTs was detected.

The most prevalent malignancy among women is breast cancer. Phytochemicals and their derivatives are rapidly being recognized as possible cancer complementary therapies because they can modify signaling pathways that lead to cell cycle control or directly alter cell cycle regulatory molecules. The phytochemicals\' poor bioavailability and short half-life make them unsuitable as anticancer drugs. Applying PLGA-PEG NPs improves their solubility and tolerance while also reducing drug adverse effects. According to the findings, combining anti-tumor phytochemicals can be more effective in regulating several signaling pathways linked to tumor cell development. The point of the study was to compare the anti-proliferative impacts of combined artemisinin and metformin on cell cycle arrest and expression of cyclin D1 and apoptotic genes (bcl-2, Bax, survivin, caspase-7, and caspase-3), and also hTERT genes in breast cancer cells. T-47D breast cancer cells were treated with different concentrations of metformin (MET) and artemisinin (ART) co-loaded in PLGA-PEG NPs and free form. The MTT test was applied to assess drug cytotoxicity in T47D cells. The cell cycle distribution was investigated using flow cytometry and the expression levels of cyclin D1, hTERT, Bax, bcl-2, caspase-3, and caspase-7, and survivin genes were then determined using real-time PCR. The findings of the MTT test and flow cytometry revealed that each state was cytotoxic to T47D cells in a time and dose-dependent pattern. Compared to various state of drugs (free and nano state, pure and combination state) Met-Art-PLGA/PEG NPs demonstrated the strongest anti-proliferative impact and considerably inhibited the development of T-47D cells; also, treatment with nano-formulated forms of Met-Art combination resulted in substantial downregulation of hTERT, Bcl-2, cyclin D1, survivin, and upregulation of caspase-3, caspase-7, and Bax, in the cells, as compared to the free forms, as indicated by real-time PCR findings. The findings suggested that combining an ART/MET-loaded PLGA-PEG NP-based therapy for breast cancer could significantly improve treatment effectiveness.

Exposure to Endocrine-Disrupting Chemicals (EDCs) at an early age can lead to chronic diseases. 2,4-Dichlorophenol (2,4-DCP) and Triclocarban (TCC) are among EDCs that disrupt the endocrine system and alter the body\'s metabolism. In the present study, the hypothesis that exposure to 2,4-DCP and TCC affects obesity and predictors of cardiovascular diseases was investigated. Fasting Blood Sugar (FBS), Total Cholesterol (TC), Triglyceride (TG), Low-Density Lipoprotein (LDL), High-Density Lipoprotein (HDL (tests were performed on 79 children and adolescents. Also, blood pressure, Body Mass Index (BMI), and BMI z-score were measured to examine the hypothesis. Urinary concentrations of TCC and 2,4-DCP were measured by Gas Chromatography-Mass Spectrometry (GC/MS). Mean concentrations of TCC and 2,4-DCP (µg/L) were higher in obese individuals (5.50 ± 2.35, 0.29 ± 0.13, respectively). After adjusting for possible confounding factors, the results showed an increase in TCC concentration among girls and a decrease in 2,4-DCP among boys with increasing age. The 2,4-DCP concentration among girls increased by 0.007 and 0.01 units with a one-unit increase in Diastolic Blood Pressure (DBP) and FBS, respectively. There was a significant relationship between TCC and TG (Odds Ratio (OR) = 1.02, p-value = 0.007), LDL (OR = 1.05, p-value = 0.003), and HDL (OR = 0.88, p-value = 0.002). There was also a significant relationship between 2,4-DCP and TG (OR = 1.02, p-value = 0.002), LDL (OR = 1.12, p-value = 0.007), and HDL (OR = 0.92, p-value = 0.02). Exposure to TCC and 2,4-DCP can increase some heart risk factors and increase the risk of cardiovascular diseases and obesity. However, to confirm the results of the present study, it is necessary to conduct further studies, such as cohort and case-control studies, with a larger sample size to examine the causal relationships.

The current work aimed to investigate the degradation of the triclocarban (TCC) in aqueous solution using a modified zeolite/TiO2 composite (MZTC) synthesized by applying the electrochemical anodization (ECA). The synthesis process was conducted at different voltages (10, 40, and 60) V in 1 h and using electrophoresis deposition (EPD) in doping zeolite. The MZTC was covered with the array ordered, smooth and optimum elongated nanotubes with 5.1 μm of the length, 120.3 nm of the inner diameter 14.5 nm of the wall thickness with pure titanium and crystalline titania as determined by FESEM/EDS, and XRD. The kinetic study by following Langmuir-Hinshelwood(L-H) model and pseudo first order, the significant constant rate was obtained at pH 11 which was 0.079 ppm/min, 0.75 cm2 of MZTC catalyst loading size achieved 0.076 ppm/min and 5 ppm of TCC initial concentration reached 0.162 ppm/min. The high-performance liquid chromatography (HPLC) analysis for mechanism study of TCC photocatalytic degradation revealed eleven intermediate products after the whole process of photocatalysis. In regard of toxicology assessment by the bacteria which is Photobacterium phosphoreum, the obtained concentration of TCC at minute 60 was less satisfied with remained 0.36 ppm of TCC was detected indicates that the concentration was above allowable level. Where the allowable level of TCC in stream is 0.1 ppm.

Bisphenol analogues (BPs), triclocarban (TCC), and triclosan (TCS) are well-known environmental endocrine disrupters. Many studies have characterized their occurrence in the freshwater environment. However, their environmental behaviors in the coastal marine environment remain poorly understood. Here, matched seawater and sediment samples were collected from East China Sea, and analyzed for 13 BPs (including halogenated derivatives of bisphenol A), TCC, and TCS. Bisphenol A (BPA; mean 23 ng/L) was the predominant BP in seawaters, followed by tetrabromobisphenol A (TBBPA; 2.3 ng/L) and bisphenol S (BPS; 2.2 ng/L). Seawater concentrations of TCS (

Laboratory studies have suggested that triclosan and triclocarban can influence energy metabolism by multiple mechanisms and are potential obesogens, but the effect on obesity risk has not been well investigated in human.
To examine the associations of triclosan and triclocarban in urine with childhood obesity.
We investigated 458 school children aged 7-11 years who entered a dynamic cohort of children established in Shanghai in 2019 and 2020. Triclosan and triclocarban were determined in first morning urine by liquid chromatography coupled to mass spectrometry. Body mass index (BMI) and waist circumference (WC) were used to identify general overweight/obesity and central obesity, respectively. Logistic regression and linear models of generalized estimating equations (GEE) were used to investigate the association between urinary triclosan and triclocarban with obesity prevalence.
After adjusting for potential confounders, children with detectable triclocarban in urine had a higher proportion of general overweight/obesity (odds ratio (OR): 1.84; 95% confidential interval (95% CI): 1.19, 2.85) or central obesity (OR: 1.71; 95% CI: 1.03, 2.84). Compared to the low tertile, children in the median tertile of triclosan showed a higher proportion of central obesity (OR: 1.78; 95 %CI: 0.98, 3.24) and children in the high tertile of triclocarban had a higher proportion of general overweight/obesity (OR: 2.25; 95 %CI: 1.31, 3.88) and central obesity (OR: 2.08; 95 %CI: 1.12, 3.87). When the tertiles of triclocarban in urine were treated as a continuous variable, a positive exposure-response relationship was found with general overweight/obesity (OR: 1.50; 95 %CI: 1.15, 1.96) and central obesity (OR: 1.44; 95 %CI: 1.06, 1.95). Multiple linear regression showed a positive exposure-response relationship between triclocarban and BMI (β: 0.45; 95 %CI: 0.11, 0.80) values.
Exposure to triclosan and triclocarban was associated with increased risk of childhood obesity. Given the cross-sectional design, more studies are needed to interrogate these findings.

Triclocarban (TCC), an antimicrobial compound commonly added to a wide range of household and personal hygiene care products, is one of the most prevalent endocrine-disrupting substances (EDS). This study was conducted to elucidate whether in utero and lactational exposure to TCC could adversely affect folliculogenesis and the onset of puberty in female rat offspring. Twenty pregnant Sprague Dawley rats were equally divided into Control and TCC dam groups (supplemented daily with drinking water enriched with 0.5 mg/L of TCC) from gestational day5 to postnatal day21 (PND21). Female offspring, 20 from control and 20 from TCC dams, were subdivided into 4 subgroups (PND21, PND28, PND35 & PND42). The day of vaginal opening and first estrous cycle were determined. Ovarian sections of the offspring were processed for H&E staining and for immunohistochemical expression of Ki67, Caspase-3 and androgen receptors (AR) on the granulosa cells of ovarian follicles. Follicular count and atretic index were assessed besides, serum estradiol, progesterone, FSH and LH, C-reactive protein (CRP), malondialdehyde (MDA) and total antioxidant capacity (TAC) were measured. TCC offspring exhibited a significant delay in the onset of puberty and impedance of normal transition of the primordial follicles to more developed ones with altered cyctoarchitecture. Also, TCC decreased follicular count, proliferation and gonado-somatic index while it increased atretic index, apoptosis and AR of the granulosa cells along with disturbance of the feminine hormonal profile and oxidant/antioxidant balance. This study highlighted the potential long-term consequences of in utero and lactational exposure to TCC on the postnatal development of the ovary in rat offspring.