2,4-dinitrophenol enhances cisplatin and etoposide cytotoxic activity on prostate cancer cell line.

INTRODUCTION AND OBJECTIVE: Including additional compounds that disturb the energy metabolism of cancer cells in advanced cancer therapy regimens may be an approach to overcome the problem of drug resistance and the therapeutic effectiveness of classic chemotherapeutics. One of the compounds that decouple oxidative phosphorylation, and thus alter the activity of energy-producing pathways, is 2,4-DNP (2,4- dinitrophenol). OBJECTIVE: The aim of the study was to assess the ability of the 2,4-DNP to sensitize prostate cancer cells to the action of cisplatin and etoposide, or to intensify their action. MATERIAL AND METHODS: The research was carried out on three prostate cancer cell lines (LNCaP, PC-3, DU-145. To assess the effect of cisplatin or etoposide with 2,4-DNP on prostate cancer cells, MTT assay, analysis of the cell cycle and apoptosis detection was performed. Oxidative stress was investigated by CellRox fluorescence staining and expression of genes related to antioxidant defence. In addition, analysis was conducted of the expression of genes related to cell cycle inhibition, transporters associated with multi-drug resistance and DNA repair. RESULTS: The study showed that the simultaneous incubation of 2,4-DNP with cisplatin or etoposide enhances the cytotoxic effect of the chemotherapeutic agent only in LNCaP cells (oxidative phenotype). CONCLUSIONS: The enhanced cytotoxic effect of chemotherapeutics by 2,4-DNP may be the result of disturbed redox balance, reduced ability of cells to repair DNA, and the oxidative metabolic phenotype of prostate cancer cells.

Prenatal exposure to a mixture of organophosphate flame retardants and infant neurodevelopment: A prospective cohort study in Shandong, China.

BACKGROUND: Previous studies have suggested that prenatal exposure to organophosphate flame retardants (OPFRs) may have adverse effect on early neurodevelopment, but limited data are available in China, and the overall effects of OPFRs mixture are still unclear. OBJECTIVE: This study aimed to investigate the association between prenatal exposure to OPFR metabolites mixture and the neurodevelopment of 1-year-old infants. METHODS: A total of 270 mother-infant pairs were recruited from the Laizhou Wan (Bay) Birth Cohort in China. Ten OPFR metabolites were measured in maternal urine. Neurodevelopment of 1-year-old infants was assessed using the Gesell Developmental Schedules (GDS) and presented by the developmental quotient (DQ) score. Multivariate linear regression and weighted quantile sum (WQS) regression models were conducted to estimate the association of prenatal exposure to seven individual OPFR metabolites and their mixture with infant neurodevelopment. RESULTS: The positive rates of seven OPFR metabolites in the urine of pregnant women were greater than 70% with the median concentration ranged within 0.13-3.53 µg/g creatinine. The multivariate linear regression model showed significant negative associations between bis (1-chloro-2-propyl) phosphate (BCIPP), din-butyl phosphate (DnBP), and total OPFR metabolites exposure and neurodevelopment in all infants. Results from the WQS model consistently revealed that the OPFR metabolites mixture was inversely associated with infant neurodevelopment. Each quartile increased in the seven OPFR metabolites mixture was associated with a 1.59 decrease (95% CI: 2.96, -0.21) in gross motor DQ scores, a 1.41 decrease (95% CI: 2.38, -0.43) in adaptive DQ scores, and a 1.08 decrease (95% CI: 2.15, -0.02) in social DQ scores, among which BCIPP, bis (1, 3-dichloro-2-propyl) phosphate (BDCIPP) and DnBP were the main contributors. CONCLUSION: Prenatal exposure to a mixture of OPFRs was negatively associated with early infant neurodevelopment, particularly in gross motor, adaptive, and social domains.

The study of the protective effect of mitochondrial uncouplers during acute toxicity of the fungicide difenoconazole in different organs of mice.

Pesticides represent a serious problem for agricultural workers due to their neurotoxic effects. The aim of this study was to evaluate the ability of pharmacological oxidative phosphorylation uncouplers to reduce the effect of the difenoconazole fungicide on mitochondrial DNA (mtDNA) of various organs in mice. Injections of difenoconazole caused cognitive deficits in mice, and the protonophore 2,4-dinitrophenol (2,4-DNP) and Azur I (AzI), a demethylated metabolite of methylene blue (MB), prevented the deterioration of cognitive abilities in mice induced by difenoconazole. Difenoconazole increased the rate of reactive oxygen species (ROS) production, likely through inhibition of complex I of the mitochondrial respiratory chain. After intraperitoneal administration of difenoconazole lungs, testes and midbrain were most sensitive to the accumulation of mtDNA damage. In contrast, the cerebral cortex and hippocampus were not tolerant to the effects of difenoconazole. The protonophore 2,4-DNP reduced the rate of ROS formation and significantly reduced the amount of mtDNA damage caused by difenoconazole in the midbrain, and partially, in the lungs and testes. MB, an alternative electron carrier capable of bypassing inhibited complex I, had no effect on the effect of difenoconazole on mtDNA, while its metabolite AzI, a demethylated metabolite of MB, was able to protect the mtDNA of the midbrain and testes. Thus, mitochondria-targeted therapy is a promising approach to reduce pesticide toxicity for agricultural workers.

The BCKDK inhibitor BT2 is a chemical uncoupler that lowers mitochondrial ROS production and de novo lipogenesis.

Elevated levels of branched chain amino acids (BCAAs) and branched-chain α-ketoacids are associated with cardiovascular and metabolic disease, but the molecular mechanisms underlying a putative causal relationship remain unclear. The branched-chain ketoacid dehydrogenase kinase (BCKDK) inhibitor BT2 (3,6-dichlorobenzo[b]thiophene-2-carboxylic acid) is often used in preclinical models to increase BCAA oxidation and restore steady-state BCAA and branched-chain α-ketoacid levels. BT2 administration is protective in various rodent models of heart failure and metabolic disease, but confoundingly, targeted ablation of Bckdk in specific tissues does not reproduce the beneficial effects conferred by pharmacologic inhibition. Here, we demonstrate that BT2, a lipophilic weak acid, can act as a mitochondrial uncoupler. Measurements of oxygen consumption, mitochondrial membrane potential, and patch-clamp electrophysiology show that BT2 increases proton conductance across the mitochondrial inner membrane independently of its inhibitory effect on BCKDK. BT2 is roughly sixfold less potent than the prototypical uncoupler 2,4-dinitrophenol and phenocopies 2,4-dinitrophenol in lowering de novo lipogenesis and mitochondrial superoxide production. The data suggest that the therapeutic efficacy of BT2 may be attributable to the well-documented effects of mitochondrial uncoupling in alleviating cardiovascular and metabolic disease.

Pollution characteristics, sources, and health risks of phthalate esters in ambient air: A daily continuous monitoring study in the central Chinese city of Nanchang.

In recent years, the atmospheric pollution caused by phthalate esters (PAEs) has been increasing due to the widespread use of PAE-containing materials. Existing research on atmospheric PAEs lacks long-term continuous observation and samples from cities in central China. To investigate the pollution characteristics, sources, and health risks of PAEs in the ambient air of a typical city in central China, daily PM2.5 samples were collected in Nanchang from November 2020 to October 2021. In this study, the detection and quantification of six significant PAE contaminants, namely diethyl phthalate (DEP), di-n-butyl phthalate (DnBP), diisobutyl phthalate (DIBP), Di-2-ethylhexyl phthalate (DEHP), di-n-octyl phthalate (DnOP), and diisodecyl phthalate (DIDP), were accomplished using gas chromatography and mass spectrometry. The results revealed that the concentrations of DEP, DnBP, DEHP, and DnOP were relatively high. Higher temperatures promote the volatilization of PAEs, leading to an increase in the gaseous and particulate PAE concentrations in warm seasons and winter pollution scenarios. The results of principal component analysis show that PAEs mainly come from volatile products and polyvinylchloride plastics. Using positive matrix factorization analysis, it is shown that these two sources contribute 67.0% and 33.0% in atmosphere PAEs, respectively. Seasonally, the contribution of volatile products to both gaseous and particulate PAEs substantially increases during warm seasons. The residents in Nanchang exposed to PAEs have a negligible non-cancer risk and a potential low cancer risk. During the warm seasons, more PAEs are emitted into the air, which will increase the toxicity of PAEs and their impact on human health.

Dysregulation of CITED2 in abnormal lung development in the nitrofen rat model.

PURPOSE: CITED2 both modulates lung, heart and diaphragm development. The role of CITED2 in the pathogenesis of congenital diaphragmatic hernia (CDH) is unknown. We aimed to study CITED2 during abnormal lung development in the nitrofen model. METHODS: Timed-pregnant rats were given nitrofen on embryonic day (E) 9 to induce CDH. Fetal lungs were harvested on E15, 18 and 21. We performed RT-qPCR, RNAscope™ in situ hybridization and immunofluorescence staining for CITED2. RESULTS: We observed no difference in RT-qPCR (control: 1.09 ± 0.22 and nitrofen: 0.95 ± 0.18, p = 0.64) and in situ hybridization (1.03 ± 0.03; 1.04 ± 0.03, p = 0.97) for CITED2 expression in E15 nitrofen and control pups. At E18, CITED2 expression was reduced in in situ hybridization of nitrofen lungs (1.47 ± 0.05; 1.14 ± 0.07, p = 0.0006), but not altered in RT-qPCR (1.04 ± 0.16; 0.81 ± 0.13, p = 0.33). In E21 nitrofen lungs, CITED2 RNA expression was increased in RT-qPCR (1.04 ± 0.11; 1.52 ± 0.17, p = 0.03) and in situ hybridization (1.08 ± 0.07, 1.29 ± 0.04, p = 0.02). CITED2 protein abundance was higher in immunofluorescence staining of E21 nitrofen lungs (2.96 × 109 ± 0.13 × 109; 4.82 × 109 ± 0.25 × 109, p < 0.0001). CONCLUSION: Our data suggest that dysregulation of CITED2 contributes to abnormal lung development of CDH, as demonstrated by the distinct spatial-temporal distribution in nitrofen-induced lungs.

Evaluating the risk of phthalate and non-phthalate plasticizers in dust samples from 100 Japanese houses.

Phthalates are widely used as plasticizer and associated with various health issues. Recently, non-phthalate plasticizers are replacing phthalates; however, the exposure to these substances and the risk in Japan is unclear. In this study, we assessed the concentrations of phthalates, non-phthalate plasticizers, and phthalate degradation products in house dust and determined their respective exposure risks via oral and dermal routes. Twelve phthalates, seven non-phthalate plasticizers, and two degradation products were determined in the house dust obtained from 100 Japanese homes. The median concentration of di(2-ethylhexyl) phthalate (DEHP), accounting for 85 % of the total concentration of phthalates and non-phthalate plasticizers detected in this study, was 2.1 × 103 µg/g of dust. Apart from DEHP, diisononyl phthalate (DINP) and di(2-ethylhexyl) terephthalate (DEHT) were the most abundant in the house dust, accounting for 6.2 % (median: 1.7 × 102 µg/g of dust) and 6.1 % (median: 1.7 × 102 µg/g of dust) of the total concentrations, respectively. DEHP and DEHT concentrations in house dust were higher in apartment and small houses (floor area: ≤30 m2 or 31-60 m2 for DEHP and 31-60 m2 for DEHT) than in detached and large houses (floor area: ≥121 m2). Conversely, di-n-butyl phthalate (DnBP) concentrations were significantly higher in detached and large houses (floor area: ≥121 m2) than in apartment and small houses (floor area: ≤30 m2). The total hazard quotient (HQ), using the maximum concentration in house dust, revealed that oral and dermal exposure to house dust was 1.3 × 10-6-0.11 for adults (all substances) and 1.6 × 10-5-2.2 × 10-2 for preschool children (except for DnBP and DEHP), suggesting no risk. The HQs for DnBP and DEHP exposure via house dust for preschool children using the maximum values were 0.46 and 1.2, and 6.0 × 10-3 and 0.18 using the median values, indicating that risk of DEHP exposure should be exhaustively determined by considering other exposure routes that were not evaluated in this study, such as diet.

Phenolic compounds in water: Review of occurrence, risk, and retention by membrane technology.

Phenolic compounds are one of the main contributors to water source contamination worldwide. In this review, the data collected on Elsevier, Scopus, and Pubmed, considering papers published between 2000 and 2023, showed more than 60 different phenols have been identified in water matrix (<0.065-179,000,000 ng L-1). The highest concentration reported was in surface water canals in India. The most recurrent and studied compound was bisphenol A (n = 93) in concentrations ranging from 0.45 to 2,970,000 ng L-1. The solid phase extraction (HBL Oasis cartridge) and methanol as solvent was the method of pre-concentration most used followed by gas chromatography for the determination of phenols in water samples. The importance of drinking water guidelines incorporating more phenolic compounds was emphasized given the variety of these compounds quantified in water matrix. The human health risk assessment (HRA) was performed for the min-max concentrations of the pollutants reported in the literature. High HRA even at the lowest concentrations for 2-nitrophenol, 2,6-dichlorophenol, 3,4,5-trichlorophenol, 2,3,4,6-tetrachlorophenol, and 2,4-dinitrophenol was recognized. The cancer risk estimated was considered possible for 3-methylphenol, 2,4-dimethylphenol, 2,4,6-trichlorophenol, pentachlorophenol, and 2,4-dinitrophenol in the highest concentrations. The in-depth discussion of mechanisms, advantages, challenges, and carbon footprint of membrane technologies in water treatment and phenols retention demonstrated the great potential and trends for the production of safe drinking water, highlighting reverse osmosis, as a mature technology, and membrane distillation, as an emergent technology.

Label-Free Detection of Unbound Bilirubin and Nitrophenol Explosives in Water by a Mechanosynthesized Dual Functional Zinc Complex: Recognition of Picric Acid in Various Common Organic Media.

High levels of unconjugated bilirubin (UB) in serum lead to asymptomatic and neonatal jaundice and brain dysfunctions. Herein, we have reported the detection of UB at as low as 1 µM in an aqueous alkaline medium using a Zn(II) complex. The specificity of the complex has been validated by the HPLC in the concentration window 6-90 µM, which is rare. The sensory response of the probe at physiological pH against nitro explosives developed it as an instant-acting fluorosensor for picric acid (PA) and 2,4-dinitrophenol (2,4-DNP). Spectroscopic titration provided a binding constant of 4×105  M-1 with PA. The naked eye detection was found to be 15 µM. The solid-state photoluminescent nature of the complex enabled it for PA sensing in the solid phase. Interestingly, the probe remained fluorescent in various volatile and non-volatile organic solvents. As a result, it can also detect PA and 2,4-DNP in a wide range of common organic media. NMR studies revealed the coordination of PA, 2,4-DNP, and UB to the Zn(II) center of the probe, which is responsible for the observed quenching of the probe with the analytes.

Sublethal toxicities of 2,4-dinitrophenol as inferred from online self-reports.

INTRODUCTION: 2,4-dinitrophenol (DNP) is a mitochondrial toxin sometimes used as a weight loss agent. Reports of fatalities from DNP have been increasing since 2000, suggesting an increase in use. Our understanding of DNP toxicity in humans comes from reports to Poison Control and postmortem analyses, sources that are biased to more extreme presentations. This leads to a gap in our knowledge about the adverse effects of DNP at nonlethal doses. Here we investigate the doses and effects of DNP as reported online. METHODS: We analyzed publicly available Internet posts that we collected from 2017-2019. The posts came from anonymous users or users who voluntarily self-identified. We collected data from websites whose terms of use allow for the secondary analysis of data that their users agree to make public. We used natural language processing techniques that we had previously developed to extract doses, effects, and substances mentioned in each post. RESULTS: We collected 1,630 posts across 5 online forums and the Reddit forum r/DNP. The posts were from 1,234 unique usernames. The most commonly reported doses were between 150 to 300 mg each day followed by 300 to 450 mg each day. At those doses, the most reported adverse effects were profuse sweating and fatigue. Reports of thermoregulatory (sweating, feeling hot flashes or flushed), fatigue-related, and neurologically related symptoms were statistically significantly more frequent at reported daily doses greater than 150 mg than doses below 150 mg (post-hoc χ2-test with Bonferroni correction). The effects were judged as plausible by two board-certified medical toxicologists. Triiodothyronine, clenbuterol, testosterone, and trenbolone, an androgenic anabolic steroid were the most significantly co-mentioned substances. CONCLUSIONS: Fatigue, increased body temperature, and paresthesias from DNP are reported more frequently at doses greater than 150 mg each day than at doses less than 150 mg each day. Online discussions of DNP frequently mention androgenic anabolic steroids and other weight loss agents.

2,4-Dinitrophenol does not exert neuro-regenerative potential in experimental autoimmune neuritis.

OBJECTIVE: We evaluated the potential neuro-regenerative effects of the mitochondrial uncoupler 2,4-Dinitrophenol in experimental autoimmune neuritis, an animal model for an acute autoimmune neuropathy. METHODS: Experimental autoimmune neuritis was induced in Lewis rats. Different concentrations of 2,4-Dinitrophenol (1 mg/kg, 0.1 mg/kg and 0.01 mg/kg) were applied during the recovery phase of the neuritis (at days 18, 22 and 26) and compared to the vehicle. Any effects were assessed through functional, electrophysiological, and morphological analysis via electron microscopy of all groups at day 30. Additional immune-histochemical analysis of inflammation markers and remyelination of the sciatic nerves were performed for the dosage of 1 mg/kg and control. RESULTS: No enhancement of functional or electrophysiological recovery was observed in all 2,4-Dinitrophenol-treated groups. Cellular inflammation markers of T cells (CD3+) were comparable to control, and an increase of macrophages (IbA1+) invasion in the sciatic nerves was observed. Treatment with 2,4-Dinitrophenol reduced axonal swelling in myelinated and unmyelinated fibers with an increased production of brain-derived neurotrophic factor. CONCLUSION: Our findings do not support the hypothesis that repurposing of the mitochondrial uncoupler 2,4-Dinitrophenol exerts functionally relevant neuro-regenerative effects in autoimmune neuritis.

Source apportionment of gaseous Nitrophenols and their contribution to HONO formation in an urban area.

Nitrophenols (NPs) have significant impacts on human health, climate, and atmospheric chemistry. Despite numerous measurements of particulate NPs, still little is known about their gaseous atmospheric abundances, sources, and fate. Here, four gaseous NPs [2,4-dinitrophenol (2,4-DNP), 4-nitrophenol (4-NP), 2-nitrophenol (2-NP), and 2-Methyl-4-nitrophenol (2-Me-4-NP)] were continuously monitored during late Spring at an urban site in Houston, Texas. Among the four NPs, 4-NP showed the highest abundance, followed by 2-Me-4-NP, 2-NP, and 2,4-DNP with average concentrations of 1.07 ± 0.19 ppt, 0.47 ± 0.12 ppt, 0.41 ± 0.16 ppt, and 0.27 ± 0.09 ppt, respectively. The positive matrix factorization (PMF) model identified seven sources: industrial NPs, secondary formation, phenol sources, acetonitrile source, natural gas/crude oil, traffic, and petrochemical industries/oil refineries. A zero-dimensional photochemical box model was used to simulate the observed 2-NP and 2,4-DNP. A 50.0% and 70.0% jNO2 was found to be consistent with the measured 2-NP and 2,4-DNP. This yields a nitrous acid (HONO) production of 7.5 ± 2.5 ppt/h from 06:00 to 18:00 Central Standard Time (CST) from both NPs. An extrapolation including other known NPs suggests a maximum HONO formation of 13.8 ppt/h. The results of this study suggest that using PMF analysis supplemented by photochemical box model provides identification of the NPs sources and their atmospheric implication to HONO formation.

Non-Cardiotoxic Tetradecanoic Acid-2,4-Dinitrophenol Ester Nanomicelles in Microneedles Exert Potent Anti-Obesity Effect by Regulating Adipocyte Browning and Lipogenesis.

Sustained oral uncoupler 2,4-dinitrophenol (DNP) administration exerts prominent anti-obesity effects, but the adipose tissue off-target disadvantage leads to systemic adverse effects. A novel non-cardiotoxicity DNP delivery method using a biocompatible microneedles patch containing the amphiphilic tetradecanoic acid-DNP ester (TADNP) is described, which is synthesized via esterification on the phenolic hydroxyl of DNP. The TADNP is self-assembled as nanomicelles, which enhance the endocytosis rate of DNP by adipocytes and its permeation in isolated adipose tissues. The microenvironment of adipose tissues promotes the massive release of DNP and plasma and simulated gastrointestinal fluids. The microneedles-delivered TADNP nanomicelles (MN-TADNP) effectively deliver DNP in treated adipose tissues and reduce DNP content in off-target organs. Both oral and MN patch-delivered TADNP micelles effectively exert anti-obesity effects in a mouse model of high-fat diet-induced obesity; and noteworthily, MN-TADNP exhibit more satisfactory biosafety than oral administration. Here, a smart MN patch loaded with tetradecanoic acid-modified DNP is reported, which enhances its accumulation in adipose tissues and exerts an anti-obesity effect without causing any systemic toxicity.

Structural basis for the binding of DNP and purine nucleotides onto UCP1.

Uncoupling protein 1 (UCP1) conducts protons through the inner mitochondrial membrane to uncouple mitochondrial respiration from ATP production, thereby converting the electrochemical gradient of protons into heat1,2. The activity of UCP1 is activated by endogenous fatty acids and synthetic small molecules, such as 2,4-dinitrophenol (DNP), and is inhibited by purine nucleotides, such as ATP3-5. However, the mechanism by which UCP1 binds to these ligands remains unknown. Here we present the structures of human UCP1 in the nucleotide-free state, the DNP-bound state and the ATP-bound state. The structures show that the central cavity of UCP1 is open to the cytosolic side. DNP binds inside the cavity, making contact with transmembrane helix 2 (TM2) and TM6. ATP binds in the same cavity and induces conformational changes in TM2, together with the inward bending of TM1, TM4, TM5 and TM6 of UCP1, resulting in a more compact structure of UCP1. The binding site of ATP overlaps with that of DNP, suggesting that ATP competitively blocks the functional engagement of DNP, resulting in the inhibition of the proton-conducting activity of UCP1.

Cloning of two gene clusters involved in the catabolism of 2,4-dinitrophenol by Paraburkholderia sp. strain KU-46 and characterization of the initial DnpAB enzymes and a two-component monooxygenases DnpC1C2.

Little is currently known about the metabolism of the industrial pollutant 2,4-dinitrophenol (DNP), particularly among gram-negative bacteria. In this study, we identified two non-contiguous genetic loci spanning 22 kb of Paraburkholderia (formerly Burkholderia) sp. strain KU-46. Additionally, we characterized four key initial genes (dnpA, dnpB, and dnpC1C2) responsible for DNP degradation, providing molecular and biochemical evidence for the degradation of DNP via the formation of 4-nitrophenol (NP), a pathway that is unique among DNP utilizing bacteria. Reverse transcription polymerase chain reaction (PCR) analysis indicated that dnpA, which encodes the initial hydride transferase, and dnpB which encodes a nitrite-eliminating enzyme, were induced by DNP and organized in an operon. Moreover, we purified DnpA and DnpB from recombinant Escherichia coli to demonstrate their effect on the transformation of DNP to NP through the formation of a hydride-Meisenheimer complex of DNP, designated as H--DNP. The function of DnpB appears new since all homologs of the DnpB sequences in the protein database are annotated as putative nitrate ABC transporter substrate-binding proteins. The gene cluster responsible for the degradation of DNP after NP formation was designated dnpC1C2DXFER, and DnpC1 and DnpC2 were functionally characterized as the FAD reductase and oxygenase components of the two-component DNP monooxygenase, respectively. By elucidating the hqdA1A2BCD gene cluster, we are now able to delineate the final degradation pathway of hydroquinone to ß-ketoadipate before it enters the tricarboxylic acid cycle.

The Adsorption Efficiency of Regenerable Chitosan-TiO2 Composite Films in Removing 2,4-Dinitrophenol from Water.

In this work, the great performance of chitosan-based films blended with TiO2 (CH/TiO2) is presented to adsorb the hazardous pollutant 2,4-dinitrophenol (DNP) from water. The DNP was successfully removed, with a high adsorption %: CH/TiO2 exhibited a maximum adsorption capacity of 900 mg/g. For pursuing the proposed aim, UV-Vis spectroscopy was considered a powerful tool for monitoring the presence of DNP in purposely contaminated water. Swelling measurements were employed to infer more information about the interactions between chitosan and DNP, demonstrating the presence of electrostatic forces, deeply investigated by performing adsorption measurements by changing DNP solutions' ionic strength and pH values. The thermodynamics, adsorption isotherms, and kinetics were also studied, suggesting the DNP adsorption's heterogeneous character onto chitosan films. The applicability of pseudo-first- and pseudo-second-order kinetic equations confirmed the finding, further detailed by the Weber-Morris model. Finally, the adsorbent regeneration was exploited, and the possibility of inducing DNP desorption was investigated. For this purpose, suitable experiments were conducted using a saline solution that induced the DNP release, favoring the adsorbent reuse. In particular, 10 adsorption/desorption cycles were performed, evidencing the great ability of this material that does not lose its efficiency. As an alternative approach, the pollutant photodegradation by using Advanced Oxidation Processes, allowed by the presence of TiO2, was preliminary investigated, opening a novel horizon in the use of chitosan-based materials for environmental applications.

Pollution and risk assessment of phenolic compounds in drinking water sources from South-Western Nigeria.

This study reports the occurrence and risk assessment of 2,4-dinitrophenol (2,4-DNP), phenol (PHE), and 2,4,6-trichlorophenol (2,4,6-TCP) in drinking water sources in three south-western States in Nigeria (Osun, Oyo, and Lagos). Groundwater (GW) and surface water (SW) were collected during dry and rainy seasons of a year. The detection frequency of the phenolic compounds followed the trend Phenol > 2,4-DNP > 2,4,6-TCP. The mean concentrations of 2,4-DNP, Phenol, and 2,4,6-TCP in GW/SW samples from Osun State were 639/553 µg L-1, 261/262 µg L-1, and 169/131 µg L-1 during the rainy season and 154/7 µg L-1, 78/37 µg L-1, and 123/15 µg L-1 during the dry season, respectively. In Oyo State, the mean concentrations were 165/391 µg L-1 for 2,4-DNP and 71/231 µg L-1 for Phenol in GW/SW samples, respectively, during the rainy season. Generally, in the dry season, these values decreased. In any case, these concentrations are higher than those previously reported in water from other countries. The concentration of 2,4-DNP in water posed serious ecological risks to Daphnia on the acute scale while it was algae on the chronic scale. Estimated daily intake and hazard quotient calculations suggest that 2,4-DNP and 2,4,6-TCP in water pose serious toxicity concerns to humans. Additionally, the concentration of 2,4,6-TCP in water from Osun State in both seasons of the year and in both groundwater and surface water poses significant carcinogenic risks to persons ingesting water from these sources in the State. Every exposure group studied were at risk from ingesting these phenolic compounds in water. However, this risk decreased with increasing age of the exposure group. Results from the principal component analysis indicate that 2,4-DNP in water samples is from an anthropogenic source different from that for Phenol and 2,4,6-TCP. There is a strong need to treat water from GW and SW systems in these States before ingesting while assessing their quality regularly.

Disruption of mitochondrial function augments the radiosensitivity of prostate cancer cell lines.

INTRODUCTION: Ionizing radiation is one of the most widely used therapeutic methods in the treatment of prostate cancer, but the problem is developing radioresistance of the tumour. There is evidence that metabolic reprogramming in cancer is one of the major contributors to radioresistance and mitochondria play a crucial role in this process. OBJECTIVE: The aim of the study was to assess the influence of oxidative phosphorylation uncoupling to radiosensitivity of prostate cancer cells differing in metabolic phenotype. MATERIAL AND METHODS: LNCaP, PC-3 and DU-145 cells were exposed to X-rays and simultaneously treated with 2,4-dinitrophenol (2,4-DNP). The radiosensitive of cell lines was determined by cell clonogenic assay and cell cycle analysis. The cytotoxic effect was evaluated with MTT and CVS (Crystal violet staining) assay, apoptosis detection and cell cycle analysis. The phenotype of the cells was determined by glucose uptake and lactate release, ATP level measurement as well as basal reactive oxygen species level and mRNA expression of genes related to oxidative stress defence. RESULTS: The synergistic effect of 2,4-dinitrophenol and X-ray was observed only in the case of the LNCaP cell line. CONCLUSIONS: Phenotypic analysis indicates that this may be due to the highest dependence of these cells on oxidative phosphorylation and sensitivity to disruption of their redox status.

The preparation of 2,2'-bithiophene-based conjugated microporous polymers by direct arylation polymerization and their application in fluorescence sensing 2,4-dinitrophenol.

In this paper, we report the synthetic strategy of direct arylation polymerization (DAP) for four 2,2'-bithiophene-based conjugated microporous polymers (the 2,2'-BTh-based CMPs) by coupling 2,2'-bithiophene with the building blocks containing bromine. Compared to conventional coupling polymerization, this synthetic scheme is simple, facile and atomically efficient owing to neither preactivating the C-H bonds in 2,2'-bithiophene using organometallic reagents nor synthesis of complex thiophene-based building blocks. The resulting 2,2'-BTh-based CMPs exhibit excellent thermal stability, high specific surface areas, and good microporosity. Their specific surface areas are higher than that of other previously reported CMPs prepared with DAP. The four 2,2'-BTh-based CMPs can be utilized for multicolor fluorescence sensing of 2,4-dinitrophenol (DNP) with the high sensitivity and selectivity. The sensitivities appear to increase with the degree of structural distortion.