This study was designed to explore the possibility of using ascitic mouse sarcoma cell line (S180) to validate the mouse tumor cell attachment assay for developmental toxicants, and to test the inhibitory effects of v...This study was designed to explore the possibility of using ascitic mouse sarcoma cell line (S180) to validate the mouse tumor cell attachment assay for developmental toxicants, and to test the inhibitory effects of various developmental toxicants. The results showed that 2 of 3 developmental toxicants under consideration, sodium pentobarbital and ethanol, significantly inhibited S180cells attachment to Concanavalin A-coaed surfaces. Inhibition was dependent on concentration, and the IC50 (the concentration tha reduced attachment by 50% ), of these 2 chemicals was 1.2×10-3mol/L and 1 .0 mol/L, respectively. Anoher developmental toxiant, hydmiortisone, did not show inhibitory activity. Two non-developmental toxicants, sodium chloride and glycine were also tested and these did not decrease attachment rates. The main results reported here were generally sindlar to those obtained with ascitic mouse ovdrian tumor cells as a model. Therefore, this study added further evidence to the conclusion that cell specificity does not lindt attachment inhibition to Con A-coated surfaces, so S180 cell may serve as an altemative cell model, especially when other cell lines are unavailable. Furthermore, after optimal validation, it can be suggested that an S180 cell attachment assay may be a candidate for a series of assays to detect developmental toxicants.展开更多
The luminous intensity of dark variant (S1) separated from photobacterium phosph oreum (A2) was 1/10 000 less than that of wild type. Ethidium bromide (EB) (0.6 mg/L), Mytomycin C (MC, 0.05 mg/L), 2 amino fluorene ...The luminous intensity of dark variant (S1) separated from photobacterium phosph oreum (A2) was 1/10 000 less than that of wild type. Ethidium bromide (EB) (0.6 mg/L), Mytomycin C (MC, 0.05 mg/L), 2 amino fluorene (2 AF, 1.0 mg/L) all cou ld strongly induce reversion mutation for S1 within 24 h and increase reversion ratio significantly. The results of experiments indicated that these revertants had stable genetic characteristic and the mutation may take place at gene levels . The mutagenesis to S1 caused by EB, MC and 2 AF was detected and it may be us ed as a new rapid, simple and sensitive method for gene toxicant monitoring.展开更多
Isolated ovarian tissues from the common carp, Cyprinus carpio were incubated in vitro to obtain a discrete effect of four common toxicants of industrial origin, namely phenol, sulfide, mercuric chloride and cadmium c...Isolated ovarian tissues from the common carp, Cyprinus carpio were incubated in vitro to obtain a discrete effect of four common toxicants of industrial origin, namely phenol, sulfide, mercuric chloride and cadmium chloride, on gonadotropin-induced alteration of nonesterified and esterified cholesterol and steroidogenic enzymes, △5-3β-HSD and 17β-HSD activity. Stage II ovarian tissue containing 30-40% mature oocytes were shown to be most responsive to gonadotropins in depleting only nonesterified cholesterol moiety and stimulating the activity of both. Safe doses of above mentioned toxicants when added separately to stage II ovarian tissue with oLH (1 μg/incubation) gonadotropin-induced depletion of nonesterified cholesterol and gonadotropin-induced stimulation of the activity of both enzymes was significantly inhibited. Esterified cholesterol remained almost unaltered. Findings clearly indicate the impairment of gonadotropin induced fish ovarian steroidogenesis by the four toxicants separately.展开更多
This paper established a modified Leslie-Gower and Holling-type IV stochastic predator-prey model with Lévy noise and impulsive toxicant input. We study the stability in distribution of solutions by inequality te...This paper established a modified Leslie-Gower and Holling-type IV stochastic predator-prey model with Lévy noise and impulsive toxicant input. We study the stability in distribution of solutions by inequality techniques and ergodic method. By comparison method and It<span style="white-space:nowrap;">ô</span>’s formula, we obtain the sufficient conditions for the survival of each species. Some numerical simulations are introduced to show the theoretical results.展开更多
Male infertility is a major public health issue predominantly caused by defects in germ cell development. In the past, studies on the genetic regulation of spermatogenesis as well as on negative environmental impacts ...Male infertility is a major public health issue predominantly caused by defects in germ cell development. In the past, studies on the genetic regulation of spermatogenesis as well as on negative environmental impacts have been hampered by the fact that human germ cell development is intractable to direct analysis in vivo. Compared with model organisms including mice, there are fundamental differences in the molecular processes of human germ cell development. Therefore, an in vitro model mimicking human sperm formation would be an extremely valuable research tool. In the recent past, both human embryonic stem （ES） cells and induced pluripotent stem （iPS） cells have been reported to harbour the potential to differentiate into primordial germ cells and gametes. We here discuss the possibility to use human amniotic fluid stem （AFS） ceils as a biological model. Since their discovery in 2003, AFS cells have been characterized to differentiate into cells of all three germ layers, to be genomically stable, to have a high proliferative potential and to be non-tumourigenic. In addition, AFS cells are not subject of ethical concerns. In contrast to iPS cells, AFSs cells do not need ectopic induction of pluripotency, which is often associated with only imperfectly cleared epigenetic memory of the source cells. Since AFS cells can be derived from amniocentesis with disease-causing mutations and can be transfected with high efficiency, they could be used in probing gene functions for spermatogenesis and in screening for male reproductive toxicity.展开更多
Biomass-derived N-doped carbon(BNC)is an important environmental material and widely used in the fields of water purification and soil remediation.However,the toxicant in the commonly used synthesis process of BNC mat...Biomass-derived N-doped carbon(BNC)is an important environmental material and widely used in the fields of water purification and soil remediation.However,the toxicant in the commonly used synthesis process of BNC materials have been largely ignored.Herein,we firstly report the presence of a highly toxic by-product(KCN)in the activation process of BNC materials consequential of the carbothermal reduction reaction.Because this carbothermal reduction reaction also regulates the N-doping and pore development of BNC materials,the KCN content directly relates with the properties of BNC material properties.Accordingly,a high KCN content(-611 mg)can occur in the production process of per g BNC material with high specific surface area(-3600 m^2/g).Because the application performance of BNC material is determined by the surface area and available N doping,therefore,production of a BNC material with high performance entails high risk.Undoubtedly,this study proves a completely new risk recognition on a familiar synthesis process of biomass-based material.And,strict protective device should be taken in fabrication process of biomass-derived carbon material.展开更多
Environmental toxicants pervade air,water,soil,and food,complicating causal attribution in pollution-related deaths and intoxications.This review outlines two complementary evidentiary domains:The relatively stable an...Environmental toxicants pervade air,water,soil,and food,complicating causal attribution in pollution-related deaths and intoxications.This review outlines two complementary evidentiary domains:The relatively stable ante-mortem gut microbiome,which encodes exposure history,and the highly dynamic postmortem thanatomicrobiome,whose rapid succession and translocation may obscure premortem signals.We summarize current evidence that microbial metabolism reshapes toxicokinetics through hydrolysis,reduction,and deconjugation,thereby reactivating conjugates within the enterohepatic cycle and altering exposure windows,dose–response relationships,and target-organ delivery.Conversely,heavy metals,persistent organic pollutants,pesticides,antibiotics,and therapeutic drugs can remodel microbial communities,impair epithelial integrity,and disrupt the bile acid–short-chain fatty acid axis,generating functional biomarkers of forensic value.Analytical recommendations include parallel untargeted/targeted mass spectrometry,quantitative profiling of conjugated–free–reactivated pairs,molecularly imprinted polymer enrichment,and time-sensitive sampling with enzymatic inhibition to preserve postmortem metabolic spectra.Finally,the Daubert/Frye admissibility frameworks are evaluated with respect to validation,known error rates,and protocol standardization,emphasizing a shift from correlative to functionally anchored interpretations.Collectively,this framework integrates microbiota–toxin–host interactions with forensic practice,enhancing causal inference in environmental and drug-related investigations.展开更多
We study a model for the long-term behavior of a single-species population with some degree of pollution tolerance in a polluted environment. The model consists of three ordinary differential equations： one for the p...We study a model for the long-term behavior of a single-species population with some degree of pollution tolerance in a polluted environment. The model consists of three ordinary differential equations： one for the population density, one for the amount of toxicant inside the living organisms, and one for the amount of toxicant in the environment. We derive sufficient conditions for the persistence and the extinction of the population depending on the exogenous input rate of the toxicant into the environment and the level of pollution tolerance of the organisms. Numerical simulations are carried out to illustrate our main results.展开更多
The influence of toxicants on the competition of n populations for time variablenutriellt input rate and time variable washout rate in a chemostat model is investigated.After proving some qualitative properties of the...The influence of toxicants on the competition of n populations for time variablenutriellt input rate and time variable washout rate in a chemostat model is investigated.After proving some qualitative properties of the solutions, the threshold between persistence and extinction of the populations has been obtained.展开更多
Ammonium toxicity in plants remains poorly understood despite extensive research.While nitrate is known to benefit plant growth,the synergistic effects of nitrate in mitigating ammonium toxicity,even at low concentrat...Ammonium toxicity in plants remains poorly understood despite extensive research.While nitrate is known to benefit plant growth,the synergistic effects of nitrate in mitigating ammonium toxicity,even at low concentrations,are not fully elucidated.This review delves into the physiological and molecular nature of this phenomenon.To date,nitrate-dependent alleviation of ammonium toxicity is the result of cumulative consequences of the role of nitrate as a nutrient and signal in plant performance.The ability to counteract the ammonium-induced acidification through nitrate uptake and metabolism,the enhancement of potassium uptake as an essential nitrate counterion,and the nitratedependent signaling of key factors involved in ammonium assimilation,ROS scavenging,and growth hormone biosynthesis,are the most relevant hallmarks.In addition,evidence suggests that the availability of nitrate and ammonium has driven ecological selection in plants,determining current N preferences,and may have led to the selection of nitrate-dependent and ammonium-sensitive domesticated crops and the inefficient use of N fertilizers in agriculture.As ammonium toxicity limits N fertilization options and reduces agricultural yields,when it could be a more sustainable and cheaper alternative to nitrate,this review provides a better understanding of how plants use nitrate to counteract the problematic aspects of ammonium nutrition.展开更多
Micro/nanoplastics(M/NPs)have become pervasive environmental pollutants,posing significant risks to human health through various exposure routes,including ingestion,inhalation,and direct contact.This review systematic...Micro/nanoplastics(M/NPs)have become pervasive environmental pollutants,posing significant risks to human health through various exposure routes,including ingestion,inhalation,and direct contact.This review systematically examined the potential impacts of M/NPs on ocular health,focusing on exposure pathways,toxicological mechanisms,and resultant damage to the eye.Ocular exposure to M/NPs can occur via direct contact and oral ingestion,with the latter potentially leading to the penetration of particles through ocular biological barriers into ocular tissues.The review highlighted that M/NPs can induce adverse effects on the ocular surface,elevate intraocular pressure,and cause abnormalities in the vitreous and retina.Mechanistically,oxidative stress and inflammation are central to M/NP-induced ocular damage,with smaller particles often exhibiting greater toxicity.Overall,this review underscored the potential risks of M/NPs to ocular health and emphasized the need for further research to elucidate exposure mechanisms,toxicological pathways,and mitigation strategies.展开更多
Objective:To study the potential of Pituranthos chloranthus essential oil(PC)as a chemoprotective agent.Methods:In the in vitro study,cell proliferation were determined in CT26,SW620,and SW480 cells.Cells were exposed...Objective:To study the potential of Pituranthos chloranthus essential oil(PC)as a chemoprotective agent.Methods:In the in vitro study,cell proliferation were determined in CT26,SW620,and SW480 cells.Cells were exposed to in creasing concentrations of PC(0,6.25,12.5,25,50,100,and 200μg/mL).Combination index was calculated by applying the Chou-Talalay method,apoptopsis was analyzed by annexin V/propidium iodide staining,reactive oxygen species accumulation,and theΔψm drop were also assessed.In the in vivo study,mice were divided into 5 groups:the normal control group,the CT26 tumor-bearing group,the CT26 tumor-bearing mice+PC group,the CT26 tumor-bearing mice+cisplatin group,and the CT26 tumor-bearing mice+cisplatin+PC group.Organ coefficients and tumor volume were calculated.Alanine aminotransferase,aspartate aminotransferase,creatinine,and tumor necrosis factor-αlevels were assessed.Results:Cisplatin with PC induced a synergistic effect,allowing for reduced cisplatin dose while maintaining the same therapeutic efficacy.PC-cisplatin combinations inhibited cell viability by significantly inducing apoptosis,increasing reactive oxygen species accumulation and reducing mitochondrial membrane potential.Co-treatment with cisplatin and PC restored organ coefficients,reduced tumor volume,and alleviated nephrotoxicity in CT26 tumor-bearing mice by restoring kidney function markers and ameliorating kidney inflammation status.Conclusions:PC shows a chemoprotective potential by enhancing the antitumor effect of cisplatin while alleviating its side effects.展开更多
Objective:Artemether is a semi-synthetic derivative of artemisinin and is widely used in the treatment of Plasmodium(P.)falciparum malaria.This study aimed to characterize the safety profile of artemether based on 15-...Objective:Artemether is a semi-synthetic derivative of artemisinin and is widely used in the treatment of Plasmodium(P.)falciparum malaria.This study aimed to characterize the safety profile of artemether based on 15-year data retrived from FDA adverse event reporting system(FAERS).Methods:This is a retrospective analysis on 15-year data of artemether-related adverse effects(AEs)retrieved from the FAERS.AEs were classified according to System Organ Class(SOC)and Preferred Terms(PT).Signal detection was performed using Reporting Odds Ratios(ROR),Proportional Reporting Ratios(PRR),and Empirical Bayes Geometric Mean(EBGM).Stratified analyses examined the impact of demographic factors such as sex,age,and time-to-onset.Temporal patterns and associated risk factors were also investigated.Results:Haemolytic anaemia and haemolysis emerged as the most frequently reported AEs,exhibiting significantly elevated RORs(males:ROR 381.36,95%CI 247.06-588.60;females:ROR 455.11,95%CI 286.43-723.12).Sex-specific differences were evident,with females showing a higher incidence of reproductive-related AEs,including spontaneous abortion and premature labour.Temporal trend analysis revealed that the majority of AEs occurred within the first 30 days after the initiation of artemether administration,indicating a rapid onset.The most affected SOCs were blood and lymphatic system disorders and hepatobiliary disorders.Conclusions:Artemether is associated with a notable frequency of early-onset AEs,particularly hematological and hepatobiliary disorders.The observed sex-specific vulnerability to reproductive AEs highlights the need for sex-conscious clinical approaches.Enhanced post-treatment monitoring and further investigations into the drug’s pharmacokinetics and mechanistic pathways are recommended.展开更多
Poly-and perfluoroalkyl substances(PFAS),including perfluorooctanoic acid(PFOA)and perfluorooctane sul-fonate(PFOS),are persistent environmental pollutants with potential toxicological effects on human health.The aim ...Poly-and perfluoroalkyl substances(PFAS),including perfluorooctanoic acid(PFOA)and perfluorooctane sul-fonate(PFOS),are persistent environmental pollutants with potential toxicological effects on human health.The aim of this study was to investigate the impact of PFOS and PFOA on the effectiveness of selected drugs used in the treatment of prostate cancer based on in vitro tests on cell lines.Three cell lines were used in the study:two human prostate cancer cells(DU-145 and PC3)and one human normal prostate cell line(PNT1A).Using dose-response experiments,it was observed that PFAS had differential effects on cancer and normal cells.At low concentrations,PFOA and PFOS stimulated the proliferation of cancer cells,particularly PC3,while higher concentrations led to reduced viability.In normal cells,PFOS exhibited greater cytotoxicity compared to PFOA.Furthermore,PFOS enhanced docetaxel cytotoxicity in PC3 cells but reduced its efficacy in DU-145 cells.Similarly,PFOA diminished cabazitaxel effectiveness in DU-145 cells,suggesting PFAS-drug interactions may depend on the cell type,drug,and PFAS concentration.Results suggest that PFAS may influence cellular processes through receptor-mediated pathways,oxidative stress modulation,and protein binding,altering drug bioavailability and cellular uptake.The study also highlights the non-monotonic dose-response relationships observed in PFAS-treated cells.These findings raise concerns about the potential risks associated with PFAS exposure,particularly in the context of cancer treatment.Future studies should focus on long-term,low-dose PFAS exposure,the use of primary cells,and the molecular mechanisms driving these interactions to better inform therapeutic strategies.展开更多
Objectives:B-cell maturation antigen(BCMA)-targeted antibody–drug conjugates(ADCs)have emerged as promising therapies for relapsed/refractory multiple myeloma(RRMM),but the overall efficacy and safety profile is uncl...Objectives:B-cell maturation antigen(BCMA)-targeted antibody–drug conjugates(ADCs)have emerged as promising therapies for relapsed/refractory multiple myeloma(RRMM),but the overall efficacy and safety profile is unclear.This study aimed to synthesize the available evidence on the safety and efficacy of BCMA-ADCs in development for RRMM.Methods:A systematic search was conducted using six bibliographic databases and ClinicalTrials.gov up to November 2024.Studies were eligible if they were human clinical trials or animal studies evaluating BCMA-ADCs and reported efficacy and safety outcomes.Data extraction and quality assessments were conducted using validated tools,including ROBINS-I and SYRCLE’s risk of bias tool.Results:A total of 21 studies were included:16 clinical trials and five animal studies.Key findings included that belantamab mafodotin demonstrated variable but generally durable response rates(32%–85%)and a broad range of progression-free survival(PFS)(2.8–36.6 months),albeit with ocular toxicities in 51%–96%.Among newer candidates,MEDI2228 showed median PFS 5.1–6.6 months with 14%discontinuation for ocular symptoms,while AMG 224 had an overall response rate(ORR)of 23%(9/40)with anemia 21%,thrombocytopenia 24%,and ocular adverse events(AEs)21%.Animal studies supported the tumor-eradicating potential of all BCMA-ADC candidates,although safety signals such as hepatic and renal toxicity were noted with HDP-101.The risk of bias assessment revealed generally moderate to serious concerns in human trials,while the overall quality of the animal studies was acceptable.Conclusions:BCMA-targeted ADC candidates show encouraging efficacy in RRMM,particularly belantamab mafodotin.However,frequent AEs,especially ocular and hematologic toxicities,underscore the need for optimization in ADC design.Further research should prioritize enhancing safety while maintaining clinical benefit.展开更多
Objective:To investigate the sterilizing potential of zinc gluconate,calcium chloride(CaCl_(2))and cadmium chloride(CdCl_(2))following a single intratesticular administration in adult male rats.Methods:60 adult male W...Objective:To investigate the sterilizing potential of zinc gluconate,calcium chloride(CaCl_(2))and cadmium chloride(CdCl_(2))following a single intratesticular administration in adult male rats.Methods:60 adult male Wistar albino rats(Rattus norvegicus)weighing 160-200 g and aged 5-6 months randomly received a single intratesticular injection of normal saline(Group A),zinc gluconate 13.3 mg/mL plus L-Arginine(Group B),20%CaCl_(2)(Group C),and CdCl_(2)0.5 mg/kg body weight plus ethylenediaminetetraacetic acid(EDTA)(Group D),respectively,along the entire route from the caudoventral aspect of each testis.They were euthanized up to 180 days to evaluate reproductive tract toxicology.Results:The reproductive organ weights were markedly reduced,with testes severely atrophied in group B,pea-sized and stony hard in group C,and moderately reduced in group D.Azoospermia was evident in groups B and C,while sperm concentration was reduced to<1 million/mL with zero sperm motility in group D.Rats of groups B and C failed to show mounting and copulatory behaviour.A completely disorganized mesh of cellular elements was observed in the seminiferous tubules of group B,while pyknotic germ cell and arrest of spermatogenesis,exfoliated germ cells,occasional syncytial bodies and smaller Leydig cells were evident in groups C and D.Significantly reduced testosterone levels,increased luteinizing hormone(LH)and follicle-stimulating hormone(FSH)levels,returned to normal after 90 days in group D.Conclusions:Zinc gluconate and CaCl_(2)injections severely affected the reproductive organs and libido and rats treated with CdCl_(2)exhibited diminished spermatogenesis with normal libido.Thus,the need-based selection of intratesticular agents should consider their distinct effects on spermatogenesis,libido,and hormonal balance for achieving targeted sterilization outcomes.展开更多
Background:Epidemiological studies have confirmed that longer exposure to insecticides like cypermethrin(CYP)significantly increases the risk of male reproductive toxicity.Crocus sativus L.has been recognized due to i...Background:Epidemiological studies have confirmed that longer exposure to insecticides like cypermethrin(CYP)significantly increases the risk of male reproductive toxicity.Crocus sativus L.has been recognized due to its therapeutic properties,but its exact role and molecular mechanisms in treatment of reproductive dysfunction remain unclear.Methods:During this study,36 rats were randomly divided into six groups(n=6):control,CYP-induced(60 mg/kg),standard(leuprolide 3 mg/kg)and three treatment groups receiving aqueous,ethanolic,and oil extracts(50 mg/kg or 20 mL/kg)for post-toxicity induction.Results:The finding represented that exposure of CYP significantly increased oxidative stress,disrupted testicular architecture,and markedly reduced testosterone levels(P<0.05).Importantly,Crocus sativus L.treatment alleviated these changes by increasing the expression of Nrf2(nuclear factor erythroid 2-related factor 2),restoring the activity of antioxidant enzymes,and enhancing testicular histomorphology.Surprisingly,molecular docking established a high binding affinity of Crocus sativus L.phytoconstituents such as gallic acid,cinnamic acid and quercetin to the Nrf2-Keap1 complex.It is worth noting that,Crocus sativus L.exhibited a high level of protection against reproductive toxicity caused by CYP in male rats,which was mediated by the activation of Nrf2 pathway,reduction of oxidative damage,and favorable ADMET characteristics.Conclusion:Notably,this research provides a more valid,safe,and effective method of developing new drugs for reproductive disorders,however,further investigation is needed to support the research findings and implement it in clinical practice.展开更多
Remarkable antibacterial activity of BPA analogues especially for tetrabromobi-sphenol A against Staphylococcus aureus 25923(Sa25923)and methicillin-resistant Staphylococcus aureus(MRSA)has been reported in our previo...Remarkable antibacterial activity of BPA analogues especially for tetrabromobi-sphenol A against Staphylococcus aureus 25923(Sa25923)and methicillin-resistant Staphylococcus aureus(MRSA)has been reported in our previous studies.However,the toxic effects of the compounds as environmental contaminants on the endocrine system limited their applications in the field of medicine and health.Given the abuse of antibiotics has led to the emergence of multiple super-resistant bacteria,we considered that structural modifications based on the BPA structure will be available for molecular designing of potential antimicrobial agents without drug resistance.In this study,to further improve the antibacterial activity and reduce the biological toxicity,we performed the computational models to evaluate the binding affinities of BPA analogues to the potential target DltA protein in the biosynthesis of cell wall.A series of synthesized achiral analogues ofα,α,α′-tris(4-hydroxyphenyl)-1-ethyl-4-isopropylbenzene(α,α,α′-TEIB)exhibited low minimum inhibitory concentration against Sa25923 and MRSA(2 or 1μg mL−1).Especially,the analogue A4 did not induce the drug-resistant mutants for all tested Gram-positive bacterial strains and exhibited relatively lower cytotoxicity in HepG2 cells.The developed classification model based on the light gradient boosting algorithm showed the superior performances on the internal robustness and generalization ability for the ligand-based virtual screening of bisphenol and polyphenol antimicrobial substances.Collectively,our findings suggest that the molecular structure ofα,α,α′-TEIB is promising as a scaffold,which is expected to achieve a breakthrough in the development of antibiotics which can prevent the invasion of MRSA and other super bacteria.展开更多
With the help of a continuation theorem based on Gaines and Mawhin's coincidence degree, we study the global existence of positive periodic solutions of a 'food-limited' population model with toxicants and...With the help of a continuation theorem based on Gaines and Mawhin's coincidence degree, we study the global existence of positive periodic solutions of a 'food-limited' population model with toxicants and time delays. Some new results are obtained.展开更多
Neuronal toxic pollutants in environment possess hazards to human health. It is essential to determine the causative neuronal toxicants in environmental samples. In the present study, viability of primary cultured cer...Neuronal toxic pollutants in environment possess hazards to human health. It is essential to determine the causative neuronal toxicants in environmental samples. In the present study, viability of primary cultured cerebellar granule neurons (CGNs), combined with sample extraction, chemical fractionation and identification, was applied for screening acid-resistant neuronal toxic substances in environmental samples. River sediments and agricultural soils along the river near a brominated flame retardant (BFR) manufacturing plant in South China were collected to screen the key neuronal toxicants. The results indicated that the manufacturing plant was a source of neuronal toxicity risks. In the sediment and soil near the plant, one of the causative toxicants was identified as tris-(2,3-dibromopropyl) isocyanurate (TBC) using HPLC-MS/MS. In addition, an unknown chemical possibly causing significant neuronal toxicity was isolated from all the soil samples in the region.展开更多
文摘This study was designed to explore the possibility of using ascitic mouse sarcoma cell line (S180) to validate the mouse tumor cell attachment assay for developmental toxicants, and to test the inhibitory effects of various developmental toxicants. The results showed that 2 of 3 developmental toxicants under consideration, sodium pentobarbital and ethanol, significantly inhibited S180cells attachment to Concanavalin A-coaed surfaces. Inhibition was dependent on concentration, and the IC50 (the concentration tha reduced attachment by 50% ), of these 2 chemicals was 1.2×10-3mol/L and 1 .0 mol/L, respectively. Anoher developmental toxiant, hydmiortisone, did not show inhibitory activity. Two non-developmental toxicants, sodium chloride and glycine were also tested and these did not decrease attachment rates. The main results reported here were generally sindlar to those obtained with ascitic mouse ovdrian tumor cells as a model. Therefore, this study added further evidence to the conclusion that cell specificity does not lindt attachment inhibition to Con A-coated surfaces, so S180 cell may serve as an altemative cell model, especially when other cell lines are unavailable. Furthermore, after optimal validation, it can be suggested that an S180 cell attachment assay may be a candidate for a series of assays to detect developmental toxicants.
文摘The luminous intensity of dark variant (S1) separated from photobacterium phosph oreum (A2) was 1/10 000 less than that of wild type. Ethidium bromide (EB) (0.6 mg/L), Mytomycin C (MC, 0.05 mg/L), 2 amino fluorene (2 AF, 1.0 mg/L) all cou ld strongly induce reversion mutation for S1 within 24 h and increase reversion ratio significantly. The results of experiments indicated that these revertants had stable genetic characteristic and the mutation may take place at gene levels . The mutagenesis to S1 caused by EB, MC and 2 AF was detected and it may be us ed as a new rapid, simple and sensitive method for gene toxicant monitoring.
文摘Isolated ovarian tissues from the common carp, Cyprinus carpio were incubated in vitro to obtain a discrete effect of four common toxicants of industrial origin, namely phenol, sulfide, mercuric chloride and cadmium chloride, on gonadotropin-induced alteration of nonesterified and esterified cholesterol and steroidogenic enzymes, △5-3β-HSD and 17β-HSD activity. Stage II ovarian tissue containing 30-40% mature oocytes were shown to be most responsive to gonadotropins in depleting only nonesterified cholesterol moiety and stimulating the activity of both. Safe doses of above mentioned toxicants when added separately to stage II ovarian tissue with oLH (1 μg/incubation) gonadotropin-induced depletion of nonesterified cholesterol and gonadotropin-induced stimulation of the activity of both enzymes was significantly inhibited. Esterified cholesterol remained almost unaltered. Findings clearly indicate the impairment of gonadotropin induced fish ovarian steroidogenesis by the four toxicants separately.
文摘This paper established a modified Leslie-Gower and Holling-type IV stochastic predator-prey model with Lévy noise and impulsive toxicant input. We study the stability in distribution of solutions by inequality techniques and ergodic method. By comparison method and It<span style="white-space:nowrap;">ô</span>’s formula, we obtain the sufficient conditions for the survival of each species. Some numerical simulations are introduced to show the theoretical results.
文摘Male infertility is a major public health issue predominantly caused by defects in germ cell development. In the past, studies on the genetic regulation of spermatogenesis as well as on negative environmental impacts have been hampered by the fact that human germ cell development is intractable to direct analysis in vivo. Compared with model organisms including mice, there are fundamental differences in the molecular processes of human germ cell development. Therefore, an in vitro model mimicking human sperm formation would be an extremely valuable research tool. In the recent past, both human embryonic stem （ES） cells and induced pluripotent stem （iPS） cells have been reported to harbour the potential to differentiate into primordial germ cells and gametes. We here discuss the possibility to use human amniotic fluid stem （AFS） ceils as a biological model. Since their discovery in 2003, AFS cells have been characterized to differentiate into cells of all three germ layers, to be genomically stable, to have a high proliferative potential and to be non-tumourigenic. In addition, AFS cells are not subject of ethical concerns. In contrast to iPS cells, AFSs cells do not need ectopic induction of pluripotency, which is often associated with only imperfectly cleared epigenetic memory of the source cells. Since AFS cells can be derived from amniocentesis with disease-causing mutations and can be transfected with high efficiency, they could be used in probing gene functions for spermatogenesis and in screening for male reproductive toxicity.
基金the National Natural Science Foundation of China(No.21876030)。
文摘Biomass-derived N-doped carbon(BNC)is an important environmental material and widely used in the fields of water purification and soil remediation.However,the toxicant in the commonly used synthesis process of BNC materials have been largely ignored.Herein,we firstly report the presence of a highly toxic by-product(KCN)in the activation process of BNC materials consequential of the carbothermal reduction reaction.Because this carbothermal reduction reaction also regulates the N-doping and pore development of BNC materials,the KCN content directly relates with the properties of BNC material properties.Accordingly,a high KCN content(-611 mg)can occur in the production process of per g BNC material with high specific surface area(-3600 m^2/g).Because the application performance of BNC material is determined by the surface area and available N doping,therefore,production of a BNC material with high performance entails high risk.Undoubtedly,this study proves a completely new risk recognition on a familiar synthesis process of biomass-based material.And,strict protective device should be taken in fabrication process of biomass-derived carbon material.
文摘Environmental toxicants pervade air,water,soil,and food,complicating causal attribution in pollution-related deaths and intoxications.This review outlines two complementary evidentiary domains:The relatively stable ante-mortem gut microbiome,which encodes exposure history,and the highly dynamic postmortem thanatomicrobiome,whose rapid succession and translocation may obscure premortem signals.We summarize current evidence that microbial metabolism reshapes toxicokinetics through hydrolysis,reduction,and deconjugation,thereby reactivating conjugates within the enterohepatic cycle and altering exposure windows,dose–response relationships,and target-organ delivery.Conversely,heavy metals,persistent organic pollutants,pesticides,antibiotics,and therapeutic drugs can remodel microbial communities,impair epithelial integrity,and disrupt the bile acid–short-chain fatty acid axis,generating functional biomarkers of forensic value.Analytical recommendations include parallel untargeted/targeted mass spectrometry,quantitative profiling of conjugated–free–reactivated pairs,molecularly imprinted polymer enrichment,and time-sensitive sampling with enzymatic inhibition to preserve postmortem metabolic spectra.Finally,the Daubert/Frye admissibility frameworks are evaluated with respect to validation,known error rates,and protocol standardization,emphasizing a shift from correlative to functionally anchored interpretations.Collectively,this framework integrates microbiota–toxin–host interactions with forensic practice,enhancing causal inference in environmental and drug-related investigations.
基金Supported by National Natural Science Foundation of China(No.11201075)Natural Science Foundation of Fujian Province(No.2016J01015)Scholarship under Education Department of Fujian Province
文摘We study a model for the long-term behavior of a single-species population with some degree of pollution tolerance in a polluted environment. The model consists of three ordinary differential equations： one for the population density, one for the amount of toxicant inside the living organisms, and one for the amount of toxicant in the environment. We derive sufficient conditions for the persistence and the extinction of the population depending on the exogenous input rate of the toxicant into the environment and the level of pollution tolerance of the organisms. Numerical simulations are carried out to illustrate our main results.
文摘The influence of toxicants on the competition of n populations for time variablenutriellt input rate and time variable washout rate in a chemostat model is investigated.After proving some qualitative properties of the solutions, the threshold between persistence and extinction of the populations has been obtained.
基金supported by an MCIN RyC Programme MCIN/AEI/10.13039/501100011033the‘European Union Next Generation EU/PRTR’under grant no.RYC2021-032345-I+1 种基金supported by the AEI(grant no.PID2019-107463RJ-I00/AEI/10.13039/501100011033)the Regional Research and Development Programme of the Government of Navarre(call 2019,project NitroHealthy,PC068).
文摘Ammonium toxicity in plants remains poorly understood despite extensive research.While nitrate is known to benefit plant growth,the synergistic effects of nitrate in mitigating ammonium toxicity,even at low concentrations,are not fully elucidated.This review delves into the physiological and molecular nature of this phenomenon.To date,nitrate-dependent alleviation of ammonium toxicity is the result of cumulative consequences of the role of nitrate as a nutrient and signal in plant performance.The ability to counteract the ammonium-induced acidification through nitrate uptake and metabolism,the enhancement of potassium uptake as an essential nitrate counterion,and the nitratedependent signaling of key factors involved in ammonium assimilation,ROS scavenging,and growth hormone biosynthesis,are the most relevant hallmarks.In addition,evidence suggests that the availability of nitrate and ammonium has driven ecological selection in plants,determining current N preferences,and may have led to the selection of nitrate-dependent and ammonium-sensitive domesticated crops and the inefficient use of N fertilizers in agriculture.As ammonium toxicity limits N fertilization options and reduces agricultural yields,when it could be a more sustainable and cheaper alternative to nitrate,this review provides a better understanding of how plants use nitrate to counteract the problematic aspects of ammonium nutrition.
基金Supported by the Guangdong Provincial Natural Science Foundation(No.2114050001527).
文摘Micro/nanoplastics(M/NPs)have become pervasive environmental pollutants,posing significant risks to human health through various exposure routes,including ingestion,inhalation,and direct contact.This review systematically examined the potential impacts of M/NPs on ocular health,focusing on exposure pathways,toxicological mechanisms,and resultant damage to the eye.Ocular exposure to M/NPs can occur via direct contact and oral ingestion,with the latter potentially leading to the penetration of particles through ocular biological barriers into ocular tissues.The review highlighted that M/NPs can induce adverse effects on the ocular surface,elevate intraocular pressure,and cause abnormalities in the vitreous and retina.Mechanistically,oxidative stress and inflammation are central to M/NP-induced ocular damage,with smaller particles often exhibiting greater toxicity.Overall,this review underscored the potential risks of M/NPs to ocular health and emphasized the need for further research to elucidate exposure mechanisms,toxicological pathways,and mitigation strategies.
基金funded by The Tunisian Ministry of Research and Higher Education.
文摘Objective:To study the potential of Pituranthos chloranthus essential oil(PC)as a chemoprotective agent.Methods:In the in vitro study,cell proliferation were determined in CT26,SW620,and SW480 cells.Cells were exposed to in creasing concentrations of PC(0,6.25,12.5,25,50,100,and 200μg/mL).Combination index was calculated by applying the Chou-Talalay method,apoptopsis was analyzed by annexin V/propidium iodide staining,reactive oxygen species accumulation,and theΔψm drop were also assessed.In the in vivo study,mice were divided into 5 groups:the normal control group,the CT26 tumor-bearing group,the CT26 tumor-bearing mice+PC group,the CT26 tumor-bearing mice+cisplatin group,and the CT26 tumor-bearing mice+cisplatin+PC group.Organ coefficients and tumor volume were calculated.Alanine aminotransferase,aspartate aminotransferase,creatinine,and tumor necrosis factor-αlevels were assessed.Results:Cisplatin with PC induced a synergistic effect,allowing for reduced cisplatin dose while maintaining the same therapeutic efficacy.PC-cisplatin combinations inhibited cell viability by significantly inducing apoptosis,increasing reactive oxygen species accumulation and reducing mitochondrial membrane potential.Co-treatment with cisplatin and PC restored organ coefficients,reduced tumor volume,and alleviated nephrotoxicity in CT26 tumor-bearing mice by restoring kidney function markers and ameliorating kidney inflammation status.Conclusions:PC shows a chemoprotective potential by enhancing the antitumor effect of cisplatin while alleviating its side effects.
文摘Objective:Artemether is a semi-synthetic derivative of artemisinin and is widely used in the treatment of Plasmodium(P.)falciparum malaria.This study aimed to characterize the safety profile of artemether based on 15-year data retrived from FDA adverse event reporting system(FAERS).Methods:This is a retrospective analysis on 15-year data of artemether-related adverse effects(AEs)retrieved from the FAERS.AEs were classified according to System Organ Class(SOC)and Preferred Terms(PT).Signal detection was performed using Reporting Odds Ratios(ROR),Proportional Reporting Ratios(PRR),and Empirical Bayes Geometric Mean(EBGM).Stratified analyses examined the impact of demographic factors such as sex,age,and time-to-onset.Temporal patterns and associated risk factors were also investigated.Results:Haemolytic anaemia and haemolysis emerged as the most frequently reported AEs,exhibiting significantly elevated RORs(males:ROR 381.36,95%CI 247.06-588.60;females:ROR 455.11,95%CI 286.43-723.12).Sex-specific differences were evident,with females showing a higher incidence of reproductive-related AEs,including spontaneous abortion and premature labour.Temporal trend analysis revealed that the majority of AEs occurred within the first 30 days after the initiation of artemether administration,indicating a rapid onset.The most affected SOCs were blood and lymphatic system disorders and hepatobiliary disorders.Conclusions:Artemether is associated with a notable frequency of early-onset AEs,particularly hematological and hepatobiliary disorders.The observed sex-specific vulnerability to reproductive AEs highlights the need for sex-conscious clinical approaches.Enhanced post-treatment monitoring and further investigations into the drug’s pharmacokinetics and mechanistic pathways are recommended.
文摘Poly-and perfluoroalkyl substances(PFAS),including perfluorooctanoic acid(PFOA)and perfluorooctane sul-fonate(PFOS),are persistent environmental pollutants with potential toxicological effects on human health.The aim of this study was to investigate the impact of PFOS and PFOA on the effectiveness of selected drugs used in the treatment of prostate cancer based on in vitro tests on cell lines.Three cell lines were used in the study:two human prostate cancer cells(DU-145 and PC3)and one human normal prostate cell line(PNT1A).Using dose-response experiments,it was observed that PFAS had differential effects on cancer and normal cells.At low concentrations,PFOA and PFOS stimulated the proliferation of cancer cells,particularly PC3,while higher concentrations led to reduced viability.In normal cells,PFOS exhibited greater cytotoxicity compared to PFOA.Furthermore,PFOS enhanced docetaxel cytotoxicity in PC3 cells but reduced its efficacy in DU-145 cells.Similarly,PFOA diminished cabazitaxel effectiveness in DU-145 cells,suggesting PFAS-drug interactions may depend on the cell type,drug,and PFAS concentration.Results suggest that PFAS may influence cellular processes through receptor-mediated pathways,oxidative stress modulation,and protein binding,altering drug bioavailability and cellular uptake.The study also highlights the non-monotonic dose-response relationships observed in PFAS-treated cells.These findings raise concerns about the potential risks associated with PFAS exposure,particularly in the context of cancer treatment.Future studies should focus on long-term,low-dose PFAS exposure,the use of primary cells,and the molecular mechanisms driving these interactions to better inform therapeutic strategies.
文摘Objectives:B-cell maturation antigen(BCMA)-targeted antibody–drug conjugates(ADCs)have emerged as promising therapies for relapsed/refractory multiple myeloma(RRMM),but the overall efficacy and safety profile is unclear.This study aimed to synthesize the available evidence on the safety and efficacy of BCMA-ADCs in development for RRMM.Methods:A systematic search was conducted using six bibliographic databases and ClinicalTrials.gov up to November 2024.Studies were eligible if they were human clinical trials or animal studies evaluating BCMA-ADCs and reported efficacy and safety outcomes.Data extraction and quality assessments were conducted using validated tools,including ROBINS-I and SYRCLE’s risk of bias tool.Results:A total of 21 studies were included:16 clinical trials and five animal studies.Key findings included that belantamab mafodotin demonstrated variable but generally durable response rates(32%–85%)and a broad range of progression-free survival(PFS)(2.8–36.6 months),albeit with ocular toxicities in 51%–96%.Among newer candidates,MEDI2228 showed median PFS 5.1–6.6 months with 14%discontinuation for ocular symptoms,while AMG 224 had an overall response rate(ORR)of 23%(9/40)with anemia 21%,thrombocytopenia 24%,and ocular adverse events(AEs)21%.Animal studies supported the tumor-eradicating potential of all BCMA-ADC candidates,although safety signals such as hepatic and renal toxicity were noted with HDP-101.The risk of bias assessment revealed generally moderate to serious concerns in human trials,while the overall quality of the animal studies was acceptable.Conclusions:BCMA-targeted ADC candidates show encouraging efficacy in RRMM,particularly belantamab mafodotin.However,frequent AEs,especially ocular and hematologic toxicities,underscore the need for optimization in ADC design.Further research should prioritize enhancing safety while maintaining clinical benefit.
基金financially assisted to Timanshi Chansoriya of the fellowship grant of UGC-NFPwD,New Delhi sanctioned vide UGC F.No.01-01/2019-Sch dated 06.11.2020(Serial No.352 ID:NFPWD-2018-20-UTP-6522).
文摘Objective:To investigate the sterilizing potential of zinc gluconate,calcium chloride(CaCl_(2))and cadmium chloride(CdCl_(2))following a single intratesticular administration in adult male rats.Methods:60 adult male Wistar albino rats(Rattus norvegicus)weighing 160-200 g and aged 5-6 months randomly received a single intratesticular injection of normal saline(Group A),zinc gluconate 13.3 mg/mL plus L-Arginine(Group B),20%CaCl_(2)(Group C),and CdCl_(2)0.5 mg/kg body weight plus ethylenediaminetetraacetic acid(EDTA)(Group D),respectively,along the entire route from the caudoventral aspect of each testis.They were euthanized up to 180 days to evaluate reproductive tract toxicology.Results:The reproductive organ weights were markedly reduced,with testes severely atrophied in group B,pea-sized and stony hard in group C,and moderately reduced in group D.Azoospermia was evident in groups B and C,while sperm concentration was reduced to<1 million/mL with zero sperm motility in group D.Rats of groups B and C failed to show mounting and copulatory behaviour.A completely disorganized mesh of cellular elements was observed in the seminiferous tubules of group B,while pyknotic germ cell and arrest of spermatogenesis,exfoliated germ cells,occasional syncytial bodies and smaller Leydig cells were evident in groups C and D.Significantly reduced testosterone levels,increased luteinizing hormone(LH)and follicle-stimulating hormone(FSH)levels,returned to normal after 90 days in group D.Conclusions:Zinc gluconate and CaCl_(2)injections severely affected the reproductive organs and libido and rats treated with CdCl_(2)exhibited diminished spermatogenesis with normal libido.Thus,the need-based selection of intratesticular agents should consider their distinct effects on spermatogenesis,libido,and hormonal balance for achieving targeted sterilization outcomes.
文摘Background:Epidemiological studies have confirmed that longer exposure to insecticides like cypermethrin(CYP)significantly increases the risk of male reproductive toxicity.Crocus sativus L.has been recognized due to its therapeutic properties,but its exact role and molecular mechanisms in treatment of reproductive dysfunction remain unclear.Methods:During this study,36 rats were randomly divided into six groups(n=6):control,CYP-induced(60 mg/kg),standard(leuprolide 3 mg/kg)and three treatment groups receiving aqueous,ethanolic,and oil extracts(50 mg/kg or 20 mL/kg)for post-toxicity induction.Results:The finding represented that exposure of CYP significantly increased oxidative stress,disrupted testicular architecture,and markedly reduced testosterone levels(P<0.05).Importantly,Crocus sativus L.treatment alleviated these changes by increasing the expression of Nrf2(nuclear factor erythroid 2-related factor 2),restoring the activity of antioxidant enzymes,and enhancing testicular histomorphology.Surprisingly,molecular docking established a high binding affinity of Crocus sativus L.phytoconstituents such as gallic acid,cinnamic acid and quercetin to the Nrf2-Keap1 complex.It is worth noting that,Crocus sativus L.exhibited a high level of protection against reproductive toxicity caused by CYP in male rats,which was mediated by the activation of Nrf2 pathway,reduction of oxidative damage,and favorable ADMET characteristics.Conclusion:Notably,this research provides a more valid,safe,and effective method of developing new drugs for reproductive disorders,however,further investigation is needed to support the research findings and implement it in clinical practice.
基金supported by grants from the National Key Research and Development Program of China(2020YFA0907500)the National Natural Science Foundation of China(22193051,21277062,21806058)+1 种基金the Excellent Discipline Cultivation Project by JHUN(2023XKZ029)the PLA Logistics Research Project of China(2023).
文摘Remarkable antibacterial activity of BPA analogues especially for tetrabromobi-sphenol A against Staphylococcus aureus 25923(Sa25923)and methicillin-resistant Staphylococcus aureus(MRSA)has been reported in our previous studies.However,the toxic effects of the compounds as environmental contaminants on the endocrine system limited their applications in the field of medicine and health.Given the abuse of antibiotics has led to the emergence of multiple super-resistant bacteria,we considered that structural modifications based on the BPA structure will be available for molecular designing of potential antimicrobial agents without drug resistance.In this study,to further improve the antibacterial activity and reduce the biological toxicity,we performed the computational models to evaluate the binding affinities of BPA analogues to the potential target DltA protein in the biosynthesis of cell wall.A series of synthesized achiral analogues ofα,α,α′-tris(4-hydroxyphenyl)-1-ethyl-4-isopropylbenzene(α,α,α′-TEIB)exhibited low minimum inhibitory concentration against Sa25923 and MRSA(2 or 1μg mL−1).Especially,the analogue A4 did not induce the drug-resistant mutants for all tested Gram-positive bacterial strains and exhibited relatively lower cytotoxicity in HepG2 cells.The developed classification model based on the light gradient boosting algorithm showed the superior performances on the internal robustness and generalization ability for the ligand-based virtual screening of bisphenol and polyphenol antimicrobial substances.Collectively,our findings suggest that the molecular structure ofα,α,α′-TEIB is promising as a scaffold,which is expected to achieve a breakthrough in the development of antibiotics which can prevent the invasion of MRSA and other super bacteria.
基金Supported by the National Natural Sciences Foundation of China (No.10171010) Key Project on Sciences and Technology of the Ministry of Education of China (No. Key 01061)the Natural Sciences Foundation for Young Scholar of Northeast Normal Unive
文摘With the help of a continuation theorem based on Gaines and Mawhin's coincidence degree, we study the global existence of positive periodic solutions of a 'food-limited' population model with toxicants and time delays. Some new results are obtained.
基金supported by the National Basic Research Program of China (973 Program 2009CB421605)the National Natural Science Foundation of China (20890111, 20921063 & 20931160427)the Ministry of Science and Technology of China (2008IM041300)
文摘Neuronal toxic pollutants in environment possess hazards to human health. It is essential to determine the causative neuronal toxicants in environmental samples. In the present study, viability of primary cultured cerebellar granule neurons (CGNs), combined with sample extraction, chemical fractionation and identification, was applied for screening acid-resistant neuronal toxic substances in environmental samples. River sediments and agricultural soils along the river near a brominated flame retardant (BFR) manufacturing plant in South China were collected to screen the key neuronal toxicants. The results indicated that the manufacturing plant was a source of neuronal toxicity risks. In the sediment and soil near the plant, one of the causative toxicants was identified as tris-(2,3-dibromopropyl) isocyanurate (TBC) using HPLC-MS/MS. In addition, an unknown chemical possibly causing significant neuronal toxicity was isolated from all the soil samples in the region.
