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Enhanced hepatic metabolic perturbation of polystyrene nanoplastics by UV irradiation-induced hydroxyl radical generation

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Journal of Environmental Sciences 2024年第8期142卷 259-268页

作者： Shiyu He Jingran Wang Lihong Zhou Zhen Mao Xiaodan Zhang Jin Cai Peili Huang School of Public Health and Beijing Key laboratory of Environmental toxicology Capital Medical UniversityBeijing 100069China

The environmental behavior of and risks associated with nanoplastics(NPs)have attracted considerable attention.However,compared to pristine NPs,environmental factors such as ultraviolet(UV)irradiation that lead to changes in the toxicity of NPs have rarely been studied.We evaluated the changes in morphology and physicochemical properties of polystyrene(PS)NPs before and after UV irradiation,and compared their hepatotoxicity in mice.The results showed that UV irradiation caused particle size reduction and increased the carbonyl index(CI)and negative charge on the particle surface.UV-aged PS NPs(aPS NPs)could induce the generation of hydroxyl radicals(·OH),but also further promoted the generation of·OH in the Fenton reaction system.Hepatic pathological damage was more severe in mice exposed to aPS NPs,accompanied by a large number of vacuoles and hepatocyte balloon-like changes and more marked perturbations in blood glucose and serum lipoprotein,alanine aminotransferase and aspartate aminotransferase levels.In addition,exposure to PS NPs and aPS NPs,especially aPS NPs,triggered oxidative stress and significantly damaged the antioxidant capacity of mice liver.Compared with PS NPs,exposure to aPS NPs increased the number of altered metabolites in hepatic and corresponding metabolic pathways,especially glutathione metabolism.Our research suggests that UV irradiation can disrupt the redox balance in organisms by promoting the production of·OH,enhancing PS NPs-induced liver damage and metabolic disorders.This study will help us understand the health risks of NPs and to avoid underestimation of the risks of NPs in nature.

关键词： Polystyrene nanoplastics Ultraviolet-aged nanoplastics Metabolic pathway Metabolomics Hydroxyl radical

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Dual-targeting AAV9P1-mediated neuronal reprogramming in a mouse model of traumatic brain injury

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Neural Regeneration Research 2024年第3期19卷 629-635页

作者： Jingzhou Liu Xin Xin Jiejie Sun Yueyue Fan Xun Zhou Wei Gong Meiyan Yang Zhiping Li Yuli Wang Yang Yang Chunsheng Gao State Key laboratory of toxicology and Medical Countermeasures Beijing Institute of Pharmacology and ToxicologyBeijingChina Academy of Medical Engineering and Translational Medicine Medical CollegeTianjin UniversityTianjinChina

Traumatic brain injury results in neuronal loss and glial scar formation.Replenishing neurons and eliminating the consequences of glial scar formation are essential for treating traumatic brain injury.Neuronal reprogramming is a promising strategy to convert glial scars to neural tissue.However,previous studies have reported inconsistent results.In this study,an AAV9P1 vector incorporating an astrocyte-targeting P1 peptide and glial fibrillary acidic protein promoter was used to achieve dual-targeting of astrocytes and the glial scar while minimizing off-target effects.The results demonstrate that AAV9P1 provides high selectivity of astrocytes and reactive astrocytes.Moreover,neuronal reprogramming was induced by downregulating the polypyrimidine tract-binding protein 1 gene via systemic administration of AAV9P1 in a mouse model of traumatic brain injury.In summary,this approach provides an improved gene delivery vehicle to study neuronal programming and evidence of its applications for traumatic brain injury.

关键词： AAV9P1 astrocytes astrocyte-to-neuron conversion GFAP promoter glial scar induced neurons neuronal reprogramming P1 peptide PTBP1 traumatic brain injury

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Comparative Studies of Different Organs of Nyctanthes arbortristis in Modulation of Cytokines in Murine Model of Arthritis

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Biomedical and Environmental Sciences 2007年第2期20卷 154-159页

作者： BRIJESH RATHORE BHOLANATH PAUL BHUSAN P CHAUDHURY ASHOK KUMAR SAXENA ANAND PRAKASH SAHU YOGENDRA KUMAR GUPTA Immunobiology laboratory Central Pathology laboratory Preventive toxicology laboratory Industrial toxicology Research Centre M. G. MargLucknow 226001India

Objective To study the modulation effect of pro- and anti-inflammatory cytokines following long term use of water soluble ethanol extracts from different organs of Nyctanthes arbortristis （NAT） in mouse model of arthritis. Methods Arthritis was induced in mice by two injections of Freund＇s complete adjuvant on days 0 and 12 in the sub-planter surface of the right hind paw. Results Injection of adjuvant resulted in a maximum primary edema of the footpad with erythema, and edema and distortion of joints of the right hind paw after 24-48 hours. Second injection of FCA led to the formation of secondary swellings persisting more than four weeks that spread onto the other hind limb but to a lesser extent. Histological analysis of the ankle on day 47 showed marked evidence of cartilage destruction in association with pannus formation and moderate bone resorption. Proinfiammatory cytokine levels in the inflamed joint homogenate were elevated on days 2, 14, and 47. Oral administration of leaf and fruit extracts in arthritic mice reduced joint homogenate levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 on days 2, 14, and 47 in comparison to untreated arthritic mice. Intedeukin-10 level was elevated in the inflamed joint on days 2, 14, and 47 in comparisons to untreated arthritic mice. Confusion Evidence of lesser inflammation of the footpad and joint and associated histological observation support the therapeutic benefit of leaf and fruit extracts from Nyctanthes arbortristis. This study helps in understanding the mechanism of anti-inflammatory action of Nyctanthes arbortristis in the light of pro- and anti-inflammatory cytokine balance.

关键词： Nyctanthes arbortristis Arthritis TNF-α IL- 1β IL-6 IL-10

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A mix & act liposomes of phospholipase A2-phosphatidylserine for acute brain detoxification by blood‒brain barrier selective-opening

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1827-1844页

作者： Zinan Zhang Wenbin Cao Huanchun Xing Shuai Guo Lijuan Huang Lin Wang Xin Sui Kui Lu Yuan Luo Yongan Wang Jun Yang State Key laboratory of toxicology and Medical Countermeasures Beijing Institutes of Pharmacology and ToxicologyBeijing 100850China Tianjin University of Science and Technology Tianjin 300222China Hebei University of Science and Technology Shijiazhuang 050018China

In the treatment of central nervous system disease,the blood-brain barrier(BBB)is a major obstruction to drug delivery that must be overcome.In this study,we propose a brain-targeted delivery strat-egy based on selective opening of the BBB.This strategy allows some simple bare nanoparticles to enter the brain when mixed with special opening material;however,the BBB still maintains the ability to completely block molecules from passing through.Based on the screening of BBB opening and matrix delivery mate-rials,we determined that phospholipase A2-catalyzed 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoserine li-posomes can efficiently carry drugs into the brain immediately.At an effective dose,this delivery system is safe,especially with its effect on the BBB being reversible.This mix&act delivery system has a simple structure and rapid preparation,making it a strong potential candidate for drug delivery across the BBB.

关键词： Liposomes Phospholipase A2 Phosphoserine Blood-brainbarrier Selectively open Mix&act

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Silica Induced Early Fibrogenic Reaction in Lung of Mice Ameliorated by Nyctanthes arbortristis Extract

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Biomedical and Environmental Sciences 2002年第3期15卷 215-222页

作者： BHOLA NATH PAUL ANAND PRAKASH SIRISH KUMAR AJAY KYADAV UMANI ASHOK KSAXENA ANAND PRAKASH SAHU KEWAL LAL KALYAN KDUTTA Immunobiology laboratory Industrial Toxicology Research CentreM.G.MargLucknow 226001U.P.India Inhalation toxicology laboratory Industrial Toxicology Research CentreM.G.MargLucknow 226001U.P.India Preventive toxicology laboratory Industrial Toxicology Research CentreM.G.MargLucknow 226001U.P.India

Objective To investigate the pharmacological effect of Nyctanthes arbortristis (NAT) leaf extract in the prevention of lung injury induced by silica particles. Method Lung injury was induced in Swiss mice through inhalation exposure to silica particles (<5m) using a Flow Past Nose Only Inhalation Chamber at the rate of -10 mg/m3 respirable mass for 5 h. Lung bronchoalveolar lavage (BAL) fluid collected between 48 and 72 h was subjected to protein profiling by electrophoresis and cytokine evaluation by solid phase sandwich ELISA. Lung histopathology was performed to evaluate lung injury. Results Inhalation of silica increased the level of tumor necrosis factor-a (TNF-a), and of the 66 and 63 kDa peptides in the BAL fluid in comparison to sham-treated control. Pre-treatment of silica exposed mice with NAT leaf extract significantly prevented the accumulation of TNF-a in the BAL fluid, but the 66 and 63 kDa peptides remained unchanged. The extract was also effective in the prevention of silica-induced early fibrogenic reactions like congestion, edema and infiltration of nucleated cells in the interstitial alveolar spaces, and thickening of alveolar septa in mouse lung. Conclusion NAT leaf extract helps in bypassing silica induced initial lung injury in mice.

关键词： Nyctanthes arbortristis Lung-injury Silica Mice prevention

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Decabromodiphenyl ether induces the chromosome association disorders of spermatocytes and deformation failures of spermatids in mice

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Journal of Environmental Sciences 2024年第4期138卷 531-542页

作者： Jinglong Xue Xiangyang Li Yafei Chi Leqiang Gao Yue Zhang Yan Wang Moxuan Zhao Jialiu Wei Zhixiong Shi Xianqing Zhou Department of toxicology and Hygienic Chemistry School of Public HealthCapital Medical UniversityBeijing 100069China Beijing Key laboratory of Environmental toxicology Capital Medical UniversityBeijing 100069China laboratory Animal Center Capital Medical UniversityBeijing 100069China Key laboratory of Cardiovascular Epidemiology&Department of Epidemiology Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China

The environmental presence of decabromodiphenyl ether(BDE-209),which is toxic to the male reproductive system,is widespread.The current study investigated its mechanism of toxicity in mice.The results showed,that BDE-209 induced DNA damage,decreased the expression of the promoter of meiosis spermatogenesis-and oogenesis-specific basic helix-loop-helix 1(Sohlh1),meiosis related-factors Lethal(3)malignant brain tumor like 2(L3MBTL2),PIWI-like protein 2(MILI),Cyclin-dependent kinase 2(CDK2),Cyclin A,synaptonemal complex protein 1(SYCP1)and synaptonemal complex protein 3(SYCP3),and caused spermatogenic cell apoptosis,resulting in a decrease in sperm quantity and quality.Furthermore,BDE-209 downregulated the levels of anaphase-promoting complex/cyclosome(APC/C),increased the expression of PIWI-like protein 1(MIWI)in the cytoplasm of elongating spermatids,and decreased the nuclear levels of RING finger protein 8(RNF8),ubiquitinated(ub)-H2A/ub-H2B,and Protamine 1(PRM1)/Protamine 2(PRM2),while increasing H2A/H2B nuclear levels in spermatids.The reproductive toxicity was persistent for 50 days following the withdrawal of BDE-209 exposure.The results suggested that BDE-209 inhibits the initiation of meiosis by decreasing the expression of Sohlh1.Furthermore,the reduced expression of L3MBTL2 inhibited the formation of chromosomal synaptonemal complexes by depressing the expression of meiosis regulators affecting the meiotic progression and also inhibited histone ubiquitination preventing the replacement of histones by protamines,by preventing RNF8 from entering nuclei,which affected the evolution of spermatids into mature sperm.

关键词： BDE-209 Meiosis L3MBTL2 Sperm RNF8 Histone ubiquitination

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Acetylcholinesterase Characteristics of Termite Queen Exposed to Anticholinesterase Compounds

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Biomedical and Environmental Sciences 1992年第2期5卷 178-183页

作者： SHELLEY BHATTACHARYA PROBODH GHOSH SHAMPA GHOSH NINA GHOSH B.BHATTACHARYA P.HALDER Environmental toxicology laboratory Department of Zoology Visva-Bharati University Santiniketan-731235Environmental Toxicology Laboratory Department of Zoology Visva-Bharati University Santiniketan-731235Environmental Toxicology Laboratory Department of Zoology Visva-Bharati University Santiniketan-731235Environmental Toxicology Laboratory Department of Zoology Visva-Bharati University Santiniketan-731235Environmental Toxicology Laboratory Department of Zoology Visva-Bharati University Santiniketan-731235Environmental Toxicology Laboratory Department of Zoology Visva-Bharati University Santiniketan-731235 IndiaIndiaIndiaIndiaIndia Entomology LaboratoryIndia Entomology Laboratory

A regional profile of AChE activity was noted in the Indian termite queen Odontotermes redemanni with the head recording the higher and body the lower range of activity. The enzyme characteristics such as substrate and temperature optima were more or less similar while pH requirement for optimum AChE activity varied from 7.0 to 7.6 In vitro inhibition of head and body AChE was studied using pure and commercial anticholinesterase compounds. Interestingly, the commercial formulations like Metacid-50 and Carbaryl are potent enough at 1×10^(-8) M to produce 50% in vitro inhibition of AChE of head and body regions within 15 min of preincubation. A 20 min of preincubation (t0.5) was necessary to record 50% in vitro inhibition of AChE with known and pure anticholinesterase compounds such as DFP (3.5×10^(-10)M) and physostigmine (3.6 ×10^(-10)M). It is surmised that (a) the response of the head and body AChE to the commercial formulations of the insecticides may be used as a reliable and sensitive bioindicator of pesticidal contamination of the terrestrial environment and (b) termite control may be successfully done with the application of organophosphate or carbamate compounds.

关键词： AChE Acetylcholinesterase Characteristics of Termite Queen Exposed to Anticholinesterase Compounds

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Incense smoke(IS)inhalation exposure system:Physicochemical characterization,IS particle deposition and clearance in human airway using MPPD model

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Particuology 2024年第4期87卷 271-285页

作者： Vyas Kumar Hafsa Hashmi Anshita Nasreen Ghazi Ansari Jyotsna Singh Inhalation toxicology Facility Regulatory Toxicology GroupCSR-Indian Institute of Toxicology ResearchLucknow22001UPIndi Academy of Scientific and Innovative Research(AcsSIR) Ghaziabad201002UPIndia Analytical Chemistry Regulatory Toxicology GroupCSIR-Indian Institute of Toxicology ResearchLucknow226001UPIndia

Incense smoke(IS)is source of indoor air pollution and key risk for diverse human diseases.Less in-formation is available regarding controlled IS rodent inhalation exposure system and IS particulate matter(PM)deposition in human airways.Study aimed to demonstrate stable ISPM physicochemical parameters of 10 incense products inside the customized whole body inhalation exposure chamber(without animal)connected to smoke generation unit via aerosol mixing device.IS analyzed for size segregated PM emission,ISPM in vitro aerodynamics(MMAD and GSD determination),fine and ultrafine particle's SEM,SEM-EDX and PAH analysis.Using real life exposure scenario by utilizing MMAD,GSD and PM concentration after Tier 1 exposure assessment as key input parameters,ISPM dosimetry in infant(3 months)and adult(21 years male and female)human airways was calculated using multiple-path particle dosimetry(MPPD 3.04)modeling.Mass median aerodynamic diameter(MMAD)and geo-metric standard deviation(GSD)ranged between 0.55 and 2.10μm and 1.22 to 1.77(polydisperse)respectively.PM1.0 and PM0.1 showed multiple morphology and presence of heavy and trace elements.PAH like acenaphthylene,anthracene,fluorene,naphthalene and phenanthrene were detected(0.84-143.17μg/g).MPPD results showed higher ISPM deposition in pulmonary region and lowest in trachea bronchial region.ISPM deposition in tissue was higher in lower,peripheral lung as compared to upper and central lung tissue.Whole body inhalation exposure system showed stable IS atmosphere(physi-cochemical parameters)indicating the device suitability in future inhalation studies.MPPD ISPM deposition fraction and clearance data showed deep lung penetrating and retention behavior with higher risk in infant followed by female and then male.These modeled particle deposition and clearance data may be useful in risk assessment analysis of IS.

关键词： Inhalation Incense smoke Multiple-path particle dosimetry(MPPD) Particle deposition Particulate matter(PM) Mass median aerodynamic diameter (MMAD) Human airway

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Identification of overlay differentially expressed genes in both rats and goats with blast lung injury through comparative transcriptomics

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Chinese Journal of Traumatology 2024年第1期27卷 34-41页

作者： Hong Wang Jun-Hong Gao Xiao-Lin Fan Qing Lu Liang Li Ning Ma Qi Wang Yu-Hao Zhang Xi'an Key laboratory of toxicology and Biological Effects Research Center for Toxicological and Biological EffectsInstitute for Hygiene of Ordnance IndustryXi'an710065China

Purpose:To identify the potential target genes of blast lung injury(BLI)for the diagnosis and treatment.Methods:This is an experimental study.The BLI models in rats and goats were established by conducting a fuel-air explosive power test in an unobstructed environment,which was subsequently validated through hematoxylin-eosin staining.Transcriptome sequencing was performed on lung tissues from both goats and rats.Differentially expressed genes were identified using the criteria ofq≤0.05 and|log2 fold change|≥1.Following that,enrichment analyses were conducted for gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathways.The potential target genes were further confirmed through quantitative real-time polymerase chain reaction and enzyme linked immunosorbent assay.Results:Observations through microscopy unveiled the presence of reddish edema fluid,erythrocytes,and instances of focal or patchy bleeding within the alveolar cavity.Transcriptome sequencing analysis identified a total of 83 differentially expressed genes in both rats and goats.Notably,49 genes exhibited a consistent expression pattern,with 38 genes displaying up-regulation and 11 genes demonstrating down-regulation.Enrichment analysis highlighted the potential involvement of the interleukin-17 signaling pathway and vascular smooth muscle contraction pathway in the underlying mechanism of BLI.Furthermore,the experimental findings in both goats and rats demonstrated a strong association between BLI and several key genes,including anterior gradient 2,ankyrin repeat domain 65,bactericidal/permeability-increasing fold containing family A member 1,bactericidal/permeability-increasing fold containing family B member 1,and keratin 4,which exhibited up-regulation.Conclusions:Anterior gradient 2,ankyrin repeat domain 65,bactericidal/permeability-increasing fold containing family A member 1,bactericidal/permeability-increasing fold containing family B member 1,and keratin 4 hold potential as target genes for the prognosis,diagnosis,and treatment of BL

关键词： Blast lung injury Transcriptomic Target genes Differentially expressed genes

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Hepatotoxic Alterations Induced by Subchronic Exposure of Rats to Formulated Fenvalerate (20% EC) by Nose Only Inhalation

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Biomedical and Environmental Sciences 2004年第3期17卷 309-314页

作者： U.MANI A.K.PRASAD V.SURESHKUMAR P.KUMAR KEWAL LAL B.K.MAJI K.K.DUTTA Inhalation toxicology laboratory and Animal House Industrial Toxicology Research Centre M. G. Marg P. Box. No.80 Lucknow-226 001 IndiaInhalation Toxicology Laboratory and Animal House Industrial Toxicology Research Centre M. G. Marg P. Box. No.80 Lucknow-226 001 IndiaInhalation Toxicology Laboratory and Animal House Industrial Toxicology Research Centre M. G. Marg P. Box. No.80 Lucknow-226 001 India Inhalation Toxicology Laboratory and Animal House Industrial Toxicology Research Centre M. G. Marg P. Box. No.80 Lucknow-226 001 IndiaInhalation Toxicology Laboratory and Animal House Industrial Toxicology Research Centre M. G. Marg P. Box. No.80 Lucknow-226 001 India

Objective Fenvalerate (20% EC) is a synthetic pyrethroid, which is commonly used in India by farmers for the protection of many food and vegetable crops against a wide variety of insects. However, its inhalation toxicity data is very limited in the literature due to the fact that the exposure levels associated with these effects were usually not reported. Hence, inhalation exposure was carried out to investigate the hepatotoxic effects. Method Adult male rats were exposed to fen for 4 h/day, 5 days a week for 90 days by using Flow Past Nose Only Inhalation Chamber. Sham treated control rats were exposed to compressed air in the inhalation chamber for the same period. Results The results indicated hepatomegaly, increased activities of serum clinical enzymes (indicative of liver damage/dysfunction) along with pronounced histopathological damage of liver. Conclusion The hepatotoxic potential of formulated Fen (20% EC) in rats exposed by nose only inhalation is being reported for the first time and warrant adequate safety measures for human beings exposed to this insecticide, particularly by inhalation route.

关键词： Fenvalerate Rat Inhalation Hepatotoxicity

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