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Acta Pharmaceutica Sinica B 2021年第12期11卷 3756-3767页

作者： Regina D.Schnegelberger Anna L.Lang Gavin E.Arteel Juliane I.Beier department of Pharmacology&Chemical Biology University of PittsburghPittsburghPA 15213USA department of Neurology University of Miami Miller School of MedicineMiamiFL 33136USA department of Medicine Division of GastroenterologyHepatology&NutritionUniversity of PittsburghPittsburghPA 15213USA Pittsburgh Liver Research Center University of PittsburghPittsburghPA 15213USA Department of Environmental&Occupational Health University of PittsburghPittsburghPA 15213USA

occupational and environmental exposures to industrial chemicals are well known to cause hepatotoxicity and liver injury.However,despite extensive evidence showing that exposure can lead to disease,current research approaches and regulatory policies fail to address the possibility that subtle changes caused by low level exposure to chemicals may also enhance preexisting conditions.In recent years,the conceptual understanding of the contribution of environmental chemicals to liver disease has progressed significantly.Mitochondria are often target of toxicity of environmental toxicants resulting in multisystem disorders involving different cells,tissues,and organs.Here,we review persistent maladaptive changes to mitochondria in response to environmental toxicant exposure as a mechanism of hepatotoxicity.With better understanding of the mechanism(s) and risk factors that mediate the initiation and progression of toxicant-induced liver disease,rational targeted therapy can be developed to better predict risk,as well as to treat or prevent this disease.

关键词： Organochlorines Metals Persistent organic pollutants TASH Liver disease Hepatotoxicity Mitochondrial maladaptation Mitohormesis

Di(2-ethylhexyl) phthalate Disorders Lipid Metabolism via TYK2/STAT1 and Autophagy in Rats

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Biomedical and environmental Sciences 2019年第6期32卷 406-418页

作者： ZHANG Yue Zhu ZHANG Zhao Ming ZHOU Li Ting ZHU Jian ZHANG Xiao Han QI Wen DING Shuang XU Qi HAN Xu ZHAO Ya Ming SONG Xin Yue ZHAO Tian Yang YE Lin department of occupational and environmental health School of Public Health Jilin University

Objective Previous studies have indicated that the plasticizer di(2-ethylhexyl) phthalate(DEHP) affects lipid accumulation;however, its underlying mechanism remains unclear. We aim to clarify the effect of DEHP on lipid metabolism and the role of TYK2/STAT1 and autophagy. Methods In total, 160 Wistar rats were exposed to DEHP [0, 5, 50, 500 mg/(kg·d)] for 8 weeks. Lipid levels, as well as mRNA and protein levels of TYK2, STAT1, PPARγ, AOX, FAS, LPL, and LC3 were detected. Results The results indicate that DEHP exposure may lead to increased weight gain and altered serum lipids. We observed that DEHP exposure affected liver parenchyma and increased the volume or number of fat cells. In adipose tissue, decreased TYK2 and STAT1 promoted the expression of PPARγ and FAS. The mRNA and protein expression of LC3 in 50 and 500 mg/(kg·d) groups was increased significantly. In the liver, TYK2 and STAT1 increased compensatorily;however, the expression of FAS and AOX increased, while LPL expression decreased. Joint exposure to both a high-fat diet and DEHP led to complete disorder of lipid metabolism. Conclusion It is suggested that DEHP induces lipid metabolism disorder by regulating TYK2/STAT1. Autophagy may play a potential role in this process as well. High-fat diet, in combination with DEHP exposure, may jointly have an effect on lipid metabolism disorder.

关键词： DEHP TYK2 STAT1 High-fat diet Autophagy Lipid metabolism

Melatonin and probiotics ameliorate nanoplastics-induced hematopoietic injury by modulating the gut microbiotametabolism

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Nano Research 2023年第2期16卷 2885-2894页

作者： Lei Zhang Jiaru Jing Lin Han Ziyan Liu Jingyu Wang Wei Zhang Ai Gao department of occupational health and environmental health School of Public HealthCapital Medical UniversityBeijing 100069China Beijing Key Laboratory of environmental Toxicology Capital Medical UniversityBeijing 100069China

Plastic pollution has become a non-negligible global pollution problem.Nanoplastics(NP)can reach the bone marrow with blood circulation and develop hematotoxicity,but potential mechanisms and prevention strategies are lacking.Here,we report the biological distribution of NP particles in the bone marrow of mice and hematopoietic toxicity after exposure to 60μg of 80 nm NP for 42 days.NP exposure inhibited the capability of bone marrow hematopoietic stem cells to renew and differentiate.Notably,probiotics and melatonin supplementation significantly ameliorated NP-induced hematopoietic damage,and the former was superior to the latter.And interestingly,melatonin and probiotic interventions may involve different microbes and metabolites.After melatonin intervention,creatine showed a stronger correlation with NP-induced gut microbiota disorders.In contrast,probiotic intervention reversed the levels of more gut microbes and plasma metabolites.Of these,threonine,malonylcarnitine,and 3-hydroxybutyric acid might be potential performers in the regulation of hematopoietic toxicity by gut microbes,as they had a more significant relationship with the identified microbes.In conclusion,supplementation with melatonin or probiotics may be two candidates to prevent hematopoietic toxicity attributable to NP exposure.Also,the multi-omics results may lay the foundation for future investigations into in-depth mechanisms.

关键词： gut microbiota-metabolism melatonin probiotics nanoplastics exposure hematopoietic injury

Significance of school greenspaces in preventing childhood myopia

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The Innovation 2024年第1期5卷 11-12页

作者： Bo-Yi Yang department of occupational and environmental health School of Public HealthSun Yat-Sen UniversityGuangzhou 510080China

THE BURDEN OF MYOPIA IN CHINESE CHILDREN Childhood myopia has emerged as a critical and underestimated public health issue globally,particularly in China and east Asian countries.The prevalence of myopia in Chinese children and adolescents is alarmingly high,with rates of 72%and 81%among middle school(ages 11–13 years)and high school(ages 14–17 years)students,respectively,resulting in an overall prevalence of approximately 54%.

关键词： globally myopia school

Characterizing drug-metabolizing enzymes and transporters that are bona fide CAR-target genes in mouse intestine

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Acta Pharmaceutica Sinica B 2016年第5期6卷 475-491页

作者： Shinhee Park Sunny Lihua Cheng Julia Yue Cui department of environmental and occupational health Sciences University of Washington

Intestine is responsible for the biotransformation of many orally-exposed chemicals.The constitutive androstane receptor(CAR/Nr1i3) is known to up-regulate many genes encoding drugmetabolizing enzymes and transporters(drug-processing genes/DPGs) in liver,but less is known regarding its effect in intestine.Sixty-day-old wild-type and Car / mice were administered the CARligand TCPOBOP or vehicle once daily for 4 days.In wild-type mice,Car m RNA was down-regulated by TCPOBOP in liver and duodenum.Car / mice had altered basal intestinal expression of many DPGs in a section-specific manner.Consistent with the liver data(Aleksunes and Klaassen,2012),TCPOBOP upregulated many DPGs(Cyp2b10,Cyp3a11,Aldh1a1,Aldh1a7,Gsta1,Gsta4,Gstm1-m4,Gstt1,Ugt1a1,Ugt2b34,Ugt2b36,and Mrp2–4) in specific sections of small intestine in a CAR-dependent manner.However,the m RNAs of Nqo1 and Papss2 were previously known to be up-regulated by TCPOBOP in liver but were not altered in intestine.Interestingly,many known CAR-target genes were highest expressed in colon where CAR is minimally expressed,suggesting that additional regulators are involved in regulating their expression.In conclusion,CAR regulates the basal expression of many DPGs in intestine,and although many hepatic CAR-targeted DPGs were bona fide CAR-targets in intestine,pharmacological activation of CAR in liver and intestine are not identical.

关键词： Drug-processing genes Intestine Mice CAR Drug-metabolizing enzymes Transporters

Novel technique of abdominal wall nerve block for laparoscopic colostomy: Rectus sheath block with transperitoneal approach

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World Journal of Gastrointestinal Surgery 2017年第8期9卷 182-185页

作者： Jun Nagata Jun Watanabe Yusuke Sawatsubashi Masaki Akiyama Koichi Arase Noritaka Minagawa Takayuki Torigoe Kotaro Hamada Yoshifumi Nakayama Keiji Hirata department of Gastroenterological and General Surgery Wakamatsu Hospital University of Occupational and Environmental Health department of Surgery Yokosuka Kyosai Hospital department of Surgery University of Occupational and Environmental Health department of Anesthesiology Wakamatsu Hospital University of Occupational and Environmental Health

A 62-year-old man who had acute rectal obstruction due to a large rectal cancer is presented. He underwent emergency laparoscopic colostomy. We used the laparoscopic puncture needle to inject analgesia with the novel transperitoneal approach. In this procedure, both ultrasound and laparoscopic images assisted with the accurate injection of analgesic to the correct layer. The combination of laparoscopic visualization and ultrasound imaging ensured infiltration of analgesic into the correct layer without causing damage to the bowel. Twentyfour hours postoperatively, the patient's pain intensity as assessed by the numeric rating scale was 0-1 during coughing, and a continuous intravenous analgesic was not needed. Colostomy is often necessary in colon obstruction. Epidural anesthesia for postoperative pain cannot be used in patients with a coagulation disorder. We report the use of a novel laparoscopic rectus sheath block for colostomy. There has been no literature described about the nerve block with transperitoneal approach. The laparoscopic rectus sheath block was performed safely and had enough analgesic efficacy for postoperative pain. This technique could be considered as an optional anesthetic regimen in acute situations.

关键词： Colorectal 癌症权利鞘块结肠阻塞手术后的疼痛

Evaluation of disinfection byproducts for their ability to affect mitochondrial function

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Journal of environmental Sciences 2022年第7期34卷 295-304页

作者： George William Kajjumba Rachael E.Bokota Matias Attene-Ramos Erica J.Marti department of Civil and environmental Engineering University of NevadaLas VegasNVUSA department of environmental and occupational health Milken Institute School of Public HealthGeorge Washington UniversityWashington DCUSA

In the race to deliver clean water to communities through potable water reuse, disinfection and water quality assessment are and will continue to be fundamental factors. There are over 700 disinfection byproducts(DBPs) in water;evaluating each compound is practically impossible and very time consuming. A bioanalytical approach could be an answer to this challenge. In this work, the response of four major classes of DBPs toward mitochondrial membrane potential( Δψm) and cytoplasmic adenosine triphosphate(C-ATP) was investigated with human carcinoma(Hep G2) cells. Within 90 min of cell exposure, only the haloacetic acid(HAA) mixture caused a cytotoxic response as measured by C-ATP. All four groups(haloacetonitriles(HANs), trihalomethanes(THMs), nitrosamines(NOAs), and HAAs) responded well to Δψm, R 2 > 0.70. Based on the half-maximum concentration that evoked a 50% response in Δψm, the response gradient was HANs >> HAAs ~ THM > NOAs. The inhibition of the Δψm by HANs is driven by dibromoacetonitrile(DBAN), while dichloroacetonitrile(DCAN) did not cause a significant change in the Δψm at less than 2000 μM. A mixture of HANs exhibited an antagonistic behavior on the Δψm compared to individual compounds. If water samples are concentrated to increase HAN concentrations, especially DBAN, then Δψm could be used as a biomonitoring tool for DBP toxicity.

关键词： Disinfection byproducts Toxicity Mitochondrial membrane potential Dose-response curve In vitro bioassay Emerging contaminants

TBBPA rather than its main derivatives enhanced growth of endometrial cancer via p53 ubiquitination

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Journal of environmental Sciences 2024年第3期137卷 82-95页

作者： Hongyan Yu Jingxu Zhang Jing Liu Ruonan Pan Yu Wang Xiaoting Jin Rifat Zubair Ahmed Yuxin Zheng department of occupational health and environmental health School of Public HealthQingdao UniversityQingdao 266071China State Key Laboratory of environmental Chemistry and Ecotoxicology Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China department of Genetics University of KarachiKarachi 75270Pakistan

Tetrabromobisphenol A(TBBPA)and its derivatives widely exist in various environments and biota.Although the available data indicate that TBBPA exposure is highly associated with the increased incidence of endometrial cancer(EC),the effects of TBBPA and its main derivatives on EC proliferation and the involved crucial mechanism remain unclear.The present study aimed to investigate the effects of TBBPA and its derivatives under environmental concentrations on the proliferation of EC,and the crucial mechanism on the progression of EC caused by bromine fame retardants exposure.In this research,TBBPA and two of the most common TBBPA derivatives including TBBPA bis(2-hydroxyethyl ether)(TBBPABHEE)and TBBPA bis(dibromopropyl ether)(TBBPA-BDBPE)were screened for their capacities in induced EC proliferation and explored the related mechanism by in vitro cell culture model and in vivo mice model.Under environmental concentrations,TBBPA promoted the proliferation of EC,the main derivatives of TBBPA(TBBPA-BHEE and TBBPA-BDBPE)did not present the similar facilitation effects.The ubiquitination degradation of p53 was crucial in TBBPA induced EC proliferation,which resulted in the increase of downstream cell cycle and decrease of apoptosis.The further molecular docking result suggested the high affinity between TBBPA and ubiquitinated proteasome.This finding revealed the effects of TBBPA and its derivatives on EC proliferation,thus providing novel insights into the underlying mechanisms of TBBPA-caused EC.

关键词： Tetrabromobisphenol A(TBBPA) Endometrial cancer(EC) Derivatives Ubiquitin proteases p53

Protein Expression in Silica Dust-induced Transdifferentiated Rats Lung Fibroblasts

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Biomedical and environmental Sciences 2013年第9期26卷 750-758页

作者： HAO Chang Fu LI Xiao Fang YAO Wu department of occupational health and environmental health College of Public HealthZhengzhou University

Objective To analyze the expression of different proteins in free silica-induced transdifferentiated rat lung fibrob^asts. Methods Rat lung fibroblasts and alveolar macrophages were cultured. A transdifferentiation model of rat lung fibroblasts was established. Free silica was used as a stimulator for rat lung fibroblasts. Changes in a-SMA were detected by immunohistochemistry and Western blot, respectively. Protein of lung fibroblasts was extracted and analyzed by two-dimensional electrophoresis （2-DE）. Results Six protein spots were identified by mass spectrometry, including glyceraldehyde 3-phosphate-dehydrogenase, peroxiredoxin 5, heterogeneous nuclear ribonucleoprotein A2, transgelin 2, keratin K6 and vimentin. Conclusion Some proteins are changed in free silica-induced transdifferentiaed rat lung fibroblasts

关键词： Transdifferentiation, Myofibrob^ast Two-dimensional electrophoresis Crystalline silica

Research Trends of Macrophage Polarization:A Bibliometric Analysis

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Chinese Medical Journal 2018年第24期131卷 2968-2975页

作者： Han Gao Feng-Yan Huang Zhi-Ping Wang department of occupational and environmental health School of Public HealthShandong UniversityJinanShandong 250012China

Background:Macrophage polarization is involved in the development of many diseases such as obesity,diabetes,and cancer.This study aimed to understand the trends and hotspots ofmacrophage polarization research. Methods:We searched through the Web of Science Core Collection database to obtain original articles in this research domain.CiteSpace, HistCite,and VOSviewer software were used to facilitate the analysis and visualization of scientific productivity and emerging trends. Results:The survey included 3064 articles,and the annual number of publications exhibited an exponential increase.These articles have received a total of 74,801 citations,and the number of annual citations grew from 68 to 18,074 in a decade.Research on macrophage polarization was performed in 76 countries,and the USA ranked first in terms of research output by contributing 1129 (36.8%)articles. The USA also had the highest H-index,total citations,and highly cited article number.PLOS One,Journal of Immunology,and Scientific Reports were the three journals that published the most articles.Interdisciplinary research areas involving macrophage polarization,such as biomaterials,cancer,and diabetes,were identified by journal citation analysis.The top 20 most productive institutions were located mainly in the USA,France,and China,and top authors originated mainly from the USA and Italy.Tumor biology,obesity,and infection were research hotspots and may be promising in the next few years. Conclusions:This study provides a comprehensive analysis that delineates the scientific productivity,collaboration,and research hotspots of macrophage polarization research.

关键词： Bibliometric Analysis Macrophage Macrophage Polarization