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Construction of functional neural network tissue combining CBD-NT3-modified linear-ordered collagen scaffold and TrkC-modified iPSC-derived neural stem cells for spinal cord injury repair

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Bioactive Materials 2024年第5期35卷 242-258页

作者： Zhaoping Wu Yi Zhou Xianglin Hou Weidong Liu Wen Yin Lei Wang Yudong Cao Zhipeng Jiang Youwei Guo Quan Chen Wen Xie Ziqiang Wang Ning Shi Yujun Liu Xiang Gao Longlong Luo Jianwu Dai Caiping Ren Xingjun Jiang Department of Neurosurgery Xiangya HospitalCentral South UniversityChangshaHunan Province410008China National Clinical Research Center for Geriatric disorders Xiangya HospitalCentral South UniversityChangshaHunan Province410008China State Key laboratory of Molecular developmental Biology Institute of Genetics and developmental Biology Chinese Academy of SciencesBeijing100080China School of Basic Medical Science Central South UniversityChangshaHunan Province410078China The NHC Key laboratory of Carcinogenesis and the Key laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education Central South UniversityChangshaHunan Province410078China College of Biology Hunan UniversityChangsha410000China State Key laboratory of toxicology and Medical Countermeasures Beijing Institute of Pharmacology and ToxicologyBeijing100080China

Induced pluripotent stem cells(iPSCs)can be personalized and differentiated into neural stem cells(NSCs),thereby effectively providing a source of transplanted cells for spinal cord injury(SCI).To further improve the repair efficiency of SCI,we designed a functional neural network tissue based on TrkC-modified iPSC-derived NSCs and a CBD-NT3-modified linear-ordered collagen scaffold(LOCS).We confirmed that transplantation of this tissue regenerated neurons and synapses,improved the microenvironment of the injured area,enhanced remodeling of the extracellular matrix,and promoted functional recovery of the hind limbs in a rat SCI model with complete *** sequencing and metabolomic analyses also confirmed the repair effect of this tissue from multiple perspectives and revealed its potential mechanism for treating ***,we constructed a functional neural network tissue using human iPSCs-derived NSCs as seed cells based on the interaction of receptors and ligands for the first *** tissue can effectively improve the therapeutic effect of SCI,thus confirming the feasibility of human iPSCs-derived NSCs and LOCS for SCI repair and providing a valuable direction for SCI research.

关键词： Spinal cord injury Induced pluripotent stem cells LOCS Neural network tissue Neurotrophin-3

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Comparison of Mineral Contents in Three Different Tobacco Formulations

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Biomedical and Environmental Sciences 2017年第1期30卷 52-58页

作者： HOUAS Ikram TEYEB Hassen Arancha ROCHINA-MARCO DOUKI Wahiba NAJJAR Mohamed Fadhel GAHA Lotfi CERVERA MariaLuisa DE LA GUARDIA Miguel Research laboratory 'Vulnerability to Psychotic disorders LR 05 ES 10' Department of Psychiatry Faculty of Medicine University of Monastir Monastir 5000 Tunisia Biochemistry and toxicology laboratory Monastir University Hospital Monastir 5000 Tunisia Department of Analytical Chemistry University of Valencia Burjassot 46100 Spain

We identified and quantified a variety of mineral elements in 18 tobacco samples purchased from a Tunisian market. In total, 25 mineral elements have been measured in cigarettes, water pipe tobacco, and smokeless tobacco using inductively coupled plasma-optical emission spectroscopy following microwave-assisted digestion. Statistical analyses were performed using SPSSTM, version 18.0. The lowest concentrations of all studied elements were observed in water pipe tobacco. Significantly higher concentrations of Al, Fe, Mg, Na, Ca, Cr, and Co were found in smokeless tobacco, while cigarettes brands contained the highest concentrations of K, Mn, Ni, Ba, and Sr. There was no significant difference between the mineral contents of local and foreign cigarettes and conventional and light cigarettes. Our findings demonstrated that local smokeless tobacco appears to be the most hazardous tobacco type. The concentration of minerals in light cigarettes was not significantly different from the concentration in conventional cigarettes.

关键词： Comparison of Mineral Contents in Three Different Tobacco Formulations

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developmental impacts and toxicological hallmarks of silver nanoparticles across diverse biological models

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Environmental Science and Ecotechnology 2024年第3期19卷 60-79页

作者： Yán Wāng Yapeng Han De-Xiang Xu Department of toxicology School of Public Health&Key Laboratory of Environmental Toxicology of Anhui Higher Education InstitutesAnhui Medical UniversityHefei230032China

Silver nanoparticles(AgNPs),revered for their antimicrobial prowess,have become ubiquitous in a range of products,from biomedical equipment to food ***,amidst their rising popularity,concerns loom over their possible detrimental effects on fetal development and subsequent adult *** review delves into the developmental toxicity of AgNPs across diverse models,from aquatic species like zebrafish and catfish to mammalian rodents and in vitro embryonic stem *** focus encompasses the fate of AgNPs in different contexts,elucidating associated hazardous results such as embryotoxicity and adverse pregnancy ***,we scrutinize the enduring adverse impacts on offspring,spanning impaired neurobehavior function,reproductive disorders,cardiopulmonary lesions,and *** hallmarks of developmental harm are identified,encompassing redox imbalances,inflammatory cascades,DNA damage,and mitochondrial ***,we explore potential explanations,linking immunoregulatory dysfunction and disrupted epigenetic modifications to AgNPsinduced developmental *** substantial progress,our understanding of the developmental risks posed by AgNPs remains incomplete,underscoring the urgency of further research in this critical area.

关键词： Silver nanoparticles(AgNPs) developmental toxicity Maternal exposure Fetal development Redox imbalance Mitochondrial dysfunction

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Role of the anterior insular cortex microcircuits in observation fear of mice

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中国药理学与毒理学杂志 2023年第7期37卷 551-552页

作者： LI Fengan FU Yuan XIAO Zhiyong SHI Tianyao ZHOU Wenxia State Key laboratory of toxicology and Medical Countermeasures Beijing Institute of Pharmacology and Toxicology Nanjing University of Chinese Medicine

OBJECTIVE Fear can be learned indirectly, but excessive transmission of fear is essential for the development of mental illness. Previous research has indicated that the anterior insular cortex(AIC) may play a crucial role in the process of fear transmission,and abnormal AIC activity is a possible mechanism underlying various affective disorders. Inhibitory neurons are crucial for maintaining local microcircuit *** the support of novel specific neuroregulatory techniques, it is now possible to monitor and regulate different types of neurons in real-time. Therefore, investigating distinct subtypes of inhibitory neurons in the AIC that are involved in fear contagion may provide valuable insights into potential mechanisms underlying mental *** We established a modified observational fear(OF) model. A demonstrator(DM) mouse was placed in an acrylic cup at the center of the apparatus,and two observer(OB) mice were allowed to explore the DM mouse simultaneously from separate areas on either side. During the OF training, electric foot shocks were administered to the DM mouse and freezing, the side and corner time, and social interaction behavior were scored. Next, we characterized the activity patterns of distinct neuronal subtypes in the AIC using GCaMPbased calcium recording. Finally, we employed a Credependent optogenetic approach to selectively modulate excitatory or inhibitory neurons in the AIC, and investigated empathic fear behavior across different Cre transgenic mouse lines(CK2-Cre, PV-Cre, SOM-Cre, VIP-Cre).RESULTS During the training phase, the OB mice exhibited significantly higher levels of fear compared to the control group(which did not observe a traumatic event),as evidenced by increased freezing time, decreased interaction time, and increased corner zone time. Calcium fiber recording results suggested that CK2 neurons are involved in risk prediction, while PV and VIP neurons exert inhibitory control on this behavior. Optogenetic

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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 *** current study investigated its mechanism of toxicity in *** 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 ***,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 *** reproductive toxicity was persistent for 50 days following the withdrawal of BDE-209 *** results suggested that BDE-209 inhibits the initiation of meiosis by decreasing the expression of ***,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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Loss of O-GlcNAcylation on MeCP2 at Threonine 203 Leads to Neurodevelopmental disorders

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Neuroscience Bulletin 2022年第2期38卷 113-134页

作者： Juanxian Cheng Zhe Zhao Liping Chen Ying Li Ruijing Du Yan Wu Qian Zhu Ming Fan Xiaotao Duan Haitao Wu Department of Neurobiology Beijing Institute of Basic Medical SciencesBeijing 100850China Chinese Institute for Brain Research Beijing 102206China Key laboratory of Neuroregeneration Co-innovation Center of NeuroregenerationNantong UniversityNantong 226019China State Key laboratory of toxicology and Medical Countermeasures Beijing Institute of Pharmacology and ToxicologyBeijing 100850China

Mutations of the X-linked methyl-CpG-binding protein 2(MECP2)gene in humans are responsible for most cases of Rett syndrome(RTT),an X-linked progressive neurological *** genome-wide screens in clinical trials have revealed several putative RTT-associ-ated mutations in MECP2,their causal relevance regarding the functional regulation of MeCP2 at the etiologic sites at the protein level requires more *** this study,we demonstrated that MeCP2 was dynamically modified by O-linked-P-N-acetylglucosamine(O-GlcNAc)at threonine 203(T203),an etiologic site in RTT *** of the O-GlcNAcylation of MeCP2 specifically at T203 impaired dendrite development and spine maturation in cultured hippocampal neurons,and disrupted neuronal migration,dendritic spine morphogenesis,and caused dysfunction of synaptic transmission in the developing and juvenile mouse cerebral ***,genetic disruption of O-GlcNAcylation at T203 on MeCP2 decreased the neuronal activity-induced induction of Bdnf *** study highlights the critical role of MeCP2 T203 O-GlcNAcylation in neural development and synaptic transmission potentially via brain-derived neurotrophic factor.

关键词： MeCP2 O-GlcNAcylation-Dendrite development Synaptic transmission Braiderived neurotrophic factor

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Natural compounds modulate the autophagy with potential implication of stroke

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Acta Pharmaceutica Sinica B 2021年第7期11卷 1708-1720页

作者： Anil Ahsan Mengru Liu Yanrong Zheng Wenping Yan Ling Pan Yue Li Shijia Ma Xingxian Zhang Ming Cao Zhanxun Wu Weiwei Hu Zhong Chen Xiangnan Zhang Institute of Pharmacology&toxicology College of Pharmaceutical SciencesKey Laboratory of Medical Neurobiology of the Ministry of Health of ChinaZhejiang UniversityHangzhou 310058China

Stroke is considered a leading cause of mortality and neurological disability,which puts a huge burden on individuals and the *** date,effective therapy for stroke has been limited by its complex pathological *** refers to an intracellular degrading process with the involvement of *** plays a critical role in maintaining the homeostasis and survival of cells by eliminating damaged or non-essential cellular *** evidence support that autophagy protects neuronal cells from ischemic ***,under certain circumstances,autophagy activation induces cell death and aggravates ischemic brain *** naturally derived compounds have been found to modulate autophagy and exert neuroprotection against *** the present work,we have reviewed recent advances in naturally derived compounds that regulate autophagy and discussed their potential application in stroke treatment.

关键词： Autophagy Cerebral ischemia Neuroprotection Mitochondria Lysosomal activation Mitophagy Natural compounds Neurological disorders

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Microplastic exposure disturbs sleep structure,reduces lifespan,and decreases ovary size in Drosophila melanogaster

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Zoological Research 2024年第4期45卷 805-820页

作者： Wei Yan Zi-Jie Li Zi-Yi Lin Shu-Qin Ji William Ka Fai Tse Zhi-Qiang Meng Chang Liu Lei Li Shenzhen-Hong Kong Institute of Brain Science Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518000China CAS Key laboratory of Brain Connectome and Manipulation the Brain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518000China laboratory of developmental disorders and toxicology Center for Promotion of International Education and ResearchFaculty of AgricultureKyushu UniversityFukuokaFukuoka 819-0395Japan Shenzhen Key laboratory of Drug Addiction the Brain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518000China Guangdong Provincial Key laboratory of Brain Connectome and Behavior Brain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518000China

The organ-specific toxicity resulting from microplastic(MP)exposure has been extensively explored,particularly concerning the gut,liver,testis,and ***,under natural conditions,these effects are not restricted to specific organs or *** whether MP exposure presents a systemic threat to an entire organism,impacting factors such as lifespan,sleep,and fecundity,is *** this study,we investigated the effects of dietary exposure to two different doses of MPs(1–5μm)using the terrestrial model organism Drosophila *** indicated that the particles caused gut damage and remained within the digestive *** MP exposure significantly shortened the lifespan of adult *** short-term exposure disrupted sleep patterns,increasing the length of daytime sleep ***,one week of MP exposure reduced ovary size,with a trend towards decreased egg-laying in mated *** MPs did not penetrate the brain or ovaries,transcriptome analysis revealed altered gene expression in these *** the ovary,Gene Ontology(GO)analysis indicated genotoxic effects impacting inflammation,circadian regulation,and metabolic processes,with significant impacts on extracellular structure-related *** the brain,GO analysis identified changes in pathways associated with proteolysis and carbohydrate ***,this study provides compelling evidence of the systemic negative effects of MP exposure,highlighting the urgent need to address and mitigate environmental MP pollution.

关键词： Microplastics Sleep Lifespan Reproduction Risk assessment Drosophila melanogaster

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The metabolome identity:basis for discovery of biomarkers in neurodegeneration

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Neural Regeneration Research 2019年第3期14卷 387-390页

作者： Julie-Myrtille Bourgognon Joern R.Steinert MRC toxicology Unit University of Leicester

Neurodegenerative disorders are often associated with cellular dysfunction caused by underlying protein-misfolding signalling. Numerous neuropathologies are diagnosed at late stage symptomatic changes which occur in response to these molecular malfunctions and treatment is often too late or restricted only to the slowing of further cell death. Important new strategies to identify early biomarkers with predictive value to intervene with disease progression at stages where cell dysfunction has not progressed irreversibly is of paramount importance. Thus, the identification of these markers presents an essential opportunity to identify and target disease pathways. This review highlights some important metabolic alterations detected in neurodegeneration caused by misfolded prion protein and discusses common toxicity pathways identified across different neurodegenerative diseases. Thus, having established some commonalities between various degenerative conditions, detectable metabolic changes may be of extreme value as an early diagnostic biomarker in disease.

关键词： metabolome neurodegeneration neuroinflammation nitric oxide redox stress biomarker misfolded protein prion disease

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Assessment of risks, implications, and opportunities of waterborne neurotoxic pesticides

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Journal of Environmental Sciences 2023年第3期125卷 735-741页

作者： Delaram Dara Andrei P.Drabovich Division of Analytical and Environmental toxicology Department of Laboratory Medicine and PathologyFaculty of Medicine and DentistryUniversity of AlbertaAlberta T6G 2G3Canada

Pesticides are a well-known family of chemicals that have contaminated water systems globally. Four common subfamilies of pesticides include organochlorines, organophosphates, pyrethroids, and carbamate insecticides which have been shown to adversely affect the human nervous system. Studies have shown a link between pesticide exposure and decreased viability, proliferation, migration, and differentiation of murine neural stem cells. Besides human exposure directly through water systems, additional factors such as pesticide bioaccumulation, biomagnification and potential synergism due to co-exposure to other environmental contaminants must be considered. A possible avenue to investigate the molecular mechanisms and biomolecules impacted by the various classes of pesticides includes the field of-omics. Discovery of the precise molecular mechanisms behind pesticidemediated neurodegenerative disorders may facilitate development of targeted ***, discovery of pesticide biodegradation pathways may enable novel approaches for water system bioremediation using genetically engineered microorganisms. In this minireview, we discuss recently established harmful impacts of various categories of pesticides on the nervous system and the application of-omics field for discovery, validation, and mitigation of pesticide neurotoxicity.

关键词： Neurotoxic pesticides Water pollution Neural stem cells Omics approaches Drug discovery

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