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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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Platelet indices as predictors of poor glucoregulation in type 2 diabetes mellitus adults at Bishoftu General Hospital,Ethiopia

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World Journal of Diabetes 2024年第9期15卷 1889-1902页

作者： Dereje Abebe Regassa Gebeyaw Arega Berihun Bisrat Fikadu Habtu Woyesa Beyene Haile Rahel Shumi Nagaash Girum Tesfaye Kiya department of medical laboratory Sciences Wolkite UniversityWolkite 11330Ethiopia School of medical laboratory Sciences Jimma UniversityJimma 47Ethiopia department of medical laboratory Sciences Dire Dawa UniversityDire Dawa 3000Ethiopia

BACKGROUND Diabetes is a chronic metabolic syndrome that has become a global public health problem with significant morbidity and *** is a pro-inflammatory and pro-thrombotic condition characterized by increased platelet activation and alterations in platelet ***,the use of platelet indices as predictors of poor glucoregulation has not been fully evaluated in this context,and evidence for their role as predictors of poor glycemic status in diabetic patients is *** To evaluate platelet indices and determine their prognostic significance in relation to inadequate glucoregulation among individuals diagnosed with type 2 diabetes at Bishoftu General Hospital in Ethiopia,from June 15 to August 12,*** A comparative cross-sectional study was conducted in 261 participants including 174 individuals with type 2 diabetes mellitus(T2DM)and 87 non-diabetic *** systematic random sampling technique was used to select *** were collected using structured questionnaires,physical measurements,checklists,and laboratory *** parameters and fasting blood glucose levels were determined from blood samples using Sysmex-XN550 and CobasC311 analyzers,*** hematology analyzer output was checked and participants were also screened for malaria parasites using a prepared blood *** data were entered into Epi-data version 3.1 and exported to SPSS version 25 for ***χ2 test,Mann-Whitney U test,Kruskal-Wallis test,post hoc test,Spearman correlation,and receiver operating characteristic curve were used for analysis.A P value<0.05 was considered statistically *** The results of our study indicate that diabetic patients have significantly higher levels of platelet distribution width(PDW),mean platelet volume(MPV),platelet large cell ratio(PLCR),and plateletcrit(PCT)compared to healthy individuals(P<0.001).Furthermore,these indices were found to be significantly elevated in individuals wi

关键词： Platelet indices Type 2 diabetes mellitus Controls Adult Ethiopia

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Brain circuits for retching-like behavior

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National Science Review 2024年第1期11卷 145-160页

作者： Lifang Huo Zhimin Ye Meiling Liu Ziqing He Meizhu Huang Dapeng Li Qian Wu Qian Wang Xiaoqun Wang Peng Cao Ji Dong Congping Shang School of Basic medical Sciences Guangzhou National Laboratory The Fifth Afflliated Hospital Guangzhou Medical University Bioland laboratory (Guangzhou Regenerative Medicine and Health Guangdong laboratory) department of Neurobiology School of Basic Medical Sciences Beijing Key Laboratory of Neural Regeneration and Repair Advanced Innovation Center for Human Brain Protection Capital Medical University State Key laboratory of Cognitive Neuroscience and Learning IDG/McGovern Institute for Brain Research Beijing Normal University Changping Life Science laboratory National Institute of Biological Sciences

Nausea and vomiting are important defensive responses to cope with pathogens and toxins that invade the body. The nucleus of the solitary tract(NTS) is important for initiating these responses. However, the molecular heterogeneities and cellular diversities of the NTS occlude a better understanding of these defensive responses. Here, we constructed the single-nucleus transcriptomic atlas of NTS cells and found multiple populations of NTS neurons that may be involved in these defensive responses. Among these, we identified Calbindin1-positive(Calb1+) NTS neurons that are molecularly distinct from Tac1+*** Calb1+neurons are critical for nausea and retching induced by cereulide; an emetic toxin secreted by Bacillus Cereus. Strikingly, we found that cereulide can directly modulate vagal sensory neurons that innervate Calb1+NTS neurons, a novel mechanism distinct from that for nausea and retching induced by Staphylococcal enterotoxin A. Together, our transcriptomic atlas of NTS neurons and the functional analyses revealed the neural mechanism for cereulide-induced retching-like behavior. These results demonstrate the molecular and cellular complexities in the brain that underlie defensive responses to the diversities of pathogens and toxins.

关键词： vomiting nausea nucleus of the solitary tract Calbindin1 neural circuits

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Dopamine in the prefrontal cortex plays multiple roles in the executive function of patients with Parkinson's disease

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Neural Regeneration Research 2024年第8期19卷 1759-1767页

作者： Zihang Zhou Yalong Yan Heng Gu Ruiao Sun Zihan Liao Ke Xue Chuanxi Tang department of Neurobiology Xuzhou Key Laboratory of NeurobiologyXuzhou Medical UniversityXuzhouJiangsu ProvinceChina

Parkinson’s disease can affect not only motor functions but also cognitive abilities,leading to cognitive *** common issue in Parkinson’s disease with cognitive dysfunction is the difficulty in executive *** functions help us plan,organize,and control our actions based on our *** brain area responsible for executive functions is called the prefrontal co *** acts as the command center for the brain,especially when it comes to regulating executive *** role of the prefrontal cortex in cognitive processes is influenced by a chemical messenger called ***,little is known about how dopamine affects the cognitive functions of patients with Parkinson’s *** this article,the authors review the latest research on this *** start by looking at how the dopaminergic syste m,is alte red in Parkinson’s disease with executive ***,they explore how these changes in dopamine impact the synaptic structure,electrical activity,and connection components of the prefrontal *** authors also summarize the relationship between Parkinson’s disease and dopamine-related cognitive *** information may offer valuable insights and directions for further research and improvement in the clinical treatment of cognitive impairment in Parkinson’s disease.

关键词： dopamine dopamine receptor dopamine transporter executive dysfunction neural network neural oscillation prefrontal cortex synaptic plasticity

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Oncogenic MORC2 in cancer development and beyond

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Genes & Diseases 2024年第2期11卷 861-873页

作者： Shan Zhang Ayao Guo Huan Wang Jia Liu Chenshuang Dong Junyi Ren Guiling Wang Key laboratory of Cell Biology Department of Cell BiologyMinistry of Public Health and Key Laboratory of Medical Cell BiologyMinistry of EducationChina Medical UniversityShenyangLiaoning 110122China department of Breast Surgery The First Affiliated Hospital of China Medical UniversityShenyangLiaoning 110001China

Microrchidia CW-type zinc finger 2(MORC2)is a member of the MORC superfamily of nuclear *** evidence has shown that MORC2 not only participates in gene transcription and chromatin remodeling but also plays a key in human disease and tumor development by regulating the expression of downstream oncogenes or tumor *** present review provides an updated overview of MORC2 in the aspect of cancer hallmark and therapeutic resistance and summarizes its upstream regulators and downstream target *** systematic review may provide a favorable theoretical basis for emerging players of MORC2 in tumor development and new insight into the potential clinical application of basic science discoveries in the future.

关键词： Cancer development Hallmarks of cancer MORC2 Therapeutic target Treatment resistance

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STAT3 ameliorates truncated tau-induced cognitive deficits

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Neural Regeneration Research 2024年第4期19卷 915-922页

作者： Bingge Zhang Huali Wan Maimaitijiang Maierwufu Qian Liu Ting Li Ye He Xin Wang Gongping Liu Xiaoyue Hong Qiong Feng department of Pathophysiology School of Basic Medicine and the Collaborative Innovation Center for Brain ScienceKey Laboratory of Ministry of Education of China and Hubei Province for Neurological DisordersTongji Medical CollegeHuazhong University of Science and Technology department of laboratory Medicine Guangdong ProvincialPeople's Hospital(Guangdong Academy of Medical Sciences)Southern Medical University department of laboratory Medicine Zhongnan Hospital of Wuhan University department of Pathology Wuhan Children's HospitalTongji Medical CollegeHuazhong University of Science and Technology

Proteolytic cleavage of tau by asparagine endopeptidase(AEP)creates tau-N368 fragments,which may drive the pathophysiology associated with synaptic dysfunction and memory deterioration in the brain of Alzheimer’s disease ***,the molecular mechanisms of truncated tau-induced cognitive deficits remain *** suggests that signal transduction and activator of transcription-3(STAT3)is associated with modulating synaptic plasticity,cell apoptosis,and cognitive *** luciferase reporter assays,electrophoretic mobility shift assays,western blotting,and immunofluorescence,we found that human tau-N368 accumulation inhibited STAT3 activity by suppressing STAT3 translocation into the *** of STAT3 improved tau-N368-induced synaptic deficits and reduced neuronal loss,thereby improving the cognitive deficits in tau-N368 ***,in tau-N368 mice,activation of STAT3 increased N-methyl-D-aspartic acid receptor levels,decreased Bcl-2 levels,reversed synaptic damage and neuronal loss,and thereby alleviated cognitive deficits caused by *** together,STAT3 plays a critical role in truncated tau-related neuropathological *** indicates a new mechanism behind the effect of tau-N368 on synapses and memory ***3 can be used as a new molecular target to treat tau-N368-induced protein pathology.

关键词： Alzheimer’s disease apoptosis cognitive deficit memory neurodegenerative disease neuron loss N-methyl-D-aspartic acid receptor STAT3 synapse tau-N368

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Intermittent fasting boosts antitumor immunity by restricting CD11b^(+)Ly6C^(low)Ly6G^(low) cell viability through glucose metabolism in murine breast tumor model

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Food Science and Human Wellness 2024年第4期13卷 2327-2345页

作者： Chenghao Fu Zhehao Liang Zemiao Niu Ning Chen Yuemin Li Zhenhua Liang Yanwei Huo Hao Xi Rong Wang Yonghuan Yan Xiaoruo Gan Mengtian Wang Yun Huang Yan Zhang Mingming Gao Pin Lü Postdoctoral Station for Basic Medicine Cardiovascular Medical Science CenterDepartment of Cell BiologyKey Laboratory of Neural and Vascular Biology of Ministry of EducationHebei Medical UniversityShijiazhuang 050017China Hebei Key laboratory of Forensic Medicine College of Forensic MedicineHebei Medical UniversityShijiazhuang 050017China Hebei Food Safety Key laboratory Hebei Food Inspection and Research InstituteShijiazhuang 050091China laboratory of Lipid Metabolism Department of Biochemistry and Molecular BiologyKey Laboratory of Medical Biotechnology of Hebei ProvinceShijiazhuang 050017China

Intermittent fasting can benefit breast cancer patients undergoing chemotherapy or ***,it is still uncertain how to select immunotherapy drugs to combine with intermittent *** we observed that two cycles of fasting treatment significantly inhibited breast tumor growth and lung tissue metastasis,as well as prolonged overall survival in mice bearing 4T1 and 4T07 breast *** this process,both the immunosuppressive monocytic-(M-)and granulocytic-(G-)myeloid-derived suppressor cell(MDSC)decreased,accompanied by an increase in interleukin(IL)7R^(+)and granzyme B^(+)T cells in the tumor ***,we observed that Ly6G^(low)G-MDSC sharply decreased after fasting treatment,and the cell surface markers and protein mass spectrometry data showed potential therapeutic *** investigation revealed that glucose metabolism restriction suppressed the splenic granulocytemonocyte progenitor and the generation of colony-stimulating factors and IL-6,which both contributed to the accumulation of *** the other hand,glucose metabolism restriction can directly induce the apoptosis of Ly6G^(low)G-MDSC,but not Ly6G^(high)*** summary,these results suggest that glucose metabolism restriction induced by fasting treatment attenuates the immune-suppressive milieu and enhances the activation of CD3^(+)T cells,providing potential solutions for enhancing immune-based cancer interventions.

关键词： Intermittent fasting Ly6G^(low)myeloid-derived suppressor cell apoptosis Extramedullary hematopoiesis Colony stimulating factor Glucose metabolism restriction

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Effects of Bisphenol A and Its Substitute, Bisphenol F, on the Gut Microbiota in Mice

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Biomedical and Environmental Sciences 2024年第1期37卷 19-30页

作者： MENG Li Ying TAO Wen Fu LI Jing ZHU Min ZHONG De Bin ZHOU Jing QIN Xue WEI Rong Guo department of Clinical laboratory The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021GuangxiChina department of Clinical laboratory The Fifth Affiliated Hospital of Guangxi Medical UniversityNanning 530021GuangxiChina Jiangsu Key laboratory of Environmental Engineering Jiangsu Academy of Environmental SciencesNanjing 210000JiangsuChina

Objective The aim of this study was to assess the impact of bisphenol A(BPA)and its substitute,bisphenol F(BPF),on the colonic fecal community structure and function of *** We exposed 6–8-week-old male C57BL/6 mice to 5 mg/(kg∙day)and 50μg/(kg∙day)of BPA or BPF for 14 *** samples from the colon were analyzed using 16S rRNA *** Gut microbiome community richness and diversity,species composition,and function were significantly altered in mice exposed to BPA or *** change was characterized by elevated levels of Ruminococcaceae UCG-010 and Oscillibacter and decreased levels of Prevotella 9 and ***,pathways related to carbohydrate and amino acid metabolism showed substantial *** Mice exposed to different BP analogs exhibited distinct gut bacterial community richness,composition,and related metabolic *** the essential role of gut bacteria in maintaining intestinal homeostasis,our study highlights the intestinal toxicity of BPs in vertebrates.

关键词： Bisphenol A(BPA) Bisphenol F(BPF) 16S rRNA Microbiota

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Role of cancer stem cell ecosystem on breast cancer metastasis and related mouse models

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Zoological Research 2024年第3期45卷 506-517页

作者： Xilei Peng Haonan Dong Lixing Zhang Suling Liu Fudan University Shanghai Cancer Center&Institutes of Biomedical Sciences/State Key laboratory of Genetic Engineering/Cancer Institutes/department of Oncology/Key laboratory of Breast Cancer in Shanghai/Shanghai Key laboratory of medical Epigenetics/Shanghai Key laboratory of Radiation Oncology/International Co-laboratory of medical Epigenetics and Metabolism Ministry of Science and Technology/Shanghai Medical College/Fudan UniversityShanghai 200032China

Breast cancer metastasis is responsible for most breast cancer-related deaths and is influenced by many factors within the tumor ecosystem,including tumor cells and *** cancer stem cells(BCSCs)constitute a small population of cancer cells with unique characteristics,including their capacity for self-renewal and *** have shown that BCSCs not only drive tumorigenesis but also play a crucial role in promoting metastasis in breast *** tumor microenvironment(TME),composed of stromal cells,immune cells,blood vessel cells,fibroblasts,and microbes in proximity to cancer cells,is increasingly recognized for its crosstalk with BCSCs and role in BCSC survival,growth,and dissemination,thereby influencing metastatic ***,a thorough understanding of BCSCs and the TME is critical for unraveling the mechanisms underlying breast cancer *** this review,we summarize current knowledge on the roles of BCSCs and the TME in breast cancer metastasis,as well as the underlying regulatory ***,we provide an overview of relevant mouse models used to study breast cancer metastasis,as well as treatment strategies and clinical trials addressing BCSC-TME interactions during ***,this study provides valuable insights for the development of effective therapeutic strategies to reduce breast cancer metastasis.

关键词： Breast cancer Metastasis Cancer stem cell Ecosystem Tumor microenvironment Mouse model

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Recombinant adeno-associated virus 8-mediated inhibition of microRNA let-7a ameliorates sclerosing cholangitis in a clinically relevant mouse model

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World Journal of Gastroenterology 2024年第5期30卷 471-484页

作者： Hui Hua Qian-Qian Zhao Miriam Nkesichi Kalagbor Guo-Zhi Yu Man Liu Zheng-Rui Bian Bei-Bei Zhang Qian Yu Yin-Hai Xu Ren-Xian Tang Kui-Yang Zheng Chao Yan Jiangsu Key laboratory of Immunity and Metabolism Department of Pathogenic Biology and ImmunologyNational Demonstration Center for Experimental Basic Medical Science EducationLaboratory of Infection and ImmunityXuzhou Medical UniversityXuzhou 221004Jiangsu ProvinceChina department of laboratory Medicine The Affiliated Hospital of Xuzhou Medical UniversityXuzhou 221002Jiangsu ProvinceChina

BACKGROUND Primary sclerosing cholangitis(PSC)is characterized by chronic inflammation and it predisposes to cholangiocarcinoma due to lack of effective treatment *** adeno-associated virus(rAAV)provides a promising platform for gene therapy on such kinds of diseases.A microRNA(miRNA)let-7a has been reported to be associated with the progress of PSC but the potential therapeutic implication of inhibition of let-7a on PSC has not been *** To investigate the therapeutic effects of inhibition of a miRNA let-7a transferred by recombinant adeno-associated virus 8(rAAV8)on a xenobiotic-induced mouse model of sclerosing *** A xenobiotic-induced mouse model of sclerosing cholangitis was induced by 0.1% 3,5-Diethoxycarbonyl-1,4-Dihydrocollidine(DDC)feeding for 2 wk or 6 wk.A single dose of rAAV8-mediated anti-let-7a-5p sponges or scramble control was injected in vivo into mice onset of DDC *** sacrifice,the liver and the serum were collected from each *** hepatobiliary injuries,hepatic inflammation and fibrosis were *** targets of let-7a-5p and downstream molecule NF-κB were detected using Western *** rAAV8-mediated anti-let-7a-5p sponges can depress the expression of let-7a-5p in mice after DDC feeding for 2 wk or 6 *** reduced expression of let-7a-5p can alleviate hepato-biliary injuries indicated by serum markers,and prevent the proliferation of cholangiocytes and biliary ***,inhibition of let-7a mediated by rAAV8 can increase the expression of potential target molecules such as suppressor of cytokine signaling 1 and Dectin1,which consequently inhibit of NF-κB-mediated hepatic *** Our study demonstrates that a rAAV8 vector designed for liver-specific inhibition of let-7a-5p can potently ameliorate symptoms in a xenobiotic-induced mouse model of sclerosing cholangitis,which provides a possible clinical translation of PSC of human.

关键词： Primary sclerosing cholangitis Recombinant adeno-associated virus 8 Let-7a-5p Therapeutic effects Inflammation

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