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Anti-PD1 antibody and not anti-LAG-3 antibody improves the antitumor effect of photodynamic therapy for treating metastatic breast cancer

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Journal of Innovative Optical Health Sciences 2024年第1期17卷 87-103页

作者： Shan Long Yibing Zhao Yuanyuan Xu Bo Wang Haixia Qiu Hongyou Zhao Jing Zeng Defu Chen Hui Li Jiakang Shao Xiaosong Li Ying Gu School of medicine Nankai University Tianjin300072P.R.China Department of Laser medicine The First medical Center of chinese PLA General Hospital Beijing 100853 P.R.China Department of Oncology The Seventh medical Center of chinese PLA General Hospital Beijing 100039 P.R.China School of basic medicine Guizhou Medical University Guiyang 550025GuizhouP.R.China college of medical Technology Beijing Institute of Technology Beijing 100081P.R.China medical School of chinese PLA Beijing 100853 P.R.China

Photodynamic therapy(PDT)has limited effects in treating metastatic breast *** checkpoints can deplete the function of immune cells;however,the expression of immune checkpoints after PDT is *** study investigates whether the limited e±cacy of PDT is due to upregulated immune checkpoints and tries to combine the PDT and immune checkpoint inhibitor to observe the e±cacy.A metastatic breast cancer model was treated by PDT mediated by hematoporphyrin derivatives(HpD-PDT).The anti-tumor effect of HpD-PDT was observed,as well as CD4þT,CD8þT and calreticulin(CRT)by immunohistochemistry and *** checkpoints on T cells were analyzed byflow cytometry after *** combining PDT with immune checkpoint inhibitors,the antitumor effect and immune effect were *** HpD-PDT at 100 mW/cm2 and 40,60 and 80 J/cm2,primary tumors were suppressed and CD4þT,CD8þT and CRT were elevated;however,distant tumors couldn't be inhibited and survival could not be *** checkpoints on T cells,especially PD1 and LAG-3 after HpD-PDT,were upregulated,which may explain the reason for the limited HpD-PDT *** PDT combined with anti-PD1 antibody,but not with anti-LAG-3 antibody,both the primary and distant tumors were signi-cantly inhibited and the survival time was prolonged,additionally,CD4þT,CD8þT,IFN-þCD4þT and TNF-þCD4þT cells were signi-cantly increased compared with ***-PDT could not combat metastatic breast ***1 and LAG-3 were upregulated after ***-PD1 antibody,but not anti-LAG-3 antibody,could augment the antitumor effect of HpD-PDT for treating metastatic breast cancer.

关键词： Photodynamic therapy anti-PD1 antibody anti-LAG-3 antibody anti-tumor im-mune effects metastatic breast cancer

TSPO deficiency exacerbates acute lung injury via NLRP3 inflammasome-mediated pyroptosis

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chinese medical Journal 2024年第13期137卷 1592-1602页

作者： Jingyi Han Xue Zhang Menghua Cai Feng Tian Yi Xu Hui Chen Wei He Jianmin Zhang Hui Tian Department of Thoracic Surgery Qilu Hospital of Shandong UniversityJinanShandong 250012China CAMS Key Laboratory of T Cell and Immunotherapy Department of ImmunologyInstitute of Basic Medical SciencesChinese Academy of Medical Sciences and School of Basic MedicinePeking Union Medical CollegeState Key Laboratory of Medical Molecular BiologyBeijing 100005China Changzhou Xitaihu Institute for Frontier Technology of Cell Therapy ChangzhouJiangsu 213000China Haihe Laboratory of Cell Ecosystem Chinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China

Background:Acute respiratory distress syndrome(ARDS)is a common cause of respiratory failure in many critically ill *** inflammasome activation plays an important role in the induction of acute lung injury(ALI)and ARDS,the regulatory mechanism of this process is still *** cells are stimulated by inflammation,the integrity and physiological function of mitochondria play a crucial part in ***,the underlying mechanisms and function of mitochondrial proteins in the process of pyroptosis are largely not yet ***,we identified the 18-kDa translocator protein(TSPO),a mitochondrial outer membrane protein,as an important mediator regulating nucleotide-binding domain,leucine-rich repeat,and pyrin domain-containing protein 3(NLRP3)inflammasome activation in macrophages during ***:TSPO gene knockout(KO)and lipopolysaccharide(LPS)-induced ALI/ARDS mouse models were employed to investigate the biological role of TSPO in the pathogenesis of *** macrophages were used to further characterize the effect of TSPO on the NLRP3 inflammasome *** of NLRP3 inflammasome was preformed through LPS+adenosine triphosphate(ATP)co-stimulation,followed by detection of mitochondrial membrane potential,reactive oxygen species(ROS)production,and cell death to evaluate the potential biological function of *** between two groups were performed with a two-sided unpaired ***:TSPO-KO mice exhibited more severe pulmonary inflammation in response to LPS-induced *** deficiency resulted in enhanced activation of the NLRP3 inflammasome pathway,promoting more proinflammatory cytokine production of macrophages in LPS-injured lung tissue,including interleukin(IL)-1β,IL-18,and macrophage inflammatory protein(MIP)-*** in TSPO-KO macrophages tended to depolarize in response to cellular *** increased production of mitochondrial damage-associated molecular pattern led to enhanced mitochondrial membr

关键词： Acute respiratory distress syndrome Acute lung injury 18-kDa translocator protein Macrophage NLRP3 inflammasome Inflammation

Distinguished biological adaptation architecture aggravated population differentiation of Tibeto-Burman-speaking people

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Journal of Genetics and Genomics 2024年第5期51卷 517-530页

作者： Yuntao Sun Mengge Wang Qiuxia Sun Yan Liu Shuhan Duan Zhiyong Wang Yunyu Zhou Jun Zhong Yuguo Huang Xinyu Huang Qingxin Yang Xiangping Li Haoran Su Yan Cai Xiucheng Jiang Jing Chen Jiangwei Yan Shengjie Nie Liping Hu Junbao Yang Renkuan Tang Chuan-Chao Wang Chao Liu Xiaohui Deng Libing Yun Guanglin He West China School of basic Science&Forensic medicine Sichuan UniversityChengduSichuan 610041China Institute of Rare Diseases West China Hospital of Sichuan UniversitySichuan UniversityChengduSichuan 610000China Center for Archaeological Science Sichuan UniversityChengduSichuan 610000China Faculty of Forensic medicine Zhongshan School of MedicineSun Yat-sen UniversityGuangzhouGuangdong 510275China Guangzhou Forensic Science Institute GuangzhouGuangdong 510055China Department of Forensic medicine College of Basic MedicineChongqing Medical UniversityChongqing 400331China School of Clinical medical Sciences North Sichuan Medical CollegeNanchongSichuan 637100China School of basic medical Sciences North Sichuan Medical CollegeNanchongSichuan 637100China School of Forensic medicine Kunming Medical UniversityKunmingYunnan 650500China School of Stomatology North Sichuan Medical CollegeNanchongSichuan 637100China Department of medical Laboratory North Sichuan Medical CollegeNanchongSichuan 637007China School of Life Sciences Xiamen UniversityXiamenFujian 361005China Anti-Drug Technology Center of Guangdong Province GuangzhouGuangdong 510230China School of Forensic medicine Shanxi Medical UniversityJinzhongShanxi030600China

Tibeto-Burman(TB)people have endeavored to adapt to the hypoxic,cold,and high-UV high-altitude environments in the Tibetan Plateau and complex disease exposures in lowland rainforests since the late Paleolithic ***,the full landscape of genetic history and biological adaptation of geographically diverse TB-speaking people,as well as their interaction mechanism,remain ***,we generate a whole-genome meta-database of 500 individuals from 39 TB-speaking populations and present a comprehensive landscape of genetic diversity,admixture history,and differentiated adaptative features of geographically different TB-speaking *** identify genetic differentiation related to geography and language among TB-speaking people,consistent with their differentiated admixture process with incoming or indigenous ancestral source populations.A robust genetic connection between the Tibetan-Yi corridor and the ancient Yellow River people supports their Northern China origin *** finally report substructure-related differentiated biological adaptative signatures between highland Tibetans and Loloish *** signatures associated with the physical pigmentation(EDAR and SLC24A5)and metabolism(ALDH9A1)are identified in Loloish people,which differed from the high-altitude adaptative genetic architecture in ***-related genomic resources provide new insights into the genetic basis of biological adaptation and better reference for the anthropologically informed sampling design in biomedical and genomic cohort research.

关键词： Tibeto-Burman people Genetic profile Natural selection Genetic diversity Biological adaptation

The advantages of multi-level omics research on stem cell-based therapies for ischemic stroke

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Neural Regeneration Research 2024年第9期19卷 1998-2003页

作者： Yiqing Wang Chuheng Chang Renzhi Wang Xiaoguang Li Xinjie Bao 4+4 Doctor medical Program Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina Department of Neurosurgery Peking Union Medical College HospitalPeking Union Medical CollegeChinese Academy of Medical SciencesBeijingChina Beijing Key Laboratory for Biomaterials and Neural Regeneration School of Biological Science and Medical EngineeringBeihang UniversityBeijingChina Department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina

Stem cell transplantation is a potential therapeutic strategy for ischemic stroke. However, despite many years of preclinical research, the application of stem cells is still limited to the clinical trial stage. Although stem cell therapy can be highly beneficial in promoting functional recovery, the precise mechanisms of action that are responsible for this effect have yet to be fully elucidated. Omics analysis provides us with a new perspective to investigate the physiological mechanisms and multiple functions of stem cells in ischemic stroke. Transcriptomic, proteomic, and metabolomic analyses have become important tools for discovering biomarkers and analyzing molecular changes under pathological conditions. Omics analysis could help us to identify new pathways mediated by stem cells for the treatment of ischemic stroke via stem cell therapy, thereby facilitating the translation of stem cell therapies into clinical use. In this review, we summarize the pathophysiology of ischemic stroke and discuss recent progress in the development of stem cell therapies for the treatment of ischemic stroke by applying multi-level omics. We also discuss changes in RNAs, proteins, and metabolites in the cerebral tissues and body fluids under stroke conditions and following stem cell treatment, and summarize the regulatory factors that play a key role in stem cell therapy. The exploration of stem cell therapy at the molecular level will facilitate the clinical application of stem cells and provide new treatment possibilities for the complete recovery of neurological function in patients with ischemic stroke.

关键词： ischemic stroke mesenchymal stem cells metabolomics multilevel omics neural stem/progenitor cells neuroinflammation pathophysiology proteomics stem cell therapy transcriptomes

DNA damage chemotherapeutic drugs suppress basal-like breast cancer growth by down-regulating the transcription of the FOXO1-KLF5 axis

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Genes & Diseases 2024年第1期11卷 91-94页

作者： Qiuxia Cui Jian Sun Jingping Yuan Juanjuan Li Chuanyu Yang Guangshi Du Chengang Zhou Pu Qiu Jidong Gao Yuanqi Zhang Dewei Jiang Ceshi Chen Affiliated Hospital of Guangdong medical university Science&Technology of China ZhanjiangGuangdong 524000China Department of Breast Surgical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhenGuangdong 518116China Key Laboratory of Animal Models and Human Disease Mechanisms of the chinese Academy of Sciences and yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China Department of Pathology Renmin Hospital of Wuhan UniversityWuhanHubei 430060China Department of Breast and Thyroid Surgery Renmin Hospital of Wuhan UniversityWuhanHubei 430060China Translational medicine Research Center of Guizhou medical university GuiyangGuizhou 550025China Department of Breast Surgical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China yunnan Cancer Hospital and the Third Affiliated Hospital of Kunming medical university and yunnan Cancer Center KunmingYunnan 650500China Academy of Biomedical Engineering Kunming Medical UniversityKunmingYunnan 650500China

Most basal-like breast cancers(BLBCs)have a poor prognosis and high crossover with triple-negative breast cancers(TNBCs).However,approximately 50%of TNBC patients develop chemoresistance.^(1) Dexamethasone reportedly induces Krüppel-like factor 5(KLF5)and can cause docetaxel and cisplatin resistance in TNBC.A super-enhancer can maintain the transcription of KLF5.

关键词： FOXO1 drugs damage

Gut microbiome-based thiamine metabolism contributes to the protective effect of one acidic polysaccharide from Selaginella uncinata(Desv.)Spring against inflammatory bowel disease

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Journal of Pharmaceutical Analysis 2024年第2期14卷 177-195页

作者： Haochen Hui Zhuoya Wang Xuerong Zhao Lina Xu Lianhong Yin Feifei Wang Liping Qu Jinyong Peng Department of Pharmaceutical Analysis College of PharmacyDalian Medical UniversityDalianLiaoning116044China Innovation Materials Research and Development Center Botanee Research InstituteYunnan Botanee Bio-technology Group Co.Ltd.Kunming650106China Department of Traditional chinese medicine Pharmacology School of PharmacyAnhui University of Chinese MedicineHefei230012China

Inflammatory bowel disease(IBD)is a serious disorder,and exploration of active compounds to treat it is *** acidic polysaccharide named SUSP-4 was purified from Selaginella uncinata(Desv.)Spring,which contained galacturonic acid,galactose,xylose,arabinose,and rhamnose with the main chain structure of→4)-α-d-GalAp-(1→and→6)-β-d-Galp-(1→and the branched structure of→5)-α-l-Araf-(1→.Animal experiments showed that compared with Model group,SUSP-4 significantly improved body weight status,disease activity index(DAI),colonic shortening,and histopathological damage,and elevated occludin and zonula occludens protein 1(ZO-1)expression in mice induced by dextran sulfate sodium salt(DSS).16S ribosomal RNA(rRNA)sequencing indicated that SUSP-4 markedly downregulated the level of Akkermansia and *** results confirmed that SUSP-4 obviously elevated thiamine levels compared with Model mice by adjusting thiamine metabolism,which was further confirmed by a targeted metabolism *** transplantation experiments showed that SUSP-4 exerted an anti-IBD effect by altering the intestinal flora in mice.A mechanistic study showed that SUSP-4 markedly inhibited macrophage activation by decreasing the levels of phospho-nuclear factor kappa-B(p-NF-κB)and cyclooxygenase-2(COX-2)and elevating NF-E2-related factor 2(Nrf2)levels compared with Model *** conclusion,SUSP-4 affected thiamine metabolism by regulating Akkermania and inhibited macrophage activation to adjust NF-κB/Nrf2/COX-2-mediated inflammation and oxidative stress against *** is the first time that plant polysaccharides have been shown to affect thiamine metabolism against IBD,showing great potential for in-depth research and development applications.

关键词： Gut microbiota Inflammatory bowel disease Polysaccharide Selaginella uncinata(Desv.)Spring Thiamine metabolism

Research on the Employment View of Acupuncture and Tuina Undergraduates in Minority Border Areas from Students’ Perspective

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Journal of Contemporary Educational Research 2024年第8期8卷 265-275页

作者： Rongshuang Yang Kai Yuan Minjie Yin Ruilu Liu Zhihao Zhang Lijuan Wang Yanfang Yang Xinghe Zhang The Second Clinical medical college of yunnan university of chinese medicine Kunming 650500Yunnan ProvinceChina

With the popularization of higher education in China,the employment situation of college students is more complex and *** paper adopts the questionnaire method to explore the employment view of acupuncture and tuina undergraduates of yunnan university of Traditional chinese *** employment concept of acupuncture and tuina undergraduates in the minority border areas has changed *** graduation,97.95%of students choose to work in fields related to medicine and acupuncture,prefer positions close to home,and are attracted to high-salary companies,among other ***,enhancing the competitive advantages of medical students by guiding their career planning,providing employment selection advice,fostering innovation and entrepreneurship,improving basic skills,and offering graduate entrance examination guidance is crucial for broadening their employment opportunities.

关键词： Undergraduate Employment Minority border areas Acupuncture and tuina

Exploration of the relationship between the astronomical calendar and the origins of Qi,Yin and Yang,and the Five Elements

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History & Philosophy of medicine 2024年第3期6卷 16-22页

作者： Qian-Wen He Ning Li School of basic medical Sciences Yunnan University of Traditional Chinese MedicineKunming 650500China.

Background:Traditional chinese medicine(TCM)as a traditional chinese medical practice,has gradually evolved into a coherent and systematic medical science based on natural principles and applied to human beings over *** publication of the“Huangdi Neijing”(The Yellow Emperor’s Classic of Internal medicine,Written between the Warring States period and the Qin and Han Dynasties,and finally compiled in the Western Han Dynasty,from 475 B.C.E.-8 C.E.)signified the establishment of a comprehensive theoretical framework for chinese *** to the perspective of the‘correspondence between heaven and man’in TCM,the purpose of this paper is to explore the origin and development of the basic theories of TCM under the ancient astronomical view and the connection between the ***:This paper emphases on the universe uninty with the humanities,philosophy,and medicine,starting with the forms of stargazing in ancient chinese astronomy and the natural laws derived by the ancients from their observations of natural celestial ***:Astronomy,arts and crafts,divination and medical correlations are based on the sequential changes of natural ***:The operation of natural celestial phenomena and the characteristics of physical phenomena correspond to human physiology,and the development of the basic theories of chinese medicine is inextricably linked to ancient astronomy,ancient philosophy,and ancient primeval science.

关键词： basic theories of TCM ancient astronomical calendar Huangdi Neijing divination

Molecular Mechanism of Polysaccharides Extracted from chinese medicine Targeting Gut Microbiota for Promoting Health

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chinese Journal of Integrative medicine 2024年第2期30卷 171-180页

作者： ZHAO Wen-xiao WANG Tong ZHANG Ya-nan CHEN Qian WANG Yuan XING Yan-qing ZHENG Jun DUAN Chen-chen CHEN Lijun ZHAO Hai-jun WANG Shijun School of Nursing Shandong University of Traditional Chinese MedicineShandong University of Traditional Chinese MedicineJi'nan(250355)China Shandong Co-innovation Center of Classic Traditional chinese medicine Formula Shandong University of Traditional Chinese MedicineJi'nan(250355)China college of Traditional chinese medicine Shandong University of Traditional Chinese MedicineJinan(250355)China

The accumulating evidence revealed that gut microbiota plays an important role in pathological process of disease including obesity,type 2 diabetes mellitus,heart failure,and non-alcoholic fatty liver *** extracted from chinese medicine(CM)can not only alleviate pathological status but also promote health by anti-inflammatory,regulating immunity,lowering blood glucose and lipids,anti-cancer,and *** alterations of gut microbiota composition and metabolism pathways are the potential mechanisms of CM polysaccharides *** addition,they exert functions through gut-organ axis or play an indirect role by synergistic actions with other drugs or components mediated by gut *** review summarizes the molecular mechanisms of CM polysaccharides interacted with intestinal microbial inhabitants as potential prebiotics forpromoting health.

关键词： chinese medicine polysaccharides gut microbiota short-chain fatty acids lipopolysaccharides gut-organaxis synergistic actions