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

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

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Genetic diversity of food-medicinal Lycium *** China:Insights from chloroplast genome

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Chinese Herbal medicines 2024年第3期16卷 401-411页

作者： Ruyu Yao Bin Wang Michael Heinrich Qiuling Wang Peigen Xiao Institute of Medicinal Plant Development Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100193China Hainan Provincial Key Laboratory of Resources Conservation and Development of Southern medicine Hainan Branch of the Institute of Medicinal Plant DevelopmentChinese Academy of Medical Sciences and Peking Union Medical CollegeHaikou 570311China Research Group‘Pharmacognosy and Phytotherapy’ UCL School of PharmacyUniversity of LondonLondon WC1N1AXUnited Kingdom Kunming Institute of Botany Chinese Academy of SciencesKunming 650201China

Objective:Goji(fruits of Lycium spp.)is commonly consumed as food and *** increasing market demand for goji has led to its wide cultivation and broad breeding,which might cause loss of genetic *** study aims to uncover the genetic diversity of the cultivated and wild ***:The chloroplast genome(CPG)of 34 accessions of Chinese food-medicinal Lycium spp.,including the popular cultivars and their wild relatives,was re-sequenced and assembled,based on which the genetic diversity was ***:Sequence structural comparison shows that CPG is comparatively conserved within *** analysis indicates that CPG is sufficient for the discrimination of Lycium species;combined with nuclear ribosomal internal transcribed spacer(Nr ITS)sequences,materials with mixed genetic backgrounds can be *** diversity analysis reveals that the modern cultivars are probably with a common maternal parent,while the wild accessions are with higher level of genetic ***:For the first time this study reveals the intraspecies genetic diversity of Lycium *** CPG,highlighting the urgent conservation demand of wild genetic resources of *** study also demonstrates that CPG provides crucial evidence for identification of Lycium species with mixed genetic backgrounds and highlights the importance of the wild relatives in genetic diversity *** CPG-based technology will contribute to the sustainable development of medicinal plants broadly.

关键词： chloroplast genome cultivar food-medicine genetic diversity goji wild relative

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γδT cells:Major advances in basic and clinical research in tumor immunotherapy

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Chinese Medical Journal 2024年第1期137卷 21-33页

作者： Yueqi Zhao Peng Dong Wei He Jianmin Zhang Hui Chen Department of Immunology CAMS Key Laboratory for T Cell and ImmunotherapyState Key Laboratory of Medical Molecular BiologyInstitute of Basic Medical SciencesChinese Academy of Medical Sciences and School of Basic MedicinePeking Union Medical CollegeBeijing 100005China Changzhou Xitaihu Institute for Frontier Technology of Cell Therapy ChangzhouJiangsu 213000China Haihe Laboratory of Cell Ecosystem Chinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin 300020China

γδT cells are a kind of innate immune T *** have not attracted sufficient attention because they account for only a small proportion of all immune cells,and many basic factors related to these cells remain ***,in recent years,with the rapid development of tumor immunotherapy,γδT cells have attracted increasing attention because of their ability to exert cytotoxic effects on most tumor cells without major histocompatibility complex(MHC)*** increasing number of basic studies have focused on the development,antigen recognition,activation,and antitumor immune response ofγδT ***,γδT cell-based immunotherapeutic strategies are being developed,and the number of clinical trials investigating such strategies is *** review mainly summarizes the progress of basic research and the clinical application ofγδT cells in tumor immunotherapy to provide a theoretical basis for further the development ofγδT cell-based strategies in the future.

关键词： Gamma-delta T-cells T cell receptor CD1a Tumor immunotherapy Receptors,chimeric antigen Vδ1 cells αβT cells

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Construction and analysis of an ulcer risk prediction model after endoscopic submucosal dissection for early gastric cancer

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World Journal of Gastrointestinal Oncology 2022年第9期14卷 1823-1832页

作者： San-Dong Gong Huan Li Yi-Bin Xie Xiao-Hui Wang Department of Gastroenterology Hainan Hospital of Chinese PLA General HospitalSanya 572013Hainan ProvinceChina Department of Gastroenterology Sixth Medical Center of Chinese PLA General HospitalBeijing 100048China Department of Pancreatic and Gastric Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

BACKGROUND Endoscopic submucosal dissection(ESD) has been widely used in the treatment of early gastric cancer(EGC). A personalized and effective prediction method for ESD with EGC is urgently *** To construct a risk prediction model for ulcers after ESD for EGC based on LASSO *** A total of 196 patients with EGC who received ESD treatment were prospectively selected as the research subjects and followed up for one month. They were divided into an ulcer group and a non-ulcer group according to whether ulcers occurred. The general data, pathology, and endoscopic characteristics of the groups were compared, and the best risk predictor subsets were screened by LASSO regression and tenfold cross-validation. Multivariate logistic regression was applied to analyze the risk factors for ulcers after ESD in patients with EGC. A receiver operating characteristic(ROC) curve was used to estimate the predictive model *** One month after the operation, no patient was lost to follow-up. The incidence of ulcers was 20.41%(40/196)(ulcer group), and the incidence of no ulcers was 79.59%(156/196)(non-ulcer group). There were statistically significant differences in the course of disease, Helicobacter pylori infection history, smoking history, tumor number, clopidogrel medication history, lesion diameter, infiltration depth, convergent folds, and mucosal discoloration between the groups. Gray’s medication history, lesion diameter, convergent folds, and mucosal discoloration, which were the 4 nonzero regression coefficients, were screened by LASSO regression analysis. Further multivariate logistic analysis showed that lesion diameter [Odds ratios(OR) = 30.490, 95%CI: 8.584-108.294], convergent folds(OR = 3.860, 95%CI: 1.060-14.055), mucosal discoloration(OR = 3.191, 95%CI: 1.016-10.021), and history of clopidogrel(OR = 3.554, 95%CI: 1.009-12.515) were independent risk factors for ulcers after ESD in patients with EGC(P < 0.05). The ROC curve showed

关键词： Endoscopic submucosal dissection Early gastric cancer Endoscopic features Ulcer Model

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Prevalence and prognostic impact of hepatopulmonary syndrome in patients with unresectable hepatocellular carcinoma undergoing transarterial chemoembolization: a prospective cohort study

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Chinese Medical Journal 2022年第17期135卷 2043-2048页

作者： He Zhao Jiaywei Tsauo Xiaowu Zhang Huaiyuan Ma Ningna Weng Zhengqiang Yang Xiao Li Department of Interventional Therapy National Cancer Center/National Clinical Research Center/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBejing 100021China Department of Gastroenterology West China HospitalSichuan UniversityChengduSichuan 610041China

Background::To determine the prevalence and prognostic impact of hepatopulmonary syndrome(HPS)in patients with unresectable hepatocellular carcinoma(HCC)undergoing transarterial chemoembolization(TACE).Methods::Fifty-four patients with unresectable HCC undergoing TACE between December 2014 and December 2015 were prospectively screened for HPS and were followed up for a maximum of 2 years or until the end of this prospective ***::Nineteen of the 54(35.2%)patients were considered to have HPS,including one(5.3%)with severe HPS,nine(47.4%)with moderate HPS,and nine(47.4%)with mild *** median overall survival(OS)was 10.1(95%confidence interval[CI],3.9–16.3)months for patients with HPS and 15.1(95%CI,7.3–22.9)months for patients without HPS,which is not a significant difference(P=0.100).The median progression-free survival was also not significantly different between patients with and without HPS(5.2[95%CI,0–12.8]vs.8.4[95%CI,3.6–13.1]months;P=0.537).In the multivariable Cox regression analyses,carbon monoxide diffusing capacity(hazard ratio[HR]=1.033[95%CI,1.003–1.064];P=0.028)and Child-Pugh class(HR=1.815[95%CI,1.011–3.260];P=0.046)were identified to be the independent prognostic factors of ***::Mild or moderate HPS is common in patients with unresectable HCC undergoing TACE,but it does not seem to have a significant prognostic impact.

关键词： Hepatocellular carcinoma Hepatopulmonary syndrome Chemoembolization Therapeutic Prognosis Prevalence

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Antibody-drug conjugates in HER2-positive breast cancer

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Chinese Medical Journal 2022年第3期135卷 261-267页

作者： Lixi Li Di Zhang Binliang Liu Dan Lv Jingtong Zhai Xiuwen Guan Zongbi Yi Fei Ma Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Antibody-drug conjugates(ADCs)combine the high specificity of monoclonal antibodies with the high anti-tumor activity of small molecular cytotoxic *** anti-tumor activity of ADCs is mainly achieved by the direct blocking of the receptor by monoclonal antibodies,direct action and bystander effect of cytotoxic drugs,and antibody-dependent cell-mediated cytotoxicity and complement-dependent *** have been used in adjuvant therapy and rescue treatment of human epidermal receptor 2(HER2)-positive breast cancer,greatly improving the prognosis of breast cancer *** ongoing clinical trials of ADC for breast cancer and other solid tumors proved the potential of ADCs will provide more promising treatment options for patients with malignant *** review introduces the mechanism and latest clinical progress of ADC drugs approved for HER2-positive breast cancer to guide clinical practice and conduct research.

关键词： Antibody-drug conjugate HER2-positive Breast cancer T-DM1 DS-8201

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Functional isolation,culture and cryopreservation of adult human primary cardiomyocytes

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Signal Transduction and Targeted Therapy 2022年第8期7卷 3093-3108页

作者： Bingying Zhou Xun Shi Xiaoli Tang Quanyi Zhao Le Wang Fang Yao Yongfeng Hou Xianqiang Wang Wei Feng Liqing Wang Xiaogang Sun Li Wang Shengshou Hu State Key Laboratory of Cardiovascular Disease Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Shenzhen Key Laboratory of Cardiovascular Disease Fuwai Hospital Chinese Academy of Medical SciencesShenzhenShenzhenChina Department of Cardiac Surgery Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Present address:18 Jinma Industrial Park Fangshan DistrictBeijingChina

Cardiovascular diseases are the most common cause of death *** modeling cardiac homeostasis,dysfunction,and drug response lies at the heart of cardiac *** human primary cardiomyocytes(hPCMs)are a promising cellular model,but unstable isolation efficiency and quality,rapid cell death in culture,and unknown response to cryopreservation prevent them from becoming a reliable and flexible in vitro cardiac *** the use of a reversible inhibitor of myosinⅡATPase,(-)-blebbistatin(Bleb),and multiple optimization steps of the isolation procedure,we achieved a 2.74-fold increase in cell viability over traditional methods,accompanied by better cellular morphology,minimally perturbed gene expression,intact electrophysiology,and normal neurohormonal *** optimization of culture conditions established a method that was capable of maintaining optimal cell viability,morphology,and mitochondrial respiration for at least 7 *** importantly,we successfully cryopreserved hPCMs,which were structurally,molecularly,and functionally intact after undergoing the freeze-thaw *** demonstrated greater sensitivity towards a set of cardiotoxic drugs,compared to human-induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs).Further dissection of cardiomyocyte drug response at both the population and single-cell transcriptomic level revealed that hPCM responses were more pronouncedly enriched in cardiac function,whereas hiPSC-CMs responses reflected cardiac ***,we established a full set of methodologies for the efficient isolation and prolonged maintenance of functional primary adult human cardiomyocytes in vitro,unlocking their potential as a cellular model for cardiovascular research,drug discovery,and safety pharmacology.

关键词： cardiomyocytes unstable culture

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Escaping alveolar macrophage endosomal retention explains massive expansion of SARS-CoV-2 delta variant

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Signal Transduction and Targeted Therapy 2022年第1期7卷 28-30页

作者： Zhenfeng Wang Yabo Zhou Linlin Bao Dan Li Jiadi Lv Dianheng Wang Shunshun Li Wei-Min Tong Jiangning Liu Chuan Qin Bo Huang Department of Immunology&National Key Laboratory of Medical Molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical Sciences(CAMS)&Peking Union Medical College100005 BeijingChina NHC Key Laboratory of Human Disease Comparative medicine Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious DiseasesInstitute of Laboratory Animal ScienceCAMS and Comparative Medicine CenterPeking Union Medical CollegeBeijingChina Department of Pathology Institute of Basic Medical SciencesCAMS and Peking Union Medical CollegeBeijingChina Department of Biochemistry&Molecular Biology Tongji Medical CollegeHuazhong University of Science&Technology430030 WuhanChina

Dear Editor,Genetic variant Delta(B.1.617.2)of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),which possesses a remarkable ability to transmit and spread,is currently becoming predominant *** its great harm to human beings,how the Delta variant with T478K,P681R and L452R mutations achieves its ultrafast spread remains *** of SARS-CoV-2 into host cells is mediated by a rapid enzymatic hydrolysis.

关键词： retention massive delta

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Identification of multi-target anti-cancer agents from TCM formula by in silico prediction and in vitro validation

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Chinese Journal of Natural medicines 2022年第5期20卷 332-351页

作者： ZHANG Bao-Yue ZHENG Yi-Fu ZHAO Jun KANG De WANG Zhe XU Lv-Jie LIU Ai-Lin DU Guan-Hua State Key Laboratory of Bioactive Substance and Function of Natural medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China School of Life Sciences Tsinghua UniversityBeijing 100084China

Cancer is a complex disease associated with multiple gene mutations and malignant phenotypes,and multi-target drugs provide a promising therapy idea for the treatment of *** products with abundant chemical structure types and rich pharmacological characteristics could be ideal sources for screening multi-target antineoplastic *** this paper,50 tumor-related targets were collected by searching the Therapeutic Target Database and Thomson Reuters Integrity database,and a multi-target anti-cancer prediction system based on mt-QSAR models was constructed by using naïve Bayesian and recursive partitioning algorithm for the first *** the multi-target anti-cancer prediction system,some dominant fragments that act on multiple tumor-related targets were analyzed,which could be helpful in designing multi-target anti-cancer ***-cancer traditional Chinese medicine(TCM)and its natural products were collected to form a TCM formula-based natural products library,and the potential targets of the natural products in the library were predicted by multi-target anti-cancer prediction *** a result,alkaloids,flavonoids and terpenoids were predicted to act on multiple tumor-related *** predicted targets of some representative compounds were verified according to literature review and most of the selected natural compounds were found to exert certain anti-cancer activity in vitro biological *** conclusion,the multi-target anti-cancer prediction system is very effective and reliable,and it could be further used for elucidating the functional mechanism of anti-cancer TCM formula and screening for multi-target anti-cancer *** anti-cancer natural compounds found in this paper will lay important information for further study.

关键词： Cancer Multi-target mt-QSAR model Nave Bayesian Recursive partitioning TCM formulae

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Evaluation of the diagnostic value of serum-based proteomics for colorectal cancer

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World Journal of Gastrointestinal Oncology 2022年第8期14卷 1562-1573页

作者： Hui-Juan Wang Yi-Bin Xie Peng-Jun Zhang Tao Jiang Department of Respiratory and Critical Care medicine Beijing Chao-Yang HospitalBeijing Institute of Respiratory MedicineCapital Medical UniversityBeijing 100020China Department of Pancreatic and Gastric Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Interventional Therapy DepartmentPeking University Cancer Hospital and InstituteBeijing 100142China Medical Innovation Research Division of Chinese PLA General Hospital Beijing 100853China

BACKGROUND Colorectal cancer(CRC)is a highly malignant cancer with a high incidence and mortality in *** is urgent to find a diagnostic marker with higher sensitivity and specificity than the traditional approaches for CRC *** To provide new ideas for the diagnosis of CRC based on serum *** Specimens from 83 healthy people,62 colon polyp(CRP)patients,and 101 CRC patients were analyzed by matrix-assisted laser desorption/ionization time-offlight mass *** diagnostic value of the profiles of differentially expressed proteins was then *** Compared with the healthy control group,CRC patients had elevated expression of 5 proteins and reduced expression of 14 *** area under the curve(AUC)for a differentially expressed protein with a mass-to-charge ratio of 2022.34 was the largest;the AUC was 0.843,which was higher than the AUC of 0.717 observed with carcinoembryonic antigen(CEA),and the sensitivity and specificity of this identified marker were 75.3%and 79.5%,*** cross-validation,the accuracy of diagnosis using levels of this differentially expressed protein was 82.37%.Compared with the CRP group,the expression of 3 proteins in the serum of CRC patients was elevated and 11 proteins were expressed at reduced *** possessing mass-to-charge ratio values of 2899.38 and 877.3 were selected to establish a classification tree *** results showed that the accuracy of CRC diagnosis was 89.5%,the accuracy of CRP diagnosis was 81.6%,and the overall accuracy of this approach was 86.3%.The overall sensitivity and specificity of diagnosis using the proteomics approach were 81.8%and 66.75%,*** sensitivities and specificities of diagnoses based on CEA and carbohydrate antigen 19-9 expression were 55.6%and 91.3%and 65.4%and 65.2%,*** We demonstrated that serum proteomics may be helpful for the detection of CRC,and it may assist clinical practice for CRC diagnosis

关键词： Colorectal cancer Colorectal polyps Serum Proteomics Diagnostic value

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