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MicroRNA changes of bone marrow-derived mesenchymal stem cells differentiated into neuronal-like cells by Schwann cell-conditioned medium

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Neural Regeneration Research 2019年第8期14卷 1462-1469页

作者： Zhi-Jian Wei Bao-You Fan Yang Liu Han Ding Hao-Shuai Tang Da-Yu Pan Jia-Xiao Shi Peng-Yuan Zheng Hong-Yu Shi Heng Wu Ang Li Shi-Qing Feng Department of Orthopedics Tianjin Medical University General Hospital Tianjin China tianjin key laboratory of lung cancer metastasis and tumor Microenvironment Tianjin Lung Cancer Inst让ute Tianjin Medical University General Hospital Tianjin China Department of Orthopedics Henan Provincial People's Hospital Zhengzhou Henan Province China

Bone marrow-derived mesenchymal stem cells differentiate into neurons under the induction of Schwann cells. However, key microRNAs and related pathways for differentiation remain unclear. This study screened and identified differentially expressed microRNAs in bone marrow- derived mesenchymal stem cells induced by Schwann cell-conditioned medium, and explored targets and related pathways involved in their differentiation into neuronal-like cells. Primary bone marrow-derived mesenchymal stem cells were isolated from femoral and tibial bones, while primary Schwann cells were isolated from bilateral saphenous nerves. Bone marrow-derived mesenchymal stem cells were cultured in unconditioned (control group) and Schwann cell-conditioned medium (bone marrow-derived mesenchymal stem cell + Schwann cell group). Neuronal differentiation of bone marrow-derived mesenchymal stem cells induced by Schwann cell-conditioned medium was observed by time-lapse imaging. Upon induction, the morphology of bone marrow-derived mesencaymal stem cells changed into a neural shape with neurites. Results of quantitative reverse transcription-polymerase chain reaction revealed that nestin mRNA expression was upregulated from 1 to 3 days and downregulated from 3 to 7 days in the bone marrow-derived mesenchymal stem cell + Schwann cell group. Compared with the control group, microtubule-associated protein 2 mRNA expression gradually increased from 1 to 7 days in the bone marrow-derived mesenchymal stem cell + Schwann cell group. After 7 days of induction, microRNA analysis iden:ified 83 significantly differentially expressed microRNAs between the two groups. Gene Ontology analysis indicated enrichment of microRNA target genes for neuronal projection development, regulation of axonogenesis, and positive regulation of cell proliferation. Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that Hippo, Wnt, transforming growth factor-beta, and Hedgehog signaling pathv/ays were potenti

关键词： nerve regeneration microRNA analysis bone marrow-derived mesenchymal stem cells: Schwann cells neuronal-like cells neuronal differentiation Gene Ontology analysis Hippo signaling pathway Wnt signaling pathway transforming growth factor-beta signaling pathway Hedgehog signaling pathway neural regeneration

A nomogram-based immune-serum scoring system predicts overall survival in patients with lung adenocarcinoma

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cancer Biology & Medicine 2021年第2期18卷 517-529页

作者： Qiujuan Huang Tongyuan Qu Lisha Qi Changxu Liu Yuhong Guo Qianru Guo Guangning Li Yalei Wang Wenshuai Zhang Wei Zhao Danyang Ren Leina Sun Shengguang Wang Bin Meng Baocun Sun Bin Zhang Wenjuan Ma Wenfeng Cao Department of Pathology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China Department of Pathology Tianjin Academy of Traditional Chinese Medicine Affiliated HospitalTianjin 300120China Department of lung cancer Tianjin Lung Cancer Center Department of Breast cancer Department of Breast Imaging Key Laboratory of Breast Cancer Prevention and TherapyTianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China

Objective:The immunoscore,which is used to quantify immune infiltrates,has greater relative prognostic value than tumor,node,and metastasis(TNM)stage and might serve as a new system for classification of colorectal ***,a comparable immunoscore for predicting lung adenocarcinoma(LUAD)prognosis is currently ***:We analyzed the expression of 18 immune features by immunohistochemistry in 171 *** relationship of immune marker expression and clinicopathologic factors to the overall survival(OS)was analyzed with the Kaplan-Meier method.A nomogram was developed by using the optimal features selected by least absolute shrinkage and selection operator(LASSO)regression in the training cohort(n=111)and evaluated in the validation cohort(n=60).Results:The indicators integrated in the nomogram were TNM stage,neuron-specific enolase,carcino-embryonic antigen,CD8 center of tumor(CT),CD8 invasive margin(IM),Fox P3 CT,and CD45 *** calibration curve showed prominent agreement between the observed 2-and 5-year OS and that predicted by the *** simplify the nomogram,we developed a new immune-serum scoring system(I-SSS)based on the points awarded for each factor in the *** I-SSS was able to stratify same-stage patients into different risk *** combination of I-SSS and TNM stage had better prognostic value than the TNM stage ***:Our new I-SSS can accurately and individually predict LUAD prognosis and may be used to supplement prognostication based on the TNM stage.

关键词： lung adenocarcinoma immune microenvironment nomogram immunoscore prognosis

Autologous exosome facilitates load and target delivery of bioactive peptides to repair spinal cord injury

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Bioactive Materials 2023年第7期25卷 766-782页

作者： Ning Ran Wenxiang Li Renjie Zhang Caorui Lin Jianping Zhang Zhijian Wei Zonghao Li Zhongze Yuan Min Wang Baoyou Fan Wenyuan Shen Xueying Li Hengxing Zhou Xue Yao Xiaohong Kong Shiqing Feng Orthopedic Research Center of Shandong University&Advanced Medical Research Institute Cheeloo College of MedicineShandong UniversityJinanShandongChina Department of Orthopedics Qilu Hospital of Shandong UniversityJinanShandongChina tianjin key laboratory of Spine and Spinal Cord National Spinal Cord Injury International Cooperation BaseDepartment of OrthopedicsTianjin Medical University General HospitalTianjinChina Fujian key laboratory of laboratory Medicine The First Affiliated HospitalFujian Medical UniversityFuzhouFujianChina laboratory of Medical Molecular Virology School of MedicineNankai UniversityTianjinChina tianjin key laboratory of lung cancer metastasis and tumor Microenvironment Tianjin Lung Cancer InstituteTianjin Medical University General HospitalTianjinChina

Spinal cord injury(SCI)causes motor,sensory and automatic impairment due to rarely axon *** effective treatment for SCI in the clinic is extremely challenging because of the restrictive axonal regenerative ability and disconnection of neural elements after injury,as well as the limited systemic drug delivery efficiency caused by blood spinal cord *** develop an effective non-invasive treatment strategy for SCI in clinic,we generated an autologous plasma exosome(AP-EXO)based biological scaffold where AP-EXO was loaded with neuron targeting peptide(RVG)and growth-facilitating peptides(ILP and ISP).This scaffold can be targeted delivered to neurons in the injured area and elicit robust axon regrowth across the lesion core to the levels over 30-fold greater than naïve treatment,thus reestablish the intraspinal circuits and promote motor functional recovery after spinal cord injury in *** importantly,in ex vivo,human plasma exosomes(HP-EXO)loaded with combinatory peptides of RVG,ILP and ISP showed safety and no liver and kidney toxicity in the application to nude SCI *** the efficacy and safety,the AP-EXO-based personalized treatment confers functional recovery after SCI and showed immense promising in biomedical applications in treating *** is helpful to expand the application of combinatory peptides and human plasma derived autologous exosomes in promoting regeneration and recovery upon SCI treatment.

关键词： Spinal cord injury Targeted repair Autologous plasma exosome Drug loading Axon regeneration

Morphine-3-glucuronide upregulates PD-L1 expression via TLR4 and promotes the immune escape of non-small cell lung cancer

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cancer Biology & Medicine 2021年第1期18卷 155-171页

作者： Kaiyuan Wang Jian Wang Ting Liu Wenwen Yu Nan Dong Chen Zhang Wenbin Xia Feng Wei Lili Yang Xiubao Ren Department of Anesthesiology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerKey Laboratory of Cancer Immunology and BiotherapyTianjin 300060China Department of Immunology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerKey Laboratory of Cancer Immunology and BiotherapyTianjin 300060China Department of cancer Biobank Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerKey Laboratory of Cancer Immunology and BiotherapyTianjin 300060China Department of Biotherapy Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerKey Laboratory of Cancer Immunology and BiotherapyTianjin 300060China

Objective:Patients with cancer pain are highly dependent on morphine analgesia,but studies have shown a negative correlation between morphine demand and patient *** long-term use of morphine may result in abnormally elevated serum morphine-3-glucuronide(M3G)***,the effects of M3G on tumor progression are worth ***:The effects of M3G on PD-L1 expressions in human non-small cell lung cancer(NSCLC)cell lines were first *** of TLR4 downstream pathways after M3G treatment was then determined by Western *** effects of M3G on human cytotoxic T lymphocytes(CTL)cytotoxicity and INF-γrelease was also ***,the LLC murine lung adenocarcinoma cell line were used to establish a murine lung cancer model,and the effects of M3G on tumor growth and metastasis were ***:M3G promoted the expressions of PD-L1 in the A549 and H1299 cell lines in a TLR4-dependent manner(Ptumor growth and lung metastasis through the upregulation of tumor expressed PD-L1 and the reduction of CTL in the tumor ***:M3G specifically activated TLR4 in NSCLC cells and upregulated PD-L1 expression through the PI3 K signaling pathway,thereby inhibiting CTL cytotoxicity and finally promoting tumor immune escape.

关键词： Non-small cell lung cancer TLR4 PD-L1 morphine-3-glucuronide immune escape

Oncoprotein HBXIP promotes tumorigenesis through MAPK/ERK pathway activation in non-small cell lung cancer

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cancer Biology & Medicine 2021年第1期18卷 105-119页

作者： Jun Zhang Bei Sun Xianhui Ruan Xiukun Hou Jingtai Zhi Xiangrui Meng Xiangqian Zheng Ming Gao Department of Breast cancer Key Laboratory of Breast Cancer Prevention and TherapyTianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China Department of Outpatient Office Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China Department of Thyroid and Neck tumor Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China Department of Lymphoma Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China

Objective:The oncoprotein,hepatitis B X-interacting protein(HBXIP),has been reported to play an important role in human ***,its functions in non-small cell lung cancer(NSCLC)are poorly *** goal of the present study was to identify the role of HBXIP in the regulation of NSCLC ***:The level of HBXIP expression in NSCLC tissue was assessed by immunohistochemical and Western blot analyses,and its relationships with clinicopathological features and outcomes were statistically *** effects of HBXIP on NSCLC cell progression were assessed through cell viability,colony formation,and flow cytometry analyses in *** mechanism by which HBXIP regulated the MAPK pathway was studied by Western blot,immunofluorescence,and immunoprecipitation *** addition,in vivo experiments were performed to evaluate the progression of NSCLC and ERK signaling pathway activation after HBXIP ***:HBXIP was overexpressed in human NSCLC and was correlated with the invasiveness of *** high expression of HBXIP in NSCLC was significantly correlated with gender(P=0.033),N stage(P=0.002),and tumor-node-metastasis stage(P=0.008).In vitro experiments using an NSCLC cell line revealed that HBXIP knockdown resulted in the suppression of cell proliferation and colony formation,which was consistent with the enhanced cell cycle arrest in G1 *** results of a mechanistic investigation suggested that binding of HBXIP to MEK1 protein promoted MAPK/ERK signaling pathway activation in NSCLC by preventing the proteasome-mediated degradation of *** addition,the results obtained using in vivo subcutaneous tumor xenografts confirmed that HBXIP deficiency decreased MEK1 protein levels and NSCLC tumor ***:Taken together,our results showed that the HBXIP-MEK interaction promoted oncogenesis via the MAPK/ERK pathway,which may serve as a novel therapeutic target for cancers in which MAPK/ERK signaling is a dominant featur

关键词： HBXIP non-small cell lung cancer MEK1 tumor progression

Human umbilical cord mesenchymal stem cell-derived exosomes loaded into a composite conduit promote functional recovery after peripheral nerve injury in rats

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Neural Regeneration Research 2024年第4期19卷 900-907页

作者： Haoshuai Tang Junjin Li Hongda Wang Jie Ren Han Ding Jun Shang Min Wang Zhijian Wei Shiqing Feng Department of Othopaedics Tianjin Medical University General Hospital International Science and Technology Cooperation Base of Spinal Cord Injury Tianjin Key Laboratory of Spine and Spinal Cord InjuryDepartment of OrthopedicsTianjin Medical University General Hospital tianjin key laboratory of lung cancer metastasis and tumor Microenvironment Tianjin Lung Cancer InstituteTianjin Medical University General Hospital Department of Othopaedics Qilu Hospital of Shandong UniversityShandong University Centre for OthopedicsAdvanced Medical Research InstituteShandong University Orthopedic Research Center of Shandong University&Advanced Medical Research Institute Cheeloo College of MedicineShandong University

Complete transverse injury of peripheral nerves is challenging to *** secreted by human umbilical cord mesenchymal stem cells are considered to play an important role in intercellular communication and regulate tissue *** previous studies,a collagen/hyaluronic acid sponge was shown to provide a suitable regeneration environment for Schwann cell proliferation and to promote axonal *** three-dimensional(3D)composite conduit contains a collagen/hyaluronic acid inner sponge enclosed in an electrospun hollow poly(lactic-co-glycolic acid)***,whether there is a synergy between the 3D composite conduit and exosomes in the repair of peripheral nerve injury remains *** this study,we tested a comprehensive strategy for repairing long-gap(10 mm)peripheral nerve injury that combined the 3D composite conduit with human umbilical cord mesenchymal stem cell-derived *** effectiveness was evaluated by sciatic functional index,sciatic nerve compound muscle action potential recording,recovery of muscle mass,measuring the cross-sectional area of the muscle fiber,Masson trichrome staining,and transmission electron microscopy of the regenerated nerve in *** results showed that transplantation of the 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes promoted peripheral nerve regeneration and restoration of motor function,similar to autograft *** CD31-positive endothelial cells were observed in the regenerated nerve after transplantation of the loaded conduit than after transplantation of the conduit without exosomes,which may have contributed to the observed increase in axon regeneration and distal nerve ***,the use of a 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes represents a promising cell-free therapeutic option for the treatment of peripheral nerve injury.

关键词： axon growth collagen exosome human umbilical cord mesenchymal stem cells hyaluronic acid muscular atrophy nerve guidance conduits peripheral nerve regeneration

Programmable endonuclease combined with isothermal polymerase amplification to selectively enrich for rare mutant allele fractions

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Chinese Chemical Letters 2022年第8期33卷 4126-4132页

作者： Junman Chen Tian Qiu Michael G.Mauk Zheng Su Yaguang Fan Dennis J.Yuan Qinghua Zhou Youlin Qiao Haim H.Bau Jianming Ying Jinzhao Song key laboratory of Clinical laboratory Diagnostics(Ministry of Education) College of Laboratory MedicineChongqing Medical UniversityChongqing 400016China The cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang cancer Hospital) Institute of Basic Medicine and Cancer(IBMC)Chinese Academy of SciencesHangzhou 310022China Department of Mechanical Engineering and Applied Mechanics University of PennsylvaniaPhiladelphiaPA 19104United States Department of Pathology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Center for Global Health School of Population Medicine and Public HealthChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China tianjin key laboratory of lung cancer metastasis and tumor Microenvironment Tianjin Lung Cancer InstituteTianjin Medical University General HospitalTianjin 300052China Sichuan lung cancer Institute Sichuan Lung Cancer CenterWest China HospitalSichuan UniversityChengdu 610041China

Liquid biopsy is a highly promising method for non-invasive detection of tumor-associated nucleic acid fragments in body fluids but is challenged by the low abundance of nucleic acids of clinical interest and their sequence homology with the vast background of nucleic acids from healthy ***,programmable endonucleases such as clustered regularly interspaced short palindromic repeats(CRISPR)associated protein(Cas)and prokaryotic Argonautes have been successfully used to remove background nucleic acids and enrich mutant allele fractions,enabling their detection with deep next generation sequencing(NGS).However,the enrichment level achievable with these assays is limited by futile binding events and off-target *** overcome these shortcomings,we conceived a new assay(Programmable Enzyme-Assisted Selective Exponential Amplification,PASEA)that combines the cleavage of wild type alleles with concurrent polymerase *** PASEA increases the numbers of both wild type and mutant alleles,the numbers of mutant alleles increase at much greater rates,allowing PASEA to achieve an unprecedented level of selective enrichment of targeted *** combining CRISPR-Cas9 based cleavage with recombinase polymerase amplification,we converted samples with0.01%somatic mutant allele fractions(MAFs)to products with 70%MAFs in a single step within 20 min,enabling inexpensive,rapid genotyping with such as Sanger ***,PASEA's extraordinary efficiency facilitates sensitive real-time detection of somatic mutant alleles at the point of care with custom designed Exo-RPA ***-time PASEA'performance was proved equivalent to clinical amplification refractory mutation system(ARMS)-PCR and NGS when testing over hundred cancer patients'*** strategy has the potential to reduce the cost and time of cancer screening and genotyping,and to enable targeted therapies in resource-limited settings.

关键词： Mutant allele enrichment Programmable endonuclease Liquid biopsy Mutation detection Point-of-care testing CRISPR-Cas9 Recombinase polymerase amplification Nucleic acid diagnostics

Methylseleninic Acid on The Apoptosis Induction and Invasion Inhibition in Human High-Meta-static Large Cell lung cancer Cell Line L9981

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中国肺癌杂志 2009年第6期12卷 501-502页

作者： Jiewei LIU Yu FAN Li MA Jun CHEN Sen WEI Zhigang LI Hongyu LIU Haisu WAN Zhihao WU Qinghua ZHOU tianjin key laboratory o flung cancer metastasis and tumor Microenvironment Tianjin Lung Cancer Institute Tianjin Medical University Hospital Tianjin 300052 China

Background and Objective lung cancer, which has been proved to have fastest increasing rate of morbidity and mortality, appears to be one of the most dangerous malignant tumor that

关键词：肺癌癌细胞扩散化疗

DNA Repair Gene Polymorphisms in the Nucleotide Excision Repair Pathway and lung cancer Risk: A Meta-analysis

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Chinese Journal of cancer Research 2011年第2期23卷 79-91页

作者： Chao-rong Mei Meng Luo Hong-mei Li Wen-jun Deng Qing-hua Zhou tianjin key laboratory of lung cancer metastasis and tumor Microenvironment Tianjin Lung Cancer Institute Tianjin Medical University General Hospital Tianjin 300052 China West China Hospital Sichuan University Chengdu 610041 China cancer Center the Affiliated Hospital Qingdao University Medical College Qingdao 266003 China

Objective： A number of studies have reported the association of ＂XPA＂, ＂XPC＂, ＂XPD/ERCC2＂ gene polymorphisms with lung cancer risk. However, the results were conflict. To clarify the impact of polymorphisms of ＂XPA＂, ＂XPC＂, ＂XPD/ERCC2＂, on lung cancer risk, a meta-analysis was performed in this study. Methods： The electronic databases PubMed and Embase were retrieved for studies included in this meta-analysis by ＂XPA＂, ＂XPC＂, ＂XPD/ERCC2＂, ＂lung＂, ＂cancer/neoplasm/tumor/carcinoma＂, ＂polymorphism＂（An upper date limit of October, 31, 2009）. A meta-analysis was performed to evaluate the relationship among XPA, XPC and XPD polymorphism and lung cancer risks. Results： A total of 31 publications retrieved from Pubmed and Embase included in this study. XPC A939C CC genotype increased lung cancer risk in total population （recessive genetic model： OR=1.23, 95% CI：1.05-1.44; homozygote comparison： OR=1.21,95%CI：1.02-1.43and CC vs. CA contrast： OR=1.25,95%CI：1.06-1.48）, except in Asians. XPD A751C, 751C allele and CC genotype also increased lung cancer risk in total population and in Caucasians （recessive genetic model： Total population： OR=1.20, 95%CI：1.07-1.35）. No significant correlation was found between XPD A751C and lung cancer risk in Asians and African Americans. XPD G312A AA genotype increased lung cancer risk in total population, in Asians and Caucasians（recessive genetic model： Total population： OR=1.20, 95%CI： 1.06-1.36）. No significant association was found between XPA G23A, XPC C499T, XPD C156A and lung cancer risk. Conclusion： Our results suggest that the polymorphisms in XPC and XPD involve in lung cancer risks. XPA polymorphisms is less related to lung cancer risk.

关键词： Nucleotide excision repair Polymorphism lung cancer Meta-analysis