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Transcriptomic landscape regulated by the 14 types of bone morphogenetic proteins(BMPs)in lineage commitment and differentiation of mesenchymal stem cells(MSCs)

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Genes & Diseases 2019年第3期6卷 258-275页

作者： Linghuan Zhang Qing Luo Yi Shu Zongyue Zeng Bo Huang Yixiao Feng Bo Zhang Xi Wang Yan Lei Zhenyu Ye Ling Zhao Daigui Cao Lijuan Yang Xian Chen Bin Liu William Wagstaff Russell R*Reid Hue H*Luu Rex C*Haydon Michael J*Lee Jennifer Moriatis Wolf Zhou Fu Tong-Chuan He Quan Kang stem cell biology and Therapy laboratory Ministry of Education Key Laboratory of Child Development and DisordersThe Children’s Hospital of Chongqing Medical UniversityChongqing 400014China Molecular Oncology laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA c Ministry of Education Key laboratory of Diagnostic Medicine School of Laboratory MedicineChicagoIL 60637USA d The Affiliated Hospitals of Chongqing Medical University Chongqing 400016China e department of Clinical laboratory Medicine The Second Affiliated Hospital of Nanchang UniversityNanchang 330006China f Key laboratory of Orthopaedic surgery of Gansu Province Departments of Orthopaedic Surgery and Obstetrics and GynecologyThe First and Second Hospitals of Lanzhou UniversityLanzhou 730030China g department of General surgery The Second Affiliated Hospital of Soochow UniversitySuzhou 215004China department of Clinical laboratory Medicine The Affiliated Hospital of Qingdao UniversityQingdao 266061China department of biology School of Life SciencesSouthwest UniversityChongqing 400715China department of surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

Mesenchymal stem cells(MSCs)are ubiquitously-existing multipotent progenitors that can self-renew and differentiate into multiple lineages including osteocytes,chondrocytes,adipocytes,tenocytes and *** represent one of the most commonly-used adult progenitors and serve as excellent progenitor cell models for investigating lineagespecific differentiation regulated by various cellular signaling pathways,such as bone morphogenetic proteins(BMPs).As members of TGFb superfamily,BMPs play diverse and important roles in development and adult *** least 14 BMPs have been identified in *** BMPs exert distinct but overlapping biological *** a comprehensive analysis of 14 BMPs in MSCs,we demonstrated that BMP9 is one of the most potent BMPs in inducing osteogenic differentiation of ***,a global mechanistic view of BMP signaling in regulating the proliferation and differentiation of MSCs remains to be fully ***,we conducted a comprehensive transcriptomic profiling in the MSCs stimulated by 14 types of *** clustering analysis classifies 14 BMPs into three subclusters:an osteo/chondrogenic/adipogenic cluster,a tenogenic cluster,and BMP3 *** also demonstrate that six BMPs(e.g.,BMP2,BMP3,BMP4,BMP7,BMP8,and BMP9)can induce ISmads effectively,while BMP2,BMP3,BMP4,BMP7,and BMP11 up-regulate Smad-independent MAP kinase ***,we show that many BMPs can upregulate the expression of the signal mediators of Wnt,Notch and PI3K/AKT/mTOR *** the reported transcriptomic changes need to be further validated,our expression profiling represents the first-of-its-kind to interrogate a comprehensive transcriptomic landscape regulated by the 14 types of BMPs in MSCs.

关键词： Bone morphogenetic proteins(BMPs) MAP kinase signaling Mesenchymal stem cells Notch signaling PI3K/AKT/mTOR pathway Smad signaling TGFb superfamily Wnt signaling

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Gallbladder Burkitt's lymphoma mimicking gallbladder cancer:A case report

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World Journal of Gastroenterology 2022年第6期28卷 675-682页

作者： Kiyotaka Hosoda Akira Shimizu Koji Kubota Tsuyoshi Notake Hikaru Hayashi Koya Yasukawa Kentaro Umemura Atsushi Kamachi Takamune Goto Hidenori Tomida Shiori Yamazaki Yuri Narusawa Naoko Asano Takeshi Uehara Yuji Soejima Division of Gastroenterological Hepato-Biliary-PancreaticTransplantation and Pediatric SurgeryDepartment of SurgeryShinshu University School of MedicineMatsumoto 390-8621Japan department of laboratory Medicine Shinshu University School of MedicineMatsumoto 390-8621Japan

BACKGROUND Malignant lymphoma is a rare form of gallbladder *** of these malignancies are diffuse large B-cell lymphomas or mucosa-associated lymphoid tissue-type lymphomas;however,Burkitt’s lymphoma of the gallbladder is extremely rare,and only two previous reports are available in the ***,we report a rare case of Burkitt’s lymphoma of the gallbladder mimicking gallbladder *** SUMMARY An 83-year-old man with no abdominal complaints was found to have a gallbladder tumor and periportal lymph node enlargement on computed tomography(CT)performed for hypertension *** laboratory data revealed slightly elevated serum levels of carcinoembryonic antigen and soluble interleukin 2 *** examinations revealed two irregular and contrastenhanced masses extending into the gallbladder lumen,but these did not infiltrate the ***,a periportal lymph node had enlarged to 30 *** on these findings,we diagnosed the patient as having gallbladder adenocarcinoma with lymph node metastasis,which was treated using bile duct resection with gallbladder bed resection and periportal lymph node ***,the patient was finally diagnosed as having Burkitt’s *** the surgical margin was pathologically negative,recurrence was noted at the hepatic radical margin and superior pancreaticoduodenal lymph nodes on positron emission tomography/CT soon after ***,he was referred to a hematologist and started receiving treatment with reduced-dose cyclophosphamide,doxorubicin,vincristine,and *** Burkitt’s lymphoma can occur in the *** can be useful in cases with findings suggestive of gallbladder malignant lymphoma.

关键词： Gallbladder Malignant lymphoma Burkitt’s lymphoma Gallbladder cancer Lymphadenopathy Case report

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miR-181b-5p/SOCS2/JAK2/STAT5 axis facilitates the metastasis of hepatoblastoma

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Precision Clinical Medicine 2023年第4期6卷 189-199页

作者： Yong Lv Xiaolong Xie Guoyou Zou Meng Kong Jiayin Yang Jing Chen Bo Xiang department of pediatric surgery and laboratory of pediatric surgery West China HospitalSichuan UniversityChengdu 610041China department of General surgery People’s Hospital of Tibet Autonomous RegionTibet 850000China department of pediatric surgery Children’s Hospital Affiliated to Shandong UniversityJinan 250022China Liver Transplantation Center Department of General SurgeryWest China HospitalSichuan UniversityChengdu 610041China

Introduction:Hepatoblastoma(HB)is a malignant liver tumor predominantly found in children and tumor metastasis is one of the main causes of poor prognosis in affected *** precise molecular mechanisms responsible for HB metastasis remain incom-pletely ***,there is evidence suggesting a connection between the dysregulation of microRNAs(miRNAs)and the progression of tumor metastasis in ***:The study utilized weighted gene co-expression network analysis(WGCNA)to analyze a miRNA microarray dataset of *** expression of miR-181b-5p in HB tissues and cells was detected using quantitative real-time *** impact of miR-181b-5p on the metastatic capacity of HB was evaluated through scratch and Transwell *** effects of exogenously expressing miR-181b on the metastatic phenotypes of HB cells were evaluated in ***,a luciferase reporter assay was performed to validate a potential target of miR-181b-5p in ***:We found that miR-181b-5p was highly expressed in HB tissues and HB cell *** of miR-181b enhanced scratch healing,cell migration,and invasion abilities in vitro,as well as enhancing HB lung metastasis potential in ***-luciferase reporter assays showed that Suppressor Of Cytokine Signaling 2(SOCS2)was a direct target of *** overexpression of miR-181b resulted in the suppression of SOCS2 expression,subsequently activating the epithelial-mesenchymal transition and JAK2/STAT5 signaling *** rescue experiment showed that SOCS2 overexpression attenuated the effects of miR-181b on HB ***:Our study showed that miR-181b promotes HB metastasis by targeting SOCS2 and may be a potential therapeutic target for HB.

关键词： miR-181b SOCS2 metastasis hepatoblastoma children

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Fast-track surgery in elderly patients undergoing colorectal cancer radical resection

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International Journal of Nursing Sciences 2014年第4期1卷 381-384页

作者： Hong-Yan Kong Ai-Ling Yang Cai-Ya Ying Zhen-Fang Kong Ling-Ling Yuan Shan-Shan Hu Shun Zhang department of Anorectal surgery Ningbo No.2 HospitalNingboChina School of Medicine Ningbo UniversityNingboChina laboratory of stem cell Ningbo No.2 HospitalNingboChina

Purpose:To investigate the efficacy of applying fast-track surgery(FTS)to elderly patients undergoing radical resection of colorectal ***:Elderly patients undergoing radical resection of colorectal cancer received FTS(n=31)or routine(n=31)nursing *** time to first anal exhaust,oral feeding and leaving the bed,duration of postoperative hospital stay and the incidence of complications were compared between the two ***:Patients receiving FTS nursing demonstrated significantly shorter times to exhaust,oral feeding and leaving the bed compared with those receiving routine nursing(all psurgery,but places higher demands on nursing care.

关键词： Aged Colorectal neoplasms Fast-track surgery Nursing care

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Wip1 inhibits neutrophil extracellular traps to promote abscess formation in mice by directly dephosphorylating Coronin-1a

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cellular & Molecular Immunology 2023年第8期20卷 941-954页

作者： Yifang Chen Chenxu Zhao Han Guo Weilong Zou Zhaoqi Zhang Dong Wei Hezhe Lu Lianfeng Zhang Yong Zhao State Key laboratory of Membrane biology Institute of ZoologyChinese Academy of SciencesBeijingChina University of Chinese Academy of Sciences BeijingChina Beijing Institute for stem cell and Regeneration BeijingChina department of Hepatobiliary surgery The Affiliated Hospital of Guizhou Medical UniversityGuiyangGuizhouChina Shenzhen Institute of Advanced Technology Chinese Academy of SciencesShenzhenChina Key laboratory of Human Diseases Comparative Medicine Ministry of Health Institute of laboratory Animal Science Chinese Academy of Medical SciencesBeijingChina

Neutrophil extracellular traps (NETs) participate in the rapid inhibition and clearance of pathogens during infection;however, the molecular regulation of NET formation remains poorly understood. In the current study, we found that inhibition of the wild-type p53-induced phosphatase 1 (Wip1) significantly suppressed the activity of Staphylococcus aureus (S. aureus) and accelerated abscess healing in S. aureus-induced abscess model mice by enhancing NET formation. A Wip1 inhibitor significantly enhanced NET formation in mouse and human neutrophils in vitro. High-resolution mass spectrometry and biochemical assays demonstrated that Coro1a is a substrate of Wip1. Further experiments also revealed that Wip1 preferentially and directly interacts with phosphorylated Coro1a than compared to unphosphorylated inactivated Coro1a. The phosphorylated Ser426 site of Coro1a and the 28–90 aa domain of Wip1 are essential for the direct interaction of Coro1a and Wip1 and for Wip1 dephosphorylation of p-Coro1a Ser426. Wip1 deletion or inhibition in neutrophils significantly upregulated the phosphorylation of Coro1a-Ser426, which activated phospholipase C and subsequently the calcium pathway, the latter of which promoted NET formation after infection or lipopolysaccharide stimulation. This study revealed Coro1a to be a novel substrate of Wip1 and showed that Wip1 is a negative regulator of NET formation during infection. These results support the potential application of Wip1 inhibitors to treat bacterial infections.

关键词： Wild-type p53-induced phosphatase 1(Wip1) Coro1a Calcium pathway Neutrophils Neutrophil extracellular trap(NET) Abscess

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RNAi-mediated Human Nestin Silence Inhibits Proliferation and Migration of Malignant Melanoma cells by G1/S Arrest via Akt-GSK3β-Rb Pathway

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2017年第6期37卷 895-903页

作者：杨旭辉夏添张杰杨少芬汤惠霞唐婷黄志承钟跃思何峰项鹏 Assisted Reproductive Center Guangdong Women and Children’s Hospital Center for stem cell biology and Tissue Engineering Sun Yat-sen University Oncological surgery Affiliated Children’s Hospital of Zhejiang University department of Hepatobiliary surgery the Third Affiliated Hospital of Sun Yat-sen University School of Pharmaceutical Sciences Sun Yat-sen University

Human Nestin（hNestin） has been found to express in melanoma, and its expression is positively correlated with the advanced stage of melanoma. However, the precise role of hNestin in the development of melanoma has not been fully understood. The present study aimed to explore the role of hNestin in the proliferation and invasion of melanoma cells. The lentivirus vector carrying a short hairpin RNAs（shRNAs） targeting hNestin（hNestin-sh RNA-LV） was stably infected into human melanoma cells UACC903, which expressed high levels of hNestin. The effects of hNestin knockdown on the proliferation, apoptosis, migration of melanoma cells and the related signaling pathways were investigated by immunofluorence, Western blotting and reverse transcription polymerase chain reaction（RT-PCR）, respectively. The results showed that hNestin was expressed in most melanoma specimens and the melanoma cells studied. Knockdown of hNestin expression significantly inhibited the proliferation of melanoma cells, blocked the formation of cell colony, arrested cell cycle at G1/S stage and suppressed the activation of Akt and GSK3β. hNestin-silent cells also showed a sheet-like appearance with tight cell-cell adhesion, decreased membrane expression of N-cadherin and β-catenin, and attenuated migration. Furthermore, hNestin silence resulted in the inhibition of tumor growth in vivo. Our study indicates that hNestin knockdown suppresses the proliferation of melanoma cells, which might be through affecting Akt-GSK3β-Rb pathway-mediated G1/S arrest, and hNestin silence inhibits the migration by selectively modulating the expression of cell adhesion molecules in the process of epithelial-mesenchymal transition.

关键词： hNestin proliferation migration melanoma cell RNA interference

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An immortalized rat pancreatic stellate cell line RP-2 as a new cell model for evaluating pancreatic fibrosis,inflammation and immunity

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Hepatobiliary & Pancreatic Diseases International 2015年第6期14卷 651-659页

作者： Rong-Li Piao Ming Xiu David R Brigstock Run-Ping Gao department of Hepatic-biliary-pancreatic Medicine the First Hospital of Jilin University The Research Institute at Nationwide Children's Hospital Division of pediatric surgery Department of Surgerythe Ohio State University

BACKGROUND： Pancreatic stellate cells （PSCs） play a critical role in the pathogenesis of pancreatic fibrosis and have emerging functions as progenitor cells, immune cells or intermediaries in pancreatic exocrine secretion. Increasing evidence has shown that desmin as an exclusive cytoskeleton marker of PSC is only expressed in part of these cells. This study was to establish a desmin-positive PSC cell line and evaluate its actions on pancreatic fibrosis, inflammation and immunity.

关键词： pancreatic stellate cell pancreatic fibrosis Toll-like receptor 4 inflammation immunity

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Overexpression of mechanical sensitive miR-337-3p alleviates ectopic ossification in rat tendinopathy model via targeting IRS1 and Nox4 of tendon-derived stem cells

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Journal of Molecular cell biology 2020年第4期12卷 305-317页

作者： Yiyun Geng Xiaoying Zhao Jiajia Xu Xudong Zhang Guoli Hu Sai-Chuen Fu Kerong Dai Xiaodong Chen Yung shu-huang Patrick Xiaoling Zhang department of Orthopedic surgery Xinhua HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200092China Shenzhen Key laboratory of Tissue Engineering Shenzhen Second People's Hospital(The First Hospital Affiliated to Shenzhen University)Shenzhen 518035China The Key laboratory of stem cell biology Shanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200031China department of Orthopaedics and Traumatology Faculty of MedicineThe Chinese University of Hong KongHong Kong SARChina

Tendinopathy,which is characterized by the ectopic ossification of tendon,is a common disease occurring in certain population,such as athletes that suffer from repetitive tendon ***,the molecular mechanism underlying the pathogenesis of tendinopathy caused by the overuse of tendon is still ***,we found that the mechanosensitive miRNA,miR-337-3p,had lower expression under uniaxial cyclical mechanical loading in tendon-derived stem cells(TDSCs)and negatively controlled chondro-osteogenic differentiation of ***,downregulation of miR-337-3p expression was also observed in both rat and human calcified tendons,and overexpressing miR-337-3p in patellar tendons of rat tendinopathy model displayed a robust therapeutic ***,we found that the proinflammatory cytokine interleukin-1^was the upstream factor of miR-337-3p that bridges the mechanical loading with its ***,the target genes of miR-337-3p,NADPH oxidase 4,and insulin receptor substrate 1,activated chondro-osteogenic differentiation of TDSCs through JNK and ERK signaling,***,these findings not only provide novel insight into the molecular mechanisms underlying ectopic ossification in tendinopathy but also highlight the significance of miR-337-3p as a putative therapeutic target for clinic treatment of tendinopathy.

关键词： mechanosensitive miRNA tendon-derived stem cells mechanical loading chondro-osteogenesis tendinopathy

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Metastatic tumor cells- genotypes and phenotypes

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Frontiers in biology 2018年第4期13卷 277-286页

作者： Dingcheng Gao Vivek Mittal Yi Ban Ana Rita Lourenco Shira Yomtoubian Sharrell Lee department of Cardiothoracic surgery Department of Cell and Developmental Biology Neuberger Berman Lung Cancer Center WeillCornell Medicine New York NY10065 USA

BACKGROUND： Metastasis is the primary cause of mortality in cancer patients. Therefore, elucidating the genetics and epigenetics of metastatic tumor cells and the mechanisms by which tumor cells acquire metastatic properties constitute significant challenges in cancer research. OBJECTIVE： To summarize the current understandings of the specific genotype and phenotype of the metastatic tumor cells. METHOD and RESULT： In-depth genetic analysis of tumor cells, especially with advances in the next-generation sequencing, have revealed insights of the genotypes of metastatic tumor cells. Also, studies have shown that the cancer stem cell （CSC） and epithelial to mesenchymal transition （EMT） phenotypes are associated with the metastatic cascade. CONCLUSION： In this review, we will discuss recent advances in the field by focusing on the genomic instability and phenotypic dynamics of metastatic tumor cells.

关键词： metastasis epithelial to mesenchymal transition (EMT) cancer stem cell circulating tumor cells cellular plasticity phenotype dynamics

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Hydrogel-exosome system in tissue engineering:A promising therapeutic strategy

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Bioactive Materials 2024年第8期38卷 1-30页

作者： Ming-Hui Fan Jin-Kui Pi Chen-Yu Zou Yan-Lin Jiang Qian-Jin Li Xiu-Zhen Zhang Fei Xing Rong Nie Chen Han Hui-Qi Xie department of Orthopedic surgery and Orthopedic Research Institute Laboratory of Stem Cell and Tissue EngineeringState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduSichuan610041PR China Core Facilities West China HospitalSichuan UniversityChengduSichuan610041PR China Frontier Medical Center Tianfu Jincheng LaboratoryChengduSichuan610212PR China

Characterized by their pivotal roles in cell-to-cell communication,cell proliferation,and immune regulation during tissue repair,exosomes have emerged as a promising avenue for“cell-free therapy”in clinical ***,possessing commendable biocompatibility,degradability,adjustability,and physical properties akin to biological tissues,have also found extensive utility in tissue engineering and regenerative *** synergistic combination of exosomes and hydrogels holds the potential not only to enhance the efficiency of exosomes but also to collaboratively advance the tissue repair *** review has summarized the advancements made over the past decade in the research of hydrogel-exosome systems for regenerating various tissues including skin,bone,cartilage,nerves and tendons,with a focus on the methods for encapsulating and releasing exosomes within the *** has also critically examined the gaps and limitations in current research,whilst proposed future directions and potential applications of this innovative approach.

关键词： Exosome Hydrogel Tissue engineering Regenerative medicine

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