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SH-2-containing protein tyro-sine phosphatase 1 is required for IL-4-induced IL-4R expression in spleen cells

Chinese Science Bulletin 2005年第14期50卷 1456-1461页

作者： CAO Xin HUANG Zan FAN Jingyi Department of Cell Biology and medical Genetics Nanjing Medical University Nanjing 210029 China Molecular Biology Program Stritch School of Medicine Loyola University at Chicago Maywood IL 60153 USA Department of Organismal Biology and Anatomy University of Chicago Chicago IL 60637 USA

To investigate the role of SH-2-containing pro- tein tyrosine phosphatase 1, SHP-1, in IL-4-induced IL-4 receptor (IL-4R) expression, we examined IL-4 receptor α-chain (IL-4Rα) mRNA expression in Na3VO4-treated wild type (WT) spleen cells and measured IL-4R mRNA in IL-4-stimulated spleen cells of viable motheaten mice (mev/mev). It is found that IL-4-induced IL-4R mRNA ex- pression was impaired in Na3VO4-treated WT spleen cells and IL-4-stimulated mev/mev spleen cells. Here we show that the impaired IL-4-induced IL-4Rα mRNA expression was due to reduced expression of IL-4R that led to impaired STAT6 signaling. We further demonstrate that reduction of IL-4Rα protein expression in mev/mev spleen cells was due to alteration in cell compositions. In mev/mev spleen, the per- centages of CD4+, CD8+, and CD19+ cells expressing rela- tively high levels of IL-4R were reduced dramatically while the percentages of Mac-1+ and Gr-1+ cells with relative low levels of IL-4R increased greatly. Despite the profound effect of reduced expression of IL-4R protein, the IL-4Rα mRNA expression was comparable in spleen cells of littermate con- trol mice (+/?) and mev/mev mice and no differences were found in B cells, T cells, and macrophages, suggesting cell type-specific downregulation of IL-4R expression in macro- phages through a posttranscriptional mechanism. Our study suggests that SHP-1 is required for IL-4-meidated function and indirectly regulates IL-4-meidated function in spleen cells by affecting hematopoiesis.

关键词：蛋白质酪氨酸磷酸酶脾细胞

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The wonders of BMP9:From mesenchymal stem cell differentiation,angiogenesis,neurogenesis,tumorigenesis,and metabolism to regenerative medicine

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Genes & Diseases 2019年第3期6卷 201-223页

作者： Sami Mostafa Mikhail Pakvasa Elam Coalson Allen Zhu Alex Alverdy Hector Castillo Jiaming Fan Alex Li Yixiao Feng Di Wu Elliott Bishop Scott Du Mia Spezia Alissa Li Ofir Hagag Alison Deng Winny Liu Mingyang Li Sherwin S·Ho Aravind Athiviraham Michael J·Lee Jennifer Moriatis Wolf Guillermo A·Ameer Hue H·Luu Rex C·Haydon Jason Strelzow Kelly Hynes Tong-Chuan He Russell R·Reid The University of chicago Pritzker school of Medicine ChicagoIL 60637USA Laboratory of Craniofacial Biology and Development Section of Plastic and Reconstructive SurgeryDepartment of SurgeryThe University of Chicago MedicineChicagoIL 60637USA Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Rosalind Franklin University Chicago Medical SchoolNorth ChicagoIL 60064USA SIR Program Illinois Math and Science Academy(IMSA)AuroraIL 60506USA Department of Biomedical Engineering Northwestern UniversityEvanstonIL60208USA The Department of Surgery Feinberg School of MedicineNorthwestern UniversityChicagoIL60616USA

Although bone morphogenetic proteins(BMPs)initially showed effective induction of ectopic bone growth in muscle,it has since been determined that these proteins,as members of the TGF-b superfamily,play a diverse and critical array of biological *** roles include regulating skeletal and bone formation,angiogenesis,and development and homeostasis of multiple organ *** of the members of the TGF-b/BMP superfamily result in severe skeletal and extra-skeletal irregularities,suggesting high therapeutic potential from understanding this family of BMP *** it was once one of the least characterized BMPs,BMP9 has revealed itself to have the highest osteogenic potential across numerous experiments both in vitro and in vivo,with recent studies suggesting that the exceptional potency of BMP9 may result from unique signaling pathways that differentiate it from other *** effectiveness of BMP9 in inducing bone formation was recently revealed in promising experiments that demonstrated efficacy in the repair of critical sized cranial defects as well as compatibility with bone-inducing bio-implants,revealing the great translational promise of ***,emerging evidence indicates that,besides its osteogenic activity,BMP9 exerts a broad range of biological functions,including stem cell differentiation,angiogenesis,neurogenesis,tumorigenesis,and *** review aims to summarize our current understanding of BMP9 across biology and the body.

关键词： Adipogenesis Bone morphogenetic proteins(BMPs) BMP9/GDF2 Mesenchymal stem cells(MSCs) Metabolism Osteogenesis Regenerative medicine Tumorigenesis

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Up-to-constants comparison of Liouville first passage percolation and Liouville quantum gravity

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Science China Mathematics 2023年第5期66卷 1053-1072页

作者： Jian Ding Ewain Gwynne school of Mathematical Sciences Peking UniversityBeijing 100871China Department of Mathematics The University of ChicagoChicagoIL 60637USA

Liouville rst passage percolation(LFPP)with the parameterξ>0 is the family of random distance functions{D_(h)^(ϵ)}ϵ>0 on the plane obtained by integrating e^(ξh),along paths,where{h_(ϵ)}ϵ>0 is a smooth molli cation of the planar Gaussian free *** works have shown that for allξ>0,the LFPP metrics,appropriately re-scaled,admit non-trivial subsequential limiting *** the caseξ0,each possible subsequential limiting metric is nearly bi-Lipschitz equivalent to the LFPP metric D_(h)^(ϵ)whenϵis small,even ifϵdoes not belong to the appropriate *** this result,we obtain bounds for the scaling constants for LFPP which are sharp up to polylogarithmic *** also prove that any two subsequential limiting metrics are bi-Lipschitz *** results are an input in subsequent works which shows that the subsequential limits of LFPP induce the same topology as the Euclidean metric whenξ=ξ_(crit)and that the subsequential limit of LFPP is unique whenξ≥ξcrit.

关键词： Liouville quantum gravity Gaussian free eld LQG metric Liouville rst passage percolation supercritical LQG

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Understanding the metal-to-insulator transition in La_(1−x)Sr_(x)CoO_(3−δ) and its applications for neuromorphic computing

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npj Computational Materials 2020年第1期6卷 261-269页

作者： Shenli Zhang Giulia Galli Pritzker school of Molecular Engineering The University of ChicagoChicagoILUSA Argonne National Laboratory ArgonneILUSA Department of Chemistry The University of ChicagoChicagoILUSA

Transition metal oxides that exhibit a metal-to-insulator transition(MIT)as a function of oxygen vacancy concentration are promising systems to realize energy-efficient platforms for neuromorphic ***,the current lack of understanding of the microscopic mechanism driving the MIT hinders the realization of effective and stable *** we investigate defective cobaltites and we unravel the structural,electronic,and magnetic changes responsible for the MIT when oxygen vacancies are introduced in the *** show that,contrary to accepted views,cooperative structural distortions instead of local bonding changes are responsible for the MIT,and we describe the subtle interdependence of structural and magnetic ***,we present a model,based on first principles,to predict the required electric bias to drive the transition,showing good agreement with available measurements and providing a paradigm to establish design rules for low-energy cost devices.

关键词： transition insulator hinder

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Syrosingopine,an anti-hypertensive drug and lactate transporter(MCT1/4)inhibitor,activates hepatic stellate cells and exacerbates liver fibrosis in a mouse model

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Genes & Diseases 2024年第4期11卷 28-30页

作者： Meichun Guo Yannian Gou Xiangyu Dong Jiamin Zhong Aohua Li Ailing Hao Tongchuan He Jiaming Fan Ministry of Education Key Laboratory of Diagnostic Medicine and the School of Laboratory Diagnostic MedicineChongqing Medical UniversityChongqing 400016China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA

Syrosingopine is an anti-hypertensive drug and can cause high intracellular lactate levels and end-product inhibition of lactate dehydrogenase by inhibiting the lactate transporters MCT1 and *** studies have shown that syrosingopine plays an essential role in the process of glycolytic blockade,ATP depletion,and cell death in cancer due to high intracellular levels of lactate.

关键词： hypertensive MCT1 drug

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Niclosamide(NA)overcomes cisplatin resistance in human ovarian cancer

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Genes & Diseases 2023年第4期10卷 1687-1701页

作者： Linjuan Huang Jing Zhang Youling Deng Hao Wang Piao Zhao Guozhi Zhao Wei Zeng Yonghui Wang Connie Chen William Wagstaff Rex C.Haydon Russell R.Reid Tong-Chuan He Le Shen Hue H.Luu Ling Zhao Departments of Obstetrics and Gynecology Orthopaedic Surgery and UrologyThe First Affiliated Hospital of Chongqing Medical UniversityChongqing 400046China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Department of Neurology The Second Affiliated Hospital of Jianghan UniversityWuhanHubei 430050China Department of Clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China Laboratory of Craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Department of Surgery The University of Chicago Medical CenterChicagoIL 60637USA

Ovarian cancer(OC)is one of the most lethal malignancies of the female reproduc-tive *** patients are usually diagnosed at advanced stages due to the lack of early *** standard treatment for OC includes a combination of debulking surgery and platinum-taxane chemotherapy,while several targeted therapies have recently been approved for maintenance *** vast majority of OC patients relapse with chemoresistant tu-mors after an initial ***,there is an unmet clinical need to develop new therapeu-tic agents to overcome the chemoresistance of *** anti-parasite agent niclosamide(NA)has been repurposed as an anti-cancer agent and exerts potent anti-cancer activities in human cancers including ***,we investigated whether NA could be repurposed as a therapeutic agent to overcome cisplatin-resistant(CR)in human OC *** this end,we first established two CR lines SKOV3CR and OVCAR8CR that exhibit the essential biological characteristics of cisplatin resistance in human *** showed that NA inhibited cell proliferation,sup-pressed cell migration,and induced cell apoptosis in both CR lines at a low micromole ***,NA inhibited multiple cancer-related pathways including AP1,ELK/SRF,HIF1,and TCF/LEF,in SKOV3CR and OVCAR8CR *** was further shown to effectively inhibit xenograft tumor growth of SKOV3CR ***,our findings strongly suggest that NA may be repurposed as an efficacious agent to combat cisplatin resistance in chemoresistant hu-man OC,and further clinical trials are highly warranted.

关键词： Chemotherapy resistance Cisplatin Drug repurposing Niclosamide Ovarian cancer

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Minimally invasive esophagectomy

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World Journal of Gastroenterology 2010年第30期16卷 3811-3815页

作者： Fernando A Herbella Marco G Patti Department of Surgery University of Chicago Pritzker School of MedicineChicagoIL 60637United States

Esophageal resection is associated with a high morbidity and mortality rate. Minimally invasive esophagectomy (MIE) might theoretically decrease this rate. We reviewed the current literature on MIE, with a focus on the available techniques, outcomes and comparison with open surgery. This review shows that the available literature on MIE is still crowded with heterogeneous studies with different techniques. There are no controlled and randomized trials, and the few retrospective comparative cohort studies are limited by small numbers of patients and biased by historical controls of open surgery. Based on the available literature, there is no evidence that MIE brings clear benef its compared to conventional esophagectomy. Increasing experience and the report of larger series might change this scenario.

关键词： Esophageal resection Transhiatal esophagectomy Transthoracic esophagectomy Esophageal cancer Minimally invasive esophagectomy Laparoscopy Thoracoscopy

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Gastroesophageal reflux disease:From pathophysiology to treatment

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World Journal of Gastroenterology 2010年第30期16卷 3745-3749页

作者： Fernando A Herbella Marco G Patti Department of Surgery University of Chicago Pritzker School of MedicineChicagoIL 60637United States

This review focuses on the pathophysiology of gastroesophageal reflux disease (GERD) and its implications for treatment. The role of the natural anti-reflux mechanism (lower esophageal sphincter, esophageal peristalsis, diaphragm, and trans-diaphragmatic pressure gradient), mucosal damage, type of refluxate, presence and size of hiatal hernia, Helicobacter pylori infection, and Barrett’s esophagus are reviewed. The conclusions drawn from this review are: (1) the pathophysiology of GERD is multifactorial; (2) because of the pathophysiology of the disease, surgical therapy for GERD is the most appropriate treatment; and (3) the genesis of esophageal adenocarcinoma is associated with GERD.

关键词： Gastroesophageal reflux disease Pathophysiology Acid reflux Non-acid reflux Esophageal manometry Ambulatory pH Barrett’s esophagus Esophageal adenocarcinoma

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SATB2:A versatile transcriptional regulator of craniofacial and skeleton development,neurogenesis and tumorigenesis,and its applications in regenerative medicine

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Genes & Diseases 2022年第1期9卷 95-107,I0005页

作者： Xia Huang Qiuman Chen Wenping Luo Mikhail Pakvasa Yuxin Zhang Liwen Zheng Shuang Li Zhuohui Yang Huan Zeng Fang Liang Fugui Zhang Daniel A.Hu Kevin H.Qin Eric J.Wang David S.Qin Russell R.Reid Tong-Chuan He Aravind Athiviraham Mostafa El Dafrawy Hongmei Zhang Stomatological Hospital of Chongqing medical University Chongqing 401147PR China Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences Chongqing 401147PR China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA The Pritzker school of Medicine The University of Chicago Medical CenterChicagoIL 60637USA Department of Surgery The University of Chicago Medical CenterChicagoIL 60637USA Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education Chongqing 401147PR China

SATB2(special AT-rich sequence-binding protein 2)is a member of the special AT-rich binding protein *** a transcription regulator,SATB2 mainly integrates higher-order chromatin ***2 expression appears to be tissue-and stage-specific,and is governed by several cellular signaling molecules and *** in branchial arches and osteoblast-lineage cells,SATB2 plays a significant role in craniofacial pattern and skeleton *** addition to regulating osteogenic differentiation,SATB2 also displays versatile functions in neural development and cancer *** an osteoinductive factor,SATB2 holds great promise in improving bone regeneration toward bone defect *** this review,we have summarized our current understanding of the physiological and pathological functions of SATB2 in craniofacial and skeleton development,neurogenesis,tumorigenesis and regenerative medicine.

关键词： Bone regeneration Development Neurogenesis SATB2 Tumorigenesis

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Red ginseng and cancer treatment

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Chinese Journal of Natural Medicines 2016年第1期14卷 7-16页

作者： WANG Chong-Zhi Samantha ANDERSON DU Wei HE Tong-Chuan YUAN Chun-Su Tang Center for Herbal Medicine Research and Department of Anesthesia & Critical CareThe Pritzker School of MedicineUniversity of Chicago Ben May Department for Cancer Research The Pritzker School of MedicineUniversity of Chicago Molecular Oncology Laboratory Department of Orthopedic SurgeryThe Pritzker School of MedicineUniversity of Chicago Committee on Clinical Pharmacology and Pharmacogenomics The Pritzker School of MedicineUniversity of Chicago

The ginseng family,including Panax ginseng(Asian ginseng),Panax quinquefolius(American ginseng),and Panax notoginseng(notoginseng),is commonly used herbal *** ginseng is prepared by air-drying after harvest,while red ginseng is prepared by a steaming or heating *** anticancer activity of red ginseng is significantly increased,due to the production of active anticancer ginsenosides during the steaming treatment,compared with that of white *** far,anticancer studies have been mostly focused on Asian *** this article,we review the research progress made in the anticancer activities of red Asian ginseng,red American ginseng and red *** major anticancer mechanisms of red ginseng compounds include cell cycle arrest,induction of apoptosis/paraptosis,and inhibition of *** structure-function relationship analysis has revealed that the protopanaxadiol group ginsenosides have more potent effects than the protopanaxatriol *** molecules in ginsenosides inversely impact the antiproliferative potential of these *** addition,ginsenoside stereoselectivity and double bond position also influence the anticancer *** studies should focus on characterizing active red ginseng derivatives as potential anticancer drugs.

关键词： Red ginseng Panax ginseng Panax quinquefolius Panax notoginseng Cancer chemoprevention

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