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Cell–cell contact with proinflammatory macrophages enhances the immunotherapeutic effect of mesenchymal stem cells in two abortion models

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Cellular & Molecular Immunology 2019年第12期16卷 908-920页

作者： Yanhong Li Di Zhang Ling Xu Lin Dong Ji Zheng Yikong Lin Jiefang Huang Yanyun Zhang Yu Tao Xingxing Zang Dajin Li Meirong Du Laboratory for Reproductive Immunology NHC Key Lab of Reproduction Regulation(Shanghai Institute of Planned Parenthood Research)Shanghai Key Laboratory of Female Reproductive Endocrine Related DiseasesHospital of Obstetrics and GynecologyFudan University Shanghai Medical CollegeShanghaiChina Department of Clinical Pharmacy Zhongshan HospitalFudan UniversityShanghaiChina Department of Immunology Medical College of Soochow UniversitySuzhouJiangsuChina Key Laboratory of Stem Cell Biology Institute of Health SciencesShanghai Jiao Tong University School of Medicine(SJTUSM)&Shanghai Institutes for Biological SciencesChinese Academy of SciencesShanghaiChina Department of Medicine Montefiore Medical CenterAlbert Einstein College of MedicineBronxNYUSA

Mesenchymal stem cells(MSCs),which are pluripotent cells with immunomodulatory properties,have been considered good candidates for the therapy of several immune disorders,such as inflammatory bowel diseases,concanavalin A-induced liver injury,and graft-versus-host *** embryo is a natural allograft to the maternal immune system.A successful pregnancy depends on the timely extinction of the inflammatory response induced by embryo implantation,followed by the switch to a tolerant immune microenvironment in both the uterus and the *** infiltration of immune cells and serious inflammatory responses are triggers for embryo rejection,which results in ***,we demonstrated that adoptive transfer of MSCs could prevent fetal loss in a lipopolysaccharide(LPS)-induced abortion model and immune response-mediated spontaneous abortion *** immunosuppressive MSCs alleviated excessive inflammation by inhibiting CD4+T cell proliferation and promoting the decidual macrophage switch to M2 in a tumor necrosis factor-stimulated gene-6(TSG-6)-dependent ***-tocell contact with proinflammatory macrophages increased the TSG-6 production by the MSCs,thereby enhancing the suppressive regulation of T cells and ***,proinflammatory macrophages in contact with the MSCs upregulated the expression of CD200 on the stem cells and facilitated the reprogramming of macrophages towards an anti-inflammatory skew through the interaction of CD200 with CD200R on proinflammatory ***,the results demonstrate that a TSG-6-mediated paracrine effect,reinforced by cell-to-cell contact between MSCs and proinflammatory macrophages,is involved in the mechanism of MSC-mediated abortion relief through the induction of immune *** study also indicates the potential application of MSCs in clinical recurrent miscarriages.

关键词： inflammatory effect thereby

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Non-pulmonary allergic diseases and inflammatory bowel disease: A qualitative review

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World Journal of Gastroenterology 2014年第32期20卷 11023-11032页

作者： David S Kotlyar Mili Shum Jennifer Hsieh Wojciech Blonski David A Greenwald Medical Oncology Service NIH National Can-cer InstituteNational Institutes of Health Department of Medicine New York/Presbyterian Medical CenterNew YorkNY 10021 United States Division of Gastroenterology Department of Med-icineSUNY Stony BrookStony Brook Department of Medicine SUNY Upstate Binghamton Campus BinghamtonNY 13902 United States Medical University 53-111 Wroclaw Poland Division of Gastroenterology and Liver Dis-eases Department of MedicineMontefiore Medical Center Albert Einstein College of Medicine Bronx

While the etiological underpinnings of inflammatory bowel disease(IBD) are highly complex, it has been not-ed that both clinical and pathophysiological similarities exist between IBD and both asthma and non-pulmonary allergic phenomena. In this review, several key points on common biomarkers, pathophysiology, clinical manifesta-tions and nutritional and probiotic interventions for both IBD and non-pulmonary allergic diseases are *** and mast cell activity show common behav-iors in both IBD and in certain allergic disorders. IgE also represents a key immunoglobulin involved in both IBD and in certain allergic pathologies, though these links require further study. Probiotics remain a critically important intervention for both IBD subtypes as well as multiple allergic phenomena. Linked clinical phenomena, especially sinonasal disease and IBD, are discussed. In addition, nutritional interventions remain an underuti-lized and promising therapy for modification of both al-lergic disorders and IBD. Recommending new mothers breastfeed their infants, and increasing the duration of breastfeeding may also help prevent both IBD and al-lergic diseases, but requires more investigation. While much remains to be discovered, it is clear that non-pulmonary allergic phenomena are connected to IBD in a myriad number of ways and that the discovery of com-mon immunological pathways may usher in an era of vastly improved treatments for patients.

关键词： Inflammatory bowel disease Ulcerative colitis Crohn's disease Food intolerance Food allergies Biomarkers Pathophysiology Nutrition Probiotics

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Crosstalk between the B7/CD28 and EGFR pathways:Mechanisms and therapeutic opportunities

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Genes & Diseases 2022年第5期9卷 1181-1193页

作者： Xiaoxin Ren Yixian Li Christopher Nishimura Xingxing Zang Department of Microbiology and Immunology Albert Einstein College of MedicineNew YorkNY 10461USA Division of Pediatric Hematology/Oncology/Transplant and Cellular Therapy Children's Hospital at MontefioreBronxNY 10467USA Department of Medicine Albert Einstein College of MedicineNew YorkNY 10461USA Department of Urology Albert Einstein College of MedicineNew YorkNY 10461USA

Somatic activating mutations in the epidermal growth factor receptor(EGFR)are one of the most common oncogenic drivers in cancers such as non-small-cell lung cancer(NSCLC),metastatic colorectal cancer,glioblastoma,head and neck cancer,pancreatic cancer,and breast ***-targeted agents against EGFR signaling pathways have shown robust clinical efficacy,but patients inevitably experience acquired *** immune checkpoint inhibitors(ICIs)targeting PD-1/PD-L1 have exhibited durable anti-tumor responses in a subset of patients across multiple cancer types,their efficacy is limited in cancers harboring activating gene alterations of *** studies have demonstrated that upregulation of new B7/CD28 family members such as B7-H3,B7x and HHLA2,is associated with EGFR signaling and may contribute to resistance to EGFR-targeted therapies by creating an immunosuppressive tumor microenvironment(TME).In this review,we discuss the regulatory effect of EGFR signaling on the PD-1/PD-L1 pathway and new B7/CD28 family member *** these interactions may inform combination therapeutic strategies and potentially overcome the current challenge of resistance to EGFR-targeted *** also summarize clinical data of anti-PD-1/PD-L1 therapies in EGFR-mutated cancers,as well as ongoing clinical trials of combination of EGFR-targeted therapies and anti-PD-1/PD-L1 immunotherapies.

关键词： Combination therapies EGFR Immune checkpoint blockade New B7/CD28 members PD-1/PD-L1 pathway

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Association between donor corneal endothelial cell counts and infectious agent reactivity:an eye bank database analysis

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Annals of Eye Science 2019年第1期4卷 19-22页

作者： Bella J.Wolf Ji Won Kwon Gabriel M.Rand Jimmy K.Lee Patrick K.Gore Moonseong Heo Roy S.Chuck Department of Ophthalmology and Visual ciences Montefiore Medical CenterAlbert Einstein College of MedicineNew YorkNYUSA Department of Ophthalmology Myongji HospitalSeonam University College of MedicineGoyangKorea Lions Eye institute for Transplant&Research TampaFloridaUSA Saving Sight Eye Bank Kansas CityMissouriUSA Department of Epidemiology and Population Health at Einstein Montefiore Medical CenterAlbert Einstein College of MedicineBronxNew YorkUSA

Background:To evaluate the association between corneal central endothelial cell count(CECC)with reactivity for hepatitis B virus(HBV),hepatitis C virus(HCV),human immunodeficiency virus(HIV),human T-lymphotropic virus-1(HTLV1),and syphilis from an eye bank ***:Eye bank data included 19,159 donors and 38,318 corneas screened for HBV,HCV,HIV,HTLV1,and syphilis from July 2007-May *** and binary mixed effects models were used to determine the adjusted marginal effect a positive viral screening test had on CECC and morphology,*** models were adjusted for age,race,gender,lens status,and death to *** with missing data were excluded from the *** significance was defined as P values<***:A total of 18,097 donors and 35,136 corneas were included in the final *** CECC for eyes with negative viral screening was 2,597±436 while the average CECC for eyes screening positive for syphilis,HBV,HCV,HIV,and HTLV1 were 2,638±392(P=0.073),2,569±419(P=0.815),2,603±363(P=0.207),2,615±360(P=0.733),and 2,625±436(P=0.362)***:The presence of HBV,HCV,HIV,HTLV1,and syphilis display no association with a statistically significant difference in CECC when compared to normal non-diseased donors.

关键词： Eye bank endothelial cell count infectious reactivity hepatitis B virus(HBV) syphilis

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Bridge plating in the setting of radiocarpal instability:Does distal fixation to the second or third metacarpal matter?A cadaveric study

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World Journal of Orthopedics 2023年第4期14卷 207-217页

作者： Eloy Tabeayo James M Saucedo Ramesh C Srinivasan Amita R Shah Efstathios Karamanos Jason Rockwood E Carlos Rodriguez-Merchan Department of Orthopedic Surgery Albert Einstein College of MedicineMontefiore Medical CenterNew YorkNY 10461United States Houston Methodist institute for Academic Medicine Houston Methodist Orthopedics and Sports MedicineHoustonTX 77479United States Hand Center of San Antonio and the Department of Orthopedic Surgery University of Texas Health Science CenterThe Hand Center of San AntonioSan AntonioTX 78240United States University of Texas Health Science Center at San Antonio University of North Carolina at Chapel HillSan AntonioTX 78229United States Surgeon in the Division of Acute Care Surgery in the Department of Surgery at Henry Ford Hospital in Detroit UT Health San AntonioSan AntonioTX 78229United States Naval Hospital Yokosuka Yokosuka96350-1600Japan Department of Orthopedic Surgery La Paz University Hospital-IdiPazMadrid 28046Spain

BACKGROUND Radiocarpal dislocations are rare but potentially devastating *** outcomes are associated with inadequate or lost reduction,such as ulnar translocation,but no consensus exists on the ideal fixation *** bridge plate fixation has been described for various settings in the treatment of complex distal radius fractures and can be fixed distally to the second or third metacarpal,but its application for radiocarpal dislocations has not been *** To determine whether distal fixation to the second or third metacarpal *** Using a cadaveric radiocarpal dislocation model,the effect of distal fixation was studied in two stages:(1)A pilot study that investigated the effect of distal fixation alone;and(2)a more refined study that investigated the effect of described techniques for distal and proximal *** were measured in various parameters to determine the quality of the reduction *** The pilot study found that focusing on distal fixation alone without changing proximal fixation results in ulnar translocation and volar subluxation when fixing distally to the second metacarpal compared with the *** second iteration demonstrated that anatomic alignment in coronal and sagittal planes could be achieved with each *** In a cadaveric radiocarpal dislocation model,anatomic alignment can be maintained with bridge plate fixation to the second metacarpal or the third metacarpal if the described technique is *** considering dorsal bridge plate fixation for radiocarpal dislocations,the surgeon is encouraged to understand the nuances of different fixation techniques and how implant design features may influence proximal placement.

关键词： Wrist Instability Bridge plate Dorsal spanning plate Radiocarpal dislocation model Cadaveric study

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Renal impairment and heart failure with preserved ejection fraction early post-myocardial infarction

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World Journal of Cardiology 2010年第1期2卷 13-18页

作者： Vinod Jorapur Gervasio A Lamas Zygmunt P Sadowski Harmony R Reynolds Antonio C Carvalho Christopher E Buller James M Rankin Jean Renkin Philippe Gabriel Steg Harvey D White Carlos Vozzi Eduardo Balcells Michael Ragosta C Edwin Martin Vankeepuram S Srinivas William W Wharton III Staci Abramsky Ana C Mon Shari S Kronsberg Judith S Hochman Columbia University Division of Cardiology Mount Sinai Medical Center II Ischemic Heart Disease Department National Institute of Cardiology Leon Charney Division of Cardiology New York University School of Medicine Cardiology Division-Hospital Sao Paulo Federal University of Sao Paulo Division of Cardiology University of British Columbia Department of Cardiovascular Medicine Royal Perth Hospital Department of Cardiology UCL St Luc University Hospital INSERM U-698 Department of CardiologyHopital Bichat Cardiology Department Green Lane Cardiovascular ServiceAuckland City Hospital Interventional Cardiology Instituto de Intervenciones Cardiovasculares S.A. Cardiovascular Associates Wellmont Holston Valley Medical Center Cardiovascular Division University of Virginia Department of Medicine-Division of Cardiology York Hospital Division of Cardiology Montefiore Medical Center/Albert Einstein College of Medicine Research Department Asheville Cardiology AssociatesP.A. Maryland Medical Research institute

AIM:To study if impaired renal function is associated with increased risk of peri-infarct heart failure (HF) in patients with preserved ejection fraction (EF).METHODS:Patients with occluded infarct-related arteries (IRAs) between 1 to 28 d after myocardial infarction (MI) were grouped into chronic kidney disease (CKD) stages based on estimated glomerular filtration rate (eGFR).Rates of early post-MI HF were compared among eGFR *** regression was used to explore independent predictors of ***:Reduced eGFR was present in 71.1% of 2160 patients,with significant renal impairment (eGFR < 60 mL/min every 1.73 m2) in 14.8%.The prevalence of HF was higher with worsening renal function:15.5%,17.8% and 29.4% in patients with CKD stages 1,2 and 3 or 4,respectively (P < 0.0001),despite a small absolute difference in mean EF across eGFR groups:48.2 ± 10.0,47.9 ± 11.3 and 46.2 ± 12.1,respectively (P=0.02).The prevalence of HF was again higher with worsening renal function among patients with preserved EF:10.1%,13.6% and 23.6% (P < 0.0001),but this relationship was not significant among patients with depressed EF:27.1%,26.2% and 37.9% (P= 0.071).Moreover,eGFR was an independent correlate of HF in patients with preserved EF (P=0.003) but not in patients with depressed EF (P=0.181).CONCLUSION:A significant proportion of post-MI patients with occluded IRAs have impaired renal *** renal function was associated with an increased rate of early post-MI HF,the association being strongest in patients with preserved *** findings have implications for management of peri-infarct HF.

关键词： Heart failure Myocardial infarction Kidney disease

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