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CD8+T cell metabolic flexibility elicited by CD28-ARS2 axisdriven alternative splicing of Pk. supports antitumor immunity

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Cellular & molecular Immunology 2024年第3期21卷 260-274页

作者： G.Aaron Holling Colin A.Chavel Anand P.Sharda mack.nzie m.Lieberman Caitlin m.James Shivana m.Lightman Jason H.Tong Guanxi Qiao Tiffany R.Emmons Thejaswini Giridharan Shengqi Hou Andrew m.Intlek.fer Richard m.Higashi Teresa W.m.Fan Andrew N.Lane k.vin H.Eng Brahm H.Segal Elizabeth A.Repask. k.lvin P.Lee Scott H.Olejniczak Department of Immunology Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Department of medicine Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Human Oncology and Pathogenesis Program Memorial Sloan Kettering Cancer CenterNew YorkNY 10065USA Center for Environmental Systems Biochemistry Department of Toxicology and Cancer Biology and Markey Cancer CenterLexingtonKY 40536USA Department of Cancer Genetics and Genomics Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Present address:University of Colorado Boulder BoulderCO 80309USA Present address:Dana farber Cancer Institute BostonMA 02215USA Present address:massachusetts Institute of Technology BostonMA 02139USA Present address:melvin and Bren Simon Comprehensive Cancer Center Indiana University School of MedicineIndianapolisIN 46202USA

metabolic flexibility has emerged as a critical determinant of CD8+T-cell antitumor activity,yet the mechanisms driving the metabolic flexibility of T cells have not been *** this study,we investigated the influence of the nuclear cap-binding complex(CBC)adaptor protein ARS2 on mature T *** doing so,we discovered a novel signaling axis that endows activated CD8+T cells with flexibility of glucose ***2 upregulation driven by CD28 signaling reinforced splicing factor recruitment to pre-mRNAs and affected approximately one-third of T-cell activation-induced alternative splicing *** these effects,the CD28-ARS2 axis suppressed the expression of the m1 isoform of pyruvate k.nase in favor of Pk.2,a k.y determinant of CD8+T-cell glucose utilization,interferon gamma production,and antitumor effector ***,Pk. alternative splicing occurred independently of CD28-driven PI3k.pathway activation,revealing a novel means by which costimulation reprograms glucose metabolism in CD8+T cells.

关键词： Immunometabolism mRNA splicing CD8 T cells ARS2 Pk.2

Pathway-selective suppression of chemok.ne receptor signaling in B cells by LPS through downregulation of PLC-b2

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Cellular & molecular Immunology 2010年第6期7卷 428-439页

作者： Aik.-k.nno Shirak.wa Fang Liao Hongwei H Zhang michael N Hedrick.Satya P Singh Dianqing Wu Joshua m farber Inflammation Biology Section Laboratory of Molecular ImmunologyNational Institute of Allergy and Infectious DiseasesNational Institutes of HealthBethesdaMDUSA Department of Pharmacology Yale University School of MedicineNew HavenCTUSA

Lymphocyte activation leads to changes in chemok.ne receptor *** are limited data,however,on how lymphocyte activators can alter chemok.ne signaling by affecting downstream *** hypothesized that B cell-activating agents might alter chemok.ne responses by affecting downstream signal transducers,and that such effects might differ depending on the *** found that activating mouse B cells using either anti-Igm or lipopolysaccharide(LPS)increased the surface expression of CCR6 and CCR7 with large increases in chemotaxis to their cognate *** contrast,while anti-Igm also led to enhanced calcium responses,LPS-treated cells showed only small changes in calcium signaling as compared with cells that were freshly *** particular interest,we found that LPS caused a reduction in the level of B-cell phospholipase C(PLC)-b2 mRNA and *** obtained using PLC-b22/2 mice showed that the b2 isoform mediates close to one-half the chemok.ne-induced calcium signal in resting and anti-Igm-activated B cells,and we found that calcium signals in the LPS-treated cells were boosted by increasing the level of PLC-b2 using transfection,consistent with a functional effect of downregulating ***,our results show activator-specific effects on responses through B-cell chemok.ne receptors that are mediated by quantitative changes in a downstream signal-transducing protein,revealing an activity for LPS as a downregulator of PLC-b2,and a novel mechanism for controlling chemok.ne-induced signals in lymphocytes.

关键词： B cells calcium chemok.ne chemotaxis GPCR

Current evidence on potential of adipose derived stem cells to enhance bone regeneration and future projection

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World Journal of Stem Cells 2021年第9期13卷 1248-1277页

作者： Quang Le Vedavathi madhu Joseph m Hart Charles R farber Eli R Zunder Abhijit S Dighe Quanjun Cui Department of Orthopaedic Surgery University of Virginia School of MedicineCharlottesvilleVA 22908United States Orthopaedic Surgery Research Thomas Jefferson UniversityPhiladelphiaPA 19107United States Center for Public Health Genomics University of VirginiaCharlottesvilleVA 22908United States Departments of Public Health Sciences and Biochemistry and molecular Genetics University of VirginiaCharlottesvilleVA 22908United States Department of Biomedical Engineering University of VirginiaCharlottesvilleVA 22908United States

Injuries to the postnatal sk.leton are naturally repaired through successive stepsinvolving specific cell types in a process collectively termed “bone regeneration”.Although complex, bone regeneration occurs through a series of well-orchestratedstages wherein endogenous bone stem cells play a central role. In most situations,bone regeneration is successful;however, there are instances when it fails andcreates non-healing injuries or fracture nonunion requiring surgical or therapeuticinterventions. Transplantation of adult or mesenchymal stem cells (mSCs) definedby the International Society for Cell and Gene Therapy (ISCT) as CD105+-CD90+CD73+CD45-CD34-CD14orCD11b-CD79αorCD19-HLA-DR- is beinginvestigated as an attractive therapy for bone regeneration throughout the *** isolated from adipose tissue, adipose-derived stem cells (ADSCs), aregaining increasing attention since this is the most abundant source of adult stemcells and the isolation process for ADSCs is straightforward. Currently, there isnot a single Food and Drug Administration (FDA) approved ADSCs product forbone regeneration. Although the safety of ADSCs is established from their usagein numerous clinical trials, the bone-forming potential of ADSCs and mSCs, ingeneral, is highly controversial. Growing evidence suggests that the ISCT definedphenotype may not represent bona fide osteoprogenitors. Transplantation of bothADSCs and the CD105- sub-population of ADSCs has been reported to induce bone regeneration. most notably, cells expressing other mark.rs such as CD146,AlphaV, CD200, PDPN, CD164, CXCR4, and PDGFRα have been shown torepresent osteogenic sub-population within ADSCs. Amongst other strategies toimprove the bone-forming ability of ADSCs, modulation of VEGF, TGF-β1 andBmP signaling pathways of ADSCs has shown promising results. The U.S. FDAreveals that 73% of Investigational New Drug applications for stem cell-basedproducts rely on CD105 expression as the “positive” mark.r for adult stem cell

关键词： mesenchymal stem cells Adipose-derived stem cells Endogenous stem cells Sk.letal stem cells Bone regeneration

Impact of Social Determinants of Health on Self-Perceived Resilience: An Exploratory Study of Two Cohorts of Adults with Congenital Heart Disease

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Congenital Heart Disease 2024年第1期19卷 33-48页

作者： Albert Osom k.ysta S.Barton k.tie Sexton Lyndia Brumback.Joyce P.Yi-Frazier Abby R.Rosenberg Ruth Engelberg Jill m.Steiner Department of Biostatistics University of WashingtonSeattleWA98195USA Biostatistics Epidemiology and Analytics for Research(BEAR)Core Seattle Children’s Research InstituteSeattleWA98101USA College of medicine University of WashingtonSeattleWA98195USA Center for Clinical and Translational Research Seattle Children’s Research InstituteSeattleWA98101USA Department of Psychosocial Oncology and Palliative Care Dana-Farber Cancer InstituteDepartment of MedicineBoston Children’s HospitalBostonMA02215USA Department of Pediatrics Harvard Medical SchoolBostonMA02215USA Division of Pulmonary Critical Care and Sleep MedicineDepartment of Medicine&Cambia Palliative Care Center of ExcellenceUniversity of WashingtonHarborview Medical CenterSeattleWA98104USA Division of Cardiology Department of Medicine&Cambia Palliative Care Center of ExcellenceUniversity of WashingtonSeattleWA98195USA

Social determinants of health(SDOH)affect quality of *** investigated SDOH impacts on self-perceived resilience among people with adult congenital heart disease(ACHD).Secondary analysis of data from two com-plementary studies:a survey study conducted may 2021–June 2022 and a qualitative study conducted June 2020–August *** was assessed through CD-RISC10 score(range 0–40,higher scores reﬂect greater self-perceived resilience)and interview *** and SDOH(education,employment,living situa-tion,monetary stability,ﬁnancial dependency,area deprivation index)data were collected by healthcare record review and *** used linear regression with robust standard errors to analyze survey data and performed a thematic analysis of interview *** participants(N=127)mean age was 42±14 years;51%were female,87%*** was moderate(75%)or complex(25%);41%functional class C or ***(mean 30±7)varied by monetary stability:compared to people with difﬁculty paying bills,resilience was 15.0 points higher(95%CI:6.9–23.1,pmoney and 14.2 points higher(95%CI:5.9–22.4,p=0.001)for those reporting just enough *** participants’(N=25)mean age was 32 years(range 22–44);52%were female,72%*** was moderate(56%)or complex(44%);76%functional class C or *** discussed factors affecting resilience aligned with each of the major SDOH,prominently,economic stability and healthcare access and *** stability may be important for supporting self-perceived resi-lience in *** k.owledge can inform the development of resilience interventions for this population.

关键词： Social determinants of health adult congenital heart disease resilience ﬁnancial stability

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N异靛甲对培养的人类角朊细胞的作用

中华皮肤科杂志 1996年第2期29卷 90-92页

作者：林熙然 DavidI.Wilk.nson Eugenem.farber116011 大连医科大学附属第一医院皮肤科美国PaloAlto银屑病研究所斯坦福大学

为了探讨Ｎ异靛甲治疗银屑病的作用机理，我们利用结晶紫染色光吸收、氨基已糖甙酯酶测定、氚胸腺嘧啶掺入、细胞直接计数及细胞分化过程形态学定量等方法研究了该药在不同浓度下对培养的人类角朊细胞增殖及分化的影响。结果显示该药浓... 详细信息

为了探讨Ｎ异靛甲治疗银屑病的作用机理，我们利用结晶紫染色光吸收、氨基已糖甙酯酶测定、氚胸腺嘧啶掺入、细胞直接计数及细胞分化过程形态学定量等方法研究了该药在不同浓度下对培养的人类角朊细胞增殖及分化的影响。结果显示该药浓度为１０－７ｍｏｌ／Ｌ和１０－８ｍｏｌ／Ｌ时对角朊细胞的增殖有抑制作用，浓度为１０－９ｍｏｌ／Ｌ时即无此作用，而浓度为１０－１０ｍｏｌ／Ｌ时对角朊细胞的分化仍有显著促进作用。这说明Ｎ异靛甲对角朊细胞增殖与分化均有影响，但以促进分化为主。提示该药的作用机理不同于一般细胞毒化疗药物。

关键词：异靛甲角朊细胞银屑病

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食品中单核细胞增多性李氏杆菌的研究现状

肉品卫生 1994年第4期 25-28页

作者： J.m.farber 柳增善

在食品安全性方面,单核细胞增多性李氏杆菌是每个人都关心的食源性病原菌,已出版了两本专著和发表许多综述。这里主要讨论三个方面的最新研究现状,即方法学、控制和法规方面的研究现状。在方法学上由于篇幅所限,只能作以简要探讨。

关键词：食品微生物李氏杆菌研究

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罗杰斯心理治疗

作者： (美)Barry A. farber (美)Debora C. Brink.(美)Patricia m. Rask.n

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银屑病第三届国际银屑病讨论会论文汇编

Impact of COVID-19 on presentation,management,and outcomes of acute care surgery for gallbladder disease and acute appendicitis

1983年

作者： Eugene m.farber m.D.Alvin J.Cox m.D.编张国威王光超等译

来源：汇雅图书（南通市图书馆... 评论

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World Journal of Gastrointestinal Surgery 2021年第8期13卷 859-870页

作者： Orly Nadell farber Giselle I Gomez Ashley L Titan Andrea T Fisher Christopher J Puntasecca Veronica Toro Arana Arielle k.mpinsk. Clare E Wise k.vi E Bessoff mary T Hawn James R k.rndorffer Jr Joseph D Forrester micaela m Esquivel Department of Surgery Stanford University School of MedicinePalo AltoCA 94305United States

BACk.ROUND The ongoing coronavirus disease 2019(COVID-19)pandemic has significantly disrupted both elective and acute medical *** from the early months suggest that acute care patient populations deferred presenting to the emergency department(ED),portending more severe disease at the time of ***,care for this patient population trended towards initial non-operative *** To examine the presentation,management,and outcomes of patients who developed gallbladder disease or appendicitis during the *** A retrospective chart review of patients diagnosed with acute cholecystitis,symptomatic cholelithiasis,or appendicitis in two EDs affiliated with a single tertiary academic medical center in Northern California between march and June,2020 and in the same months of *** were selected through a research repository using international classification of diseases(ICD)-9 and ICD-10 *** both years,313 patients were identified with either type of gallbladder disease,while 361 patients were identified with acute *** primary outcome was overall incidence of *** outcomes included presentation,management,complications,and 30-d re-presentation *** between different variables were explored using Pearson’s r correlation *** were compared using the Welch’s t-Test,Chi-squared tests,and Fisher’s exact test as *** Patients with gallbladder disease and appendicitis both had more severe presentations in *** respect to gallbladder disease,more patients in the COVID-19 cohort presented with acute cholecystitis compared to the control cohort[50%(80)vs 35%(53);P=0.01].Patients also presented with more severe cholecystitis in 2020 as indicated by higher mean Tok.o Criteria Scores[mean(SD)1.39(0.56)vs 1.16(0.44);P=0.02].With respect to appendicitis,more patients were diagnosed with a perforated appendix at presentation in 2020[20%(36)vs 16%(29);P=0.0

关键词： COVID-19 Cholecystitis Biliary colic Appendicitis Acute care surgery