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Taxane resistance in castration-resistant prostate cancer: mechanisms and therapeutic strategies

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Acta Pharmaceutica Sinica B 2018年第4期8卷 518-529页

作者： brandon Bumbaca Wei Li Department of Pharmaceutical Sciences College of Pharmacythe University of Tennessee Health Science Center

Despite its good initial response and significant survival benefit in patients with castrationresistant prostate cancer(CRPC), taxane therapy inevitably encounters drug resistance in all patients.Deep understandings of taxane resistant mechanisms can significantly facilitate the development of new therapeutic strategies to overcome taxane resistance and improve CRPC patient survival. Multiple pathways of resistance have been identified as potentially crucial areas of intervention. First, taxane resistant tumor cells typically have mutated microtubule binding sites, varying tubulin isotype expression,and upregulation of efflux transporters. These mechanisms contribute to reducing binding affinity and availability of taxanes. Second, taxane resistant tumors have increased stem cell like characteristics,indicating higher potential for further mutation in response to therapy. Third, the androgen receptor pathway is instrumental in the proliferation of CRPC and multiple hypotheses leading to this pathway reactivation have been reported. The connection of this pathway to the AKT pathway has received significant attention due to the upregulation of phosphorylated AKT in CRPC. This review highlights recent advances in elucidating taxane resistant mechanisms and summarizes potential therapeutic strategies for improved treatment of CRPC.

关键词： Castration-resistant prostate cancer Drug efflux transporters Taxane resistance Androgen receptor pi3K/AKT pathway Microtubules Cancer stem cells Efflux transporter

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若死亡来敲门

科学新闻 2023年第2期 59-60页

作者： brandon Brown Annie Lu Nguyen 倪伟波加州大学河滨分校医学院南加州大学Keck医学院

事情始于4月一次团队会议上的一个幽默尝试。首席研究员（pi）brandon对团队成员Chris的工作表示感谢，然后他抱怨道，如果Chris被公共汽车撞了，他就得去填补巨大的空缺。不久前，一位朋友兼同事突然去世，我们看到了与他共事最密切的...

事情始于4月一次团队会议上的一个幽默尝试。首席研究员（pi）brandon对团队成员Chris的工作表示感谢，然后他抱怨道，如果Chris被公共汽车撞了，他就得去填补巨大的空缺。不久前，一位朋友兼同事突然去世，我们看到了与他共事最密切的人在悲痛中感到的担忧和疑惑。他们将继续研究、为研究生提供建议、追踪数据文件并领导国家协调中心。疫情暴发以来，我们都采取了个人临终规划措施，并意识到这可能与我们的工作生活有关。

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Evolving technologies for growing,imaging and analyzing 3D root system architecture of crop plants

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Journal of Integrative Plant Biology 2016年第3期58卷 230-241页

作者： Miguel A.pieros brandon G.Larson Jon E.Shaff David J.Schneider Alexandre Xavier Falcao Lixing Yuan Randy T.Clark Eric J.Craft Tyler W.Davis pierre-Luc Pradier Nathanael M.Shaw Ithipong Assaranurak Susan R.Mc Couch Craig Sturrock Malcolm Bennett Leon V.Kochian USDA-ARS Robert Holley Center for Agriculture and Health538 Tower RoadIthacaNY 14580USA Department of Information Systems Institute of ComputingUniversity of CampinasAv.Albert Einstein1251CEP 13083-852CampinasSPBrazil Department of Plant Nutrition China Agricultural UniversityBeijing 100193China Department of Plant Breeding and Genetics Cornell UniversityIthacaNY 14853USA Centre for Plant Integrative Biology School of BiosciencesUniversity of NottinghamSutton BoningtonLE12 5RDUK College of Science King Saud UniversityRiyadh 11451Kingdom of Saudi Arabia

A plant＇s ability to maintain or improve its yield under limiting conditions,such as nutrient de ficiency or drought,can be strongly in fluenced by root system architecture（RSA）,the three-dimensional distribution of the different root types in the soil. The ability to image,track and quantify these root system attributes in a dynamic fashion is a useful tool in assessing desirable genetic and physiological root traits. Recent advances in imaging technology and phenotyping software have resulted in substantive progress in describing and quantifying RSA. We have designed a hydroponic growth system which retains the three-dimensional RSA of the plant root system,while allowing for aeration,solution replenishment and the imposition of nutrient treatments,as well as high-quality imaging of the root system. The simplicity and flexibility of the system allows for modi fications tailored to the RSA of different crop species and improved throughput. This paper details the recent improvements and innovations in our root growth and imaging system which allows for greater image sensitivity（detection of fine roots and other root details）,higher ef ficiency,and a broad array of growing conditions for plants that more closely mimic those found under field conditions.

关键词： Abiotic stress digital root phenotyping mineral nutrition root system architecture

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Human immunodeficiency virus type-1 induces a regulatory B cell-like phenotype in vitro

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Cellular & Molecular Immunology 2018年第10期15卷 917-933页

作者： Jacobo Lopez-Abente Adrián Prieto-Sanchez Maria-Ángeles Muñoz-Fernandez Rafael correa-Rocha Marjorie pion Laboratorio de Inmuno-Regulación Immunology DepartmentPabellón de Medicina y Cirugía ExperimentalHospital General Universitario Gregorio MarañónInstituto de Investigación Sanitaria Gregorio Marañón(IiSGM)Calle Máiquez9Madrid 28009Spain Laboratorio de Inmuno-Biología Molecular Immunology DepartmentHospital General Universitario Gregorio MarañónInstituto de Investigación Sanitaria Gregorio Marañón(IiSGM)C/Dr.Esquerdo 46Madrid 28007Spain Networking Research Center on Bioengineering Biomaterials and Nanomedicine(CIBER-BBN)C/Monforte de Lemos 3-5Pabellón 11Madrid 28029Spain

Individuals infected with human immunodeficiency virus type-1(HIV-1)usually show a general dysregulation and hyper-activation of the immune system.A direct influence of HIV-1 particles on B-cell phenotypes and functions has been previously described.However,the consequences of B-cell dysregulation are still poorly understood.We evaluated the phenotypic changes in primary B cells after direct contact with HIV-1 particles in comparison with different types of stimuli.The functionality of treated B cells was challenged in co-culture experiments with autologous CD4+and CD8+T cells.We demonstrated that HIV-1 induces a phenotypic change in B cells towards a regulatory B-cell phenotype,showing a higher level of IL-10,TGF-β1,EBI3 or IL-12(p35)mRNA expression and acquiring an immunosuppressive profile.The acquisition of a Breg phenotype was confirmed by co-culture experiments where HIVtreated B cells reduced the proliferation and the TNFαproduction of CD4+or CD8+T cells.This suppressive ability of HIV-treated B cells was dependent on cell-to-cell contact between these B cells and effector cells.To our knowledge,these data provide the first evidence that HIV-1 can directly induce a regulatory B cell-like immunosuppressive phenotype,which could have the ability to impair specific immune responses.This dysregulation could constitute one of the mechanisms underlying unsuccessful efforts to develop an efficient vaccine against HIV-1.

关键词： HIV-1 immune hyper-activation regulatory B cells

Implications of Klotho in vascular health and disease

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World Journal of Cardiology 2014年第12期6卷 1262-1269页

作者： Ernesto Martín-Núez Javier Donate-correa Mercedes Muros-de-Fuentes Carmen Mora-Fernández Juan F Navarro-González Research Unit University Hospital Nuestra Se?ora de Candelaria 38010 Santa Cruz de Tenerife Spain Clinical Analysis Service and Research Unit University Hospital Nuestra Se ora de Candelaria 38010 Santa Cruz de Tenerife Spain Nephrology Service and Research Unit University Hospital Nuestra Se ora de Candelaria 38010 Santa Cruz de Tenerife Spain

Cardiovascular disease(CVD) is a prevalent condition in general population and the first cause of death overall. Klotho, a pleiotropic protein related to longevity that acts as a co-receptor of the fibroblast growth factor 23, has been proposed as a key regulator of the development of CVD. In the few clinical studies made, it has been observed a relationship between low levels of soluble Klotho and the occurrence and severity of CVD, as well as a reduction of cardiovascular risk when they are high. Also, different polymorphisms of human Klotho gene have been related to the incidence of cardiovascular events. Moreover, several experimental studies indicate that this protein acts in the maintenance of vascular homeostasis. Klotho improves endothelial dysfunction through promotion of NO production and mediates antiinflammatory and anti-aging effects such as suppression of adhesion molecules expression, attenuation of nuclear factor-kappa B or inhibition of Wnt signaling. Furthermore,this protein is related to the attenuation of vascular calcification as well as prevention of cardiac hypertrophy. The expression of this protein in the vascular wall implies a new scenario for the treatment of vascular disorders. The purpose of this review is to provide an overview of the relationship between the Klotho protein and CVD, in addition to its role in the maintenance of functional vascular integrity.

关键词： maintenance cardiovascular hypertrophy homeostasis suppression severity prevalent overview attenuation scenario

Incidenee and time-varying predictors of HIV and sexually transmitted infections among male sex workers in Mexico City

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Infectious Diseases of Poverty 2021年第1期10卷 36-45页

作者： Karla Y.Ganley Marta Wilson-Barthes Andrew R.Zullo Sandra G.Sosa-Rubi Carlos J.Conde-Glez Santa Garcia-Cisneros Mark N.Lurie brandon D.L.Marshall Don Operario Kenneth H.Mayer Omar Galarraga Department of Narrative Medicine Columbia UniversityNew YorkNYUSA Department of Epidemiology School of Public HealthBrown UniversityProvide neeRlUSA Department of Health Services Policyand PracticeSchool of Public HealthBrown University121 South Main StreetBox G-121S-2ProvidenceRl 02912USA National Institute of Public Health(INSP) CuernavacaMorelosMexico Department of Behavioral and Social Science School of Public HealthBrown UniversityProvidenceRlUSA Fenway Health and Harvard University BostonMAUSA.

Background:Male sex workers are at high-risk for acquisition of sexually transmitted infections(STIs),including human immunodeficiency virus(HIV).We quantified incidence rates of STIs and identified their time-varying predictors among male sex workers in Mexico City.Methods:From January 2012 to May 2014,male sex workers recruited from the largest HIV clinic and community sites in Mexico City were tested for chlamydia,gonorrhea,syphilis,hepatitis,and HIV at baseline,6-months,and 12-months.Incide nee rates with 95%bootstrapped confide nee limits were calculated.We examined potential timevarying predictors using generalized estimating equations for a population averaged model.Results:Among 227 male sex workers,median age was 24 and baseline HIV prevalence was 32%.Incidence rates(per 100 person-years)were as follows:HIV[5.23;95%confidence interval(CI):2.15-10.31],chlamydia(5.15;95%CI:2.58-9.34),gonorrhea(3.93;95%CI:1.88-7.83),syphilis(13.04;95%CI:8.24-19.94),hepatitis B(2.11;95%CI:0.53-4.89),hepatitis C(0.95;95%CI:0.00-3.16),any STI except HIV(30.99;95%CI:21.73-40.26),and any STI including HIV(50.08;95%CI:37.6062.55).In the multivariable-adjusted model,incident STI(excluding HIV)were lower among those who reported consistently using condoms during anal and vaginal intercourse(odds ratio=0.03,95%CI:0.00-0.68)compared to those who reported inconsistently using condoms during anal and vaginal intercourse.Conclusions:Incidence of STIs is high among male sex workers in Mexico City.Consistent condom use is an important protective factor for STIs,and should be an important comp on ent of interventions to prevent incide nt infect i ons.

关键词： Male sex worker Men who have sex with men HIV Sexually transmitted infection Transmission Risk factor Mexico

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