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Asian Journal of Andrology 2019年第6期21卷 557-564页

作者： fernanda lopez-moncada Maria Jose Torres Enrique A Castellon Hector R Contreras Department of Basic and Clinic Oncology Faculty of Medic泊eUniversity of ChileSantiago 8389100Chile

Secreted protein acidic and rich in cysteine(SPARC)is a matricellular protein highly expressed in bone tissue that acts as achemoattractant factor promoting the arrival of prostate cancer(PCa)cells to the bone ***,the contribution of SPARCduring the early stages of tumor progression remains *** this study,we show that SPARC is highly expressed in PCa tissueswith a higher Gleason *** stable knockdown and overexpression of SPARC in PC3 and LNCaP cells,respectively,here wedem on strate that en doge nous SPARC induces the epithelial-mesenchymal tran sition(EMT),decreasing E-cadheri n and cytokeratin18 and increasing N-cadheri n and vime ***,SPARC in duces the expression of EMT regulatory tran scription factors Snailfamily transcriptional repressor 1(Snail),Snail family transcriptional repressor 2(Slug),and zinc finger E-box binding homeobox 1(Zeb1).In addition,SPARC knockdown in PC3 cells decreases migration and invasion in vitro,without modifying cell *** results indicate that SPARC might facilitate tumor progression by modifying the cellular phenotype in cancer cells.

关键词： epithelial-mesenchymal transition invasion migration prostate cancer secreted protein acidic and rich in cysteine(SPARC)

Fractions of a chloroform extract of ajenjo leaves (Artemisiamendozana DC. var. mendozana) inhibit the proliferation,viability and clonogenicity of B16-F0 melanoma cells

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BIOCELL 2020年第3期44卷 293-299页

作者： MARÍA ELISA MILLÁN MARÍA fernanda MARRA LEONARDO ANDRÉS SALVARREDI EMILIO FERNANDO LIZARRAGA LUIS ALBERTO lopez Universidad Nacional de Cuyo MendozaArgentina Comisión Nacional de Energía Atómica Buenos AiresArgentina Fundación Escuela de Medicina Nuclear MendozaArgentina Fundación Miguel Lillo y Universidad Nacional de Tucumán San Miguel de TucumánArgentina

The ajenjo,Artemisia mendozana ***(Asteraceae),grows in the Andean foothills of Mendoza and San Juan,Argentina,and is used as a medicinal plant for its antispasmodic and antifungal *** aim of this work was to obtain fractions of a chloroform extract of ajenjo leaves and to evaluate the in vitro effects on proliferation,viability and clonogenicity of B16-F0 melanoma *** a silica gel chromatography column,120 fractions were collected and grouped according to the chromatographic profile in 9 main fractions(F1–F9).Their major compounds identified were:terpenes(F1),terpenes and sesquiterpene lactones(F2–F3),sesquiterpenes(F4–F6)and phenols and sesquiterpenes(F7-9).B16-F0 cells were incubated for 72 h with DMSO(vehicle)or 0.1 mg/ml F1–*** 72 h of culture,F1 decreased both the growing index(GI)and cell viability.F2 and F3 both decreased GI and only F3 decreased clonogenic activity.F4 and F5 both decreased *** F5 decreased cell viability and F4 decreased ***,fractions F6–F8 did not affect any of the cell parameters assayed,while F9 decreased cell viability and inhibited clonogenicity.

关键词： Terpenes Sesquiterpene lactones Sesquiterpenes Phenols

Bruton’s tyrosine kinase inhibitors in primary central nervous system lymphoma:New hopes on the horizon

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World Journal of Clinical Oncology 2024年第5期15卷 587-590页

作者： Leonardo S Lino-Silva Sabrina B Martínez-Villavicencio Luisa fernanda Rivera-moncada Department of Pathology Oncology National Cancer Institute(Mexico)TlalpanMexico City 14080Mexico

In this editorial,we comment on the article by Wang et *** manuscript explores the potential synergistic effects of combining zanubrutinib,a novel oral inhibitor of Bruton’s tyrosine kinase,with high-dose methotrexate(HD-MTX)as a therapeutic intervention for primary central nervous system lymphoma(PCNSL).The study involves a retrospective analysis of 19 PCNSL patients,highlighting clinicopathological characteristics,treatment outcomes,and genomic *** results indicate the combination’s good tolerance and strong antitumor activity,with an 84.2%overall response *** authors emphasize the potential of zanubrutinib to modulate key genomic features of PCNSL,particularly mutations in myeloid differentiation primary response 88 and cluster of differentiation ***,the study investigates the role of circulating tumor DNA in cerebrospinal fluid for disease surveillance and treatment response *** essence,the study provides valuable insights into the potential of combining zanubrutinib with HD-MTX as a frontline therapeutic regimen for *** findings underscore the importance of exploring alternative treatment modalities and monitoring genomic and liquid biopsy markers to optimize patient *** the findings suggest promise,the study’s limitations should be considered,and further research is needed to establish the clinical relevance of this therapeutic approach for PCNSL.

关键词： Primary central nervous system lymphoma Zanubrutinib Bruton’s tyrosine kinase Prognosis Myeloid differentiation primary response 88 gene Cluster of differentiation 79B gene

Intravenous vs intraperitoneal mesenchymal stem cells administration:What is the best route for treating experimental colitis?

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World Journal of Gastroenterology 2014年第48期20卷 18228-18239页

作者： Fabiany da Costa Goncalves Natália Schneider fernanda Otesbelgue Pinto Fabíola Schons Meyer fernanda Visioli Bianca Pfaffenseller Patrícia Luciana da Costa lopez Eduardo Pandolfi Passos Elizabeth Obino Cirne-Lima Luíse Meurer Ana Helena Paz Centro de Pesquisa Experimental do Hospital de Clínicas de Porto Alegre Porto Alegre 90035-903Rio Grande do SulBrazil Programa de Pós-Gradua??o:Ciências em Gastroenterologia e Hepatologia Universidade Federal do Rio Grande do SulPorto Alegre 90035-903Rio Grande do SulBrazil Faculdade de Odontologia Universidade Federado Rio Grande do SulPorto Alegre 90035-003Rio Grande doSulBrazil

AIM:To investigate the therapeutic effects of mesenchymal stem cells(MSCs)transplanted intraperitoneally andintravenously in a murine model of ***:MSCs were isolated from C57BL/6 mouse adipose *** cultures were analyzed according to morphology,cellular differentiation potential,and surface molecular *** acute colitis was induced in C57BL/6 mice by oral administration of2%dextran sulfate sodium(DSS)in drinking water ad libitum from days 0 to *** mice were treated with1×106 MSCs via intraperitoneal or intravenous injection on days 2 and *** disease activity index was determined daily based on the following parameters:weight loss,stool consistency and presence of blood in the feces and *** compare morphological and functional differences in tissue regeneration between different MSC injection modalities,mice were euthanized on day 8,and their colons were examined for length,weight,and histopathological *** responses were determined by measuring the levels of different serum cytokines using a CBA Th1/Th2/Th17 *** rates were evaluated by terminal deoxynucleotidyl transferase-mediated d UDPbiotin nick end labeling ***:Intravenous infusion of MSCs was more effective than intraperitoneal treatment(P<0.001)in reducing the clinical and histopathologic severity of colitis,which includes weight loss,diarrhea and *** histological evaluation demonstrated decreased colonic inflammation based on reduced crypt loss and reduced infiltration of inflammatory *** therapeutic effect was most likely mediated by the down-regulation of pro-inflammatory cytokines[interleukin(IL)-6 and tumor necrosis factor(TNF)];and by the up-regulation of anti-inflammatory cytokines(IL-10 and IL-4).Intravenous transplantation alsoinduced high levels of IFN that lead to activation of the immunosuppressive activity of the MSCs,which did not occur with intraperitoneal transplantation(P=0.006).An increase in a

关键词： Ulcerative colitis Dextran sulfate sodium Inflammatory bowel disease Mesenchymal stem cell Cell transplantation Intravenous injection Immunomodulation

The human olfactory system in two proteinopathies: Alzheimer’s and Parkinson’s diseases

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Translational Neurodegeneration 2020年第2期9卷 270-289页

作者： Isabel Ubeda-Bañon Daniel Saiz-Sanchez Alicia Flores-Cuadrado Ernesto Rioja-Corroto Melania Gonzalez-Rodriguez Sandra Villar-Conde Veronica Astillero-lopez Juan Pablo Cabello-de la Rosa Maria Jose Gallardo-Alcañiz Julia Vaamonde-Gamo fernanda Relea-Calatayud Lucia Gonzalez-lopez Alicia Mohedano-Moriano Alberto Rabano Alino Martinez-Marcos Neuroplasticity and Neurodegeneration Laboratory Ciudad Real Medical SchoolCRIBUniversity of Castilla-La Mancha13005Ciudad RealSpain Neurology Service Ciudad Real General University Hospital13005Ciudad RealSpain Pathology Service Ciudad Real General University Hospital13005Ciudad RealSpain Faculty of Health Sciences University of Castilla-La ManchaTalavera de la ReinaSpain Neuropathology Department and Tissue Bank CIEN FoundationCarlos III Health InstituteMadridSpain

Alzheimer’s and Parkinson’s diseases are the most prevalent neurodegenerative *** etiologies are idiopathic,and treatments are symptomatic and orientated towards cognitive or motor ***,both are proteinopathies with pathological aggregates(plaques of amyloid-β peptide and neurofibrillary tangles of tau protein in Alzheimer’s disease,and Lewy bodies mostly composed of α-synuclein in Parkinson’s disease).These deposits appear in the nervous system in a predictable and accumulative sequence with six neuropathological *** disorders present a long prodromal period,characterized by preclinical signs including ***,the olfactory system,particularly the anterior olfactory nucleus,is initially and preferentially affected by the *** atrophy revealed by magnetic resonance imaging must be complemented by histological analyses to ascertain whether neuronal and/or glial loss or neuropil remodeling are responsible for volumetric *** has been proposed that these proteinopathies could act in a prion-like manner in which a misfolded protein would be able to force native proteins into pathogenic folding(seeding),which then propagates through neurons and glia(spreading).Existing data have been examined to establish why some neuronal populations are vulnerable while others are resistant to pathology and to what extent glia prevent and/or facilitate proteinopathy *** approaches reveal a number of hubs in the olfactory system(anterior olfactory nucleus,olfactory entorhinal cortex and cortical amygdala)that are key interconnectors with the main hubs(the entorhinal–hippocampal–cortical and amygdala–dorsal motor vagal nucleus)of network dysfunction in Alzheimer’s and Parkinson’s diseases.

关键词： α-Synuclein Amyloid-β Anterior olfactory nucleus Hyposmia Tau protein

Effective prophylaxis with rFVIIa in young haemophiliacs with inhibitors using a schedule similar to FVIII prophylaxis in non-inhibitor patients

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Health 2013年第7期5卷 1151-1157页

作者： Maria fernanda lopez-Fernandez Carmen Altisent Victor Jimenez-Yuste Faustino Garcia-Candel Carmen Sedano Ana Cid Eva Mingot Ramiro Nunez Maria Jose Paloma Inmaculada Soto Manuel Prieto Haematology Complejo Hospitalario Universitario A CorunaA CorunaSpain Haemophilia Unit Hospital Universitario Vall d’HebronBarcelonaSpain Haemophilia Unit Hospital UniversitarioMadridSpain Haemophilia Unit Hospital Universitario Virgen de la ArreixacaMurciaSpain Haematology Complejo Hospitalario Universitario Marques de ValdecillaSantanderSpain Congenital Coagulophaties Unit Hospital Universitario La FeValenciaSpain Haematology Hospital Universitario Carlos HayaMalagaSpain Haematology Hospital Universitario Virgen del RocíoSevillaSpain Haematology Hospital Virgen del CaminoPamplonaSpain Haematology Hospital General de AsturiasOviedoSpain Haematology Hospital General YagüeBurgosSpain

Objective: To assess the role of early prophylaxis with recombinant activated factor VII (rFVIIa) in young haemophiliacs with inhibitors and to determine whether it can reduce bleeding episodes and prevent joint damage. Patients and Methods: Ten severe haemophiliacs, less of three years old, with up to four joint bleeds and inhibitors to FVIII who started early prophylaxis with rFVIIa, were included. A number of haemorrhages/year/patient and haemarthroses/ year/patient were compared before the start of prophylaxis, which include both the time before (initial period) and after inhibitor diagnosis (inhibitor period), with those during prophylaxis (prophylaxis period). Results: The mean time of inhibitor diagnosis was 15.6 months (range: 2.3-34.1). The mean time between inhibitor diagnosis and the start of prophylaxis was 7.1 months (range: 0-23.2), shorter than the time of rFVIIa prophylaxis (mean: 10.3 months;range: 4.1-32.0). Bleeding episodes for the three time periods were 45, 36 and 17, respectively, or 0.29 and 0.51 haemorrhages/year/patient in the two periods prior to prophylaxis compared to 0.17 during prophylaxis. Total haemarthroses for the three-time periods were 7, 5 and 5, respectively. The haemarthroses/year/patient in the pre-prophylaxis period were 0.032 and 0.070, compared to0.049 inthe prophylaxis period. rFVIIa schedules were either 90 μg/kg three times weekly or 90 μg/kg daily. Conclusions: Early prophylaxis with rFVIIa may be efficacious in young haemophiliacs with inhibitors, reducing joint bleeds. After the risky period of inhibitor presence, they are able to continue rFVIII prophylaxis with success assured to prevent arthropathy.

关键词： rFVIIa Haemarthroses Haemophilia Inhibitors Prophylaxis

IMT504: A New and Potent Adjuvant for Rabies Vaccines Permitting Significant Dose Sparing

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World Journal of Vaccines 2012年第4期2卷 182-188页

作者： Alejandro D. Montaner Analia De Nichilo Juan M. Rodriguez Andres Hernando-Insua Juan Fló Ricardo A. lopez Verónica Sierra Claudio Paolazzi Oscar Larghi David L. Horn Jorge Zorzopulos fernanda Elias David Horn LLC Doylestown PA USA. Immunotech S.A. Buenos Aires Argentina Instituto de Investigaciones Biomédicas Fundación Pablo Cassará Buenos Aires Argentina Instituto San Jorge Bagó Buenos Aires Argentina Instituto San Jorge Bagó Buenos Aires Argentina. nstituto de Investigaciones Biomédicas Fundación Pablo Cassará Buenos Aires Argentina

Background: Rabies virus infection causes encephalitis, which is almost always fatal. Vaccination can be extremely effective at preventing disease but is prohibitively costly. Vaccine formulations allowing dose-sparing and fewer inoculations with faster antibody response would be extremely desirable. IMT504, an immunostimulatory non-CpG oligo-deoxynucleotide, is a highly potent vaccine adjuvant. Methods: Human and rat antibody measurements, and rat chal-lenge studies were performed. Results: In rats, highly effective immune responses with IMT504 were observed even after diluting vaccine up to 1/625. In highly lethal, live intracerebral rabies challenge studies, protection occurred even with extremely dilute vaccine plus IMT504. In humans, antibody titers developed faster and were significantly higher with IMT504-adjuvanted diluted vaccine vs non-adjuvanted vaccine (full strength or diluted). All five administered IMT504-adjuvanted diluted vaccine reached protective antibodies (≥0.5 IU/ml) after the second injection. After the third injection, individuals receiving IMT504-adjuvanted diluted vaccine reached levels approximately 10 times higher than controls (M ± SEM: 31.0 ± 10.9 vs 3.40 ± 0.99 IU/ml). Conclusions: These data suggest that IMT504 may allow fewer inoculations, highly significant dose-sparing of vaccine, rapid antibody production and protection from rabies. Extensive clinical studies are necessary to confirm if the use of IMT504 will permit significantly greater access to highly effective life-saving rabies vaccines.

关键词： IMT504 Adjuvant Rabies Vaccine Human Animal

The Viable but Non-culturable State in Xanthomonas citri subsp, citri is a Reversible State Induced by Low Nutrient Availability and Copper Stress Conditions

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Journal of Life Sciences 2013年第10期7卷 1019-1029页

作者： Morteza Golmohammadi Jaime Cubero Maria M. lopez Pablo Llop Centre of Plant Protection and Biotechnology Valencian Institute of Agricultural Research (IVIA) Ctra Moncada-Naquera Km4-5 Moncada (Valencia) 46113 Spain Department of Plant Protection lran Citrus Research Institute Ramsar Iran Dpt. Plant Protection National Institute for Agricultural Research and Technology (1NIA) Ctra. de La Coruna Km 7-5 Madrid28040 Spain

Xcc （Xanthomonas citri subsp, citri） causes citrus bacterial canker, a leaf, stem and fruit spotting disease that affects most commercial citrus species and cultivars. Copper compounds, widely used for management of this pathogen, have been reported as inducers of a VBNC （viable but non-culturable state） in plant pathogenic bacteria. VBNC may be considered as a state preceding bacterial death or as a survival mechanism under adverse conditions. Several experiments were performed to characterize the reversibility and persistence of the VBNC state in Xcc. VBNC was induced in low nutrient medium or with amendment of copper at concentrations used for field disease control. The VBNC condition was demonstrated to persist up to 150 days after copper treatment and was reversed after the addition of culture media without copper or amendment with citrus leaf extract. Xcc viability was evaluated by recovery of colonies on culture media, confirmed by membrane integrity, respiratory activity and by real-time RT-PCR targeting a sequence from the gumD gene. Besides, the colonies recovered were pathogenic on citrus leaves. These results confirm that the VBNC state in Xcc is inducible and reversible and therefore may occur in the phyllosphere when Xcc is under copper stress or starvation.

关键词： VBNC resuscitation Xanthomonas citri subsp citri.