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Functional and structural changes in internal pudendal arteries underlie erectile dysfunction induced by androgen deprivation

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Asian Journal of Andrology 2017年第5期19卷 526-532页

作者： Rheure Alves-Lopes Karla B Neves Marcondes AB Silva Vania C Olivon Silvia G Ruginsk jose antunes-rodrigues Leandra NZ Ramalho Rita C Tostes Fernando Silva Carneiro Department of Pharmacology Ribeirao Preto Medical School University of Sao Paulo Ribeirao Preto SP Brazil Department of Physics and Chemistry Faculty of Pharmaceutical Sciences of Ribeirao Preto University of Sao Paulo Ribeirao Preto SP Brazil Department of Physiological Sciences Biomedical Sciences InstituteFederal University of Alfenas Alfenas MG Brazil Department of Physiology Ribeirao Preto Medical School University of Sao Paulo Ribeirao Preto SP Brazil Department of Pathology and Legal Medicine Ribeirao Preto Medical School University of Sao Paulo Ribeirao Preto SP Brazil

Androgen deficiency is strongly associated with erectile dysfunction （ED）. Inadequate penile arterial blood flow is one of the major causes of ED. The blood flow to the corpus cavernosum is mainly derived from the internal pudendal arteries （IPAs）; however, no study has evaluated the effects of androgen deprivation on IPA＇s function. We hypothesized that castration impairs IPAs reactivity and structure, contributing to ED. In our study, Wistar male rats, 8-week-old, were castrated and studied 30 days after orchiectomy. Functional and structural properties of rat IPAs were determined using wire and pressure myograph systems, respectively. Protein expression was determined by Western blot and immunohistochemistry. Plasma testosterone levels were determined using the IMMULITE 1000 Immunoassay System. Castrated rats exhibited impaired erectile function, represented by decreased intracavernosal pressure/mean arterial pressure ratio. IPAs from castrated rats exhibited decreased phenylephrine- and electrical field stimulation （EFS）-induced contraction and decreased acetylcholine- and EFS-induced vasodilatation. IPAs from castrated rats exhibited decreased internal diameter, external diameter, thickness of the arterial wall, and cross-sectional area. Castration decreased nNOS and α-actin expression and increased collagen expression, p38 （Thr180/ryr182） phosphorylation, as well as caspase 3 cleavage. In conclusion, androgen deficiency is associated with impairment of IPA reactivity and structure and increased apoptosis signaling markers. Our findings suggest that androgen deficiency-induced vascular dysfunction is an event involving hypotrophic vascular remodeling of IPAs.

关键词： androgen castration internal pudendal artery

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Extrahepatic cholestasis associated with paracoccidioidomycosis:Challenges in the differential diagnosis of biliopancreatic neoplasia

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2531-2540页

作者： jose Sebastiao dos Santos Vitor de Moura Arrais William jose Rosseto Ferreira Ricardo Ribeiro Correa Filho Mariangela Ottoboni Brunaldi Rafael Kemp Ajith Kumar Sankanrakutty Jorge Elias Junior Fernando Bellissimo-rodrigues Roberto Martinez Edson Zangiacomi Martinez jose Celso Ardengh Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo(FMRP-USP) Departamento de Cirurgia e AnatomiaRibeirao Preto 14049-900Sao PauloBrazil Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo(FMRP-USP)Departamento de PatologiaRibeirao Preto 14048900Sao PauloBrazil Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo(FMRP-USP)Departamento de Imagens MédicasHematologia e Oncologia ClínicaRibeirao Preto 14048900Sao PauloBrazil Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo(FMRP-USP)Departamento de Medicina SocialRibeirao Preto 14015-010Sao PauloBrazil Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo(FMRP-USP)Departamento de Clínica MédicaRibeirao Preto 14015-010Sao PauloBrazil Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo(FMRP-USP)Departamento de Cirurgia e AnatomiaRibeirao Preto 14049-900Sao PauloBrazil and Hospital MoriahServico de Endoscopia DigestivaSao Paulo 04084-002Sao PauloBrazil

BACKGROUND Paracoccidioidomycosis(PCM)may involve the hepatic pedicle and peripan creatic lymph nodes,cause damage to the bile duct and manifest,exceptionally,in combination with extrahepatic cholestasis(EHC),making investigation and treatment challenging.AIM To investigate the management of patients with visceral PCM admitted with EHC.METHODS All patients diagnosed with PCM treated in a public,tertiary teaching hospital between 1982 and 2020 were retrospectively evaluated.Those also identified with EHC were allocated to two groups according to the treatment approach for the purpose of comparing clinical,laboratory,and imaging findings,resources used for etiological diagnosis,treatment results,and prognosis.Statistical analyses were performed using the linear mixed-effects model(random and fixed effects),which was adjusted using the PROC MIXED procedure of the SAS®9.0 software,and Fisher’s exact test.RESULTS Of 1645 patients diagnosed with PCM,40(2.4%)had EHC.Of these,20(50.0%)lived in the rural area and 29(72.5%)were men,with a mean age of 27.1 years(3-65 years).Jaundice as first symptom and weight loss of at least 10 kg were observed in 16 patients(40.0%),and a mass in the head of the pancreas was observed in 8(20.0%).The etiological diagnosis was made by tissue collection during surgery in 4 cases(10.0%)and by endoscopic methods in 3 cases(7.5%).Twenty-seven patients(67.5%)received drug treatment alone(Group 1),whereas 13(32.5%)underwent endoscopic and/or surgical procedures in combination with drug treatment(Group 2).EHC was significantly reduced in both groups(40.7% in Group 1,with a mean time of 3 months;and 38.4% in Group 2,with a mean time of 7.5 months),with no statistically significant difference between them.EHC recurrence rates,associated mainly with treatment nonadherence,were similar in both groups:37% in Group 1 and 15.4% in Group 2.The mortality rate was 18.5% in Group 1 and 23% in Group 2,with survival estimates of 71.3% and 72.5%,respectively,with no statistically significant difference.CONCLUSI

关键词： Cholestasis Jaundice Obstructive Blastomycosis Paracoccidioides Diagnosis Treatment

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Epidemiology and Clinical Features of Mycobacterium avium Complex Pulmonary Disease in a Brazilian Amazon Cohort

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Advances in Microbiology 2024年第6期14卷 287-302页

作者： jose Tadeu Colares Monteiro Adriana rodrigues Barretto Ruan Seguin Azevedo Quaresma Bianca Miranda Gouveia Ismari Perini Furlaneto Victória Menezes da Costa Yan Corrêa rodrigues Layana Rufino Ribeiro Ricardo J. de Paula Souza e Guimarães Alex Brito Souza Ana Roberta Fusco da Costa Karla Valéria Batista Lima Joao de Barros Barreto University Hospital Federal University of Par Belm Brazil Center for Biological and Health Sciences Ph.D. Program in Parasitic Biology in the Amazon Region (PPGBPA) State University of Par (UEPA) Belm Brazil Department of Medicine Centro Universitrio do Par CESUPA Belm Brazil Bacteriology and Mycology Section Evandro Chagas Institute (SABMI/IEC) Ministry of Health Ananindeua Brazil Geoprocessing Laboratory Evandro Chagas Institute/SVSA/MS Ananineua Brazil

The incidence of Mycobacterium avium complex pulmonary disease (MACPD) has been globally increasing. The present study aims to provide a comprehensive analysis of clinical characteristics and treatment response among patients in the Amazon region of Brazil and conduct a retrospective cohort study at a prominent referral hospital in the State of Par, Brazil, from 2012 to 2020. The M. avium group represented 58.9% of cases, followed by M. intracellulare (35.7%), M. colombiense (3.6%), and M. chimaera (1.8%). The majority of patients (73.2%) were female and with an average age of 63 years. Primary clinical manifestations included persistent cough and sputum production. The Charlson comorbidity index (CCI) averaged 2.47, with 36.3% of patients having a CCI score equal to higher than 3. Notably, over 70% of patients had received treatment for pulmonary tuberculosis before initiating treatment for MAC infection. The fibrocavitary radiologic form was the most prevalent (55.4%), frequently exhibiting a bilateral distribution (53.6%). Antimicrobial susceptibility revealed a significant prevalence of MAC resistance to drugs in the therapeutic regimen. Despite this, most of the patients experienced clinical improvement (50%). In conclusion, this study highlights a higher prevalence of MAC infections among middle-aged women, with a history of pulmonary tuberculosis treatment and presenting the fibrocavitary radiological form was predominant.

关键词： MACDP Nontuberculous Mycobacteria Mycobacterium avium Lung Disease

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Structural Health Monitoring of Different Geometry Structures With Optical Fiber Sensors

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Photonic Sensors 2012年第4期2卷 357-365页

作者： Paulo antunes Hugo rodrigues Rui TRAVANCA Licinio FERREIRA Humberto VARUM Paulo ANDRE Instituto de Telecomunicacoes Campus de Santiago 3810-193 Aveiro Portugal Departamento de Fisica Universidade de Aveiro Campus de Santiago 3810-193 Aveiro Portugal Departamento de Engenharia Civil Universidade de Aveiro Campus de Santiago 3810-193 Aveiro Portugal

在这份报纸，我们描述几结构监视的结构的健康，与不同几何学，材料和行为，用光纤维传感器。那些研究试图处于监视的结构的健康表明如此的技术的可行性，与对光纤维技术固有的所有优点。

关键词：结构健康监测光纤传感器几何结构光纤技术几何形状

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In vitro antileishmanial effects of Physalis angulata root extract on Leishmania infantum

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Journal of Integrative Medicine 2018年第6期16卷 404-410页

作者： Bruno jose Martins Da Silva Sandro Wilson Gomes Pereira Ana Paula Drummond rodrigues jose Luiz Martins Do Nascimento Edilene Oliveira Silva Laboratory of Structural Biology Institute of Biological SciencesFederal University of PardBelemPard 66075-110Brazil National Institute of Science and Technology in Structural Biology and Bioimaging(INCT-INBEB) Rio de Janeiro 21941-901Brazil Laboratory of Electron Microscopy Department of Health SurveillanceMinistry of HealthEvandro Chagas InstituteBelemPard 66087-082Brazil Laboratory of Molecular and Cellular Neurochemistry Institute of Biological SciencesFederal University of PardBelemPard 66075-110Brazil National Institute of Science and Technology in Neuroimmunomodulation(INCT-NIM) Rio de Janeiro 21040-360Brazil

Objective： In the present study, we evaluated the effects of the aqueous extract of Physalis angulata root （AEPa） on Leishmania infanturn proliferation, morphology, and the driving mechanism in leishmanicidal activity and modulatory action on macrophages. Methods： I., infantum promastigotes were treated with 50 and 100 μg/mL AEPa for 72 h and then antipro- mastigote assay was performed by counts in a Newbauer chamber, morphological changes were analyzed by transmission electron microscopy and the mechanism of the leishmanicidal activity was detected. In addition, macrophages were infected with L. infantum and were used to evaluate anti-amastigote activity of AEPa and effects of AEPa on cytokine secretion after 72-hour treatment. Results： Treatment with AEPa reduced the numbers ofL infantum promastigotes （50% inhibitory concen- tration （ICso） = 65.9μg/mL; selectivity index （SI）= 22.1） and amastigotes （ICso = 37.9 μg/mL; SI = 38.5） compared with the untreated control. Amphotericin B reduced 100% of the promastigote numbers after 72 h of treatment （IC50 = 0.2μg/mL）. AEPa induced several morphological changes and increased the production of reactive oxygen species and apoptotic death in promastigotes after treating for 72 h. AEPa （100 μg/mL） promoted tumor necrosis factor-α secretion in macrophages infected with L. infantum after 72 h of treatment, but did not induce an increase in this cytokine in noninfected macrophages. In addition, AEPa showed no cytotoxic effect on J774-A1 cells （50% cytotoxic concentration 〉1000μg/mL）. Conclusion： AEPa presented antileishmanial activity against the promastigotes and amastigotes of I.. infantum without macrophage cytotoxicity; these results show that natural products such as P. angulata have leishmanicidal potential and in the future may be an alternative treatment for leishmaniasis.

关键词： Leishmanicidal activity Leishmania infantum Reactive oxygen species Apoptosis Physalis angulata

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Regeneration of critical-sized defects, in a goat model, using a dextrin-based hydrogel associated with granular synthetic bone substitute

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Regenerative Biomaterials 2021年第1期8卷 73-82页

作者： Isabel Pereira jose Eduardo Pereira Luis Maltez Alexandra rodrigues Catarina rodrigues Manuela Oliveira Dina MSilva Ana Rita Caseiro Justina Prada Ana Colette Mauricio jose Domingos Santos Miguel Gama CEB Centre of Biological EngineeingUniversity of MinhoCampus de GualtarBraga 4710-057Portugal CECAV Animal and Veterinary Research CentreUniversity of Trias-os-Montes e Alto DouroVila Real 5001-801Portugal Department of Veterinary Sciences University of Tras-os-Montes e Alto DouroVila Real 5001-801Portugal Bios ckin Molecular and Cell Therapies S.A.Laboratorio CriovidaTecMaiaRua Engenheiro Frederico Ulrich 2650Moreira da Maia 4470-605Portugal Departamento de Clinicas Veterinarias Instituto de Ciencias Biomedicas de Abel Salazar(ICBAS)Universidade do Porto(UP)Rua de Jorge Viterbo Ferreiran°228Porto 4050-313Portugal Centro de Estudos de Ciencia Animal(CECA) Instituto de CienciasTecnologias e Agroambiente da Universidade do Porto(ICETA)Rua D.Manuel IApartado 55142Porto 4051-401 Portugal Centro de Investigaqao Vasco da Gama(CIVG)/Escola Universitaria Vasco da Gama(EUVG) Avenida Jose R.Sousa Femandesn°197 LordemaoCoimbra 3020-210Portugal REQUIMTE/LAQV Departamento de Engenharia Metalurgica e MateriaisFaculdade de EngenhariaUniversidade do PortoRua Dr Roberto FriasPorto 4200-495Portugal

The development of injectable bone substitutes(IBS)have obtained great importance in the bone re-generation field,as a strategy to reach hardly accessible defects using minimally invasive techniques and able to fit to irregular topographies.In this scenario,the association of injectable hydrogels and bone graft granules is emerging as a well-established trend.Particularly,in situ forming hydrogels have arisen as a new IBS generation.An in situ forming and injectable dextrin-based hydrogel(HG)was developed,aiming to act as a carrier of granular bone substitutes and bioactive agents.In this work,the HG was associated to a granular bone substitute(Bonelike)and implanted in goat critical-sized calvarial defects(14mm)for 3,6 and 12weeks.The results showed that HG improved the han-dling properties of the Bonelike granules and did not affect its osteoconductive features,neither impairing the bone regener ation process.Human multipotent mesenchymal stromal cells from the umbilical cord,extracellular matrix hydrolysates and the pro-angiogenic peptide LLKKK18 were also combined with the IBS.These bioactive agents did not enhance the new bone formation significantly under the conditions tested,according to micro-computed tomography and histological analysis.

关键词： polysaccharide injec table hydrogel granular ceramics Bonelike' bone regen eration calvarial defect

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Challenges in the diagnosis of intestinal neuronal dysplasia type B:A look beyond the number of ganglion cells

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World Journal of Gastroenterology 2021年第44期27卷 7649-7660页

作者： Simone antunes Terra Anderson Cesar Gonçalves Pedro Luiz Toledo de Arruda Lourenção Maria Aparecida Marchesan rodrigues Department of Pathology Faculty of MedicineSão Paulo State University(UNESP)Botucatu 18618687São PauloBrazil Department of Surgery and Orthopedics Botucatu Medical School-São Paulo State University(UNESP)Botucatu 18618970São PauloBrazil

Intestinal neuronal dysplasia type B(IND-B)is a controversial condition among gastrointestinal neuromuscular disorders.Constipation is its most common clinical manifestation in patients.Despite intense scientific research,there are still knowledge gaps regarding the diagnostic criteria for IND-B in the histopathological analysis of rectal biopsies.The guidelines published in the past three decades have directed diagnostic criteria for quantifying the number of ganglion cells in the nervous plexus of the enteric nervous system.However,it is very complex to distinguish numerically what is pathological from what is normal,mainly because of the difficulty in determining a reliable control group composed of healthy children without intestinal symptoms.Thus,a series of immunohistochemical markers have been proposed to assist in the histopathological analysis of the enteric nervous system.Several of these markers facilitate the identification of other structures of the enteric nervous system,in addition to ganglion cells.These structures may be related to the etiopathogenesis of IND-B and represent new possibilities for the histopathological diagnosis of this disease,providing a view beyond the number of ganglion cells.This review critically discusses the aspects related to the disease definitions and diagnostic criteria of this organic cause of constipation.

关键词： Intestinal neuronal dysplasia type B Constipation Diagnosis Gastrointestinal neuromuscular diseases

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MicroRNAs and cancer drug resistance: over two thousand characters in search of a role

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Cancer Drug Resistance 2019年第3期2卷 618-633页

作者： Bruno Costa Gomes jose Rueff António Sebastião rodrigues Centre for Toxicogenomics and Human Health GeneticsOncology and Human ToxicologyNOVA Medical SchoolUniversidade Nova de LisboaLisboa 1150-008Portugal

MicroRNAs(miRNAs),a group of small regulatory noncoding RNAs,transformed our thinking on gene regulation.More than two thousand human miRNAs have been identified thus far.These bind imperfectly to the 3’-untranslated region of target mRNA and have been involved in several pathological conditions including cancer.In fact,major hallmarks of cancer,such as the cell cycle,cell proliferation,survival and invasion are modulated by miRNAs.Cancer drug resistance(CDR)has also been described as being modulated by miRNAs.CDR remains a burden for cancer therapy and patients’outcome,often resulting in more aggressive tumours that tend to metastasize to distant organs.In this review we discuss the role of miRNAs influencing drug metabolism and drug influx/efflux,two important mechanisms of CDR.

关键词： MicroRNAs gene regulation cancer drug resistance drug transporters drug metabolism

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Medicinal plants from the Brazilian Amazonian region and their antileishmanial activity:a review

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Journal of Integrative Medicine 2018年第4期16卷 211-222页

作者： Bruno jose Martins Da Silva Amanda Anastacia Pinto Hage Edilene Oliveira Silva Ana Paula Drummond rodrigues Laboratory of Parasitology and Laboratory of Structural Biology Institute of Biological SdencesFederal University of PardBelemPard 66075-110Brazil National Institute of Science and Technology in Structural Biology and Bioimaging Rio de JaneiroRio de Janeiro 21941-901Brazil Laboratory of Electron Microscopy Department of Health SurveillanceMinistry of HealthEvandro Chagas InstituteBelemPard 66087-082Brazil

Leishmaniasis, a neglected disease caused by Leishmania protozoans, primarily affects people in tropical and subtropical areas. Chemotherapy based on the use of pentavalent antimonials, amphotericin B, paromomycin, miltefosine and liposomal amphotericin B is currently the only effective treatment. However, adverse effects, long-term treatment and the emergence of parasite resistance have led to the search for alternative treatments. Natural products used in traditional medicine provide an unlimited source of molecules for the identification of new drugs, and the Amazon region has abundant biodiversity that includes several species of plants and animals, providing a rich source of new products and com- pounds. Although the literature describes numerous promising compounds and extracts for combating Leishmania protozoans, the results of such research have not been embraced by the pharmaceutical industry for the development of new drugs. Therefore, this review focused on the antileishmanial activity of extracts, isolated compounds and essential oils commonly used by the local population in the Brazilian Amazonian region to treat several illnesses and described in the literature as promising compounds for combating leishmaniasis.

关键词： Amazonian plants Leishmaniasis treatment Plant compounds Plant extracts Plant oils

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Regulation of ABCB1 activity by microRNA-200c and microRNA-203a in breast cancer cells: the quest for microRNAs’ involvement in cancer drug resistance

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Cancer Drug Resistance 2019年第3期2卷 897-911页

作者： Ana Armada Bruno Costa Gomes Miguel Viveiros jose Rueff António Sebastião rodrigues Global Health and Tropical Medicine Instituto de Higiene e Medicina TropicalUniversidade NOVA de LisboaRua da Junqueira 100Lisbon 1349-008Portugal Centre for Toxicogenomics and Human Health GeneticsOncology and Human ToxicologyNOVA Medical School/Faculdade de Ciências MédicasUniversidade Nova de LisboaRua Câmara Pestana 6LisbonLisbon 1150-008Portugal.

Aim:ABCB1 is a major player in cancer drug resistance.The purpose of this study was to functionally assess the regulation of ABCB1 activity in a doxorubicin-resistant breast cancer cell line by miR-200c and miR-203.Methods:Human breast carcinoma cell lines MCF-7(Doxorubicin-sensitive and not expressing ABCB1)and KCR(Doxorubicin-resistant and expressing ABCB1)were used to evaluate the expression levels of miR-200c and miR-203 by Real-time quantitative PCR(RT-qPCR).The effects of transient ectopic expression of miRNA-200c and miR-203 on the expression of ABCB1 in KCR and MCF-7 cells was verified by RT-qPCR and Western Blot.The extrusion activity of the ABCB1 pump was analyzed by fluorescence microscopy and flow cytometry through fluorescence substrate retention assays(DiOC2)in the presence and absence of the ABCB1 inhibitor verapamil.Results:RT-qPCR results indicated a 100,000-fold increase in ABCB1 mRNA expression levels in KCR cells compared to MCF-7 cells,and is inversely correlated with the expression of miR-203 and miR-200c.The insertion of miR-200c and miR-203 led to a higher retention of DiOC2 within KCR cells,and slightly reduced the protein levels of ABCB1 in KCR cells,although the high initial expression of ABCB1 masked the reduction in protein levels.The increased intracellular accumulation of the fluorescent due DiOC2 in the presence of the ABCB1 inhibitor verapamil correlated with the inhibition caused by miR-203 and miR-200c in transfected cells.Conclusion: The present study demonstrates that miR-200c and miR-203 exert a negative modulating effect on the activity of ABCB1 associated with doxorubicin resistance.

关键词： ABCB1 drug resistance drug extrusion breast cancer miR2003 miR203

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