Memorias do Instituto Oswaldo Cruz最新文献

{"title":"Discovery of new Schistosoma mansoni aspartyl protease inhibitors by structure-based virtual screening.","authors":"Bárbara Figueira Gomes,&nbsp;Mario Roberto Senger,&nbsp;José Teófilo Moreira-Filho,&nbsp;Fabio Jorge de Vasconcellos Junior,&nbsp;Rafael Ferreira Dantas,&nbsp;Raymond Owens,&nbsp;Carolina Horta Andrade,&nbsp;Bruno Junior Neves,&nbsp;Floriano Paes Silva-Junior","doi":"10.1590/0074-02760230031","DOIUrl":"https://doi.org/10.1590/0074-02760230031","url":null,"abstract":"<p><strong>Background: </strong>Schistosomiasis is a neglected tropical disease caused by trematodes of the genus Schistosoma, with a limited treatment, mainly based on the use of praziquantel (PZQ). Currently, several aspartic proteases genes have already been identified within the genome of Schistosoma species. At least one enzyme encoded from this gene family (SmAP), named SmCD1, has been validated for the development of schistosomicidal drugs, since it has a key role in haemoglobin digestion by worms.</p><p><strong>Objective: </strong>In this work, we integrated a structure-based virtual screening campaign, enzymatic assays and adult worms ex vivo experiments aiming to discover the first classes of SmCD1 inhibitors.</p><p><strong>Methods: </strong>Initially, the 3D-structures of SmCD1, SmCD2 and SmCD3 were generated using homology modelling approach. Using these models, we prioritised 50 compounds from 20,000 compounds from ChemBridge database for further testing in adult worm aqueous extract (AWAE) and recombinant SmCD1 using enzymatic assays.</p><p><strong>Findings: </strong>Seven compounds were confirmed as hits and among them, two compounds representing new chemical scaffolds, named 5 and 19, had IC50 values against SmCD1 close to 100 μM while presenting binding efficiency indexes comparable to or even higher than pepstatin, a classical tight-binding peptide inhibitor of aspartyl proteases. Upon activity comparison against mammalian enzymes, compound 50 was selective and the most potent against the AWAE aspartic protease activity (IC50 = 77.7 μM). Combination of computational and experimental results indicate that compound 50 is a selective inhibitor of SmCD2. Compounds 5, 19 and 50 tested at low concentrations (10 uM) were neither cytotoxic against WSS-1 cells (48 h) nor could kill adult worms ex-vivo, although compounds 5 and 50 presented a slight decrease on female worms motility on late incubations times (48 or 72 h).</p><p><strong>Main conclusion: </strong>Overall, the inhibitors identified in this work represent promising hits for further hit-to-lead optimisation.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"118 ","pages":"e230031"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10481938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10182670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intravenous whole blood transfusion results in faster recovery of vascular integrity and increased survival in experimental cerebral malaria.","authors":"Saba Gul,&nbsp;Hans C Ackerman,&nbsp;Cláudio Tadeu Daniel-Ribeiro,&nbsp;Leonardo Jm Carvalho","doi":"10.1590/0074-02760220184","DOIUrl":"https://doi.org/10.1590/0074-02760220184","url":null,"abstract":"<p><strong>Background: </strong>Cerebral malaria is a lethal complication of Plasmodium falciparum infections in need of better therapies. Previous work in murine experimental cerebral malaria (ECM) indicated that the combination of artemether plus intraperitoneal whole blood improved vascular integrity and increased survival compared to artemether alone. However, the effects of blood or plasma transfusion administered via the intravenous route have not previously been evaluated in ECM.</p><p><strong>Objectives: </strong>To evaluate the effects of intravenous whole blood compared to intravenous plasma on hematological parameters, vascular integrity, and survival in artemether-treated ECM.</p><p><strong>Methods: </strong>Mice with late-stage ECM received artemether alone or in combination with whole blood or plasma administered via the jugular vein. The outcome measures were hematocrit and platelets; plasma angiopoietin 1, angiopoietin 2, and haptoglobin; blood-brain barrier permeability; and survival.</p><p><strong>Findings: </strong>Survival increased from 54% with artemether alone to 90% with the combination of artemether and intravenous whole blood. Intravenous plasma lowered survival to 18%. Intravenous transfusion provided fast and pronounced recoveries of hematocrit, platelets, angiopoietins levels and blood brain barrier integrity.</p><p><strong>Main conclusions: </strong>The outcome of artemether-treated ECM was improved by intravenous whole blood but worsened by intravenous plasma. Compared to prior studies of transfusion via the intraperitoneal route, intravenous administration was more efficacious.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"117 ","pages":"e220184"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9870258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10592405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A straightforward one-step strategy for SARS-CoV-2 diagnosis and screening of variants of concern: a multicentre study.","authors":"Marcela Fontana-Maurell,&nbsp;Fernando do Couto Motta,&nbsp;Monica Barcellos Arruda,&nbsp;Pedro Cardoso,&nbsp;Marisa Ribeiro,&nbsp;Elisabete Andrade,&nbsp;Daniela T Godoy,&nbsp;Elaine Costa,&nbsp;Daniele Rocha,&nbsp;Marilda Agudo Mt Siqueira,&nbsp;Rodrigo Brindeiro,&nbsp;Patrícia Alvarez","doi":"10.1590/0074-02760220202","DOIUrl":"https://doi.org/10.1590/0074-02760220202","url":null,"abstract":"<p><strong>Background: </strong>The prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) has changed unevenly over time around the world. Although whole genome sequencing is the gold standard for virus characterisation, the discovery of alpha VOC causing spike gene target failure (SGTF) result, when tested using an reverse transcription real-time polymerase chain reaction (RT-qPCR) assay, has provided a simple tool for tracking the frequencies of variants.</p><p><strong>Objectives: </strong>The aim of this study was to investigate if a multiplex RT-qPCR assay (BioM 4Plex VOC) could be used to detect SARS-CoV-2 and to perform a VOC screening test in a single reaction tube. Here, we present the multicentre study evaluating this assay.</p><p><strong>Methods: </strong>Twelve laboratories have participated in the multicentre study. The BioM 4Plex VOC was distributed to them with detailed instructions of how to perform the test. They were asked to test the BioM 4Plex VOC in parallel with their routine Commercial SARS-CoV-2 diagnostic assay. Additionally, they were requested to select SARS-CoV-2-positive samples with genome sequenced and lineage definition according to PANGO lineage classification.</p><p><strong>Findings: </strong>The BioM 4Plex VOC and commercial RT-PCR assay are equally effective in detecting SARS-CoV-2. Results revealed a specificity of 96.5-100% [95% confidence interval (CI)], a sensitivity of 99.8-100% (95% CI), and an accuracy of 99.8-100% (95% CI). A 99% concordance rate was found between results from the BioM 4Plex VOC and that from available genome sequencing data.</p><p><strong>Main conclusions: </strong>The BioM 4Plex VOC provides an effective solution to detect SARS-CoV-2 infections and screening for VOCs in a single reaction. It is a straightforward method to help us monitor the frequency and distribution of VOCs and develop strategies to better cope with the pandemics.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"118 ","pages":"e220202"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10023132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9187546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progressive neuropathy in patients with lepromatous leprosy after multidrug therapy.","authors":"Patricia Sola Penna,&nbsp;Izabela Jardim Rodrigues Pitta,&nbsp;Robson Teixeira Vital,&nbsp;Mariana Andrea Vilas Boas Hacker,&nbsp;Ana Maria Salles,&nbsp;Roberta Olmo Pinheiro,&nbsp;Sergio Luiz Gomes Antunes,&nbsp;Euzenir Nunes Sarno,&nbsp;Márcia Rodrigues Jardim","doi":"10.1590/0074-02760220150","DOIUrl":"https://doi.org/10.1590/0074-02760220150","url":null,"abstract":"<p><strong>Background: </strong>The lepromatous pole is a stigmatising prototype for patients with leprosy. Generally, these patients have little or no symptoms of peripheral nerve involvement at the time of their diagnosis. However, signs of advanced peripheral neuropathy would be visible during the initial neurological evaluation and could worsen during and after multidrug therapy (MDT). Disabilities caused by peripheral nerve injuries greatly affect these patients' lives, and the pathophysiological mechanisms underlying nerve damage remain unclear.</p><p><strong>Objectives: </strong>To evaluate the outcome of peripheral neuropathy in patients with lepromatous leprosy (LL) and persistent neuropathic symptoms years after completing MDT.</p><p><strong>Methods: </strong>We evaluated the medical records of 14 patients with LL who underwent nerve biopsies due to worsening neuropathy at least four years after MDT.</p><p><strong>Findings: </strong>Neuropathic pain developed in 64.3% of the patients, and a neurological examination showed that most patients had alterations in the medium- and large-caliber fibers at the beginning of treatment. Neurological symptoms and signs deteriorated despite complete MDT and prednisone or thalidomide use for years. Nerve conduction studies showed that sensory nerves were the most affected.</p><p><strong>Main conclusions: </strong>Patients with LL can develop progressive peripheral neuropathy, which continues to develop even when they are on long-term anti-inflammatory and immunosuppressive therapy.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"117 ","pages":"e220150"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9870262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10598431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enterovirus infection and its relationship with neurodegenerative diseases.","authors":"Ivanildo Pedro Sousa Junior,&nbsp;Tuane Cristine Ramos Gonçalves Vieira","doi":"10.1590/0074-02760220252","DOIUrl":"https://doi.org/10.1590/0074-02760220252","url":null,"abstract":"<p><p>Neurodegenerative diseases (NDs) are increasingly common, especially in populations with higher life expectancies. They are associated mainly with protein metabolism and structure changes, leading to neuronal cell death. Viral infections affect these cellular processes and may be involved in the etiology of several neurological illnesses, particularly NDs. Enteroviruses (EVs) frequently infect the central nervous system (CNS), causing neurological disease. Inflammation, disruption of the host autophagy machinery, and deregulation and accumulation/misfolding of proteins are the main alterations observed after infection by an EV. In this perspective, we discuss the most recent findings on the subject, examining the possible role of EVs in the development of NDs, and shedding light on the putative role played by these viruses in developing NDs.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"118 ","pages":"e220252"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10072002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9623903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Matrix-assisted laser desorption/ionisation-time of flight mass spectrometry azole susceptibility assessment in Candida and Aspergillus species.","authors":"Ana Luisa Perini Leme Giordano,&nbsp;Lais Pontes,&nbsp;Caio Augusto Gualtieri Beraquet,&nbsp;Luzia Lyra,&nbsp;Angelica Zaninelli Schreiber","doi":"10.1590/0074-02760220213","DOIUrl":"https://doi.org/10.1590/0074-02760220213","url":null,"abstract":"<p><strong>Background: </strong>Matrix-assisted laser desorption/ionisation-time of flight mass spectrometry (MALDI-TOF MS) allows rapid pathogen identification and potentially can be used for antifungal susceptibility testing (AFST).</p><p><strong>Objectives: </strong>We evaluated the performance of the MALDI-TOF MS in assessing azole susceptibility, with reduced incubation time, by comparing the results with the reference method Broth Microdilution.</p><p><strong>Methods: </strong>Resistant and susceptible strains of Candida (n = 15) were evaluated against fluconazole and Aspergillus (n = 15) against itraconazole and voriconazole. Strains were exposed to serial dilutions of the antifungals for 15 h. Microorganisms' protein spectra against all drug concentrations were acquired and used to generate a composite correlation index (CCI) matrix. The comparison of autocorrelations and cross-correlations between spectra facilitated by CCI was used as a similarity parameter between them, enabling the inference of a minimum profile change concentration breakpoint. Results obtained with the different AFST methods were then compared.</p><p><strong>Findings: </strong>The overall agreement between methods was 91.11%. Full agreement (100%) was reached for Aspergillus against voriconazole and Candida against fluconazole, and 73.33% of agreement was obtained for Aspergillus against itraconazole.</p><p><strong>Main conclusions: </strong>This study demonstrates MALDI-TOF MS' potential as a reliable and faster alternative for AFST. More studies are necessary for method optimisation and standardisation for clinical routine application.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"118 ","pages":"e220213"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10014031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9507271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heavy metal resistance in the Yanomami and Tunapuco microbiome","authors":"Liliane Costa Conteville, Joseli Oliveira-Ferreira, Ana Carolina P Vicente","doi":"10.1590/0074-02760230086","DOIUrl":"https://doi.org/10.1590/0074-02760230086","url":null,"abstract":"BACKGROUND The Amazon Region hosts invaluable and unique biodiversity as well as mineral resources. Consequently, large illegal and artisanal gold mining areas exist in indigenous territories. Mercury has been used in gold mining, and some has been released into the environment and atmosphere, primarily affecting indigenous people such as the Yanomami. In addition, other heavy metals have been associated with gold mining and other metal-dispersing activities in the region. OBJECTIVE Investigate the gut microbiome of two semi-isolated groups from the Amazon, focusing on metal resistance. METHODS Metagenomic data from the Yanomami and Tunapuco gut microbiome were assembled into contigs, and their putative proteins were searched against a database of metal resistance proteins. FINDINGS Proteins associated with mercury resistance were exclusive in the Yanomami, while proteins associated with silver resistance were exclusive in the Tunapuco. Both groups share 77 non-redundant metal resistance (MR) proteins, mostly associated with multi-MR and operons with potential resistance to arsenic, nickel, zinc, copper, copper/silver, and cobalt/nickel. Although both groups harbour operons related to copper resistance, only the Tunapuco group had the pco operon. CONCLUSION The Yanomami and Tunapuco gut microbiome shows that these people have been exposed directly or indirectly to distinct scenarios concerning heavy metals.","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"86 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135609156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ongoing HIV-1 evolution and reservoir reseeding in two elite controllers with genetically diverse peripheral proviral quasispecies.","authors":"Suwellen Sardinha Dias de Azevedo,&nbsp;Fernanda Heloise Côrtes,&nbsp;Larissa M Villela,&nbsp;Brenda Hoagland,&nbsp;Beatriz Grinsztejn,&nbsp;Valdilea Gonçalvez Veloso,&nbsp;Mariza G Morgado,&nbsp;Gonzalo Bello","doi":"10.1590/0074-02760230066","DOIUrl":"https://doi.org/10.1590/0074-02760230066","url":null,"abstract":"<p><strong>Background: </strong>Elite controllers (EC) are human immunodeficiency virus (HIV)-positive individuals who can maintain low viral loads for extended periods without antiretroviral therapy due to multifactorial and individual characteristics. Most have a small HIV-1 reservoir composed of identical proviral sequences maintained by clonal expansion of infected CD4+ T cells. However, some have a more diverse peripheral blood mononuclear cell (PBMC)-associated HIV-1 reservoir with unique sequences.</p><p><strong>Objectives: </strong>To understand the turnover dynamics of the PBMC-associated viral quasispecies in ECs with relatively diverse circulating proviral reservoirs.</p><p><strong>Methods: </strong>We performed single genome amplification of the env gene at three time points during six years in two EC with high intra-host HIV DNA diversity.</p><p><strong>Findings: </strong>Both EC displayed quite diverse PBMCs-associated viral quasispecies (mean env diversity = 1.9-4.1%) across all time-points comprising both identical proviruses that are probably clonally expanded and unique proviruses with evidence of ongoing evolution. HIV-1 env glycosylation pattern suggests that ancestral and evolving proviruses may display different phenotypes of resistance to broadly neutralising antibodies consistent with persistent immune pressure. Evolving viruses may progressively replace the ancestral ones or may remain as minor variants in the circulating proviral population.</p><p><strong>Main conclusions: </strong>These findings support that the high intra-host HIV-1 diversity of some EC resulted from long-term persistence of archival proviruses combined with the continuous reservoir's reseeding and low, but measurable, viral evolution despite undetectable viremia.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"118 ","pages":"e230066"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10292822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9710454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary infection of BALB/c mice with a dengue virus type 4 strain leads to kidney injury.","authors":"Arthur da Costa Rasinhas,&nbsp;Fernanda Cunha Jácome,&nbsp;Gabriela Cardoso Caldas,&nbsp;Ana Luisa Teixeira de Almeida,&nbsp;Daniel Dias Coutinho de Souza,&nbsp;João Paulo Rodrigues Dos Santos,&nbsp;Helver Gonçalves Dias,&nbsp;Eduarda Lima Araujo,&nbsp;Ronaldo Mohana-Borges,&nbsp;Ortrud Monika Barth,&nbsp;Flavia Barreto Dos Santos,&nbsp;Debora Ferreira Barreto-Vieira","doi":"10.1590/0074-02760220255","DOIUrl":"https://doi.org/10.1590/0074-02760220255","url":null,"abstract":"<p><strong>Background: </strong>Dengue is a disease caused by dengue virus (DENV-1 through -4). Among the four serotypes, DENV-4 remains the least studied. Acute kidney injury is a potential complication of dengue generally associated with severe dengue infection.</p><p><strong>Objectives: </strong>The goal of this study was to investigate the alterations caused by experimental dengue infection in the kidney of adult BALB/c mice.</p><p><strong>Methods: </strong>In this study, BALB/c mice were infected through the intravenous route with a DENV-4 strain, isolated from a human patient. The kidneys of the mice were procured and subject to histopathological and ultrastructural analysis.</p><p><strong>Findings: </strong>The presence of the viral antigen was confirmed through immunohistochemistry. Analysis of tissue sections revealed the presence of inflammatory cell infiltrate throughout the parenchyma. Glomerular enlargement was a common find. Necrosis of tubular cells and haemorrhage were also observed. Analysis of the kidney on a transmission electron microscope allowed a closer look into the necrotic tubular cells, which presented nuclei with condensed chromatin, and loss of cytoplasm.</p><p><strong>Main conclusions: </strong>Even though the kidney is probably not a primary target of dengue infection in mice, the inoculation of the virus in the blood appears to damage the renal tissue through local inflammation.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"118 ","pages":"e220255"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10168658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9456155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perillyl alcohol modulates activation, permeability and integrity of human brain endothelial cells induced by Plasmodium falciparum.","authors":"Adriana A Marin,&nbsp;Annette Juillard,&nbsp;Alejandro M Katzin,&nbsp;Leonardo Jm Carvalho,&nbsp;Georges Er Grau","doi":"10.1590/0074-02760230033","DOIUrl":"https://doi.org/10.1590/0074-02760230033","url":null,"abstract":"<p><strong>Background: </strong>Cerebral malaria (CM) is a severe immunovasculopathy caused for Plasmodium falciparum infection, which is characterised by the sequestration of parasitised red blood cells (pRBCs) in brain microvessels. Previous studies have shown that some terpenes, such as perillyl alcohol (POH), exhibit a marked efficacy in preventing cerebrovascular inflammation, breakdown of the brain-blood barrier (BBB) and brain leucocyte accumulation in experimental CM models.</p><p><strong>Objective: </strong>To analyse the effects of POH on the endothelium using human brain endothelial cell (HBEC) monolayers co-cultured with pRBCs.</p><p><strong>Methodology: </strong>The loss of tight junction proteins (TJPs) and features of endothelial activation, such as ICAM-1 and VCAM-1 expression were evaluated by quantitative immunofluorescence. Microvesicle (MV) release by HBEC upon stimulation by P. falciparum was evaluated by flow cytometry. Finally, the capacity of POH to revert P. falciparum-induced HBEC monolayer permeability was examined by monitoring trans-endothelial electrical resistance (TEER).</p><p><strong>Findings: </strong>POH significantly prevented pRBCs-induced endothelial adhesion molecule (ICAM-1, VCAM-1) upregulation and MV release by HBEC, improved their trans-endothelial resistance, and restored their distribution of TJPs such as VE-cadherin, Occludin, and JAM-A.</p><p><strong>Conclusions: </strong>POH is a potent monoterpene that is efficient in preventing P. falciparum-pRBCs-induced changes in HBEC, namely their activation, increased permeability and alterations of integrity, all parameters of relevance to CM pathogenesis.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"118 ","pages":"e230033"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10317308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9759484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}