Journal of Venomous Animals and Toxins Including Tropical Diseases最新文献

{"title":"O1-conotoxin Tx6.7 cloned from the genomic DNA of <i>Conus textile</i> that inhibits calcium currents.","authors":"Maojun Zhou,&nbsp;Manyi Yang,&nbsp;Huiling Wen,&nbsp;Shun Xu,&nbsp;Cuifang Han,&nbsp;Yun Wu","doi":"10.1590/1678-9199-JVATITD-2022-0085","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2022-0085","url":null,"abstract":"<p><strong>Background: </strong>Conotoxins exhibit great potential as neuropharmacology tools and therapeutic candidates due to their high affinity and specificity for ion channels, neurotransmitter receptors or transporters. The traditional methods to discover new conotoxins are peptide purification from the crude venom or gene amplification from the venom duct.</p><p><strong>Methods: </strong>In this study, a novel O1 superfamily conotoxin Tx6.7 was directly cloned from the genomic DNA of <i>Conus textile</i> using primers corresponding to the conserved intronic sequence and 3' UTR elements. The mature peptide of Tx6.7 (DCHERWDWCPASLLGVIYCCEGLICFIAFCI) was synthesized by solid-phase chemical synthesis and confirmed by mass spectrometry.</p><p><strong>Results: </strong>Patch clamp experiments on rat DRG neurons showed that Tx6.7 inhibited peak calcium currents by 59.29 ± 2.34% and peak potassium currents by 22.33 ± 7.81%. In addition, patch clamp on the ion channel subtypes showed that 10 μM Tx6.7 inhibited 56.61 ± 3.20% of the hCa_V1.2 currents, 24.67 ± 0.91% of the hCa_V2.2 currents and 7.30 ± 3.38% of the hNa_V1.8 currents. Tx6.7 had no significant toxicity to ND7/23 cells and increased the pain threshold from 0.5 to 4 hours in the mouse hot plate assay.</p><p><strong>Conclusion: </strong>Our results suggested that direct cloning of conotoxin sequences from the genomic DNA of cone snails would be an alternative approach to obtaining novel conotoxins. Tx6.7 could be used as a probe tool for ion channel research or a therapeutic candidate for novel drug development.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10241523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9592190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scorpions trapped in amber: a remarkable window on their evolution over time from the Mesozoic period to present days.","authors":"Wilson R Lourenço","doi":"10.1590/1678-9199-JVATITD-2023-0040","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2023-0040","url":null,"abstract":"<p><p>This synoptic review aims to bring some general information on fossil scorpions, namely those trapped in amber - fossilized resin - ranging from Lower Cretaceous through the Palaeocene and up to the Miocene. The question to be addressed is how the study of these fossils can be connected with possible present scorpionism problems. A precise knowledge of these ancient lineages provides information about the evolution of extant lineages, including the buthoids, which contain most known noxious species. Among the Arthropods found trapped in amber, scorpions are considered rare. A limited number of elements have been described from the Late Tertiary Dominican and Mexican amber, while the most ancient Tertiary amber from the Baltic region produced more consistent results in the last 30 years, primarily focusing on a single limited lineage. Contrarily, the Cretaceous amber from Myanmar, also called Burmite, has yielded and continues to yield a significant number of results represented by several distinct lineages, which attest to the considerable degree of diversity that existed in the Burmese amber-producing forests. As in my previous similar contributions to this journal, the content of this note is primarily addressed to non-specialists whose research embraces scorpions in various fields such as venom toxins and public health. An overview knowledge of at least some fossil lineages can eventually help to clarify why some extant elements associated with the buthoids represent dangerous species while others are not noxious.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10430024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10403519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isoliquiritigenin regulates the circ_0002860/miR-431-5p/RAB9A axis to function as a tumor inhibitor in melanoma.","authors":"Songjiang Wu,&nbsp;Jian Wang","doi":"10.1590/1678-9199-JVATITD-2022-0019","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2022-0019","url":null,"abstract":"<p><strong>Background: </strong>Isoliquiritigenin (ISL) presents antitumor effects against melanoma cells. It is known that various circular RNAs (circRNAs) are involved in the development of melanoma. Therefore, the present study aims to investigate the molecular mechanisms of ISL and circ_0002860.</p><p><strong>Methods: </strong>Circ_0002860, microRNA-431-5p (miR-431-5p) and member RAS oncogene family (RAB9A) were detected through reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay. Cell viability was examined via cell counting kit-8 assay. The proliferation ability was assessed using colony formation assay. Cell apoptosis and cell cycle were determined by flow cytometry. Transwell assay was used for detection of migration and invasion. Western blot was conducted for protein analysis. Target binding was confirmed via dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. <i>In vivo</i> research was performed through xenograft tumor assay.</p><p><strong>Results: </strong>Circ_0002860 was downregulated by ISL in melanoma cells. ISL-induced inhibitory effects on cell proliferation, cell cycle progression, migration and invasion were alleviated by circ_0002860 overexpression. MiR-431-5p was a target of circ_0002860. Circ_0002860 eliminated the ISL-induced tumor inhibition via sponging miR-431-5p in melanoma cells. Circ_0002860 elevated the RAB9A level by targeting miR-431-5p. The function of ISL was related to miR-431-5p/RAB9A axis in melanoma progression. Tumor growth was reduced by ISL <i>in vivo</i> through downregulating circ_0002860 to regulate miR-431-5p and RAB9A levels.</p><p><strong>Conclusion: </strong>The current data indicates that ISL suppressed cell malignant progression of melanoma via targeting the circ_0002860/miR-431-5p/RAB9A pathway.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10069640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9626464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First molecular detection of <i>Leishmania (Leishmania) infantum chagasi</i> in a domestic cat (<i>Felis catus</i>) from an urban area in eastern Amazon.","authors":"Délia Cristina Figueira Aguiar,&nbsp;Daniela de Nazaré Dos Santos Nascimento,&nbsp;Dinaiara Fragoso Penner,&nbsp;Brena do Socorro Lima de Castro,&nbsp;Rodrigo Rodrigues Virgolino,&nbsp;Alan Marcel Pamplona Neves,&nbsp;Andrei Dos Santos Siqueira,&nbsp;Evonnildo Costa Gonçalves","doi":"10.1590/1678-9199-JVATITD-2022-0048","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2022-0048","url":null,"abstract":"<p><strong>Background: </strong>Domestic cats have been implicated as accidental hosts of <i>Leishmania</i> sp. However, in recent years, the recurrent description of new cases in endemic and nonendemic areas draw attention to the potential epidemiological role of cats as reservoir hosts. Although dogs are considered urban reservoirs, cats could act as a secondary natural reservoirs in these areas. Thus, feline leishmaniasis has become an emerging disease in several countries worldwide.</p><p><strong>Case presentation: </strong>This study aimed to describe the first case of feline leishmaniasis in a stray animal that presented lesions compatible with the disease in Belém, Pará, Brazil, an important urban area in eastern Amazon. Serological tests for <i>Leishmania infantum</i> (ELISA and IFA) were nonreactive, whereas histopathological examination indicated infectious dermatitis caused by <i>Leishmania</i> spp. or <i>Toxoplasma gondii</i>. Cytopathological study of lesion aspirate confirmed the presence of <i>Leishmania</i> sp. amastigotes within macrophages. Finally, molecular analyses revealed that the feline infection was caused by <i>Leishmania</i> (<i>Leishmania</i>) <i>infantum chagasi</i>.</p><p><strong>Conclusion: </strong>To the best of the authors' knowledge, this study reports the first case of natural infection by <i>Leishmania</i> (<i>Leishmania</i>) <i>infantum chagasi</i> in a feline from eastern Amazon. These findings suggest domestic cats as potential secondary reservoir hosts of <i>Leishmania</i> spp. in Belém, which reinforces the importance of further epidemiological investigation of feline leishmaniasis, especially in urban areas with human cases.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10202461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9517175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A scoping study of pulmonary paracoccidioidomycosis: severity classification based on radiographic and tomographic evaluation.","authors":"Sergio Marrone Ribeiro,&nbsp;Thiago Franchi Nunes,&nbsp;Ricardo de Souza Cavalcante,&nbsp;Anamaria Mello Miranda Paniago,&nbsp;Beatriz Aparecida Soares Pereira,&nbsp;Rinaldo Poncio Mendes","doi":"10.1590/1678-9199-JVATITD-2022-0053","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2022-0053","url":null,"abstract":"<p><p>The lungs have great importance in patients with paracoccidioidomycosis since they are the portal of entry for the infecting fungi, the site of quiescent foci, and one of the most frequently affected organs. Although they have been the subject of many studies with different approaches, the severity classification of the pulmonary involvement, using imaging procedures, has not been carried out yet. This study aimed to classify the active and the residual pulmonary damage using radiographic and tomographic evaluations, according to the area involved and types of lesions.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2022-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9704082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35344054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New multienzymatic complex formed between human cathepsin D and snake venom phospholipase A₂.","authors":"Jeane do Nascimento Moraes,&nbsp;Aleff Ferreira Francisco,&nbsp;Leandro Moreira Dill,&nbsp;Rafaela Souza Diniz,&nbsp;Claudia Siqueira de Oliveira,&nbsp;Tainara Maiane Rodrigues da Silva,&nbsp;Cleópatra Alves da Silva Caldeira,&nbsp;Edailson de Alcântara Corrêa,&nbsp;Antônio Coutinho-Neto,&nbsp;Fernando Berton Zanchi,&nbsp;Marcos Roberto de Mattos Fontes,&nbsp;Andreimar Martins Soares,&nbsp;Leonardo de Azevedo Calderon","doi":"10.1590/1678-9199-JVATITD-2022-0002","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2022-0002","url":null,"abstract":"<p><strong>Background: </strong>Cathepsin D (CatD) is a lysosomal proteolytic enzyme expressed in almost all tissues and organs. This protease is a multifunctional enzyme responsible for essential biological processes such as cell cycle regulation, differentiation, migration, tissue remodeling, neuronal growth, ovulation, and apoptosis. The overexpression and hypersecretion of CatD have been correlated with cancer aggressiveness and tumor progression, stimulating cancer cell proliferation, fibroblast growth, and angiogenesis. In addition, some studies report its participation in neurodegenerative diseases and inflammatory processes. In this regard, the search for new inhibitors from natural products could be an alternative against the harmful effects of this enzyme.</p><p><strong>Methods: </strong>An investigation was carried out to analyze CatD interaction with snake venom toxins in an attempt to find inhibitory molecules. Interestingly, human CatD shows the ability to bind strongly to snake venom phospholipases A₂ (svPLA₂), forming a stable muti-enzymatic complex that maintains the catalytic activity of both CatD and PLA₂. In addition, this complex remains active even under exposure to the specific inhibitor pepstatin A. Furthermore, the complex formation between CatD and svPLA₂ was evidenced by surface plasmon resonance (SPR), two-dimensional electrophoresis, enzymatic assays, and extensive molecular docking and dynamics techniques.</p><p><strong>Conclusion: </strong>The present study suggests the versatility of human CatD and svPLA₂, showing that these enzymes can form a fully functional new enzymatic complex.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2022-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9647731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40697626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Late peripheral facial paralysis after COVID-19: a rapid systematic review and two case reports.","authors":"Thalitta Mendes Cavalcante,&nbsp;Vanessa Terezinha Gubert,&nbsp;Carolina de Deus Lima,&nbsp;Larissa Anjos Luciano,&nbsp;Mariana Garcia Croda,&nbsp;James Venturini,&nbsp;Antonio Luiz Dal Bello Gasparoto,&nbsp;Wellyngton Matheus Souza Santiago,&nbsp;Ana Rita Coimbra Motta-Castro,&nbsp;Fernanda Paes Reis,&nbsp;Ana Paula da Costa Marques,&nbsp;Aline Pedroso Lorenz,&nbsp;Wellington Santos Fava,&nbsp;Marina Castilhos Souza Umaki Zardin,&nbsp;Cláudia Elizabeth Volpe Chaves,&nbsp;Gabriel Pereira Braga,&nbsp;Anamaria Mello Miranda Paniago,&nbsp;Sandra Maria do Valle Leone de Oliveira","doi":"10.1590/1678-9199-JVATITD-2022-0020","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2022-0020","url":null,"abstract":"<p><p>Peripheral facial paralysis (PFP) has been shown to be a neurological manifestation of COVID-19. The current study presents two cases of PFP after COVID-19, along with a rapid review of known cases in the literature. Both case reports were conducted following CARE guidelines. We also performed a systematic review of PFP cases temporally related to COVID-19 using PubMed, Embase, and Cochrane Library databases on August 30, 2021, using a rapid review methodology. The two patients experienced PFP 102 and 110 days after COVID-19 symptom onset. SARS-CoV-2 RNA was detected in nasal samples through reverse-transcription real-time polymerase chain reaction (RT-qPCR) testing. Anosmia was the only other neurological manifestation. PFP was treated with steroids in both cases, with complete subsequent recovery. In the rapid review, we identified 764 articles and included 43 studies. From those, 128 patients with PFP were analyzed, of whom 42.1% (54/128) were male, 39.06% (50/128) female, and in 23 cases the gender was not reported. The age range was 18 to 59 (54.68%). The median time between COVID-19 and PFP was three days (ranging from the first symptom of COVID-19 to 40 days after the acute phase of infection). Late PFP associated with COVID-19 presents mild symptoms and improves with time, with no identified predictors. Late PFP should be added to the spectrum of neurological manifestations associated with the long-term effects of SARS-CoV-2 infection as a post COVID-19 condition.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2022-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9581522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40431099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibitory activities of propolis, nisin, melittin and essential oil compounds on <i>Paenibacillus alvei</i> and <i>Bacillus subtilis</i>.","authors":"Alessandra Aguirra Sani,&nbsp;Ana Flávia Marques Pereira,&nbsp;Alessandra Furlanetto,&nbsp;Débora Silva Marques de Sousa,&nbsp;Tatiane Baptista Zapata,&nbsp;Vera Lucia Mores Rall,&nbsp;Ary Fernandes","doi":"10.1590/1678-9199-JVATITD-2022-0025","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2022-0025","url":null,"abstract":"<p><strong>Background: </strong>Natural products represent important sources of antimicrobial compounds. Propolis and compounds from essential oils comprise good examples of such substances because of their inhibitory effects on bacterial spores, including bee pathogens.</p><p><strong>Methods: </strong>Ethanol extracts of propolis (EEP) from <i>Apis mellifera</i> were prepared using different methods: double ultrasonication, double maceration and maceration associated with ultrasonication. Together with the antimicrobial peptides nisin and melittin, and compounds present in the essential oils of clove (<i>Syzygium aromaticum</i>) and cinnamon (<i>Cinnamomum zeylanicum</i>), assays were carried out on one <i>Bacillus subtilis</i> isolate and <i>Paenibacillus alvei</i> (ATCC 6344) against vegetative and sporulated forms, using the resazurin microtiter assay. Synergism with all the antimicrobials in association with tetracycline was verified by the time-kill curve method. Potassium and phosphate efflux, release of proteins and nucleic acids were investigated.</p><p><strong>Results: </strong>EEPs showed the same MIC, 156.25 µg/mL against <i>B. subtilis</i> and 78.12 µg/mL against <i>P. alvei</i>. The peptides showed better activities against <i>B. subtilis</i> (MIC of 12 µg/mL for melittin and 37.50 µg/mL for nisin). Antimicrobials showed similar inhibitory effects, but cinnamaldehyde (39.06 µg/mL) showed the best action against <i>P. alvei</i>. Melittin and nisin showed the greatest capacity to reduce spores, regarding <i>B. subtilis</i> there was a 100% reduction at 6.25 and 0.78 µg/mL, respectively. Concerning <i>P. alvei</i>, the reduction was 93 and 98% at concentrations of 80 µg/mL of melittin and 15 µg/mL of nisin. EEPs showed the highest effects on the protein release against <i>B. subtilis</i> and <i>P. alvei</i>. Nucleic acid release, phosphate and potassium efflux assays indicated bacterial cell membrane damage. Synergism between antimicrobials and tetracycline was demonstrated against both bacteria.</p><p><strong>Conclusion: </strong>All antimicrobials tested showed antibacterial activities against vegetative and sporulated forms of <i>P. alvei</i> and <i>B. subtilis</i>, especially nisin and melittin. Synergism with tetracycline and damage on bacterial cell membrane also occurred.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2022-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9469734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40364937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antifungal activity of liriodenine on clinical strains of <i>Cryptococcus neoformans</i> and <i>Cryptococcus gattii</i> species complexes.","authors":"Adriele Dandara Levorato-Vinche,&nbsp;Marcia de Souza Carvalho Melhem,&nbsp;Lucas Xavier Bonfietti,&nbsp;Iván de-la-Cruz-Chacón,&nbsp;Carmen Sílvia Fernandes Boaro,&nbsp;Alexandre Todorovic Fabro,&nbsp;Gisela Ferreira,&nbsp;Julhiany de Fátima da Silva,&nbsp;Daniela Carvalho Dos Santos,&nbsp;Beatriz Aparecida Soares Pereira,&nbsp;Camila Marçon,&nbsp;Lariza Maza,&nbsp;Lídia Raquel de Carvalho,&nbsp;Rinaldo Poncio Mendes","doi":"10.1590/1678-9199-JVATITD-2022-0006","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2022-0006","url":null,"abstract":"<p><strong>Background: </strong>Cryptoccocal meningitis continues to present high incidence among AIDS patients. The treatment of choice is the synergistic combination of flucytosine (5-FC) with amphotericin B deoxycholate (AmBd) or its lipid formulations. However, 5-FC is unavailable in many countries and AmB demands hospitalization. The combination of AmB with the fungistatic fluconazole (FLC) or the use of high FLC daily doses alone became the choice. Nonetheless, sterilization of cerebrospinal fluid is delayed with FLC monotherapy, mainly with high fungal burden. These findings suggest the search for new antifungal compounds, such as liriodenine.</p><p><strong>Methods: </strong>Liriodenine antifungal activity was evaluated by three procedures: determining the minimum inhibitory concentration (MIC) on 30 strains of the <i>Cryptococcus neoformans</i> (<i>C. neoformans</i>) complex and 30 of the <i>Cryptococcus gattii</i> (<i>C. gattii</i>) complex, using EUCAST methodology and amphotericin B deoxycholate as control; performing the time-kill methodology in two strains of the <i>C. neoformans</i> complex and one of the <i>C. gattii</i> complex; and injury to cryptococcal cells, evaluated by transmission electron microscopy (TEM). Liriodenine absorption and safety at 0.75 and 1.50 mg.kg^-1 doses were evaluated in BALB/c mice.</p><p><strong>Results: </strong>Liriodenine MICs ranged from 3.9 to 62.5 μg.mL^-1 for both species complexes, with no differences between them. Time-kill methodology confirmed its concentration-dependent fungicidal effect, killing all the strains below the limit of detection (33 CFU.mL^-1) at the highest liriodenine concentration (32-fold MIC), with predominant activity during the first 48 hours. Liriodenine induced severe <i>Cryptococcus</i> alterations - cytoplasm with intense rarefaction and/or degradation, injury of organelles, and presence of vacuoles. Liriodenine was better absorbed at lower doses, with no histopathological alterations on the digestive tract.</p><p><strong>Conclusion: </strong>The fungicidal activity confirmed by time-kill methodology, the intense <i>Cryptococcus</i> injury observed by TEM, the absorption after gavage administration, and the safety at the tested doses indicate that the liriodenine molecule is a promising drug lead for development of anticryptococcal agents.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2022-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9469771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40364938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hemolymph of triatomines presents fungistatic activity against <i>Cryptococcus neoformans</i> and improves macrophage function through MCP-I/TNF-α increase.","authors":"Luísa Menezes-Silva, Jonatas da Silva Catarino, Laura Caroline de Faria, Bárbara Cristina Pizzolante, Leonardo Eurípedes Andrade-Silva, Marcos Vinicius da Silva, Virmondes Rodrigues, Helioswilton Sales-Campos, Carlo José Freire Oliveira","doi":"10.1590/1678-9199-JVATITD-2021-0124","DOIUrl":"10.1590/1678-9199-JVATITD-2021-0124","url":null,"abstract":"<p><strong>Background: </strong>Triatomines are blood-feeding arthropods belonging to the subfamily Triatominae (Hemiptera; Reduviidae), capable of producing immunomodulatory and water-soluble molecules in their hemolymph, such as antimicrobial peptides (AMPs). In this work, we evaluated the antifungal and immunomodulatory activity of the hemolymph of <i>Meccus pallidipennis</i> (MPH) and <i>Rhodnius prolixus</i> (RPH) against <i>Cryptococcus neoformans</i>.</p><p><strong>Methods: </strong>We assessed the activity of the hemolymph of both insects on fungal growth by a minimum inhibitory concentration (MIC) assay. Further, RAW 264.7 macrophages were cultivated with hemolymph and challenged with <i>C. neoformans</i>. Then, their phagocytic and killing activities were assessed. The cytokines MCP-1, IFN-γ, TNF-α, IL-10, IL-12, and IL-6 were measured in culture supernatants 4- and 48-hours post-infection.</p><p><strong>Results: </strong>Both hemolymph samples directly affected the growth rate of the fungus in a dose-dependent manner. Either MPH or RPH was capable of inhibiting fungal growth by at least 70%, using the lowest dilution (1:20). Treatment of RAW 264.7 macrophages with hemolymph of both insects was capable of increasing the production of MCP-I and TNF-α. In addition, when these cells were stimulated with hemolymph in the presence of <i>C. neoformans</i>, a 2- and a 4-fold increase in phagocytic rate was observed with MPH and RPH, respectively, when compared to untreated cells. For the macrophage killing activity, MPH decreased in approximately 30% the number of viable yeasts inside the cells compared to untreated control; however, treatment with RPH could not reduce the total number of viable yeasts. MPH was also capable of increasing MHC-II expression on macrophages. Regarding the cytokine production, MCP-I and TNF-α, were increased in the supernatant of macrophages treated with both hemolymphs, 4 and 48 hours after stimulation.</p><p><strong>Conclusion: </strong>These results suggested that hemolymph of triatomines may represent a source of molecules capable of presenting antifungal and immunomodulatory activity in macrophages during fungal infection.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2022-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40670905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}