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1.
Front Immunol ; 15: 1343602, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38455048

RESUMO

Introduction: Single nucleotide variations (SNVs) are specific genetic variations that commonly occur in a population and often do not manifest phenotypically. However, depending on their location and the type of nucleotide exchanged, an SNV can alter or inhibit the function of the gene in which it occurs. Immunoglobulin G (IgG) receptor genes have exhibited several polymorphisms, including rs1801274, which is found in the FcgRIIa gene. The replacement of A with T results in a Histidine (H) to Arginine (R) substitution, altering the affinity of the IgG receptor for IgG subtypes and C-reactive protein (CRP). In this study, we analyzed rs1801274 and its functional implications concerning L. Infantum uptake and cytokine production. Methods: We genotyped 201 individuals from an endemic area for visceral leishmaniasis to assess the presence of rs1801274 using Taqman probes for a candidate gene study. Additionally, we included seventy individuals from a non-endemic area for a functional study. Subsequently, we isolated and cultivated one-week adherent mononuclear cells (AMCs) derived from the peripheral blood of participants residing in the non-endemic region in the presence of L. infantum promastigotes, with and without antigen-specific IgG and/or CRP. We analyzed the rate of phagocytosis and the production of nitric oxide (NO), tumor necrosis factor (TNF)-a, interleukin (IL)-10, IL-12 p70, IL-1b, IL- 6, and IL-8 in the culture supernatants. Results and discussion: In participants from the endemic region, the A/G (H/R isoform) heterozygous genotype was significantly associated with susceptibility to the disease. Furthermore, SNVs induced a change in the phagocytosis rate in an opsonin-dependent manner. Opsonization with IgG increased the production of IL-10, TNF-a, and IL-6 in AMCs with the H/R isoform, followed by a decrease in NO production. The results presented here suggest that the rs1801274 polymorphism is linked to a higher susceptibility to visceral leishmaniasis.


Assuntos
Leishmania infantum , Leishmaniose Visceral , Humanos , Leishmaniose Visceral/genética , Leishmania infantum/genética , Receptores de IgG/genética , Interleucina-12 , Fator de Necrose Tumoral alfa , Nucleotídeos , Isoformas de Proteínas , Variação Genética , Imunoglobulina G
2.
Rev. Soc. Bras. Med. Trop ; 57: e00410, 2024. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1569585

RESUMO

ABSTRACT Background: The intensity of dengue virus (DV) replication and circulating non-structural protein 1 (NS1) levels may promote changes in the human immune response and favor severe forms of infection. We investigated the correlations between NS1 with CXCL-8, CXCL-10, IFN-γ, and IL-12p40 serum levels, and IFN-γ receptor α chain (CD119) expression, and CXCL10 production by peripheral blood mononuclear cells (PBMCs) stimulated with recombinant IFN-γ in DV-infected patients with different clinical forms. Methods: Dengue virus NS1, CXCL-8, CXCL-10, IFN-γ, and IL-12p40 serum levels were measured in 152 DV-infected patients with different clinical forms and 20 non-infected individuals (NI) using enzyme-linked immunosorbent assay (ELISA). In addition, we investigated the CXCL-10 production after in vitro IFN-γ stimulation of PBMCs from 48 DV-infected individuals (with different clinical forms of dengue fever) and 20 NI individuals using ELISA, and CD119 expression on CD14+ cells with flow cytometry. Results: Patients with dengue hemorrhagic fever (DHF) had significantly higher NS1, CXCL-8, and CXCL-10 serum levels than those with classic dengue fever (DF). The response of PBMCs to IFN-γ stimulation was lower in patients with DHF than in those with DF or dengue with complications (DWC), with lower CD119 expression and reduced CXCL-10 synthesis. In addition, these alterations are associated with high NS1 serum levels. Conclusions: Patients with DHF reported high NS1 levels, low CD119 expression, and low CXCL-10 synthesis in PBMCs, which may be associated with infection progression and severity.

3.
Rev. bras. ginecol. obstet ; 46: e, 2024. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1569733

RESUMO

Abstract Objective Eclampsia is a hypertensive disorder that occurs during pregnancy and can lead to death. The literature has gaps by not providing comprehensive data on the epidemiology of the disease, restricting analysis to limited temporal intervals and geographical locations. This study aims to characterize the epidemiological profile of women who died from eclampsia in Brazil from 2000 to 2021. Methods The maternal mortality data were obtained from the Sistema de Informações sobre Mortalidade, with the following variables of interest selected: "Federative Unit," "Year," "Age Range," "Race/Color," and "Education Level." The collection of the number of live births for data normalization was conducted in the Sistema de Informações sobre Nascidos Vivos. Statistical analyses were performed using GraphPad Prism, calculating odds ratio for variables and fixing number of deaths per 100,000 live births for calculating maternal mortality ratio (MMR). Results There was a downward trend in maternal mortality rate during the study period. Maranhão stood out as the federative unit with the highest MMR (17 deaths per 100.000 live births). Mothers aged between 40 and 49 years (OR = 3.55, CI: 3.11-4.05) presents higher MMR. Additionally, black women showed the highest MMR (OR = 4.67, CI: 4.18-5.22), as well as mothers with no educational background (OR = 5.83, CI: 4.82-7.06). Conclusion The epidemiological profile studied is predominantly composed of mothers with little or no formal education, self-declared as Black, residing in needy states and with advanced aged. These data are useful for formulating public policies aimed at combating the issue.

5.
Cancers (Basel) ; 15(21)2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37958472

RESUMO

Hodgkin's lymphoma (HL) is a lymphatic neoplasm typically found in the cervical lymph nodes. The disease is multifactorial, and in recent years, the relationships between various vascular molecules have been explored in the field of vascular biology. The connection between vascular biology and HL is intricate and the roles of several pathways remain unclear. This review summarizes the cellular and molecular relationships between vascular biology and HL. Proteins associated with various functions in vascular biology, including cytokines (TNF-α, IL-1, IL-13, and IL-21), chemokines (CXCL10, CXCL12, and CCL21), adhesion molecules (ELAM-1/VCAM-1), and growth factors (BDNF/NT-3, platelet-derived growth factor receptor-α), have been linked to tumor activity. Notable tumor activities include the induction of paracrine activation of NF-kB-dependent pathways, upregulation of adhesion molecule regulation, genome amplification, and effective loss of antigen presentation mediated by MHC-II. Preclinical study models, primarily those using cell culture, have been optimized for HL. Animal models, particularly mice, are also used as alternatives to complex biological systems, with studies primarily focusing on the physiopathogenic evaluation of the disease. These biomolecules warrant further study because they may shed light on obscure pathways and serve as targets for prevention and/or treatment interventions.

6.
Int J Infect Dis ; 137: 1-3, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37788739

RESUMO

This report presents the case of a 47-year-old male patient who worked as a mathematics teacher and experienced the sudden onset of disorientation, aphasia, and acalculia during an online class. The current study reveals the first documented case of HIV and progressive multifocal leukoencephalopathy with the detection of SARS-CoV-2 and human polyomavirus 2 (previously known as John Cunningham virus) in the cerebrospinal fluid. Furthermore, serum analysis revealed elevated concentrations of interleukin (IL)-6, IL-17, and IL-8, which are potential factors known to reduce the expression of tight junctions and adhesion molecules in the extracellular matrix, thereby affecting the permeability of the blood-brain barrier. Finally, the study discusses whether SARS-CoV-2 triggers or exacerbates progressive multifocal leukoencephalopathy.


Assuntos
COVID-19 , Infecções por HIV , Vírus JC , Leucoencefalopatia Multifocal Progressiva , Masculino , Humanos , Pessoa de Meia-Idade , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Infecções por HIV/complicações , Imageamento por Ressonância Magnética , COVID-19/diagnóstico , SARS-CoV-2
7.
Immunobiology ; 228(3): 152357, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36857907

RESUMO

Cytokines are small molecules secreted by numerous cells. Macrophage Migration Inhibitory Factor (MIF) is a cytokine initially described due to its function of inhibiting random macrophage migration. Currently, new functions have been described for MIF, such as stimulating inflammatory functions in response to infections by microorganisms including, Toxoplasma gondii. However, the primordial MIF function related to macrophages has been little addressed. The main purpose of the study was to recapitulate MIF function on macrophages in response to T. gondii infection. To achieve this goal, peritoneal macrophages were collected from C57BL/6WT and Mif1-/- mice after recruitment with thioglycolate. Macrophages were cultured, treated with 4-Iodo-6-phenylpyrimidine (4-IPP), and infected or not by T. gondii for 24 h. Following this, the culture supernatant was collected for cytokine, urea and nitrite analysis. In addition, macrophages were evaluated for phagocytic activity and T. gondii proliferation rates. Results demonstrated that T. gondii infection triggered an increase in MIF production in the WT group as well as an increase in the secretion of IL-10, TNF, IFN-γ, IL-6 and IL-17 in the WT and Mif1-/- macrophages. Regarding the comparison between groups, it was detected that Mif1-/- macrophages secreted more IL-10 compared to WT. On the other hand, the WT macrophages produced greater amounts of TNF, IFN-γ, IL-6 and IL-17. Urea production was more pronounced in Mif1-/- macrophages while nitrite production was higher in WT macrophages. T. gondii showed a greater ability to proliferate in Mif1-/- macrophages and these cells also presented enhanced phagocytic activity. In conclusion, T. gondii infection induces macrophage activation inciting cytokine production. In presence of MIF, T. gondii infected macrophages produce pro-inflammatory cytokines compatible with the M1 activation profile. MIF absence caused a dramatic reduction in pro-inflammatory cytokines that are balanced by increased levels of urea and anti-inflammatory cytokines. These macrophages presented increased phagocytic capacity and shared features activation with the M2 profile.


Assuntos
Fatores Inibidores da Migração de Macrófagos , Toxoplasma , Toxoplasmose , Animais , Camundongos , Interleucina-10 , Interleucina-17 , Interleucina-6 , Ativação de Macrófagos , Camundongos Endogâmicos C57BL , Nitritos , Toxoplasma/fisiologia
8.
Rev. Soc. Bras. Med. Trop ; 56: e0353, 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1514867

RESUMO

ABSTRACT Introduction: By July 2023, Brazil had administered approximately 540 million COVID-19 vaccine doses. This study aimed to quantify wasted doses resulting from dead space in vaccine supplies. Methods: The vaccine supply was initially weighed, filled with distilled water, and expelled to simulate administration. Weighing it again after the application determined the dead space volume. Descriptive analyses calculated the waste rate/wasted dose count. Results: The estimated total number of wasted vaccine doses using supplies with the lowest dead space was 62,097,338. Conclusions: Syringe dead space is a crucial factor in dose wastage, directly influencing the number of wasted doses.

9.
Rev. bras. enferm ; 76(supl.1): e20220173, 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS, BDENF - Enfermagem | ID: biblio-1449661

RESUMO

ABSTRACT Objectives: to compare exclusive breastfeeding prevalence versus artificial feeding in newborns of mothers with COVID-19. Methods: a systematic review of prevalence, according to JBI. Searches in PubMed®, Embase, CINAHL, LILACS and Web of Science™ databases in August 2021. Cross-sectional, longitudinal or cohort studies were selected, without language and time limitations that showed breastfeeding prevalence or that allowed calculation. Results: fifteen articles published in 2020 and 2021, cohort (60%) or cross-sectional (40%) were analyzed. The average of exclusive breastfeeding in mothers with COVID-19 was 56.76% (CI=39.90-72.88), and artificial breastfeeding, 43.23% (CI = 30.99 - 55.88), without statistically significant differences. Conclusions: despite the recommendations for maintaining breastfeeding, there was a reduction worldwide, when compared to periods prior to the pandemic. With advances in science, these rates have improved, showing the impact of evidence on practices. As limitations, study sources are cited. It is recommended to carry out new studies. PROSPERO registration CRD42021234486.


RESUMEN Objetivos: comparar la prevalencia de lactancia materna exclusiva versus alimentación artificial en recién nacidos de madres con COVID-19. Métodos: revisión sistemática de prevalencia, según JBI. Búsquedas en las bases de datos PubMed®, Embase, CINAHL, LILACS y Web of Science™ en agosto de 2021. Se seleccionaron estudios transversales, longitudinales o de cohortes, sin limitaciones de idioma y tiempo que mostraran prevalencia de lactancia materna o que permitieran calcular. Resultados: se analizaron 15 artículos publicados en 2020 y 2021, de cohorte (60%) o transversal (40%). El promedio de lactancia materna exclusiva en madres con COVID-19 fue 56,76% (IC=39,90-72,88), y lactancia artificial, 43,23% (IC = 30,99 - 55,88), sin diferencias estadísticamente significativas. Conclusiones: a pesar de las recomendaciones de mantener la lactancia materna, hubo una reducción a nivel mundial, en comparación con períodos previos a la pandemia. Con los avances de la ciencia, estas tasas han mejorado, mostrando el impacto de la evidencia en las prácticas. Como limitaciones se citan las fuentes del estudio. Se recomienda realizar nuevos estudios. Registro PROSPERO CRD42021234486.


RESUMO Objetivos: comparar as prevalências de aleitamento materno exclusivo versus aleitamento artificial em recém-nascidos de mães com COVID-19. Métodos: revisão sistemática de prevalência, segundo JBI. Buscas nas bases PubMed®, Embase, CINAHL, LILACS e Web of Science™ em agosto de 2021. Selecionados estudos transversais, longitudinais ou coortes, sem limitação de idioma e tempo que apresentavam prevalência de aleitamento materno ou que permitissem o cálculo. Resultados: 15 artigos publicados em 2020 e 2021, coortes (60%) ou transversais (40%) foram analisados. A média de aleitamento materno exclusivo em mães com COVID-19 foi 56,76% (IC=39,90-72,88), e artificial, de 43,23% (IC = 30,99 - 55,88), sem diferenças estatisticamente significantes. Conclusões: apesar das recomendações para a manutenção do aleitamento materno, houve redução mundialmente, quando comparados à períodos anteriores à pandemia. Com avanços da ciência, esses índices têm melhorado, mostrando o impacto das evidências nas práticas. Como limitações, citam-se fontes dos estudos. Recomenda-se realização de novos estudos. Registro PROSPERO CRD42021234486.

10.
Rev. bras. enferm ; 76(6): e20230070, 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS, BDENF - Enfermagem | ID: biblio-1529781

RESUMO

ABSTRACT Objective: to compare the effectiveness of different diagnostic methods to estimate postpartum blood volume loss. Methods: a systematic review of effectiveness according to PRISMA and JBI Protocol. Searches in PubMed/MEDLINE, LILACS, Scopus, Embase, Web of Science and CINAHL, with descriptor "Postpartum Hemorrhage" associated with keyword "Quantification of Blood Loss". Tabulated extracted data, presented in metasynthesis and meta-analysis was applied to quantitative data. To assess risk of bias, JBI Appraisal Tools were applied. Results: fourteen studies were included, published between 2006 and 2021. Quantification of loss by any method was superior to visual estimation and is highly recommended, however the studies' high heterogeneity did not allow estimating this association. Conclusion: the studies' high heterogeneity, with a probable margin of error given the uncontrolled factors, indicates the need for further studies, however quantification proved to be effective in relation to visual estimate. PROSPERO registration CRD 42021234486.


RESUMEN Objetivo: comparar la efectividad de diferentes métodos diagnósticos para estimar la pérdida de volumen sanguíneo posparto. Métodos: revisión sistemática de efectividad según PRISMA y Protocolo JBI. Búsquedas en bases de datos: PubMed/MEDLINE, LILACS, Scopus, Embase, Web of Science y CINAHL, con el descriptor "Postpartum Hemorrhage" asociado a la palabra clave "Quantification of Blood Loss". Los datos extraídos tabulados fueron presentados en metasíntesis y metanálisis se aplicaron a los datos cuantitativos. Para evaluar el riesgo de sesgo, se aplicaron las herramientas de evaluación de JBI. Resultados: se incluyeron 14 estudios, publicados entre 2006 y 2021. La cuantificación de pérdida por cualquier método fue superior a la estimación visual y es muy recomendable, sin embargo, la alta heterogeneidad de los estudios no permitió estimar esta asociación. Conclusión: la alta heterogeneidad de los estudios, con probable margen de error dado el descontrol de los factores, indica la necesidad de más estudios, sin embargo la cuantificación demostró ser efectiva en relación a la estimación visual. Registro PRÓSPERO CRD 42021234486.


RESUMO Objetivo: comparar a efetividade de diferentes métodos diagnósticos para estimar a perda volêmica sanguínea pós-parto. Métodos: revisão sistemática de efetividade, de acordo com protocolo PRISMA e JBI. Buscas nas bases PubMed/MEDLINE, LILACS, Scopus, Embase, Web of Science e CINAHL, com o descritor "Postpartum Hemorrhage" associado à palavra-chave "Quantification of Blood Loss". Dados extraídos tabulados, apresentados em metassíntese, e aplicou-se metanálise para dados quantitativos. Para avaliar o risco de viés, aplicou-se o JBI Appraisal Tools. Resultados: incluídos 14 estudos, publicados entre 2006 e 2021. A quantificação da perda por qualquer método apresentou superioridade em relação à estimativa visual, sendo altamente recomendada, porém a alta heterogeneidade dos estudos não permitiu estimar essa associação. Conclusão: a alta heterogeneidade dos estudos, com provável margem de erro dado aos fatores não controlados, indica a necessidade de realização de novos estudos, contudo a quantificação se mostrou efetiva em relação à estimativa visual. Registro PROSPERO CRD 42021234486.

11.
J Infect Dev Ctries ; 16(7): 1206-1217, 2022 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-35905026

RESUMO

INTRODUCTION: Candida albicans is the main agent of the most common fungal infection, Candidiasis. It is an opportunistic and dangerous pathogen, especially in immunosuppressed patients. The biological properties of Morinda citrifolia (noni) make it a potent antifungal. In this study, antifungal effect of M. citrifolia was evaluated to verify its effect on human cells. METHODOLOGY: Extract of M. citrifolia was used against strains of C. albicans (cEC 1291). Glucose consumption in C. albicans biofilm was determined at different concentrations of M. citrifolia, and germ tube formation was evaluated in the presence and absence of M. citrifolia. Fungicidal activity was determined by the kinetics of fungal cell death. THP-1 and HeLa cells were used for cell viability and apoptosis, and cell proliferation assays, respectively. RESULTS: Cells treated with M. citrifolia maintained higher concentration of glucose than the control group (p < 0.05). Germ tube formation was inhibited in cells treated with M. citrifolia (p < 0.05). M. citrifolia exerted a cytotoxic effect on C. albicans cells with 99.99% lethality after 6.82 h (1:1 and 1:2), and reduced the viability of THP-1 cells by 25% and 67% after 12 and 36 h, respectively. Annexin V expression in THP-1 increased in groups that received higher concentrations of M. citrifolia (p < 0.05), reducing the proliferation of THP-1 and HeLa cells (2.8-fold). A greater cytotoxic effect was observed in fungal cells. CONCLUSIONS: These results indicate that M. citrifolia exerts biological activity against C. albicans and reduces the viability and proliferation of human cells.


Assuntos
Antineoplásicos , Morinda , Antifúngicos/farmacologia , Candida albicans , Glucose/farmacologia , Células HeLa , Humanos , Extratos Vegetais/farmacologia
12.
J. pediatr. (Rio J.) ; 98(4): 399-405, July-Aug. 2022. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1386109

RESUMO

Abstract Objectives: Upper respiratory tract infections in children generally have significant morbidity and mortality. There is little data available about functional immaturity of the immune system and the child's susceptibility to infections at the beginning of their lives, thus, justifying a more specific immunological analysis. Method: Analysis of hemograms and innate and adaptive immune responses in 95 children between age 1 to 6 years with episodes of recurrent respiratory infections (test group n = 39) and without these episodes (control group n = 56) was carried out. The production of reactive oxygen intermediates by peripheral blood cells stimulated by phorbol myristate acetate was analyzed. Additionally, the number of B lymphocytes, auxiliary T lymphocytes, and cytotoxic cells was determined using flow cytometry. Results: Results from both groups did not show statistically significant differences in red blood cells, total leukocytes count, and the differential neutrophils, eosinophils, basophils, lymphocytes, and monocytes count. The analysis of the number of B lymphocytes, auxiliary T lymphocytes (LTCD4), and cytotoxic cells (LTCD8) also did not show any difference between both groups. However, the production of radical oxygen intermediates was significantly reduced in the test group as compared to the control group (p < 0.05). Conclusions: There was no difference in the analysis of hemograms, leukograms, or the number of lymphocytes, LTCD4, LTCD8, or LTCD19. The reduced production of oxygen intermediates in the affected group suggests that these children's microbicide capacity is compromised, which may be related to their recurrent respiratory infections.

13.
Rev. Soc. Bras. Med. Trop ; 55: e0353, 2022. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1394694

RESUMO

ABSTRACT Background: Domestic pigeons carry pathogens in their droppings, posing a potential public health problem. Methods: The phenotypic and genotypic antimicrobial resistances of Staphylococcus aureus and Enterococcus faecium in the feces of urban pigeons near hospitals with intensive care units were measured. Results: Twenty-nine samples showed Enterococcus growth, whereas one was positive for S. aureus. The S. aureus isolate was sensitive to the antibiotics tested via antibiogram, however resistance genes were identified. E. faecium isolates showed phenotypic resistance to gentamicin, erythromycin, and ciprofloxacin. Conclusions: Antimicrobial profiles harmful to health were demonstrated in bacterial pathogens isolated from the external environment of hospitals.

14.
J. venom. anim. toxins incl. trop. dis ; 28: e20210124, 2022. graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1386128

RESUMO

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 Meccus pallidipennis (MPH) and Rhodnius prolixus (RPH) against Cryptococcus neoformans. Methods: 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 C. neoformans. 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. Results: 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 C. neoformans, 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. Conclusion: 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.(AU)


Assuntos
Animais , Hemolinfa/química , Triatominae/microbiologia , Criptococose/terapia , Cryptococcus neoformans/imunologia , Antifúngicos/uso terapêutico , Imunomodulação/fisiologia
15.
J. venom. anim. toxins incl. trop. dis ; 27: e20200027, 2021. tab, graf
Artigo em Inglês | VETINDEX, LILACS | ID: biblio-1287091

RESUMO

Mycobacterium leprae and Mycobacterium lepromatosis are gram-positive bacterial pathogens and the causative agents of leprosy in humans across the world. The elimination of leprosy cannot be achieved by multidrug therapy alone, and highlights the need for new tools and drugs to prevent the emergence of new resistant strains. Methods In this study, our contribution includes the prediction of vaccine targets and new putative drugs against leprosy, using reverse vaccinology and subtractive genomics. Six strains of Mycobacterium leprae and Mycobacterium lepromatosis (4 and 2 strains, respectively) were used for comparison taking Mycobacterium leprae strain TN as the reference genome. Briefly, we used a combined reverse vaccinology and subtractive genomics approach. Results As a result, we identified 12 common putative antigenic proteins as vaccine targets and three common drug targets against Mycobacterium leprae and Mycobacterium lepromatosis. Furthermore, the docking analysis using 28 natural compounds with three drug targets was done. Conclusions The bis-naphthoquinone compound Diospyrin (CID 308140) obtained from indigenous plant Diospyros spp. showed the most favored binding affinity against predicted drug targets, which can be a candidate therapeutic target in the future against leprosy.(AU)


Assuntos
Bacilos Gram-Positivos/patogenicidade , Vacinologia , Mycobacterium leprae/patogenicidade , Mycobacterium lepraemurium/patogenicidade
16.
Rev. patol. trop ; 50(3): 179-200, 2021. ilus
Artigo em Inglês | LILACS | ID: biblio-1352889

RESUMO

This was a cross-sectional, anonymous, online survey aimed at assessing the perceptions and basic knowledge of COVID-19, a highly transmissible disease caused by SARS-CoV-2, in a sample population in the Triângulo Mineiro region, Minas Gerais, Brazil. A questionnaire devised by the researchers and distributed through social media was applied between June 16, 2020 and August 21, 2020. The survey consisted of questions about the basic aspects of COVID-19, which included symptoms, risk groups, suspicion of infection, prevention, transmission, and perception regarding social isolation. The average distribution, frequencies, similarities and differences between the responses for the different variables were evaluated. Five hundred twenty valid responses were obtained from participants aged ≥18 years. Most of the respondents showed satisfactory basic knowledge of COVID-19. Moreover, the data showed that the participants scored an average of 87.6%. Sex, age, and socioeconomic vulnerability presented a statistically significant link with knowledge of the disease; women, young participants, and the least socioeconomically vulnerable had the highest scores. This study indicated that the population in the Triângulo Mineiro region able to access social networking platforms were basically well informed regarding COVID-19, although differences were observed depending on the group analyzed.


Assuntos
Inquéritos e Questionários , Conhecimento , SARS-CoV-2 , COVID-19
17.
Cytokine ; 136: 155283, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32947151

RESUMO

Toxoplasma gondii (T. gondii) is an intracellular parasite responsible for causing toxoplasmosis. When infection occurs during pregnancy, it can produce severe congenital infection with ocular and neurologic damage to the infant. From the oral infection parasite reaches the intestine, causing inflammatory response, damage in tissue architecture and systemic dissemination. Macrophage migration inhibition factor (MIF) is a cytokine secreted from both immune and non-immune cells, including gut epithelial cells. MIF is described to promote inflammatory responses, to be associated in colitis pathogenesis and also to play role in maintaining the intestinal barrier. The aim of the present study was to evaluate the influence of the pregnancy and MIF deficiency on T. gondii infection in the intestinal microenvironment and to address how these factors can impact on the intestinal architecture and local cytokine profile. For this purpose, small intestine of pregnant and non-pregnant C57BL/6 MIF deficient mice (MIF-/-) and Wild-type (WT) orally infected with 5 cysts of ME-49 strain of T. gondii were collected on day 8th of infection. Intestines were processed for morphological and morphometric analyses, parasite quantification and for cytokines mensuration. Our results showed that the absence of MIF and pregnancy caused an increase in T. gondii infection index. T. gondii immunolocalization demonstrated that segments preferentially infected with T. gondii were duodenum and ileum. The infection caused a reduction in the size of the intestinal villi, whereas, infection associated with pregnancy caused an increase in villi size due to edema caused by the infection. Also, the goblet cell number was increased in the ileum of MIF-/- mice, when compared to the corresponding WT group. Analyses of cytokine production in the small intestine showed that MIF was up regulated in the gut of pregnant WT mice due to infection. Also, infection provoked an intense Th1 response that was more exacerbated in pregnant MIF-/- mice. We also detected that the Th2/Treg response was more pronounced in MIF-/- mice. Altogether, our results demonstrated that pregnancy and MIF deficiency interferes in the balance of the intestinal cytokines and favors a Th1-immflamatory profile, which in turn, impact in the development of pathology caused by T. gondii infection in the intestinal microenvironment.


Assuntos
Duodeno/imunologia , Íleo/imunologia , Oxirredutases Intramoleculares/imunologia , Fatores Inibidores da Migração de Macrófagos/imunologia , Complicações Parasitárias na Gravidez/imunologia , Toxoplasma/imunologia , Toxoplasmose/imunologia , Animais , Feminino , Oxirredutases Intramoleculares/genética , Fatores Inibidores da Migração de Macrófagos/genética , Camundongos , Camundongos Knockout , Gravidez , Complicações Parasitárias na Gravidez/genética , Toxoplasmose/genética
18.
Korean J Gastroenterol ; 76(3): 150-158, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32969363

RESUMO

Background/Aims: Therapies aimed at modulating cytokines have been used to treat inflammatory illnesses, such as inflammatory bowel disease. On the other hand, patients may become intolerant, refractory, or present with several side effects. Arthrospira (Spirulina) platensis (SPI) is a blue-green microalga with bioactive molecules that have been evaluated to treat inflammatory diseases. On the other hand, few studies have examined their effects on the production of specific cytokines and the intestinal architecture in dextran sulfate sodium (DSS)-induced colitis. Therefore, this study examined the effects of a treatment using SPI in a murine model of intestinal inflammation. Methods: All mice (C57BL/6 male) were evaluated daily for their food and water intake, bodyweight variations, and clinical signs of disease. Colon inflammation was induced by exposure to DSS for 6 consecutive days. SPI was given orally at 50, 100, and 250 mg/kg/day. ELISA was performed to assess the production of cytokines. Myeloperoxidase and nitric oxide were also investigated. The level of microscopic damage was assessed by staining colon sections with hematoxylin and eosin. Results: SPI attenuated the DSS-induced inflammation, with improvements in the clinical signs and a decrease in the production of inflammatory cytokines, such as tumor necrosis factor-α and interferon-γ. In addition, particularly at 250 mg/kg, SPI attenuated the severity of colitis by modulating the level of mucosal and submucosal cell infiltration, which preserved the epithelial barrier. Conclusions: SPI may be an alternative source of bioactive molecules with immunomodulatory properties, and has great potential to be used in the treatment of inflammatory diseases.


Assuntos
Colite/terapia , Interferon gama/metabolismo , Spirulina/química , Fator de Necrose Tumoral alfa/metabolismo , Animais , Colite/induzido quimicamente , Colite/patologia , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Fatores Imunológicos/química , Fatores Imunológicos/isolamento & purificação , Fatores Imunológicos/uso terapêutico , Interferon gama/análise , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico/metabolismo , Peroxidase/metabolismo , Spirulina/metabolismo , Fator de Necrose Tumoral alfa/análise
19.
Immunobiology ; 225(3): 151937, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32201094

RESUMO

Sand fly saliva presents molecules with potential to development of compounds for treatment of inflammatory diseases. Agaphelin, isolated from the saliva of the mosquito Anopheles gambiae, demonstrates anti-inflammatory properties such as neutrophils chemotaxis inhibition. Here, we extend these results and evaluated the role of agaphelin (0.1-100 nM) in an in vitro model consisting in the activation of human bronchial epithelial cells (BEAS-2B) by IL-4 (50 ng/mL) or lipopolysaccharide (LPS; 10 ng/mL). Agaphelin is non-cytotoxic for BEAS-2B cells. Notably, agaphelin markedly reduces CCL2 and IL-8 production induced by IL-4 or LPS, without altering the IL-10 production. The TLR4 expression and STAT1 phosphorylation induced by LPS were inhibited by agaphlin. In addition, agaphelin decreased the phosphorylation of STAT6 induce by IL-4, whose effect was independent of IL-4-binding activity. Taken together, these findings identify agaphelin as a potential anti-inflammatory therapeutic agent for airway inflammations.


Assuntos
Anti-Inflamatórios/farmacologia , Proteínas de Insetos/farmacologia , Interleucina-4/metabolismo , Lipopolissacarídeos/imunologia , Mucosa Respiratória/imunologia , Mucosa Respiratória/metabolismo , Proteínas e Peptídeos Salivares/farmacologia , Biomarcadores , Citocinas/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Humanos , Ligação Proteica , Fator de Transcrição STAT1/metabolismo , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo
20.
Acta ortop. bras ; 27(6): 321-324, Nov.-Dec. 2019. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1038187

RESUMO

ABSTRACT Objective: To assess the effect of chronic alcohol consumption on the longitudinal growth of the tibia and bone quality parameters in young rats under an experimental setup. METHODS: The control (n=10) rats received only water. The ethanol (n=10) rats received ethyl alcohol at concentrations established in the protocol for the induction of chronic alcohol consumption. The blood samples were immediately collected via cardiac puncture and processed to evaluate the levels of alkaline phosphatase by automated spectrophotometry. Following blood sample collection, both tibias were dissected, and weighed; the tibial length was measured., and the samples were stored in a freezer for future analysis of the bone mineral content and mechanical resistance, known as maximal load and stiffness. RESULTS: Compromised bone health, with a 35.3% decrease in the serum alkaline phosphatase levels (p < 0.01), a 10% decrease in the tibial mass (p < 0.05), and a 5.3% decrease in the tibial length (p < 0.0001) were noted. Furthermore, a 10% decrease in the bone mineral density was observed (p < 0.01), which led to a 17.2% decrease in the maximum strength (p < 0.01) and 22.6% decrease in stiffness (p < 0.001). CONCLUSION: Chronic consumption of alcohol affected the bones of young rats, making them weaker and osteopenic. In addition, the long bones were shorter, suggesting interference with growth. Level of Evidence III, Case Control Study.


RESUMO Objetivo: Verificar a influência do consumo experimental crônico de álcool no crescimento longitudinal da tíbia e em parâmetros de qualidade óssea de ratos jovens. Métodos: Dez ratos controle receberam água, outros dez receberam álcool etílico nas concentrações estabelecidas no protocolo para indução. Após eutanásia, as amostras de sangue foram coletadas por punção cardíaca e processadas para avaliar os níveis de fosfatase alcalina por espectrofotometria automatizada. Após a coleta de sangue, ambas as tíbias foram dissecadas, pesadas e medidas em comprimento. Foram realizadas análises do conteúdo mineral ósseo e resistência mecânica, por meio da análise da força máxima e rigidez. Resultados: Houve comprometimento da saúde óssea, com redução de 35,3% no nível de fosfatase alcalina no plasma (p<0,01), redução de 10% na massa da tíbia (p<0,05) e queda de 5,3% no comprimento das tíbias (p<0,0001). Também foi observada redução de 10% na densidade mineral óssea (p<0,01), que levou à redução de 17,2% na força máxima (p<0,01) e 22,6% na rigidez (p<0,001). Conclusão: O consumo crônico de álcool afetou os ossos de ratos jovens, tornando-os mais fracos e osteopênicos. Ainda, os ossos longos eram mais curtos, sugerindo interferência no crescimento. Nível de evidência III, Estudo caso-controle.

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