Advances in the understanding of leishmaniasis progression indicate that cellular interactions more complex than the Th1/Th2 paradigm define the course of infection. Th17 cells are a crucial ...modulator of adaptive immunity against
parasites acting mainly on neutrophil recruitment and playing a dual role at the site of infection. This review describes the roles of both these cell types in linking innate defense responses to the establishment of specific immunity. We focus on the Th17-neutrophil interaction as a crucial component of anti-
immunity, and the clinical evolution of cutaneous or visceral leishmaniasis. To date, information obtained through experimental models and patient evaluations suggests that the influence of the presence of interleukin (IL)-17 (the main cytokine produced by Th17 cells) and neutrophils during
infections is strictly dependent on the tissue (skin or liver/spleen) and parasite species. Also, the time at which neutrophils are recruited, and the persistence of IL-17 in the infection microenvironment, may also be significant. A clearer understanding of these interactions will enable better measurement of the influence of IL-17 and its regulators, and contribute to the identification of disease/resistance biomarkers.
Moringa oleifera is used in traditional medicine as well as in food, cosmetic, and pharmaceutical industries. Water-soluble M. oleifera lectin (WSMoL) is an anionic protein isolated from the seeds of ...this tree. Until now, immune responses promoted by this lectin in human PBMC have not been investigated.
The main objective of this study was to investigate the immunomodulatory effects of WSMoL on human PBMC through measurement of lymphocytes subsets, cytokine and nitric oxide levels.
Human peripheral blood mononuclear cells (PBMC) were isolated through Ficoll technique, were incubated with WSMoL (10 µg/mL) for 24, 48 and 72 hours, and was performed immunophenotyping assay of lymphocytes and monocytes. Culture supernatants were used to determined cytokine and nitric oxide levels. Assays with cells subsets and cytokine production were performed through cytometry. Nitric oxide release assay was determinate by spectrophotometry.
WSMoL induced the release of the cytokines TNF-α, IL-2, IL-6, IL-10 as well as nitric oxide. Incubation of PBMC with this lectin also led to activation of CD8+ T lymphocytes.
WSMoL promotes immunomodulation in human PBMC inducing a potential wound healing profile and, in future in vivo assays, can be evaluated as adjuvant in immunosuppressive diseases and wound repair.
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Biflorin (6,9-dimethyl-3-(4-methylpent-3-en-1-yl) benzodechromene-7,8-dione) is a promising substance that has been increasingly studied in the past decades due to its diverse ...pharmacological properties (i.e. antitumor, antioxidant, antiinflamatory, antimicrobial activity etc.). Aiming the comprehension of its antitumoral activity we investigated the cell proliferation and cytotoxicity habilities of biflorin against mice splenocytes Balb/c. Biflorin was able to stimulate mice splenocytes Balb/c in 48h of incubation at a concentration of 20.2μM. Its immunostimulation promoted the production of cytokines such as: TNF-α, IFN-γ, IL-2, IL-6 and IL-17, inducing the immune profile toward a Th1 response. Moreover, an original method which led to an excellent yield with less processing time compared to the methods described in the literature was developed to obtain biflorin, from sawdust of Capraria biflora L., Scrophulariaceae. This method shows a great potential of increasing the production of this pharmacological active compound.
We provide here a comparative genome analysis of ten strains within the Pseudomonas fluorescens group including seven new genomic sequences. These strains exhibit a diverse spectrum of traits ...involved in biological control and other multitrophic interactions with plants, microbes, and insects. Multilocus sequence analysis placed the strains in three sub-clades, which was reinforced by high levels of synteny, size of core genomes, and relatedness of orthologous genes between strains within a sub-clade. The heterogeneity of the P. fluorescens group was reflected in the large size of its pan-genome, which makes up approximately 54% of the pan-genome of the genus as a whole, and a core genome representing only 45-52% of the genome of any individual strain. We discovered genes for traits that were not known previously in the strains, including genes for the biosynthesis of the siderophores achromobactin and pseudomonine and the antibiotic 2-hexyl-5-propyl-alkylresorcinol; novel bacteriocins; type II, III, and VI secretion systems; and insect toxins. Certain gene clusters, such as those for two type III secretion systems, are present only in specific sub-clades, suggesting vertical inheritance. Almost all of the genes associated with multitrophic interactions map to genomic regions present in only a subset of the strains or unique to a specific strain. To explore the evolutionary origin of these genes, we mapped their distributions relative to the locations of mobile genetic elements and repetitive extragenic palindromic (REP) elements in each genome. The mobile genetic elements and many strain-specific genes fall into regions devoid of REP elements (i.e., REP deserts) and regions displaying atypical tri-nucleotide composition, possibly indicating relatively recent acquisition of these loci. Collectively, the results of this study highlight the enormous heterogeneity of the P. fluorescens group and the importance of the variable genome in tailoring individual strains to their specific lifestyles and functional repertoire.
Lipid metabolism rearrangements in nonalcoholic fatty-liver disease (NAFLD) contribute to disease progression. NAFLD has emerged as a major risk for hepatocarcinogenesis (HCC), where metabolic ...reprogramming is a hallmark. Identification of metabolic drivers might reveal therapeutic targets to improve HCC treatment. Here we investigated the contribution of transcription factors E2F1 and E2F2 to NAFLD-related HCC and their involvement in metabolic rewiring during disease progression. In mice receiving a high-fat diet (HFD) and diethylnitrosamine (DEN) administration, E2f1 and E2f2 expression was increased in NAFLD-related HCC. In human NAFLD, E2F1 and E2F2 expression was also increased and positively correlated. E2f1-/- and E2f2-/- mice were resistant to DEN-HFD-induced hepatocarcinogenesis and associated lipid accumulation. Administration of DEN-HFD in E2f1-/- and E2f2-/- mice enhanced fatty-acid oxidation (FAO) and increased expression of Cpt2, an enzyme essential for fatty-acid oxidation (FAO) whose downregulation is linked to NAFLD-related hepatocarcinogenesis. These results were recapitulated following E2f2 knockdown in liver, and overexpression of E2f2 elicited opposing effects. E2F2 binding to the Cpt2 promoter was enhanced in DEN-HFD-administered mouse livers compared to controls, implying a direct role for E2F2 in transcriptional repression. In human HCC, E2F1 and E2F2 expression inversely correlated with CPT2 expression. Collectively, these results indicate that activation of the E2F1-E2F2-Cpt2 axis provides a lipid-rich environment required for hepatocarcinogenesis.
Chagas disease, caused by the protozoan Trypanosoma cruzi, affects millions of people worldwide, especially in Latin America. Approximately 30% of the cases evolve to the chronic symptomatic stage ...due to cardiac and/or digestive damage, generally accompanied by nervous system impairment. Given the higher frequency and severity of clinical manifestations related to cardiac tissue lesion, the goal of this study was the identification of proteins associated with the disease progression towards its cardiac form. Thus, T. cruzi bloodstream trypomastigotes proteins were submitted to immunoprecipitation using antibodies from patients with the asymptomatic or cardiac (stages B1 and C) forms of the disease and from healthy donors as control. Immunoreactive proteins were identified and quantified based on mass spectrometry analysis and shifts in the recognition profile were further evaluated. Compared to asymptomatic samples, IgG from stage C patients predominantly detected the I/6 autoantigen, whereas IgG from B1 patients resulted in higher yield of dihydrolipoamide acetyltransferase precursor, calpain cysteine peptidase, and two variants of CAP5.5. In this work, CAP5.5 recognition by serum immunoglobulin from patients with early cardiomyopathy generated a 23-fold abundance variation when compared to samples from asymptomatic patients, highlighting the participation of this protein in cardiac form progression of the disease.
While T. cruzi has become the major cause of infectious cardiomyopathy in Latin America, research groups have been struggling to find alternative treatment, vaccine candidates, and improved diagnostic tests. In addition, the absence of adequate biomarkers to assess cure and progression of disease is a major setback for clinical trials and patients monitoring. Therefore, our findings may contribute to a better understanding of T. cruzi pathogenesis and evaluation of suitable candidates for vaccine and diagnostic tests, besides the clinical applicability of the potential biomarkers for patient follow-up and prognosis. Finally, the identification of T. cruzi proteins recognized by IgG from healthy donors may contribute for the understanding and discovery of epitope conservation among a broad range of pathogens.
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•First report of bloodstream trypomastigote immunoproteome•T. cruzi proteins differentially detected by patients at distinct disease stages.•Calpain-like CAP5.5: a biomarker for cardiac form progression of Chagas disease?•Several protein targets to be screened for their potential as vaccinal candidates
The data presented herein is related to the article entitled "Trypanosoma cruzi immunoproteome: calpain-like CAP5.5 differentially detected throughout distinct stages of human Chagas disease ...cardiomyopathy" 1. Electrophoretic analyses under denaturing and reducing conditions indicate that covalent immobilization of human IgG to Protein G magnetic beads by cross-linking with 50 mM dimethyl pimelimidate hinders the recognition of T. cruzi antigens in immunoprecipitation assays.
INTRODUCTION: Peripheral T-cell lymphomas (PTCL) represent a rare and heterogenous group of mature T-cell lymphomas often characterized by aggressive behavior. Previous studies evaluating the ...distribution of PTCL subtypes across Latin America (LATAM) were limited in their representation of most countries in the region. Additionally, a lack of standardized management for several subtypes and the absence of comprehensive lymphoma registries in LATAM suggests exploring real-world treatment patterns and clinical outcomes. We conducted an international pooled analysis to assess the distribution of PTCL across LATAM countries and report treatment outcomes. METHODS: We compiled data from patients aged ≥18 years with newly diagnosed PTCL from the retrospective registry of the Grupo de Estudio Latinoamericano de Linfoproliferativos (GELL, n=988, 1975-2023), the Brazilian T-cell Project (Brazilian TCP, 2015-2017, 168 cases retrospective; 2017-2023, 425 cases prospective) and the prospective registry of the International T cell Project (ITCP, n=529, 2006-2023). Data were abstracted from medical records in a standardized form. Survival data was only available from the GELL and Brazilian TCP. Overall survival (OS) was estimated from diagnosis to death from any cause, while progression-free survival (PFS) was defined from diagnosis to relapse, progression, or death from any cause. We used the Kaplan-Meier method and Log-rank test to estimate and compare survival probabilities. RESULTS: We enrolled 2110 patients from 11 LATAM countries. Overall, the median age at diagnosis was 54 years (range 18-95 years), most were male (59%), present with advanced stage disease (Ann Arbor III-IV, 67%), and had good performance status (ECOG ≤1, 71%) (Table 1). After PTCL not otherwise specified (NOS, 39%), adult T-cell leukemia/lymphoma (ATL, 18%) and extranodal NK/T cell lymphoma (ENKTL, 16%) were the most frequently diagnosed PTCL subtypes with varying distribution across LATAM countries. Peru had a higher prevalence of ATL (39%) and ENKTL was frequently diagnosed in Central America (43%). In contrast, ALK-negative (ALK-) anaplastic large T-cell lymphoma (ALCL) was the second more frequent subtype in Brazil (18%), Chile (16%), and Argentina (9%). The percentage of mature T-cell NOS was 27% in Argentina and 28% in Chile. A total of 1620 received chemotherapy. First-line chemotherapy varied across subtypes. Patients with ENKTL were frequently treated with asparaginase/platinum-based therapy (62%), while CHOP was more commonly used for ATL or PTCL NOS (46% for both). Chemotherapy with CHOEP/EPOCH was frequent for patients with ALK- ALCL (45%), ALK+ (ALCL 47%), or AITL (48%). With a median follow-up of 33 months, the 3-year OS and PFS for the overall cohort were 40% and 30%, respectively. ALK+ ALCL had superior survival estimates, with a 3-year OS of 77% and a 3-year PFS of 73%. The 3-year OS for patients with ENKTL was 48% and the PFS was 45%. Patients with ATL experienced the lowest survival rates (OS and PFS of 23% and 16% at 3 years, respectively). The use of asparaginase/platinum or CHOP-based therapy was associated with superior 3-year OS (61% and 52%, respectively; p=0.011) and PFS (57% and 49%, respectively; p=0.017) among patients with ENKTL. For ATL, the use of CHOEP/EPOCH was associated with improved 3-year OS (21%, p=0.009) and PFS (15%, p=0.024), but outcomes remained dismal. CONCLUSION: To our knowledge, we report the largest pooled cohort of PTCL subtypes across LATAM by leveraging the retrospective registry of the GELL consortium and data from the Brazilian TCP and ITCP. Our findings suggest a distinct distribution of PTCL subtypes across LATAM countries, with a higher prevalence of ATL and ENKTL compared to the epidemiological patterns in Western countries. This distribution underscores a unique opportunity to increase trial enrollment and accrual of rarer PTCL subtypes. The relatively high percentage of mature T-cell NOS suggests difficulties in providing specific lymphoma diagnoses in the region. The low survival rates for some subtypes indicate the need to develop novel therapies to improve patient outcomes. A larger prospective assessment of PTCL epidemiology and treatment outcomes is being planned to expand the ascertainment of cases, improve pathological classification of the different PTCL subtypes, and validate our results in the LATAM region.
A doença de Chagas é uma infecção sistêmica de evolução crônica cujo agente etiológico é o parasita Trypanosoma cruzi. O último relato encontrado sobre a soroprevalência da doença em doadores de ...sangue realizado na capital pernambucana, Recife, data de 1970, onde foi encontrada uma prevalência de 4,4% em doadores de um hospital local. Devido à falta de informações divulgadas sobre a infecção por T. cruzi e sendo Pernambuco uma região endêmica para esta enfermidade, o presente estudo se propôs a analisar o perfil dos doadores de sangue do Hemocentro de Pernambuco (Hemope), que apresentaram reatividade para doença de Chagas, no período de 2002 a 2007. O perfil dos doadores inaptos foi avaliado de acordo com gênero, idade e procedência segundo as mesorregiões de Pernambuco. Foi encontrada uma prevalência de 0,17% para doença de Chagas e 6,89% das bolsas descartadas deveram-se a essa reatividade. Em relação ao gênero dos doadores, foi significativamente maior a contribuição dos homens (p<0,0001). A faixa etária de 18-30 anos apresentou menor quantidade de sorologias reativas (20,21%). Foi verificado também que, na Região Metropolitana do Recife, a quantidade de reações inconclusivas foi estatisticamente maior que a quantidade de sorologias reagentes (p=0,0440). Desta forma, estudos epidemiológicos fornecem dados importantes no sentido de se avaliar diretamente o risco de transmissão de uma doença por transfusão sanguínea e permitem que também em regiões endêmicas se avalie a eficácia das medidas para o controle vetorial.
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