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1.
An Acad Bras Cienc ; 96(1): e20231088, 2024.
Article in English | MEDLINE | ID: mdl-38597494

ABSTRACT

The thorough redox alteration of a lava flow is an undescribed feature in intraplate basaltic provinces. The Early Cretaceous (134.5 Ma) Paraná Province displays that alteration in the major Muralha Flow. This oxidized and reduced flow from the southern part of the province was studied with satellite images, field surveying, petrography, and published whole rock geochemistry. The 100 x 100 km flow from the Cuesta de Haedo presents two hydrothermal tiers - lower Tier 1 is gray to white, upper Tier 2 is red. Iron oxyhydroxides characterize Tier 2. Tier 1 contains clay minerals, zeolites, pyrite and calcite, and agate (possibly amethyst) geodes. In a first event, the upper Tier 2 was oxidized by hot water from the underlying Guarani Paleoaquifer. The high water/rock ratio decreased due to porosity clogging by precipitation of secondary minerals, and the fluid became reducing. Lowering of Eh and pH was caused by reaction of water with reducing particles (calcite, organic molecules) present in the paleoerg sandstones and with fresh rock surfaces. A lower Tier 1 was then formed during slow, hot water percolation. Reduction was interrupted below 30 °C (calcite formation). Large scale, similar alteration occurred in all studied oceanic ridges and only rarely in continental environments.


Subject(s)
Calcium Carbonate , Minerals , Water/chemistry , Oxidation-Reduction , Brazil
2.
Cell Rep ; 43(3): 113932, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38457336

ABSTRACT

Innate immune cells can undergo long-term functional reprogramming after certain infections, a process called trained immunity (TI). Here, we focus on antigens of Leishmania braziliensis, which induced anti-tumor effects via trained immunity in human monocytes. We reveal that monocytes exposed to promastigote antigens of L. braziliensis develop an enhanced response to subsequent exposure to Toll-like receptor (TLR)2 or TLR4 ligands. Mechanistically, the induction of TI in monocytes by L. braziliensis is mediated by multiple pattern recognition receptors, changes in metabolism, and increased deposition of H3K4me3 at the promoter regions of immune genes. The administration of L. braziliensis exerts potent anti-tumor capabilities by delaying tumor growth and prolonging survival of mice with non-Hodgkin lymphoma. Our work reveals mechanisms of TI induced by L. braziliensis in vitro and identifies its potential for cancer immunotherapy.


Subject(s)
Leishmania braziliensis , Leishmaniasis, Cutaneous , Neoplasms , Humans , Mice , Animals , Monocytes
3.
Microb Pathog ; 188: 106550, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38262494

ABSTRACT

Cytokines of the interleukin (IL)-1 superfamily including the different IL-36 isoforms, have been reported as mediators of acute and chronic inflammation in human skin diseases, such as psoriasis. Here, we demonstrated for the first time that Sporothrix schenckii and S. brasiliensis, the fungi that cause subcutaneous infection sporotrichosis, can induce the expression of IL-36α, IL-36γ and IL-36Ra in human keratinocytes and primary peripheral blood mononuclear cells (PBMCs). Specifically, IL-36γ was differentially expressed by keratinocytes stimulated with Sporothrix yeasts when compared to the commensal microorganism Staphylococcus epidermidis. The exposure of keratinocytes to 24 h or 7-days culture supernatant of PBMCs stimulated with Sporothrix induced higher IL-36γ production compared to direct stimulation of keratinocytes with the live fungus. We identified that IL-36γ mRNA expression in keratinocytes is increased in the presence of IL-17, TNF, IL-1ß and IL-1α and these cytokines may act synergistically to maintain IL-36γ production. Lastly, using a cohort of 164 healthy individuals, we showed that individuals carrying variants of the IL36G gene (rs11690399 and rs11683399) exhibit increased IL-36γ production as well as increased innate cytokine production after Sporothrix exposure. Importantly, stimulation of PBMCs with recombinant IL-36γ increased the production of IL-1ß and IL-6, while IL-36Ra were able to decrease the concentration of these cytokines. Our findings contribute to the understanding of the pathogenesis of sporotrichosis and suggest that IL-36γ may be involved in maintaining the cytokine loop that leads to tissue destruction by exacerbating the immune response in sporotrichosis. Of high interest, we present the IL-36 signalling pathway as a potential new therapeutic target.


Subject(s)
Sporothrix , Sporotrichosis , Humans , Cytokines/metabolism , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Interleukins/genetics , Interleukins/metabolism , Keratinocytes , Leukocytes, Mononuclear , Sporothrix/genetics
4.
PLOS Digit Health ; 2(10): e0000279, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37824584

ABSTRACT

INTRODUCTION: Harnessing new digital technologies can improve access to health care but can also widen the health divide for those with poor digital literacy. This scoping review aims to assess the current situation of low digital health literacy in terms of its definition, reach, impact on health and interventions for its mitigation. METHODS: A comprehensive literature search strategy was composed by a qualified medical librarian. Literature databases [Medline (Ovid), Embase (Ovid), Scopus, and Google Scholar] were queried using appropriate natural language and controlled vocabulary terms along with hand-searching and citation chaining. We focused on recent and highly cited references published in English. Reviews were excluded. This scoping review was conducted following the methodological framework of Arksey and O'Malley. RESULTS: A total of 268 articles were identified (263 from the initial search and 5 more added from the references of the original papers), 53 of which were finally selected for full text analysis. Digital health literacy is the most frequently used descriptor to refer to the ability to find and use health information with the goal of addressing or solving a health problem using technology. The most utilized tool to assess digital health literacy is the eHealth literacy scale (eHEALS), a self-reported measurement tool that evaluates six core dimensions and is available in various languages. Individuals with higher digital health literacy scores have better self-management and participation in their own medical decisions, mental and psychological state and quality of life. Effective interventions addressing poor digital health literacy included education/training and social support. CONCLUSIONS: Although there is interest in the study and impact of poor digital health literacy, there is still a long way to go to improve measurement tools and find effective interventions to reduce the digital health divide.

5.
Nat Med ; 29(5): 1243-1252, 2023 05.
Article in English | MEDLINE | ID: mdl-37188781

ABSTRACT

We characterized the world's second case with ascertained extreme resilience to autosomal dominant Alzheimer's disease (ADAD). Side-by-side comparisons of this male case and the previously reported female case with ADAD homozygote for the APOE3 Christchurch (APOECh) variant allowed us to discern common features. The male remained cognitively intact until 67 years of age despite carrying a PSEN1-E280A mutation. Like the APOECh carrier, he had extremely elevated amyloid plaque burden and limited entorhinal Tau tangle burden. He did not carry the APOECh variant but was heterozygous for a rare variant in RELN (H3447R, termed COLBOS after the Colombia-Boston biomarker research study), a ligand that like apolipoprotein E binds to the VLDLr and APOEr2 receptors. RELN-COLBOS is a gain-of-function variant showing stronger ability to activate its canonical protein target Dab1 and reduce human Tau phosphorylation in a knockin mouse. A genetic variant in a case protected from ADAD suggests a role for RELN signaling in resilience to dementia.


Subject(s)
Alzheimer Disease , Animals , Female , Humans , Male , Mice , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Heterozygote , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Signal Transduction
6.
J Fungi (Basel) ; 9(4)2023 Mar 30.
Article in English | MEDLINE | ID: mdl-37108883

ABSTRACT

Paracoccidioidomycosis (PCM) is a systemic mycosis caused by fungi of the genus Paracoccidioides and the different clinical forms of the disease are associated with the host immune responses. Quantitative trait loci mapping analysis was performed to assess genetic variants associated with mononuclear-cells-derived cytokines induced by P. brasiliensis on 158 individuals. We identified the rs11053595 SNP, which is present in the CLEC7A gene (encodes the Dectin-1 receptor) and the rs62290169 SNP located in the PROM1 gene (encodes CD133) associated with the production of IL-1ß and IL-22, respectively. Functionally, the blockade of the dectin-1 receptor abolished the IL-1ß production in P. brasiliensis-stimulated PBMCs. Moreover, the rs62290169-GG genotype was associated with higher frequency of CD38+ Th1 cells in PBMCs cultured with P. brasiliensis yeasts. Therefore, our research indicates that the CLEC7A and PROM1 genes are important for the cytokine response induced by P. brasiliensis and may influence the Paracoccidioidomycosis disease outcome.

7.
Cell Biol Int ; 46(11): 1787-1800, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35971753

ABSTRACT

Caveolin-1 (Cav-1) is an integral membrane protein present in all organelles, responsible for regulating and integrating multiple signals as a platform. Mitochondria are extremely adaptable to external cues in chronic liver diseases, and expression of Cav-1 may affect mitochondrial flexibility in hepatic stellate cells (HSCs) activation. We previously demonstrated that exogenous expression of Cav-1 was sufficient to increase some classical markers of activation in HSCs. Here, we aimed to evaluate the influence of exogenous expression and knockdown of Cav-1 on regulating the mitochondrial plasticity, metabolism, endoplasmic reticulum (ER)-mitochondria distance, and lysosomal activity in HSCs. To characterize the mitochondrial, lysosomal morphology, and ER-mitochondria distance, we perform transmission electron microscope analysis. We accessed mitochondria and lysosomal networks and functions through a confocal microscope and flow cytometry. The expression of mitochondrial machinery fusion/fission genes was examined by real-time polymerase chain reaction. Total and mitochondrial cholesterol content was measured using Amplex Red. To define energy metabolism, we used the Oroboros system in the cells. We report that GRX cells with exogenous expression or knockdown of Cav-1 changed mitochondrial morphometric parameters, OXPHOS metabolism, ER-mitochondria distance, lysosomal activity, and may change the activation state of HSC. This study highlights that Cav-1 may modulate mitochondrial function and structural reorganization in HSC activation, being a potential candidate marker for chronic liver diseases and a molecular target for therapeutic intervention.


Subject(s)
Caveolin 1 , Hepatic Stellate Cells , Caveolin 1/genetics , Caveolin 1/metabolism , Cholesterol/metabolism , Hepatic Stellate Cells/metabolism , Humans , Liver Cirrhosis/pathology , Membrane Proteins/metabolism , Mitochondria/metabolism
8.
Sci Data ; 9(1): 487, 2022 08 10.
Article in English | MEDLINE | ID: mdl-35948551

ABSTRACT

Chest radiographs allow for the meticulous examination of a patient's chest but demands specialized training for proper interpretation. Automated analysis of medical imaging has become increasingly accessible with the advent of machine learning (ML) algorithms. Large labeled datasets are key elements for training and validation of these ML solutions. In this paper we describe the Brazilian labeled chest x-ray dataset, BRAX: an automatically labeled dataset designed to assist researchers in the validation of ML models. The dataset contains 24,959 chest radiography studies from patients presenting to a large general Brazilian hospital. A total of 40,967 images are available in the BRAX dataset. All images have been verified by trained radiologists and de-identified to protect patient privacy. Fourteen labels were derived from free-text radiology reports written in Brazilian Portuguese using Natural Language Processing.


Subject(s)
Algorithms , Natural Language Processing , Radiography, Thoracic , Brazil , Humans , X-Rays
9.
Arch. endocrinol. metab. (Online) ; 66(4): 472-480, July-Aug. 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1403226

ABSTRACT

ABSTRACT Introduction: This study aimed to evaluate the incidence, severity and presence of symptoms of respiratory tract infections and COVID-19, in patients with pre-existing thyroid dysfunction compared to individuals without thyroid diseases, during the peak month of the COVID-19 pandemic in the Netherlands. Subjects and methods: In this retrospective observational cohort study, all patients currently under follow-up at the Radboud UMC for thyroid dysfunction received a digital questionnaire. Primary outcomes were incidence of self-reported sickness and cases diagnosed with COVID-19. We compared these primary outcomes between these patients and individuals without thyroid diseases that received the same questionnaire, recruited from the Human Functional Genomics Cohort at the Radboud UMC. Results: In total, 238 patients with pre-existing thyroid dysfunction and 161 controls were included. Patients did not report more sickness (30.7% vs. 29.2%; p = 0.752) or microbiologically confirmed SARS-CoV-2 infections (1.7% vs. 0.6%; p = 0.351). COVID-19 clinical diagnosis was more frequently made in patients with thyroid diseases (4.2% vs. 0.6%; p = 0.032), despite overall lower incidence of self-reported respiratory related symptoms (52.8% vs. 63.8%; p = 0.028), compared to controls. Sub-group analysis between patients with autoimmune and not-autoimmune thyroid dysfunction did not reveal significant associations with respect to any of the outcome measures. Conclusion: This retrospective survey of a cohort of patients with from a tertiary academic hospital suggests that pre-existing thyroid dysfunction, independent from the aetiology, does not lead to an apparent risk to develop respiratory tract infections and COVID-19 related symptoms.

10.
Cell Immunol ; 378: 104555, 2022 08.
Article in English | MEDLINE | ID: mdl-35696852

ABSTRACT

Sporotrichosis is a deep mycosis caused by dimorphic species of the genus Sporothrix, with differences in pathogenicity between S. schenckii and S. brasiliensis species. Recently, it was discovered that the cell wall peptidorhamnomannan (PRM) from S. brasiliensis has additional unknown rhamnose residues. We hypothesize that the structural differences of Sporothrix spp PRMs impact the host's immune response and may explain the severity of sporotrichosis caused by S. brasiliensis. We demonstrate that S. brasiliensis yeasts and its PRM (S.b PRM) induced a strong inflammatory response in human PBMCs, with high production of TNF-α, IL-6 and IL-1ß and induction of T-helper cytokines IFN-γ, IL-17 and IL-22. In contrast, S. schenckii yeasts and its PRM induced higher concentrations of interleukin-1 receptor antagonist (IL-1Ra), which resulted in low production of T-helper cytokines such as IL-17 and IL-22. CR3 and dectin-1 were required for cytokine induction by both PRMs, while TLR2 and TLR4 were required for the response of S.s PRM and S.b PRM, respectively. IL-1ß and IL-1α production induced by S. brasiliensis yeasts and S.b PRM were dependent on inflammasome and caspase-1 activation. S. schenckii and S.s PRM were able to induce IL-1ß independent of ROS. In conclusion, these findings improve our understanding of the pathogenesis of Sporothrix spp. by reporting differences of immunological responses induced by S. schenckii and S. brasiliensis. The study also opens the gateway for novel treatment strategies targeting local inflammation and tissue destruction induced by S. brasiliensis infection through IL-1 inhibition.


Subject(s)
Sporothrix , Sporotrichosis , Cytokines , Glycoproteins , Humans , Interleukin-17 , Sporotrichosis/pathology
11.
Arch Endocrinol Metab ; 66(4): 472-480, 2022.
Article in English | MEDLINE | ID: mdl-35657122

ABSTRACT

Introduction: This study aimed to evaluate the incidence, severity and presence of symptoms of respiratory tract infections and COVID-19, in patients with pre-existing thyroid dysfunction compared to individuals without thyroid diseases, during the peak month of the COVID-19 pandemic in the Netherlands. Subjects and methods: In this retrospective observational cohort study, all patients currently under follow-up at the Radboud UMC for thyroid dysfunction received a digital questionnaire. Primary outcomes were incidence of self-reported sickness and cases diagnosed with COVID-19. We compared these primary outcomes between these patients and individuals without thyroid diseases that received the same questionnaire, recruited from the Human Functional Genomics Cohort at the Radboud UMC. Results: In total, 238 patients with pre-existing thyroid dysfunction and 161 controls were included. Patients did not report more sickness (30.7% vs. 29.2%; p = 0.752) or microbiologically confirmed SARS-CoV-2 infections (1.7% vs. 0.6%; p = 0.351). COVID-19 clinical diagnosis was more frequently made in patients with thyroid diseases (4.2% vs. 0.6%; p = 0.032), despite overall lower incidence of self-reported respiratory related symptoms (52.8% vs. 63.8%; p = 0.028), compared to controls. Sub-group analysis between patients with autoimmune and not-autoimmune thyroid dysfunction did not reveal significant associations with respect to any of the outcome measures. Conclusion: This retrospective survey of a cohort of patients with from a tertiary academic hospital suggests that pre-existing thyroid dysfunction, independent from the aetiology, does not lead to an apparent risk to develop respiratory tract infections and COVID-19 related symptoms.


Subject(s)
COVID-19 , Thyroid Diseases , COVID-19/epidemiology , Humans , Pandemics , Retrospective Studies , SARS-CoV-2 , Self Report , Thyroid Diseases/complications , Thyroid Diseases/epidemiology
12.
J Immunol Res ; 2022: 7070301, 2022.
Article in English | MEDLINE | ID: mdl-35097133

ABSTRACT

Chagas disease (CD) is an important parasitic disease caused by Trypanosoma cruzi. Interleukin-32 (IL-32) plays an important role in inflammation and in the development of Th1/Th17 acquired immune responses. We evaluated the influence of IL-32γ on the immune response profile, pathogenesis of myocarditis in acute experimental CD, and control of the disease. For this, C57BL/6 wild-type (WT) and IL-32γTg mice were infected subcutaneously with 1,000 forms of Colombian strain of T. cruzi. In the histopathological analyzes, T. cruzi nests, myocarditis, and collagen were quantified in cardiac tissue. Cytokine productions (IL-32, IFN-γ, TNF-α, IL-10, and IL-17) were measured in cardiac homogenate by ELISA. The IL-32γTg mice showed a better control of parasitemia and T. cruzi nests in the heart than WT mice. Infected-WT and -IL-32γTg mice showed similar levels of IFN-γ, TNF-α, and IL-17, but IL-10 was significantly higher expressed in IL-32γTg than in WT mice. The cytokine profile found in IL-32γTg animals contributed to body weight maintenance, parasitemia control, and survival. Our results indicate that the presence of human IL-32γ in mice infected with the Colombian strain of T. cruzi is important for infection control during the acute phase of Chagas disease.


Subject(s)
Chagas Disease , Inflammation , Interleukins , Myocardium , Parasitemia , Trypanosoma cruzi , Animals , Humans , Male , Mice , Acute Disease , Chagas Cardiomyopathy , Chagas Disease/immunology , Inflammation/genetics , Inflammation/metabolism , Interleukins/genetics , Interleukins/metabolism , Mice, Inbred C57BL , Mice, Transgenic , Models, Animal , Myocardium/pathology , Parasitemia/immunology , Trypanosoma cruzi/physiology
13.
Arq. bras. med. vet. zootec. (Online) ; 74(6): 961-968, 2022. ilus, graf
Article in English | VETINDEX | ID: biblio-1415361

ABSTRACT

The aim of this work was to evaluate, in vitro, the dynamics of nuclear and cytoplasmic maturation of bovine oocytes in traditional IVM medium (CT) and supplemented with fullerol (MF50), for 36 hours. The nuclear maturation of CT (n=300) and MF50 (n=270) every 6 hours, stained with Hoechst33342 and cytoplasmic, the mitochondrial distribution of CT (n=197) and MF50 (n=159) at every 12 hours, stained with Mitotracker Orange. At 6 hours, CT oocytes (19%) were in MI (metaphase I), while in MF50 they were in GV (germ vesicle) or GVB (GV breakeage), repeating at 12 hours. At 18 hours, 46.3% were matured in CT, and 20% in MF50. At 24 hours, 43.9% of maturation was observed in the MF50 group, and 63.8% in the CT. At 30 and 36 hours, the maturation pattern was stable, but with the onset of oocyte degeneration. There was a delay in cytoplasmic maturation with 36 hours (P < 0.05) in MF50 (53.9% of mature gametes), compared to CT (69.8%). With immature cytoplasm, they were 10.4% and 31.7% for CT and MF50 (P< 0.05), respectively. It was concluded that fullerol possibly interfered in the expansion of cumulus oophorus cells, as well as delayed the meiotic progression and cytoplasmic maturation.


O objetivo deste estudo foi avaliar, in vitro, a dinâmica da maturação nuclear e citoplasmática de oócitos bovinos em meio MIV tradicional (TC) e suplementado com fulerol (MF50), durante 36 horas. Na maturação nuclear do TC (n=300) e do MF50 (n=270) a cada seis horas, corados com Hoechst 33342, e na citoplasmática, avaliou-se a distribuição mitocondrial do TC (n=197) e do MF50 (n=159) a cada 12 horas, corados com Mitotracker Orange (Life® Technologies). Às seis horas, oócitos do TC (19%) se encontravam em MI (metáfase I), enquanto no MF50 estavam em VG (vesícula germinativa) ou QVG (quebra VG), repetindo com 12 horas. Às 18 horas, 46,3% estavam maturados no TC, e 20% no MF50. Com 24 horas, verificaram-se 43,9% de maturação no grupo MF50, e 63,8% no TC. Às 30 e 36 horas, o padrão de maturação foi estável, mas com início de degeneração oócitária. Houve retardo na maturação citoplasmática com 36 horas (P<0,05) no MF50 (53,9% de gametas maduros), comparado ao TC (69,8%). Com citoplasma imaturo, foram 10,4% e 31,7% para TC e MF50 (P<0,05), respectivamente. Conclui-se que o fulerol possivelmente interferiu na expansão das células do cumulus oophorus, bem como retardou a progressão meiótica e a maturação citoplasmática dos oócitos.


Subject(s)
Animals , Cattle , Fullerenes/administration & dosage , In Vitro Oocyte Maturation Techniques/methods , In Vitro Oocyte Maturation Techniques/veterinary , Nanoparticles/analysis , Meiosis
14.
Arq. bras. med. vet. zootec. (Online) ; 73(4): 771-780, Jul.-Aug. 2021. tab, graf, ilus
Article in English | LILACS, VETINDEX | ID: biblio-1285281

ABSTRACT

The objective of this study was to evaluate follicular growth and ovulatory rates in mares treated with an intravaginal progesterone device (P4) during the 10-day period, associated with the use of estradiol benzoate (EB). The results were compared during the transition period (ET) in the spring and the breeding season in the summer (ER). The variables were submitted to ANOVA (Tukey's test), considering P<0.05. No ovulation occurred during the permanence of the P4 implant in both experimental periods. The ovulatory rate in the ER was 100% (n = 8) and in the ET 62.5% (n = 5; P = 0.0547). Significant differences were observed (<0.001), in both periods, comparing follicular growth rates during the permanence of P4 device (ER: 1.33 ± 0.89mm/d; ET: 1.00 ± 0.81mm/d) to the period without P4 (ER: 3.63 ± 1.33 mm/d; ET: 3.31 ± 1.66 mm/d). The present study demonstrated applicability and efficiency of a hormonal protocol using P4 intravaginal device and EB for follicular control in mares, both during ET and ER.


O objetivo deste trabalho foi avaliar a taxa de crescimento folicular e a taxa ovulatória em éguas tratadas com dispositivo intravaginal de progesterona (P4) durante o período de 10 dias, associado à utilização de benzoato de estradiol (BE). Os resultados foram comparados durante o período de transição (ET) da primavera com a época de reprodução no verão (ER). As variáveis foram submetidas à ANOVA (teste de Tukey), considerando-se P<0,05. Nenhuma ovulação ocorreu durante a permanência do dispositivo de P4 em ambos os períodos experimentais. A taxa ovulatória na ER foi de 100% (n = 8) e na ET, de 62,5% (n=5; P=0,0547). Diferença significativas (<0,001) foram observadas, em ambos os períodos experimentais, comparando as taxas de crescimento folicular durante a permanência da P4 (ER: 1,33 ± 0,89mm/d; ET: 1,00 ± 0,81mm/d) com o período sem P4 (ER: 3,63 ± 1,33mm/d; ET: 3,31 ± 1,66mm/d). O presente estudo demonstrou aplicabilidade e eficiência do protocolo hormonal utilizando dispositivo intravaginal de P4 e BE para controle folicular de éguas, tanto na ET quanto na ER.


Subject(s)
Animals , Female , Progesterone/administration & dosage , Benzoates , Estradiol , Horses/physiology , Ovulation , Seasons , Administration, Intravaginal , Analysis of Variance , Ovarian Follicle/physiology
15.
J Neurosci Res ; 99(10): 2511-2524, 2021 10.
Article in English | MEDLINE | ID: mdl-34260774

ABSTRACT

Peripheral inflammation, particularly mediated by monocytes, can cause neuroinflammation in Parkinson's disease (PD). We investigated the mechanism of TLR2-induced cytokine impairment in peripheral monocytes from PD patients and the association between the presence of CD14+ TLR10+ monocytes and PD severity. Peripheral blood mononuclear cells from PD patients and healthy individuals were evaluated for TLR expression on monocyte subsets (CD14 and CD16 expression) using flow cytometry. Moreover, cytokines were evaluated using flow cytometry after stimulation with Pam3 Cys (TLR2/TLR1 agonist) in the absence or presence of neutralizing antibodies to TLR10. The severity of PD was assessed using the unified PD rating scale (UPDRS) and motor activity, anxiety (BAI), depression (BDI), and fatigue (PD Fatigue Scale-16) scales. The frequency of CD14+ TLR10+ monocytes and expression intensity of TLR2 and TLR10 were higher in patients with PD than healthy individuals. The frequency of intermediate monocytes (CD14++ CD16+ ) was not significantly increased in patients with PD, but was the main monocyte subset expressing TLR10. The TLR2/TLR1-impaired cytokine production (IL-6, TNFα, IL-8, and IL-10) in PD patients was reversed by neutralizing TLR10. The high frequency of total CD14+ TLR10+ monocytes was associated with a reduction in the severity of PD according to the evaluation of motor and nonmotor symptoms. Peripheral monocytes from patients with PD showed phenotypic and functional alterations. The expression of TLR10 on monocytes can protect against PD by controlling TLR2-induced cytokine production. Furthermore, data suggested that a low frequency of CD14+ TLR10+ monocytes indicates the severity of PD. The results identified new opportunities for the development of novel PD neuroprotective therapies.


Subject(s)
Cytokines/blood , Monocytes/metabolism , Parkinson Disease/blood , Toll-Like Receptor 10/blood , Toll-Like Receptor 2/blood , Adult , Aged , Cells, Cultured , Female , Humans , Leukocytes, Mononuclear/metabolism , Male , Middle Aged , Parkinson Disease/diagnosis , Prospective Studies
16.
Microb Pathog ; 158: 105088, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34260904

ABSTRACT

BACKGROUND: Cells of the innate immune system undergo long-term functional reprogramming in response to Bacillus Calmette-Guérin (BCG) exposure via a process called trained immunity, conferring nonspecific protection to unrelated infections. Here, we investigate whether BCG-induced trained immunity is able to protect against infections caused by different Leishmania spp., protozoa that cause cutaneous and mucosal or visceral lesions. METHODS: We used training models of human monocytes with BCG and subsequent infection by L. braziliensis, L. amazonensis and L. infantum, and the vaccination of wild-type and transgenic mice for IL-32γ before in vivo challenge with parasites. RESULTS: We demonstrated that monocytes trained with BCG presented enhanced ability to kill L. braziliensis, L. amazonensis and L. infantum through increased production of reactive oxygen species. Interleukin (IL)-32 appears to play an essential role in the development of trained immunity. Indeed, BCG exposure induced IL-32 production in human primary monocytes, both mRNA and protein. We have used a human IL-32γ transgenic mouse model (IL-32γTg) to study the effect of BCG vaccination in different Leishmania infection models. BCG vaccination decreased lesion size and parasite load in infections caused by L. braziliensis and reduced the spread of L. amazonensis to other organs in both infected wild-type (WT) and IL-32γTg mice. In addition, BCG reduced the parasite load in the spleen, liver and bone marrow of both WT and IL-32γTg mice infected with L. infantum. BCG vaccination increased inflammatory infiltrate in infected tissues caused by different Leishmania spp. In all infections, the presence of IL-32γ was not mandatory, but it increased the protective and inflammatory effects of BCG-induced training. CONCLUSIONS: BCG's ability to train innate immune cells, providing protection against leishmaniasis, as well as the participation of IL-32γ in this process, pave the way for new treatment strategies for this neglected infectious disease.


Subject(s)
BCG Vaccine , Interleukins/immunology , Leishmania , Leishmaniasis , Mycobacterium bovis , Animals , Leishmaniasis/immunology , Mice , Mice, Inbred BALB C , Mice, Transgenic
17.
An Acad Bras Cienc ; 93(3): e20201202, 2021.
Article in English | MEDLINE | ID: mdl-34287461

ABSTRACT

Modal classifications of common volcanic rocks are expensive, difficult, or impossible to attain. As a consequence, these rocks are classified using the chemical composition. However, existing classificatory diagrams are unable to identify all 16 families of common volcanic rocks; the most used is the total alkali-silica (TAS) diagram that identifies six families. Rocks not in the TAS diagram are misclassified with other rock names; their names are evolving to extinction, e.g. latite and rhyodacite. Some diagrams use Na2O, which is a complicating element rather than discriminant. Na2O is present both in alkali feldspar and plagioclase making difficult the separation of the amount associated to either feldspar. Silicon, potassium, and calcium are the three major elements with highest variations among volcanic rocks. They are selected for use in two new diagrams confronting CaO/K2O ratio with K2O content (KCK diagrams). One diagram is designed for saturated (intermediate) rocks (quartz <5 vol.%) and the other for oversaturated (acid) volcanic rocks (quartz >5%). These diagrams are tested using compositions of volcanic rocks from Uatumã magmatism in the Amazon Craton and also by plotting compositions of rocks from type-localities and the world averages. The proposed limits between rock families agree with plotted rock compositions. The KCK diagrams are an alternative to existing diagrams to classify volcanic rocks.


Subject(s)
Silicon Dioxide
18.
Microb Pathog ; 154: 104864, 2021 May.
Article in English | MEDLINE | ID: mdl-33771629

ABSTRACT

Paracoccidioidomycosis (PCM) is a systemic fungal disease caused by Paracoccidioides spp., whose clinical outcome depends on immune response. Interleukin 32 (IL-32) is a cytokine present in inflammatory and infectious diseases, including bacterial, virus and protozoan infections. Its role in fungal disease remains unclear. The axis IL-15, IL-32 and vitamin D leads to microbicidal capacity against intracellular pathogens. Thus, the aims of this study were to investigate the production of IL-32 during Paracoccidioides spp. infection and whether this cytokine and IL-15 can increase P. brasiliensis control in a vitamin D dependent manner. IL-32 was highly detected in oral lesions from patients with PCM. In addition, high production of this cytokine was intracellularly detected in peripheral blood mononuclear cells (PBMCs) from healthy donors after exposure to particulated P. brasiliensis antigens (PbAg). The IL-32γ isoform was predominantly expressed, but there was mRNA alternative splicing for IL-32α isoform. The induction of IL-32 was dependent on Dectin-1 receptor. Infection of PBMCs with P. brasiliensis yeasts did not significantly induce IL-32 production even after activation with exogenous IFN-γ or IL-15 treatments. Although IL-15 was a potent inducer of IL-32 production, treatment with this cytokine did not increase the fungal control unless vitamin D was present in high levels. In this case, both IL-15 and IL-32 increased fungicidal activity of PBMCs. Together, data showed that IL-32 is present in lesions of PCM, PbAg induces IL-32, and the axis of IL-15/IL-32/vitamin D can contribute to control fungal infection. The data suggest that exposure to molecules from P. brasiliensis, as ß-glucans, is needed to induce IL-32 production since only heat-killed and sonicated P. brasiliensis yeasts were able to increase IL-32, which was blocked by anti-Dectin-1 antibodies. This is the first description about IL-15/IL-32/vitamin D pathway role in P. brasiliensis infection.


Subject(s)
Paracoccidioides , Paracoccidioidomycosis , Humans , Interleukin-15 , Interleukins , Leukocytes, Mononuclear , Vitamin D
19.
Arq. bras. med. vet. zootec. (Online) ; 73(2): 285-292, Mar.-Apr. 2021. tab
Article in English | LILACS, VETINDEX | ID: biblio-1248937

ABSTRACT

The aim of this work was to compare results of breeding soundness examination (BSE) of Nellore bulls (n=1257) according to evaluation criteria from two different classification tables (traditional-Table1 used since 1997 and an updated-Table2-proposed in 2020). Data were separated into 3 categories: questionable animals in Table1 and Table2 (Q1Q2), animals approved in Table1 and questionable in Table2 (A1Q2) and animals approved in Table1 and Table2 (A1A2). BSE parameters were submitted to ANOVA (P<005), according to age groups. Higher (P<0.0001) scrotal perimeter (PE) were observed in A1A2 category (18-24m=33.4±2.4cm; 24-36m=34.5±2.2cm; 36-48m=36.6±1.7cm; >48m=38.6±1.7cm) compared to A1Q2 (18-24m=29.05±0.98cm; 24-36m=30.3±0.6cm; 36-48m=32.9±1.0cm; >48m=34.8±1.0cm) and to Q1Q2 (24-36m=26.8±2.0cm; 36-48m=30.0±0.1cm; >48m=31.3±1.1cm), for all age groups. At the age of 36-48months (Q1Q2=2.7±0.3; A1Q2=3.2±0.3; A1A2=3.3±0.6) and >48months (Q1Q2=3.0±0.4; A1Q2=3.3±0.5; A1A2=3.4±0.5), animals with better andrological classifications presented higher (P<0.05) body condition score (BCS). Additionally, at age >48m, higher sperm Motility (P=0.0250) and Vigor (P=0.0335) were observed in animals A1Q2 (Mot=55.5±14.7%; V=3.21±0.82) and A1A2 (Mot=55.8±12.2%; V=3.23±0.81) compared to Q1Q2 (Mot=50.2±17.4%; V=2.77±0.82). It was concluded that bulls approved using strict selection criteria demonstrated higher PE and BCS, regardless of the age. The utilization of updated classification tables is highly recommended for further reproductive potential development of Nellore bulls in the field.(AU)


O objetivo deste estudo foi comparar os resultados obtidos no exame andrológico a campo de touros Nelore (n=1257) de acordo com os critérios de avaliação de duas tabelas de classificação (uma tabela tradicional - tabela 1 - proposta em 1997 e uma nova tabela atualizada - tabela 2 - proposta em 2020). Os dados foram separados em três categorias: animais questionáveis nas tabelas 1 e 2 (Q1Q2), animais aprovados na tabela 1 e questionáveis na tabela 2 (A1Q2) e animais aprovados nas tabelas 1 e 2 (A1A2). Os parâmetros foram submetidos à análise de variância (P<0,05), por faixa etária. Observou-se maior (P<0,0001) PE no grupo A1A2 (18-24m=33,4±2,4cm; 24-36m=34,5±2,2cm; 36-48m=36,6±1,7cm; >48m=38,6±1,7cm) em comparação ao grupo A1Q2 (18-24m=29,05±0,98cm; 24-36m=30,3±0,6cm; 36-48m=32,9±1,0cm; >48m=34,8±1,0cm) e este maior (P<0,0001) que Q1Q2 (24-36m=26,8±2,0cm; 36-48m=30,0±0,1cm; >48m=31,3±1,1cm) em todas as idades. Nas faixas etárias 36-48m (Q1Q2=2,7±0,3; A1Q2=3,2±0,3; A1A2=3,3±0,6) e >48m (Q1Q2=3,0±0,4;A1Q2=3,3±0,5; A1A2=3,4±0,5), animais com melhor classificação andrológica apresentaram melhor (P<0,05) escore de condição corporal (ECC). Adicionalmente, na idade >48m, maiores motilidade (P=0,0250) e vigor (P=0,0335) foram observados nos animais A1Q2 (Mot=55,5±14,7%; V=3,21±0,82) e A1A2 (Mot=55,8±12,2%; V=3,23±0,81) comparados aos animais Q1Q2 (Mot=50,2±17,4%; V=2,77±0,82). Concluiu-se que touros aprovados na tabela com critérios mais rigorosos de classificação (tabela 2) apresentaram maior PE e ECC, independentemente da idade. Assim, a utilização de tabelas classificatórias atualizadas é fundamental para maior desenvolvimento do potencial reprodutivo de touros Nelore a campo.(AU)


Subject(s)
Animals , Male , Cattle , Scrotum/anatomy & histology , Sperm Motility , Fertility , Genitalia, Male/anatomy & histology
20.
An Acad Bras Cienc ; 93(1): e20190791, 2021.
Article in English | MEDLINE | ID: mdl-33605302

ABSTRACT

Age delimitation integrated with aeromagnetometric and aerogammaspectrometric survey advances the understanding of ophiolite evolution in the Brasiliano Orogen. We focused on the Bossoroca ophiolite, because oceanic crustal and mantle rocks contain zircon in metasomatic chloritite. A metadiorite and a metavolcanoclastic rock were also studied to delimit relationship between ophiolite and island-arc infrastructure and superstructure. Zircon crystals were dated by laser ablation inductively coupled plasma emission spectroscopy. Ages of zircon from Campestre metavolcanoclastic rock are 920-840 (peak 842) Ma, Bossoroca chloritite 900-800 (peak 868 Ma) and Capivaras metadiorite 698 Ma. Ages 920-800 Ma correspond to processes in the oceanic crust, whereas 698 Ma was a late magmatic intrusion (Capivaras metadiorite) into the island-arc infrastructure. Aeromagnetometric and aerogammaspectrometric data delimit the occurrence and structure of the ophiolite. These are major multiproxy markers of geotectonic processes early in the Brasiliano Orogen.

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