RESUMO
Background: Cell migration is essential for the immune system and is frequently analyzed in adult non-pregnant animals but poorly explored in pregnant animals. However, a physiologic increased size in the spleen and periaortic lymph nodes had been reported in pregnant mice. Methods: Using a mouse model, we transferred PKH26-stained thymocytes and splenocytes from pregnant or non-pregnant animals to receptor mice in the presence or absence of pregnancy. Percentage of PKH-26 cells and Mean Fluorescence Intensity were calculated. Non-parametric ANOVA analysis was performed. Results: We detected that the percentage of PKH26+ thymocytes in the spleen, lymph nodes, and peripheral blood is higher in females than in males (p = 0.039). Our results showed a similar frequency of thymocytes and splenocytes from pregnant and non-pregnant mice located in receptor lymphoid organs (p > 0.05). Also, the location of marked cells was similar during the perinatal period (p > 0.05). Conclusions: The mobility of thymocytes and splenocytes in pregnant and non-pregnant mice is similar. Therefore, we suggest that the larger size of the spleen and periaortic lymph nodes noted previously in pregnant mice could result from the retention of leukocytes in the secondary lymphoid organs.
RESUMO
Twenty 2-(4-alkyloxyphenyl)-imidazolines and 2-(4-alkyloxyphenyl)-imidazoles were synthesized, with the former being synthesized in two steps by using MW and ultrasonication energy, resulting in good to excellent yields. Imidazoles were obtained in moderate yields by oxidizing imidazolines with MnO2 and MW energy. In response to the urgent need to treat neglected tropical diseases, a set of 2-(4-alkyloxyphenyl)- imidazolines and imidazoles was tested in vitro on Leishmania mexicana and Trypanosoma cruzi. The leishmanicidal activity of ten compounds was evaluated, showing an IC50 < 10 µg/mL. Among these compounds, 27-31 were the most active, with IC50 values < 1 µg/mL (similar to the reference drugs). In the evaluation on epimastigotes of T. cruzi, only 30 and 36 reached an IC50 < 1 µg/mL, showing better inhibition than both reference drugs. However, compounds 29, 33, and 35 also demonstrated attractive trypanocidal activities, with IC50 values < 10 µg/mL, similar to the values for benznidazole and nifurtimox.
Assuntos
Antiprotozoários , Doença de Chagas , Imidazolinas , Leishmania mexicana , Trypanosoma cruzi , Humanos , Imidazóis/farmacologia , Compostos de Manganês , Óxidos , Antiprotozoários/farmacologiaRESUMO
Dengue is a worldwide expanding threat caused by dengue virus (DENV) infection. To date, no specific treatment or effective vaccine is available. Antibodies produced by plasma cells (PCs) might be involved concomitantly in protection and severe dengue immunopathology. Although a massive appearance of PCs has been reported during acute DENV infection in humans, this response has been poorly characterized. Here, we show the dynamic of PC generation in immune-competent mice cutaneously inoculated with DENV compared with two control experimental groups: mice inoculated with inactivated DENV or with PBS. We found that PC numbers increased significantly in the skin-draining lymph node (DLN), peaking at day 10 and abruptly decreasing by day 14 after DENV inoculation. Class-switched IgG+ PCs appeared from day 7 and dominated the response, while in contrast, the frequency of IgM+ PCs decreased from day 7 onwards. Even though the kinetic of the response was similar between DENV- and iDENV-inoculated mice, the intensity of the response was significantly different. Interestingly, we demonstrated a similar PC response to virus antigens (E and prM) by ELISPOT. In situ characterization showed that PCs were distributed in the medullary cords and in close proximity to germinal centers (GCs), suggesting both an extrafollicular and a GC origin. Proliferating PCs (Ki-67+) were found as early as 3-day postinoculation, and in-depth analysis showed that these PCs were in active phases of cell cycle during the kinetic. Finally, we found a progressive appearance of high-affinity neutralizing DENV-specific IgG further supporting GC involvement. Of note, these antibodies seem to be highly cross-reactive, as a large proportion recognizes Zika virus (ZIKV). The strong PC response to skin-inoculated DENV in this work resembles the findings already described in humans. We consider that this study contributes to the understanding of the in vivo biology of the humoral immune response to DENV in an immunocompetent murine model.
Assuntos
Vírus da Dengue/imunologia , Dengue/imunologia , Plasmócitos/imunologia , Animais , Anticorpos Neutralizantes/análise , Anticorpos Neutralizantes/metabolismo , Anticorpos Antivirais/análise , Anticorpos Antivirais/metabolismo , Reações Cruzadas , Dengue/patologia , Dengue/virologia , Modelos Animais de Doenças , Centro Germinativo/citologia , Centro Germinativo/imunologia , Centro Germinativo/metabolismo , Humanos , Masculino , Camundongos , Plasmócitos/metabolismo , Pele/imunologia , Pele/patologia , Pele/virologia , Organismos Livres de Patógenos Específicos , Zika virus/imunologiaRESUMO
Cyrtocarpa procera is a plant used in traditional Mexican medicine to treat different gastrointestinal problems. Here, we investigated the effects of a C. procera methanolic extract in DSS-induced colitis mice. Ulcerative colitis (UC) was induced by administering 4% DSS in drinking water to female BALB/c mice. Compared to untreated mice with UC, the treatment group receiving the C. procera extract presented less severe UC symptoms of diarrhea, bleeding, and weight loss. Additionally, colon shortening was significantly reduced, and at the microscopic level, only minor damage was observed. Levels of proinflammatory cytokines such as TNF-α, IL-1ß, and IFNγ in serum as well as the MPO activity in the colon were significantly reduced in the C. procera methanolic extract-treated group. Moreover, the extract of C. procera reduced oxidative stress during UC, preventing the deterioration of the activity of antioxidant enzymes such as SOD, CAT, and GPx. Additionally, the extract decreased lipid peroxidation damage and its final products, such as malondialdehyde (MDA). In agreement with this, in vitro assays with the C. procera extract displayed good antioxidant capacity, probably due to the presence of polyphenolic compounds, in particular the flavonoids that were identified, such as chrysin, naringenin, kaempferol, and catechin, which have been reported to have anti-inflammatory and antioxidant activities. Therefore, the improvement of UC by the C. procera methanolic extract may be related to the action mechanisms of these compounds.
Assuntos
Anacardiaceae , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Anacardiaceae/química , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/patologia , Colo/patologia , Citocinas/análise , Sulfato de Dextrana , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Peroxidase/metabolismo , Casca de Planta/química , Índice de Gravidade de DoençaRESUMO
Salmonella enterica infections remain a challenging health issue, causing significant morbidity and mortality worldwide. Current vaccines against typhoid fever display moderate efficacy whilst no licensed vaccines are available for paratyphoid fever or invasive non-typhoidal salmonellosis. Therefore, there is an urgent need to develop high efficacy broad-spectrum vaccines that can protect against typhoidal and non-typhoidal Salmonella. The Salmonella outer membrane porins OmpC and OmpF, have been shown to be highly immunogenic antigens, efficiently eliciting protective antibody, and cellular immunity. Furthermore, enterobacterial porins, particularly the OmpC, have a high degree of homology in terms of sequence and structure, thus making them a suitable vaccine candidate. However, the degree of the amino acid conservation of OmpC among typhoidal and non-typhoidal Salmonella serovars is currently unknown. Here we used a bioinformatical analysis to classify the typhoidal and non-typhoidal Salmonella OmpC amino acid sequences into different clades independently of their serological classification. Further, our analysis determined that the porin OmpC contains various amino acid sequences that are highly conserved among both typhoidal and non-typhoidal Salmonella serovars. Critically, some of these highly conserved sequences were located in the transmembrane ß-sheet within the porin ß-barrel and have immunogenic potential for binding to MHC-II molecules, making them suitable candidates for a broad-spectrum Salmonella vaccine. Collectively, these findings suggest that these highly conserved sequences may be used for the rational design of an effective broad-spectrum vaccine against Salmonella.
Assuntos
Proteínas de Bactérias/genética , Porinas/genética , Salmonella/genética , Sequência de Aminoácidos , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Sequência Conservada , Humanos , Filogenia , Porinas/química , Porinas/metabolismo , Conformação Proteica em alfa-Hélice , Salmonella/química , Salmonella/classificação , Salmonella/metabolismo , Infecções por Salmonella/microbiologia , Salmonella typhi/química , Salmonella typhi/classificação , Salmonella typhi/genética , Salmonella typhi/metabolismo , Alinhamento de Sequência , Febre Tifoide/microbiologiaRESUMO
Platelets are considered as significant players in innate and adaptive immune responses. The adhesion molecules they express, including P-selectin, CD40L, and CD42b, facilitate interactions with many cellular effectors. Upon interacting with a pathogen, platelets rapidly express and enhance their adhesion molecules, and secrete cytokines and chemokines. A similar phenomenon occurs after exposure of platelets to thrombin, an agonist extensively used for in vitro activation of these cells. It was recently reported that the dengue virus not only interacts with platelets but possibly infects them, which triggers an increased expression of adhesion molecule P-selectin as well as secretion of IL-1ß. In the present study, surface molecules of platelets like CD40L, CD42b, CD62P, and MHC class I were evaluated at 4 h of interaction with dengue virus serotype 2 (DENV-2), finding that DENV-2 induced a sharp rise in the membrane expression of all these molecules. At 2 and 4 h of DENV-2 stimulation of platelets, a significantly greater secretion of soluble CD40L (sCD40L) was found (versus basal levels) as well as cytokines such as GM-CSF, IL-6, IL-8, IL-10, and TNF-α. Compared to basal, DENV-2 elicited more than two-fold increase in these cytokines. Compared to the thrombin-induced response, the level generated by DENV-2 was much higher for GM-CSF, IL-6, and TNF-α. All these events induced by DENV end up in conspicuous morphological changes observed in platelets by confocal microscopy and transmission electron microscopy, very different from those elicited by thrombin in a more physiological scenery.
Assuntos
Plaquetas/metabolismo , Ligante de CD40/metabolismo , Membrana Celular/metabolismo , Vírus da Dengue/fisiologia , Dengue/sangue , Dengue/virologia , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Plaquetas/imunologia , Ligante de CD40/sangue , Estudos de Casos e Controles , Moléculas de Adesão Celular/metabolismo , Citocinas/metabolismo , Citosol/metabolismo , Dengue/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Selectina-P/metabolismo , Adesividade Plaquetária , Agregação PlaquetáriaRESUMO
More than half of the human population is exposed to mosquito-borne infections. Climate change and the emergence of strains resistant to traditionally used insecticides have motivated the search of new agents for mosquito population control. Essential oils have been effective repellents and larvicidal agents.The aim of this work was to review research studies conducted in recent years on the larvicidal activity of essential oils and their components against Aedes, Anopheles and Culex mosquitoes, as well as the latest reports about their possible mechanism of action.
Assuntos
Repelentes de Insetos , Inseticidas , Mosquitos Vetores , Óleos Voláteis , Óleos de Plantas , Aedes/crescimento & desenvolvimento , Distribuição Animal , Animais , Anopheles/crescimento & desenvolvimento , Mudança Climática , Simulação por Computador , Culex/crescimento & desenvolvimento , Interações Medicamentosas , Resistência a Inseticidas , Larva , Modelos Moleculares , Estrutura Molecular , Controle de Mosquitos , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Óleos de Plantas/química , Óleos de Plantas/farmacologia , Relação Estrutura-AtividadeRESUMO
Resumen Más de la mitad de la población humana está expuesta a contraer infecciones transmitidas por mosquitos. El cambio climático y la aparición de cepas resistentes a los insecticidas tradicionalmente utilizados han motivado la búsqueda de nuevos agentes capaces de controlar las poblaciones de mosquitos. Los aceites esenciales han resultado ser eficaces agentes repelentes y larvicidas. El objetivo de este trabajo fue revisar las investigaciones llevadas a cabo en los últimos años sobre la actividad larvicida de los aceites esenciales y sus componentes contra mosquitos de los géneros Aedes, Anopheles y Culex, así como los últimos reportes sobre su posible mecanismo de acción.
Abstract More than half of the human population is exposed to mosquito-borne infections. Climate change and the emergence of strains resistant to traditionally used insecticides have motivated the search of new agents for mosquito population control. Essential oils have been effective repellents and larvicidal agents. The aim of this work was to review research studies conducted in recent years on the larvicidal activity of essential oils and their components against Aedes, Anopheles and Culex mosquitoes, as well as the latest reports about their possible mechanism of action.
Assuntos
Animais , Óleos de Plantas , Óleos Voláteis , Mosquitos Vetores , Repelentes de Insetos , Inseticidas , Relação Estrutura-Atividade , Mudança Climática , Simulação por Computador , Óleos de Plantas/farmacologia , Óleos de Plantas/química , Resistência a Inseticidas , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Estrutura Molecular , Modelos Moleculares , Controle de Mosquitos , Aedes/crescimento & desenvolvimento , Culex/crescimento & desenvolvimento , Interações Medicamentosas , Distribuição Animal , Larva , Anopheles/crescimento & desenvolvimentoRESUMO
Intestinal homeostasis effectors, secretory IgA (SIgA) and polymeric immunoglobulin receptor (pIgR), have been evaluated in proximal and distal small intestine with moderate-exercise training but not with strenuous exercise or a combination of these two protocols. Therefore, two groups of mice (n=6-8) were submitted to strenuous exercise, one with and one without previous training. The control group had no exercise protocol. Assessment was made of intestinal SIgA and plasma adrenal hormones (by immunoenzymatic assay), alpha-chain and pIgR proteins in intestinal mucosa (by Western blot), lamina propria IgA plasma-cells (by cytofluorometry), mRNA expression (by real-time PCR) for pIgR, alpha- and J-chains in liver and intestinal mucosa, and pro- and anti-inflammatory cytokines in mucosa samples. Compared to other exercise protocols, training plus strenuous exercise elicited: (1) higher levels of SIgA and pIgR in the proximal intestine (probably by hepatobiliary contribution); (2) higher levels of SIgA in the distal segment; (3) lower mRNA expression of some SIgA- and most pro-inflammatory pIgR-producing cytokines. SIgA and pIgR in both segments were derived from an existing pool of their corresponding producing cells. The apparent decreased translation of mRNA transcripts underlies lower levels of SIgA and pIgR in distal than proximal small intestine. There was no significant difference in the relatively high adrenal hormone levels found in both exercised groups. Further study is required about the effects of training plus strenuous exercise on pool-derived SIgA levels and mRNA expression of pro-inflammatory pIgR-producing cytokines. These results could have important implications for intestinal disorders involving inflammation and infection.