RESUMO
Yerba Mate (YM) (Ilex paraguariensis) is a natural herbal supplement with a well-described anti-inflammatory capacity and beneficial effects in different inflammatory contexts such as insulin resistance or obesity. However, whether YM could improve other inflammatory conditions such as colitis or the immune cell population that can be modulated by this plant remains elusive. Here, by using 61 male and female C57BL/6/J wild-type (WT) mice and the dextran sodium sulfate (DSS)-induced acute colitis model, we evaluated the effect of YM on colitis symptoms and macrophage polarization. Our results showed that the oral administration of YM reduces colitis symptoms and improves animal survival. Increasing infiltration of anti-inflammatory M2 macrophage was observed in the colon of the mice treated with YM. Accordingly, YM promoted M2 macrophage differentiation in vivo. However, the direct administration of YM to bone marrow-derived macrophages did not increase anti-inflammatory polarization, suggesting that YM, through an indirect mechanism, is able to skew the M1/M2 ratio. Moreover, YM consumption reduced the Eubacterium rectale/Clostridium coccoides and Enterobacteriaceae groups and increased the Lactobacillus/Lactococcus group in the gut microbiota. In summary, we show that YM promotes an immunosuppressive environment by enhancing anti-inflammatory M2 macrophage differentiation, reducing colitis symptoms, and suggesting that YM consumption may be a good cost-effective treatment for ulcerative colitis.
Assuntos
Anti-Inflamatórios , Colite , Sulfato de Dextrana , Microbioma Gastrointestinal , Ilex paraguariensis , Macrófagos , Camundongos Endogâmicos C57BL , Extratos Vegetais , Animais , Macrófagos/efeitos dos fármacos , Ilex paraguariensis/química , Colite/tratamento farmacológico , Colite/induzido quimicamente , Masculino , Feminino , Anti-Inflamatórios/farmacologia , Camundongos , Extratos Vegetais/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Modelos Animais de Doenças , Colo/efeitos dos fármacos , Colo/patologia , Diferenciação Celular/efeitos dos fármacosRESUMO
The goal of this study is to review the overall prevalence, burden, and distribution of the dengue disease in Pakistan from 2000 to 2019. Literature was searched using different search engines like Google scholar, PubMed, etc. providing the keywords "Dengue disease/infection, Dengue virus, DENV, DF/DHF/ DSS Pakistan". All the published research papers/reports on the dengue virus over the period 2000 to 2019 were studied and selected data were summarized using MS Excel for windows such as total cases, age wise, gender, DENV serotype distribution, total DHF, and DSS patients. The literature providing insufficient data was excluded. The total number of cases reported during 2000-19 were 201,269. The maximum number of cases during the mentioned literature survey period was reported in Khyber Pakhtunkhwa (KP) (23.3%) followed by Punjab (3.8%) and Sindh (1.9%). The majority of dengue-infected cases were reported as Dengue fever (74.4%) followed by DHF (24.1%) and DSS (1.5%). Overall the deaths during the mentioned literature survey were 1082, of which the maximum mortalities were reported from KP (N=248) followed by Punjab (N=220). DENV remains a major public health problem in Pakistan and seems to remain endemic for a long time. The total prevalence of dengue infection is increased accordingly with time from 2000 to 2019. Moreover, all the four serotypes exist in Pakistan with increased mortalities.
A literatura foi examinada através de diferentes mecanismos de pesquisa, como Google Acadêmico, PubMed, etc., fornecendo as palavras-chave "Dengue disease/infection, Dengue virus, DENV, DF/DHF/ DSS Pakistan". Todos os trabalhos/relatórios de pesquisa publicados sobre o vírus da dengue no período de 2000 a 2019 foram analisados e os dados selecionados foram coletados e resumidos usando o MS Excel para janelas como total de casos, idade, sexo, distribuição de sorotipos, total de DHF e pacientes com DSS. A literatura que forneceu dados insuficientes foi excluída. O número total de casos notificados de 2000 a 2019 foi de 201.269. O número máximo de casos durante o período de levantamento da literatura mencionado foi relatado em KP (23,3%), seguido por Punjab (3,8%) e Sindh (1,9%). A maioria dos casos de infecção por dengue foi relatada como Dengue (74,4%), seguida por FHD (24,1%) e DSS (1,5%). No geral, as mortes durante a pesquisa de literatura mencionada foram 1.082, das quais as morbidades máximas foram relatadas em KP (248), seguidas por Punjab, com um total de 220 mortes. O DENV continua sendo um grande problema de saúde pública no Paquistão e é considerado endêmico agora e provavelmente permanecerá por muito tempo. A prevalência total de infecção por dengue foi aumentada conforme a pesquisa de literatura publicada entre 2000 e 2019. A mortalidade por DENV também aumentou. Todos os 4 sorotipos, bem como em várias formas, existem no Paquistão.
Assuntos
Saúde Pública , Dengue/epidemiologia , Vírus da Dengue , PaquistãoRESUMO
Zymomonas mobilis, a Gram-negative bacteria observed in some popular beverages, is considered safe and has been studied for its potential therapeutic benefits. In this study, we explored its effects on the inflammatory process, tissue integrity, differential gene expression, and microbiota composition in an experimental dextran sulfate sodium (DSS)-induced colitis model in mice. As a result, Z. mobilis alleviated the symptoms caused by DSS administration, as indicated by reduced weight loss, disease activity index, a significant reduction in the colon weight/length ratio, and histopathological improvement. Also, Z. mobilis could restore the mucosal barrier as well as increase the expression of Muc3 and Ocln genes. An analysis of 16S rRNA sequences showed that Z. mobilis alters gut microbiota, increasing Akkermansia muciniphila abundance and decreasing Escherichia coli. Furthermore, Z. mobilis seems to be involved in potentiating a regulatory phenotype by inducing immunomodulatory genes like Tgfb, Il5, Il10, and Foxp3 and reducing the relative mRNA expression of proinflammatory cytokines TNF, Il6, and Il17. Our data suggest that Z. mobilis could alleviate disease progression and be considered a possible probiotic adjuvant for pathologies of the bowel.
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The problems of flexible planning of the design of logistics systems for the collection of food products such as raw milk can result in a decrease in the performance of critical indicators for their performance. This paper proposes a new efficient methodology for robustly designing a first-mile logistics system for storing and refrigerating milk as a perishable product considering decisions related to open facilities and the flow of products, including sustainability indices. The proposed approach is modeled as a bi-objective problem by considering the minimization of greenhouse gas emissions (CO2) produced by milk transportation canteens and the maximization of the system configuration's net present value (NPV). We have analyzed and determined the most robust configuration for the first time and explained the robustness-NPV and robustness-CO2 relationships. The proposed mathematical model is solved by the Epsilon constraints method, and the robustness is calculated considering an extension of the FePIA methodology for multiobjective problems. A novel contribution is a balance in the possible future values generated by the company related to its cash flows and the generation of CO2 emissions when using a motorized transport frequently used in the shipment of raw milk considering a new important aspect such as the volume of product transported and the slope of the path between the production farm and the storage cooling tanks.
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Given the complete lack of instruments in Chile to measure the phenomenon of the sexual double standard (SDS), this study aimed to evaluate the psychometric properties of the sexual double standard scale (DSS). The sample contained 1036 university students from central and southern Chile. 61.1% (n = 633) were women, the average age was 20.4 years, and 31.7% (n = 259) identiï¬ed as atheist or agnostic. The DSS demonstrated a unidimensional structure, excellent reliability, and evidence of convergent and discriminant validity: the higher the score in SDS, the greater the stereotypical attitudes about gender and the lower the transcendent attitudes. The religious participants obtained higher mean scores on the DSS and men obtained signiï¬cantly higher SDS scores than women. In addition, the group of participants with extreme stereotypical attitudes obtained signiï¬cantly higher scores on the DSS than the extreme transcendent attitudes group, in both men and women samples. Based on the evidence that links the SDS with sexual functioning and satisfaction, risky sexual practices, sexual aggression and victimization, and intimate partner violence, the DSS stands out as a contribution to the development of sex-aï¬ective education programs and the identiï¬cation of individuals and groups at risk.
Ante la ausencia de instrumentos en Chile para medir el fenómeno del Doble Estándar Sexual (SDS), el presente estudio tuvo como objetivo evaluar las propiedades psicométricas de la Escala de Doble Estándar Sexual (DSS). La muestra se compuso de 1036 personas universitarias del centro y sur de Chile. El 61.1% (n = 633) fueron mujeres, la edad promedio fue de 20.4 años y un 31.7% (n = 259) se identiï¬có como ateo o agnóstico. Mediante análisis factorial conï¬rmatorio, la DSS obtuvo una estructura unidimensional en la muestra de estudio, un α Ordinal = .918, y evidencias de validez convergente y discriminante: a mayor puntuación en SDS, mayores actitudes estereotipadas sobre el género y menores actitudes trascendentes. Los participantes religiosos obtuvieron puntuaciones medias más altas en la DSS y los hombres obtuvieron puntajes de SDS signiï¬cativamente mayores que los de las mujeres. Además, tanto en el caso de los hombres como en el de las mujeres, el grupo de participantes con actitudes estereotipadas extremas obtuvo puntuaciones signiï¬cativamente más elevadas en DSS que el grupo participante con actitudes trascendentes extremas. Con base en la evidencia que asocia el SDS con el funcionamiento y satisfacción sexual, prácticas sexuales de riesgo, la agresión y victimización sexual, y la violencia en relaciones de pareja, la DSS se distingue como un aporte para el desarrollo de programas educativos sexoafectivos y la identiï¬cación de individuos y grupos de riesgo.
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Sequential infections with different dengue serotypes (DENV-1, 4) significantly increase the risk of a severe disease outcome (fever, shock, and hemorrhagic disorders). Two hypotheses have been proposed to explain the severity of the disease: (1) antibody-dependent enhancement (ADE) and (2) original T cell antigenic sin. In this work, we explored the first hypothesis through mathematical modeling. The proposed model reproduces the dynamic of susceptible and infected target cells and dengue virus in scenarios of infection-neutralizing and infection-enhancing antibody competition induced by two distinct serotypes of the dengue virus during secondary infection. The enhancement and neutralization functions are derived from basic concepts of chemical reactions and used to mimic binding to the virus by two distinct populations of antibodies. The analytic study of the model showed the existence of two equilibriums: a disease-free equilibrium and an endemic one. Using the concept of the basic reproduction number [Formula: see text], we performed the asymptotic stability analysis for the two equilibriums. To measure the severity of the disease, we considered the maximum value of infected cells as well as the time when this maximum is reached. We observed that it corresponds to the time when the maximum enhancing activity for the infection occurs. This critical time was calculated from the model to be a few days after the occurrence of the infection, which corresponds to what is observed in the literature. Finally, using as output [Formula: see text], we were able to rank the contribution of each parameter of the model. In particular, we highlighted that the cross-reactive antibody responses may be responsible for the disease enhancement during secondary heterologous dengue infection.
Assuntos
Coinfecção , Vírus da Dengue , Dengue , Anticorpos Neutralizantes , Anticorpos Antivirais , Anticorpos Facilitadores , Humanos , Conceitos Matemáticos , Índice de Gravidade de DoençaRESUMO
Resumo Os modelos conceituais de determinantes sociais da saúde (DSS) disponíveis na literatura, embora úteis para compreensão dos mecanismos que afetam os resultados do sistema de saúde sobre as condições de vida das populações, apresentam limitações quanto à sua aplicação em estudos empíricos e, consequentemente, na orientação da gestão de políticas públicas de saúde. Isso ocorre porque as categorias adotadas por esses modelos não são adequadamente representadas por indicadores ou variáveis homogêneas, sujeitas a manipulações matemáticas ou estatísticas em um sistema simples de relacionamentos. Este estudo tem por objetivo contribuir para o preenchimento dessa lacuna, ao propor um modelo conceitual de DSS passível de aplicação operacional, ou seja, de ser reproduzido em modelos matemáticos ou estatísticos, a fim de subsidiar estudos e definir estratégias de saúde pública. O esforço recorre à literatura para revisar modelos conceituais consagrados, identificar um conjunto de DSS e apresentar recomendações e critérios de escolha. Na sequência, identifica fontes de dados confiáveis que disponibilizem indicadores e variáveis dispostos em séries históricas e propõe o desenho de um modelo conceitual aplicável, cuja operacionalização requer métodos e ferramentas próprios de uma abordagem sistêmica.
Abstract The conceptual models of Social Determinants of Health (SDH) available in the literature, although useful for comprehending mechanisms that affect the results of the health system on the living conditions of the population, present limitations regarding their application in empirical studies and, consequently, in guiding public health policies. This occurs because the categories adopted by these models are not adequately represented by indicators of homogeneous variables subject to mathematical or statistical manipulations in a simple relation system. This study aims to help filling this gap by proposing an operationally applicable SDH conceptual model - reproducible as a mathematical or statistical model - to support studies and define strategies concerning public health. We resorted to the literature to review previously developed conceptual models, identifying a set of SDH and presenting recommendations and choice criteria. Then we located reliable data sources supplying indicators and variables listed in historic series and proposed an applicable conceptual model, which requires specific methods and tools for a systemic approach for operationalization.
Assuntos
Humanos , Masculino , Feminino , Sistemas de Saúde , Determinantes Sociais da Saúde , Estratégias de eSaúdeRESUMO
The deregulation of the Wnt/ß-catenin signaling pathway is a central event in colorectal cancer progression, thus a promising target for drug development. Many natural compounds, such as flavonoids, have been described as Wnt/ß-catenin inhibitors and consequently modulate important biological processes like inflammation, redox balance, cancer promotion and progress, as well as cancer cell death. In this context, we identified the chalcone lonchocarpin isolated from Lonchocarpus sericeus as a Wnt/ß-catenin pathway inhibitor, both in vitro and in vivo. Lonchocarpin impairs ß-catenin nuclear localization and also inhibits the constitutively active form of TCF4, dnTCF4-VP16. Xenopus laevis embryology assays suggest that lonchocarpin acts at the transcriptional level. Additionally, we described lonchocarpin inhibitory effects on cell migration and cell proliferation on HCT116, SW480, and DLD-1 colorectal cancer cell lines, without any detectable effects on the non-tumoral intestinal cell line IEC-6. Moreover, lonchocarpin reduces tumor proliferation on the colorectal cancer AOM/DSS mice model. Taken together, our results support lonchocarpin as a novel Wnt/ß-catenin inhibitor compound that impairs colorectal cancer cell growth in vitro and in vivo.
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BACKGROUND: Anti-Tumor Necrosis Factor-alpha therapy has become clinically important for treating inflammatory bowel disease. However, the use of conventional immunotherapy requires a systemic exposure of patients and collateral side effects. Lactic acid bacteria have been shown to be effective as mucosal delivering system for cytokine and single domain antibodies, and it is amenable to clinical purposes. Therefore, lactic acid bacteria may function as vehicles for delivery of therapeutic antibodies molecules to the gastrointestinal tract restricting the pharmacological effect towards the gut. Here, we use the mucosal delivery of Lactococcus lactis carrying an anti-TNFα scFv expression plasmid on a DSS-induced colitis model in mice. RESULTS: Experimental colitis was induced with DSS administered in drinking water. L. lactis carrying the scFv expression vector was introduced by gavage. After four days of treatment, animals showed a significant improvement in histological score and disease activity index compared to those of untreated animals. Moreover, treated mice display IL-6, IL17A, IL1ß, IL10 and FOXP3 mRNA levels similar to health control mice. Therefore, morphological and molecular markers suggest amelioration of the experimentally induced colitis. CONCLUSION: These results provide evidence for the use of this alternative system for delivering therapeutic biopharmaceuticals in loco for treating inflammatory bowel disease, paving the way for a novel low-cost and site-specific biotechnological route for the treatment of inflammatory disorders.
Assuntos
Colite/terapia , Citocinas/metabolismo , Vetores Genéticos/administração & dosagem , Lactococcus lactis/imunologia , Administração Oral , Animais , Anticorpos/genética , Anticorpos/imunologia , Anticorpos/metabolismo , Colite/induzido quimicamente , Colite/imunologia , Citocinas/genética , Citocinas/imunologia , Sulfato de Dextrana , Modelos Animais de Doenças , Vetores Genéticos/genética , Vetores Genéticos/metabolismo , Células HEK293 , Humanos , Lactococcus lactis/genética , Lactococcus lactis/metabolismo , Camundongos Endogâmicos C57BL , Anticorpos de Cadeia Única/genética , Anticorpos de Cadeia Única/imunologia , Anticorpos de Cadeia Única/metabolismo , Fator de Necrose Tumoral alfa/imunologiaRESUMO
Gluten is only partially digested by intestinal enzymes and can generate peptides that can alter intestinal permeability, facilitating bacterial translocation, thus affecting the immune system. Few studies addressed the role of diet with gluten in the development of colitis. Therefore, we investigate the effects of wheat gluten-containing diet on the evolution of sodium dextran sulphate (DSS)-induced colitis. Mice were fed a standard diet without (colitis group) or with 4·5 % wheat gluten (colitis + gluten) for 15 d and received DSS solution (1·5 %, w/v) instead of water during the last 7 d. Compared with the colitis group, colitis + gluten mice presented a worse clinical score, a larger extension of colonic injury area, and increased mucosal inflammation. Both intestinal permeability and bacterial translocation were increased, propitiating bacteria migration for peripheral organs. The mechanism by which diet with gluten exacerbates colitis appears to be related to changes in protein production and organisation in adhesion junctions and desmosomes. The protein α-E-catenin was especially reduced in mice fed gluten, which compromised the localisation of E-cadherin and ß-catenin proteins, weakening the structure of desmosomes. The epithelial damage caused by gluten included shortening of microvilli, a high number of digestive vacuoles, and changes in the endosome/lysosome system. In conclusion, our results show that wheat gluten-containing diet exacerbates the mucosal damage caused by colitis, reducing intestinal barrier function and increasing bacterial translocation. These effects are related to the induction of weakness and disorganisation of adhesion junctions and desmosomes as well as shortening of microvilli and modification of the endocytic vesicle route.
Assuntos
Translocação Bacteriana/imunologia , Colite/imunologia , Dieta/efeitos adversos , Glutens/efeitos adversos , Junções Íntimas/imunologia , Animais , Colite/induzido quimicamente , Colite/microbiologia , Colo , Sulfato de Dextrana , Modelos Animais de Doenças , Feminino , Microbioma Gastrointestinal/imunologia , Mucosa Intestinal/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Permeabilidade , Triticum/químicaRESUMO
O presente estudo teve como objetivo analisar a influência dos determinantes sociais da saúde mental do idoso, com base nos indicadores socioeconômicos e de inserção em redes de suporte social. Trata-se de um estudo transversal, exploratório-descritivo, de abordagem mista - qualitativa e quantitativa. A etapa quantitativa utilizou um questionário de caracterização sociodemográfica dos participantes e um questionário de percepção da qualidade de vida (QV) WHOQOL-Bref, enquanto a etapa qualitativa envolveu entrevistas de histórias de vida. Participaram desta pesquisa idosos acima de 60 anos de ambos os sexos que participavam do Programa Centro de Atenção à Saúde do Idoso (CASI) de Batatais-SP e do Círculo Operário de Vila Tibério (COVT) de Ribeirão Preto-SP. De acordo com os resultados sociodemográficos, pode-se verificar, nos dados mais relevantes coletados na pesquisa com 100 pessoas, que as condições de vida das pessoas idosas estão sujeitas de forma significativa a algumas tendências da sociedade contemporânea. Os dados obtidos na etapa quantitativa de discussão do Whoqol-Bref apontam para o conceito de qualidade de vida fortemente relacionado à autoestima e ao bem-estar pessoal, abrangendo aspectos como: capacidade funcional, nível socioeconômico, estado emocional, interação social, suporte familiar, atividade intelectual e de autocuidado, estado de saúde, valores culturais, éticos e religiosidade, estilo de vida, satisfação com o emprego e/ou com as atividades da vida diária e com o ambiente em que se vive. Diante dos resultados auferidos nas histórias de vidas foi possível constatar um índice significativo de vulnerabilidade social expressadas principalmente pelas condições precárias de vida das pessoas idosas entrevistadas constantes nos indicadores socioeconômicos, precariedade de inserção em redes sociais de suporte e capital social, bem como expressivas dificuldades materiais e psicossociais. Reconhece-se haver uma ampla gama de setores capaz de influenciar as condições de saúde e, em alguns casos, existem também as estruturas subjacentes responsáveis pela distribuição desigual dos determinantes entre os grupos sociais. Dessa forma, o impacto de fatores sociais na saúde varia dentro de um país de acordo com diferentes contextos socioeconômicos. Por meio desta pesquisa comprova-se que o principal desafio dos estudos sobre as relações entre determinantes sociais e saúde (DDS) está em poder compor uma estrutura de determinações entre os elementos mais gerais de natureza social, econômica, política e as mediações pelas quais esses fatores incidem sobre a situação de saúde de grupos e pessoas. Concluímos que um leque de aspectos diz muito sobre a vida de uma pessoa, e, pensando na saúde e qualidade de vida, percebe-se a necessidade de oferta de melhores recursos por parte das políticas do setor. Ademais, tendo em vista as desigualdades sociais, reafirmamos os direitos e deveres inalienáveis dos seres humanos, o pleno direito que têm de usufruir de melhores condições assistenciais, cultura e lazer, segurança, saúde e participação social. Em suma é um conceito ainda subjetivo e sujeito ao nível sociocultural, que requer um longo caminho para chegar à equidade social
The present study aimed to analyze the influence of the social determinants of mental health of the elderly, based on socioeconomic indicators and inclusion in social support networks. It is a cross-sectional, exploratory-descriptive, mixed-qualitative and quantitative approach. The quantitative stage used a sociodemographic characterization questionnaire of the participants and a questionnaire about the quality of life (QOL) of the WHOQOL-Bref, while the qualitative stage involved interviews of life histories. Elderly over 60 years of both sexes participating in the Center for Elderly Care of the Elderly (CASI) program in Batatais-SP and the Tibério Operário Circle (COVT) in Ribeirão Preto-SP participated in this study. According to the sociodemographic results, it can be verified, in the most relevant data collected in the research with 100 people, that the life conditions of the elderly people are subject in a significant way to some tendencies of the contemporary society. The data obtained in the quantitative stage of the Whoqol-Bref discussion point to the concept of quality of life strongly related to selfesteem and personal well-being, covering aspects such as: functional capacity, socioeconomic level, emotional state, social interaction, intellectual activity and self-care, health state, cultural values, ethics and religiosity, lifestyle, satisfaction with employment and/or activities of daily life and the environment in which one lives. In view of the results obtained in the life histories, it was possible to verify a significant index of social vulnerability expressed mainly by the precarious conditions of life of the interviewed elderly people in the socioeconomic indicators, precariousness of insertion in social networks of support and social capital, as well as expressive material difficulties and psychosocial. It is recognized that there is a wide range of sectors capable of influencing health conditions, and in some cases there are also the underlying structures responsible for the unequal distribution of determinants among social groups. Thus, the impact of social factors on health varies within a country according to different socioeconomic contexts. This research shows that the main challenge of the studies on the relationship between social determinants and health (DDS) is to be able to compose a structure of determinations between the more general elements of social, economic, political nature and the mediations by which these factors affect the health situation of groups and individuals. We conclude that a range of aspects tells a lot about a person's life, and thinking about health and quality of life, the need to offer better resources by the policies of the sector is perceived. In addition, in view of social inequalities, we reaffirm the inalienable rights and duties of human beings, the full right to enjoy better conditions of care, culture and leisure, safety, health and social participation. In short it is a concept still subjective and subject to the sociocultural level, which requires a long way to reach social equity
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Qualidade de Vida , Idoso , Saúde Mental , Vulnerabilidade a Desastres , Determinantes Sociais da SaúdeRESUMO
BACKGROUND AIMS: Although mesenchymal stromal cells (MSCs) have shown therapeutic potential in intestinal tissue repair, controversy concerning their short survival and poor biodistribution in recipient tissues still remains. Therefore, we investigated the paracrine role of MSC in three-dimensional culture of colon with experimental colitis. METHODS: Colitis was induced in mice by oral administration of dextran sulfate sodium (DSS) for 7 days. Inflammatory responses were assessed on the basis of clinical signs, morphological, and histopathological parameters. On days 2 and 5, colonic explants were removed, and a three-dimensional culture was performed. The structural integrity of the intestinal mucosa was tested by treating the cultures with MSC or conditioned medium (CM) for 24 h, and then the colons were analyzed for histology/immunohistochemistry and interleukin (IL)-6 production. RESULTS: Histological analysis demonstrated that both MSC and CM treatment reduced colon damage in organ culture. An increase in cell proliferation (Ki-67 staining) was observed after CM treatment. Additionally, MSC treatment was able to reduce CD3+ cells. The therapeutic effect of MSC and CM was mediated by the downregulation of IL-6. DISCUSSION: The intestinal in vitro model has shown to be potentially useful for studying cellular interactions in a three-dimensional cell arrangement. Moreover, our results provide strong evidence that both MSC and CM treatments can alleviate colonic damage in organ culture. Importantly, these results suggest that MSC-secreted factors are able to protect the colon from inflammation caused by DSS-induced colitis independent of cell transplantation.
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Colite/tratamento farmacológico , Colo/patologia , Células-Tronco Mesenquimais/metabolismo , Técnicas de Cultura de Órgãos/métodos , Animais , Complexo CD3/metabolismo , Proliferação de Células , Colite/induzido quimicamente , Meios de Cultivo Condicionados/farmacologia , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Feminino , Humanos , Interleucina-6/metabolismo , Mucosa Intestinal/citologia , Mucosa Intestinal/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Placenta/citologia , GravidezRESUMO
Helminth infection can reduce the severity of inflammatory bowel disease. However, the modulatory mechanisms elicited by helminth infection are not yet fully understood and vary depending on the experimental model. Herein we evaluated the effect of acute infection of BALB/c mice with Strongyloides venezuelensis on the clinical course of ulcerative colitis induced by Dextran Sulfate Sodium (DSS) treatment of these animals. For the experiments, S. venezuelensis-infected BALB/c mice were treated orally with 4% DSS solution for seven days. As controls, we used untreated S. venezuelensis infected, DSS-treated uninfected, and untreated/uninfected BALB/c mice. During DSS treatment, mice from the different groups were compared with regards to the clinical signs related to the severity of colitis and intestinal inflammation. Mice acutely infected with S. venezulensis and treated with DSS had reduced clinical score, shortening of the colon, and tissue inflammation. Moreover, DSS-treated and infected mice showed reduced IL-4, INF-γ, and IL-17 levels and increase of IL-10 production in the colon and/or in the supernatant of mesenteric lymph nodes cell cultures that resulted in lower eosinophil peroxidase and myeloperoxidase activity in colon homogenates, when compared with DSS-treated uninfected mice. DSS-treated infected mice also preserved the intestine architecture and had normal differentiation of goblet cells and mucus production in the colon mucosa. In conclusion, the data indicate that the clinical improvement reported in DSS-treated infected mice was accompanied by the lower production of Th1/Th2/Th17 pro-inflammatory cytokines, stimulation of IL-10, and induction of mucosal repair mechanisms.
Assuntos
Colite/imunologia , Colo/imunologia , Sulfato de Dextrana/toxicidade , Interleucina-10/imunologia , Strongyloides/imunologia , Estrongiloidíase/imunologia , Células Th1/imunologia , Células Th17/imunologia , Células Th2/imunologia , Doença Aguda , Animais , Colite/induzido quimicamente , Colite/parasitologia , Colite/patologia , Colo/parasitologia , Colo/patologia , Feminino , Células Caliciformes/imunologia , Células Caliciformes/patologia , Camundongos , Camundongos Endogâmicos BALB C , Estrongiloidíase/induzido quimicamente , Estrongiloidíase/patologia , Células Th1/patologia , Células Th17/patologia , Células Th2/patologiaRESUMO
Neozygites floridana is a pathogenic fungus and natural enemy of the two-spotted spider mite, Tetranychus urticae (Acari: Tetranychidae), which is an important polyphagous plant pest. The aim of this study was to reveal and predict what combination of temperature, relative humidity (RH), and time that enables and promotes primary conidia production and capilliconidia formation in N. floridana (Brazilian isolate ESALQ 1420), in both a detached leaf assay mimicking climatic conditions in the leaf boundary layer and in a semi-field experiment. In the detached leaf assay, a significant number of conidia were produced at 90% RH but the highest total number of primary conidia and proportion of capilliconidia was found at 95 and 100% RH at 25 °C. Positive temperature and RH effects were observed and conidia production was highest in the 8 to 12 h interval. The semi-field experiment showed that for a >90% probability of N. floridana sporulation, a minimum of 6 h with RH >90% and 10 h with temperatures >21 °C, or 6 h with temperatures >21 °C and 15 h with RH >90% was needed. Our study identified suitable conditions for primary- and capilliconidia production in this Brazilian N. floridana isolate. This information provides an important base for building models of a Decision Support System (DSS) where this natural enemy may be used as a tool in Integrated Pest Management (IPM) and a base for developing in vivo production systems of N. floridana.
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This study investigated the effects of Brazilian green propolis hydroalcoholic extract (BPE) in 3% w/v dextran sodium sulfate (DSS)-induced colitis in mice. The effects of BPE (3, 30 and 300 mg/kg, p.o, by 7 days) on the morphological (colon length and colon weight), clinical (disease activity index and weight loss), microscopic (histological score and mucin levels) and biochemical parameters were determined. The effects of BPE (300 mg/kg, p.o) in the gastrointestinal transit of mice were also evaluated. As expected, the DSS ingestion damaged the colonic tissue, lowered the body weight, decreased the mucin levels, increased MPO activity, reduced SOD activity and GSH amount. In contrast, the treatment with BPE (300 mg/kg) significantly reduced macroscopic colonic injury and the mucosal damage in colon on histopathological examination and reversed the decrease in mucin levels induced by DSS. It also significantly normalized the SOD activity and the levels of GSH, but did not elicit any effect on MPO activity in the colon. In addition, BPE did not change the gastric emptying or the intestinal transit rate of mice. Together, these results suggested that BPE reduced the signs of DSS-induced colitis in mice through maintenance of intestinal mucin barrier and favoring intestinal antioxidant defenses.
Assuntos
Colite/tratamento farmacológico , Colo/efeitos dos fármacos , Própole/uso terapêutico , Animais , Brasil , Colite/induzido quimicamente , Colite/metabolismo , Colo/química , Colo/patologia , Sulfato de Dextrana , Feminino , Trânsito Gastrointestinal/efeitos dos fármacos , Camundongos , Mucinas/análise , Peroxidase/metabolismo , Superóxido Dismutase/metabolismoRESUMO
OBJECTIVE: Chronic intestinal inflammation is a risk factor for colorectal cancer (CRC) initiation and development. Diets that are rich in Western style fats have been shown to promote CRC. This study was conducted to investigate the role of intestinal microbiome in American ginseng-mediated CRC chemoprevention in a mouse model. The population and diversity of enteric microbiome were evaluated after the ginseng treatment. METHODS: Using an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced gut inflammation and tumorigenesis mouse model, the effects of oral American ginseng on high fat diet-associated enteric pathology were determined. After establishment of a 16S rRNA illumina library from fecal samples, MiSeq sequencing was carried out to reveal the microbial population. The alpha and beta diversities of microbiome were analyzed. RESULTS: American ginseng significantly attenuated AOM/DSS-induced colon inflammation and tumorigenesis by reducing the colitis score and colon tumor multiplicity. The MiSeq results showed that the majority of sequences fell into three phyla: Firmicutes, Bacteroidetes and Verrucomicrobia. Further, two significant abundance shifts at the family level, Bacteroidaceae and Porphyromonadaceae, were identified to support ginseng's anti-colitis and anti-tumor effects. In addition, alpha and beta diversity data demonstrated that ginseng led to a profound recovery from the AOM/DSS-induced dysbiosis in the microbial community. CONCLUSION: Our results suggest that the CRC chemopreventive effects of American ginseng are mediated through enteric microbiome population-shift recovery and dysbiosis restoration. Ginseng's regulation of the microbiome balance contributes to the maintenance of enteric homeostasis.
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Carcinogênese/efeitos dos fármacos , Neoplasias do Colo/patologia , Microbioma Gastrointestinal/efeitos dos fármacos , Panax , Extratos Vegetais/farmacologia , Animais , Azoximetano/toxicidade , Carcinogênese/induzido quimicamente , Carcinogênese/patologia , Colite/etiologia , Colite/microbiologia , Colite/patologia , Neoplasias do Colo/etiologia , Neoplasias do Colo/microbiologia , Sulfato de Dextrana/toxicidade , Dieta Hiperlipídica/efeitos adversos , Masculino , Camundongos , Raízes de PlantasRESUMO
Healthcare systems are evolving towards a complex network of interconnected services due to the increasing costs and the increasing expectations for high service levels. It is evidenced in the literature the importance of implementing management techniques and sophisticated methods to improve the efficiency of healthcare systems, especially in emerging economies. This paper proposes an integrated collaboration model between two public hospitals to reach the reduction of weighted average lead time in outpatient internal medicine department. A strategic framework based on value stream mapping and collaborative practices has been developed in real case study settled in Colombia.
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Hospitais Públicos , Pacientes Ambulatoriais , Atenção à Saúde , Eficiência OrganizacionalRESUMO
Helminthiasis may ameliorate inflammatory diseases, such as inflammatory bowel disease and asthma. Information about immunomodulators from Ascaris lumbricoides is scarce, but could be important considering the co-evolutionary relationships between helminths and humans. We evaluated the immunomodulatory effects of a recombinant cystatin from A. lumbricoides on an acute model of dextran sodium sulphate (DSS)-induced colitis in mice. From an A. lumbricoides cDNA library, we obtained a recombinant cystatin (rAl-CPI). Protease activity inhibition was demonstrated on cathepsin B and papain. Immunomodulatory effects were evaluated at two intraperitoneal doses (0.5 and 0.25 µg/G) on mice with DSS-induced colitis. Body weight, colon length, Disease Activity Index (DAI), histological inflammation score, myeloperoxidase (MPO) activity, gene expression of cytokines and cytokines levels in colon tissue were analysed. Treatment with rAl-CPI significantly reduced DAI, MPO activity and inflammation score without toxic effects. Also, IL-10 and TGF-B gene overexpression was observed in rAl-CPI-treated group compared to DSS-exposed control and healthy mice. Furthermore, a reduction in IL-6 and TNF-A expression was found, and this was confirmed by the levels of these cytokines in colonic tissue. In conclusion, rAl-CPI reduces inflammation in a mouse model of DSS-induced colitis, probably by increasing the expression of anti-inflammatory cytokines and reducing pro-inflammatory ones.
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Colite/imunologia , Colite/terapia , Cistatinas/administração & dosagem , Imunossupressores/administração & dosagem , Animais , Ascaris lumbricoides/genética , Colite/induzido quimicamente , Colite/patologia , Colo/metabolismo , Cistatinas/genética , Cistatinas/imunologia , Citocinas/análise , Sulfato de Dextrana , Modelos Animais de Doenças , Feminino , Humanos , Imunossupressores/imunologia , Inflamação/patologia , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/uso terapêuticoRESUMO
Heat shock proteins (Hsps) are highly expressed at all sites of inflammation. As they are ubiquitous and immunodominant antigens, these molecules represent good candidates for the therapeutic use of oral tolerance in autoimmune and chronic inflammatory diseases. Evidences from human and animal studies indicate that inflammatory bowel disease (IBD) results from uncontrolled inflammatory responses to intestinal microbiota. Hsps are immunodominant proteins expressed by several immune cells and by commensal bacteria. Using an IBD mouse model, we showed that oral pretreatment with genetically modified Lactococcus lactis that produces and releases Mycobacterium Hsp65, completely prevented DSS-induced colitis in C57BL/6 mice. Protection was associated with reduced pro-inflammatory cytokines, such as IFN-γ, IL-6, and TNF-α; increased IL-10 production in colonic tissue; and expansion of CD4+Foxp3+ and CD4+LAP+ regulatory T cells in spleen and mesenteric lymph nodes. This effect was dependent on IL-10 and toll-like receptor 2. Thus, this approach may open alternative options for long-term management of IBD.
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PURPOSE: Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders with important impact on global health. Prebiotic and probiotic strategies are thought to be useful in the context of experimental IBD. Here, we compared the effects of preventive versus therapeutic treatment with a high fiber diet (prebiotic) in combination or not with Bifidobacterium longum (probiotic) in a murine model of chronic colitis. METHODS: Colitis was induced by adding dextran sulfate sodium (DSS) to drinking water for 6 days (acute colitis) or for 5 cycles of DSS (chronic colitis). RESULTS: Administration of the high fiber diet protected from acute colitis. Protection was optimal when diet was started 20 days prior to DSS. A 5-day pretreatment with acetate, a short-chain fatty acid, provided partial protection against acute colitis. In chronic colitis, pretreatment with the high fiber diet attenuated clinical and inflammatory parameters of disease. However, when the treatment with the high fiber diet started after disease had been established, overall protection was minimal. Similarly, delayed treatment with acetate or B. longum did not provide any protection even when the probiotic was associated with the high fiber diet. CONCLUSION: Preventive use of a high fiber diet or acetate clearly protects mice against acute and chronic damage induced by DSS in mice. However, protection is lost when therapies are initiated after disease has been established. These results suggest that any therapy aimed at modifying the gut environment (e.g., prebiotic or probiotic strategies) should be given early in the course of disease.