Protective Effect of Nelumbo nucifera Plant on Dextran Sodium Sulfate-Induced Ulcerative Colitis in Rats

Objectives?Ulcerative colitis is a global disease with increasing incidence and worldwide prevalence. So this study was undertaken to observe antiulcerative colitis activity of ethanolic extract of seeds of Nelumbo nucifera plant on dextran sodium sulfate (DSS)-induced ulcerative colitis in rats. Materials and Methods?The effect of ethanolic extract of N. nucifera seed (EENNS) was studied on DSS-induced ulcerative colitis in albino Wistar rats for 11 days. Disease pathogenesis was assessed by evaluation of disease activity index (DAI) including the following parameters: change in body weight, stool constituency, rectal bleeding in animals. Estimation of myeloperoxide (MPO), nitric oxide (NO), and antioxidant parameters like malondialdehyde (MDA), superoxide dismutase (SOD), and catalase level was performed in colon homogenate of animals. TNF-? (tumor necrosis factor- ?) level was measured in colon homogenate using rat TNF-? ELISA kit. Statistical Analysis?Significant differences (mean?±?standard error of the mean) were detected using one-way analysis of variance followed by post-test using Graphpad prism 7.0 for multiple comparisons. Results?EENNS (400?mg/kg) significantly improved the disease progression, body weight, and colon length of the animals as compared with the disease control group. Animal treated with EENNS (400?mg/kg) showed significantly improved colon mucosal damage index (1.66?±?0.21) and DAI (11.66?±?4.01) as compared with the disease control group. A higher level of SOD and catalase and a lower level of MDA were observed in animals treated with EENNS (400?mg/kg) as compared with the disease control group. Animals treated with EENNS (400?mg/kg) significantly decreased in NO and MPO levels as compared with the disease control group. A lower level of TNF-? (561.94?±?14.84) was observed in EENNS (400?mg/kg)-treated animals as compared with the disease control group (736.92?±?15.3). These observations were comparable to those of the standard control group. Histopathological data showed that EENNS (400?mg/kg) has shown reversal of tissue inflammation as compared with the disease group and evidence of less cell infiltration of lymphocytes and monocytes with normal structures of goblet cell and crypts as compared with the disease group. Conclusion?EENS (400?mg/kg) can decrease the severity of the UC produced by DSS. EENNS showed a protective effect against DSS-induced ulcerative colitis which may be due to its antioxidant and anti-inflammatory activity.

Serum Lactate as a Predictor of Severity in Dengue Infection

Background Dengue infections caused by the four antigenically distinct dengue virus serotypes (DENV1, DENV2, DENV3, DENV4) of the family Flaviviridae are the most major arboviral diseases in humans in terms of geographic spread, morbidity, and mortality. Objective: The study was conducted to assess serum lactate in cases of dengue and correlate it with severity in dengue infection. Methodology: A prospective observational study was carried out among indoor patients admitted to the general medicine department of the tertiary care hospital SMIMER Surat. The study's duration was 15 to 18 months. Result: our study found out of total 154 cases; majority of cases were belonged from 83(53.90%) cases were from less than 30 years. male was contributed 96 (62.34%), majority of cases had duration of fever 39(25.32%), 66 (42.66%) case had high LDH, comparison of serum lactate dehydrogenase with severity of dengue mean lactate dehydrogenase of dengue without severity was mean was 148.45 and SD 11.81, while in severe dengue mean serum lactate dehydrogenase 388.23 and SD 99.47 with p value 0.001 which was statically significant. Conclusion According to this study, it is preferable to monitor serial lactate levels as opposed to using a single lactate number.

Fish Oil Improves Dysbiosis of Host-microbial Interaction and Maintains Remission in Colitis Mice / 中国生物化学与分子生物学报

n-3 polyunsaturated fatty acids (PUFAs) play an active role in controlling the progression of ulcerative colitis (UC), but its mechanism is not very clear. In this study, we compared the effects of fish oil (the main component is n-3 PUFAs) in the mouse model with acute and chronic colitis induced by dextran sulfate sodium (DSS). Male C57BL/6J mice were randomly divided into six groups, and each group had ten mice. The alleviating effect of fish oil on chronic colitis was significantly better than acute colitis as indicated by the following analysis: the weight loss of mice (P < 0. 05), decreased disease activity index (DAI) score (P<0. 05), colonic edema, colon length index and histopathological score (P < 0. 05), and serum pro-inflammatory factor levels like IL-1β, TNF-α, and IL-6 (P < 0. 01). Moreover, fish oil promoted the level of serum anti-inflammatory factor IL-10 (P<0. 05). The treatment of fish oil increased the n-3 PUFA concentration in the intestinal epithelium of mice (P < 0. 01), especially EPA (P<0. 05). 16S rRNA sequencing of feces revealed that fish oil significantly increased the relative abundance of butyrate-producing flora (Clostridiales) and probiotics (Bifidobacteriales) in the feces of the maintained remission model group, reduce the proportion of aerobic, parthenogenic anaerobic and pathogenic, and improved the disorder of glycan biosynthesis and metabolism and oxidative phosphorylation (P<0. 05). Compared with the induced remission fish oil group, fish oil treatment led to an elevated expression of mechanical barrier and energy metabolism pathway proteins in the maintained remission fish oil group. Our results showed that fish oil exerted a more potent inhibitory effect in the remission mice model, which may be related to effectively strengthening the mechanical barrier, improving the composition and function of intestinal microbiota and concentration of butyric acids and improving dysbiosis of host-microbial interaction.

miR-7/TGF-β2 axis sustains acidic tumor microenvironment-induced lung cancer metastasis

Acidosis, regardless of hypoxia involvement, is recognized as a chronic and harsh tumor microenvironment (TME) that educates malignant cells to thrive and metastasize. Although overwhelming evidence supports an acidic environment as a driver or ubiquitous hallmark of cancer progression, the unrevealed core mechanisms underlying the direct effect of acidification on tumorigenesis have hindered the discovery of novel therapeutic targets and clinical therapy. Here, chemical-induced and transgenic mouse models for colon, liver and lung cancer were established, respectively. miR-7 and TGF-β2 expressions were examined in clinical tissues (n = 184). RNA-seq, miRNA-seq, proteomics, biosynthesis analyses and functional studies were performed to validate the mechanisms involved in the acidic TME-induced lung cancer metastasis. Our data show that lung cancer is sensitive to the increased acidification of TME, and acidic TME-induced lung cancer metastasis via inhibition of miR-7-5p. TGF-β2 is a direct target of miR-7-5p. The reduced expression of miR-7-5p subsequently increases the expression of TGF-β2 which enhances the metastatic potential of the lung cancer. Indeed, overexpression of miR-7-5p reduces the acidic pH-enhanced lung cancer metastasis. Furthermore, the human lung tumor samples also show a reduced miR-7-5p expression but an elevated level of activated TGF-β2; the expressions of both miR-7-5p and TGF-β2 are correlated with patients' survival. We are the first to identify the role of the miR-7/TGF-β2 axis in acidic pH-enhanced lung cancer metastasis. Our study not only delineates how acidification directly affects tumorigenesis, but also suggests miR-7 is a novel reliable biomarker for acidic TME and a novel therapeutic target for non-small cell lung cancer (NSCLC) treatment. Our study opens an avenue to explore the pH-sensitive subcellular components as novel therapeutic targets for cancer treatment.

Protective effect of Pai-Nong-San against AOM/DSS-induced CAC in mice through inhibiting the Wnt signaling pathway / 中国天然药物

Pai-Nong-San (PNS), a prescription of traditional Chinese medicine, has been used for years to treat abscessation-induced diseases including colitis and colorectal cancer. This study was aimed to investigate the preventive effects and possible protective mechanism of PNS on a colitis-associated colorectal cancer (CAC) mouse model induced by azoxymethane (AOM)/dextran sodium sulfate (DSS). The macroscopic and histopathologic examinations of colon injury and DAI score were observed. The inflammatory indicators of intestinal immunity were determined by immunohistochemistry and immunofluorescence. The high throughput 16S rRNA sequence of gut microbiota in the feces of mice was performed. Western blot was used to investigate the protein expression of the Wnt signaling pathway in colon tissues. PNS improved colon injury, as manifested by the alleviation of hematochezia, decreased DAI score, increased colon length, and reversal of pathological changes. PNS treatment protected against AOM/DSS-induced colon inflammation by regulating the expression of CD4

Suppression of AOM/DSS-induced colorectal cancer by scutellarin through downregulation of Wnt signaling pathway activity / 中国药理学与毒理学杂志

OBJECTIVE To investigate the therapeutic effect of scutellarin on colitis-associated cancer (CAC) and its underlying mechanism based on Wnt/β-catenin signaling pathway. METHODS The mouse model of CAC was estab?lished by azomethane oxide (AOM) and sodium dextran sulfate (DSS), followed by scutellarin treatment, with recording the body weight, diarrhea and hematochezia. After sacrificing the mice, the colorectal length and colorectal tumor were assessed. The levels of pro-inflammatory factors TNF-α and IL-6 in mice's sera were measured by the enzyme-linked immunosorbent assay (ELISA). The colorectal lesions were appraised by hematoxylin and eosin (H&E) staining. Theβ-catenin level in CAC tissues was probed by immunofluorescent analysis. The apoptosis-related genes Bax and Bcl-2, and Wnt signaling pathway-related genes β-catenin, GSK-3β, TCF4, c-Myc and cyclin D1 were detected by real-time quantitative RT-PCR (RT-qPCR). Finally, Western blotting analysis (WB) was employed to examine the expressions of the apoptosis and Wnt signaling pathway-related proteins. RESULTS Scutellarin significantly improved AOM/DSS-caused weight loss, colorectal length shortening, and tumor growth in mice (P<0.01). Meanwhile, colorectal lesions could be substantially alleviated by scutellarin. ELISA results showed that the levels of pro-inflammatory factors TNF-αand IL-6 were drastically lessened (P<0.01). Scutellarin also sharply inhibited the nuclear translocation of β-catenin, as evidenced by the reduction in the nuclear level ofβ-catenin protein. In addition, scutellarin attenuated the mRNA expres?sion of Wnt signaling pathway-relatedβ-catenin, TCF4, c-Myc and cyclin D1, whereas it heightened GSK-3βmRNA level. These results were consolidated by WB analysis, which indicated that scutellarin could mitigate the protein levels of phospho-GSK-3β,β-catenin, TCF4, c-Myc and cyclin D1, with the increase in GSK-3β protein in CAC tissue. Moreover, scutellarin could induce the apoptosis of CAC, demonstrated by enhanced expression of Bax and diminished expression of Bcl-2 in both mRNA and protein levels. CONCLUSION Scutellarin may ameliorate colitis-associated colorectal cancer by weakening Wnt/β-catenin signaling cascade.

Whether Platelet Count Really Influences the Outcome of Dengue Patients? A Study Done at Tertiary Care Centre in North Karnataka Region

In many parts of India, Dengue has become a major public health problem and Kalaburagi District in North Karnataka region was previously not known to be an endemic area for dengue. Three clinical syndromes, classic dengue fever, dengue haemorrhagic fever and dengue shock syndrome are seen with dengue virus infection. This present study was undertaken to find out whether platelet count really influences the outcome of dengue patients in a tertiary health care centre in Kalaburagi, Karnataka.METHODSAbout hundred patients admitted in our hospital with positive Dengue NS1 and Dengue IgM were selected. The follow up of patients is done from the onset of fever to up to twelve days or until their recovery according to discharge criteria of WHO whichever of them is earlier.RESULTSIn this study, 100 cases were studied, out of which Dengue fever was seen in 73 cases, Dengue Hemorrhagic Fever in 17 cases and Dengue Shock Syndrome in 10 cases was seen based on WHO criteria. In this study, 99 percent patients had fever. In this study 73 percent of patients were Dengue NS1 Positive and 27 percent of patients were Dengue IgM Positive. In present study, continuously increasing pattern of platelet count was seen in 55 percent cases; initial fall then rise of platelet count was seen in 38 percent cases and persistently low pattern of platelet count was seen in 7 percent cases. This study showed that 30 percent of patients had bleeding manifestations and bleeding manifestations were maximum in patients having low platelet counts. In the present study, 92% cases improved and 8% cases expired.CONCLUSIONSAmong the three clinical syndromes, Dengue fever was more common than dengue haemorrhagic fever and dengue shock syndrome. It was found that platelet count influenced the outcome of dengue patients. Management of dengue case is mainly supportive

Predictors and Outcome of Severe Dengue Illness in Children.

Dengue fever has become a major public health concern during the last few years with an alarming increase in the incidence in 2017. The state of Kerala was one among the top of the list in India reported to have severe dengue infection. The two main districts in Kerala with high prevalence were Thiruvananthapuram and Palakkad, of which latter is the main referring area to our institution. This study was conducted to evaluate the clinical and demographic profile of children affected with dengue fever and determine the predictors of severity.METHODSThis is a hospital based prospective study done at the Department of Paediatrics, Government Medical College, Trissur, during the Monsoon season in 2017. Children diagnosed to have Dengue fever and confirmed by NS1 Ag test or IgM Elisa were included. Children were classified into 3 clinical groups and compared. Comparison was also made in 2 groups as dengue with warning signs and severe dengue as per WHO 2015 clinical guidelines, to find out the predictors of severity. Qualitative data was analysed and expressed in proportions and quantitative data in mean and standard deviation. Chi-square (χ2) test was used to evaluate the association between qualitative variables and ANOVA for quantitative variables. p value less than 0.05 was considered significant. SPSS 16.0 software was used for statistical analysis.RESULTSA total of 235 children were included. 77 children (32.9%) had mild dengue fever, 106 (45.29%) had DWS and 52 (22.22%) were having DSS). Mean age was 6.61± 3.497 years. 19 cases (8.2 %) were Infants below 1 year of age. Majority of children had normal nutritional status. Myalgia, tiredness, vomiting, diarrhoea, abdominal pain, flushing, bleeding, oedema, hypotension, were found to be the common clinical manifestations. Thrombocytopenia, elevated serum hepatic enzymes both SGOT and SGPT, abnormal renal function tests, low sodium, hypoalbuminemia, hypoglycaemia, abnormal radiological findings were found to be the predictors of severity. We had many cases of expanded dengue syndrome including 3 cases of Hemophagocytic lymphohistiocytosis (HLH). The mortality was 0.6%.CONCLUSIONSDengue fever can affect children irrespective of their age or nutritional status. Older children and male sex were found to be more affected. There are definite clinical and lab parameters which can predict the severity in Dengue fever. Though severe illness is associated with high morbidity early diagnosis and timely appropriate clinical management, correction of dehydration along with proper referral system can save the children. The mortality can be reduced to zero even in patients having expanded dengue syndrome and Dengue shock syndrome. None of the comorbidities had affected the outcome.

Overexpression of miR-31 regulates TLR4/NF-κB signaling pathway and apoptotic protein in colitis model mice / 中国应用生理学杂志

To investigate the effects of miR-31 on TLR4/NF-κB signaling pathway and apoptosis-related proteins in dextran sulfate sodium (DSS) induced mouse colon colitis. Methods: ① Mouse model of colon colitis: 1% DSS was used to induce mouse ulcerative colitis (UC). Fourteen FVB non-transgenic mice were randomly divided into control group (n= 6), DSS group (n= 8), and 16 FVB miR-31 transgenic mice were randomly divided into miR-31 overexpression group (n= 8), miR-31 overexpression +DSS group (n= 8). DSS was dissolved in water and administered to mice by drinking water. The DSS group and miR-31+DSS group drank 1% DSS water in the first week, normal sterilized water in the second week, and 1% DSS water in the third week, after 5 weeks, the modeling was completed, then the colon tissues of the mice were collected. Western blot and IHC were used to detect the expressions of NF-κB p65, TLR4, Bax and Bcl-2 proteins in mouse colon tissue, TUNEL was used to detect apoptosis of mouse colon tissues. ② Cell culture experiments: Transfection of miR-31mimic and inhibitor by lipofectamine resulted in overexpression or knockdown of miR-31 in human colon epithelial cell line HCT 116 cells, each group was repeated three times and cells were collected 48 h later, Western blot was used to detect the expressions of NF-κB p65 and TLR4 protein. ① In animal experiments, compared with the control group, the expression levels of NF-κB p65, TLR4 protein and apoptotic cell index in the DSS group and miR-31 overexpression group in mouse colon tissue were significantly increased (P＜0.05 or P＜0.01), and the Bcl-2 / Bax ratio was significantly reduced (P＜0.05 or P＜0.01); and compared with the DSS group, the expression levels of NF-κB p65, TLR4 protein and apoptotic cell index in the miR-31+DSS group were significantly increased (P＜0.01), while the Bcl-2/Bax ratio was significantly decreased (P＜0.01). ② In cell experiments, compared with the control group, the expression levels of NF-κB p65 and TLR4 protein in the over-expressed miR-31 group of HCT 116 cells were significantly increased (P＜0.05 or P＜0.01), the expressions of NF-κB p65 and TLR4 protein in miR-31 knockdown group were decreased (P＜0.05). miR-31 promotes the development of colitis by promoting TLR4/NF-κB signaling pathway and mediating apoptosis of intestinal epithelial cells.

Modelo conceitual aplicável a estudos sobre determinantes sociais da saúde em municípios brasileiros / A conceptual model for studies on social determinants of health in Brazilian municipalities

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.

Clinico-epidemiological study of dengue fever in Ajmer region

Background: Dengue infection is a major challenge to public health, especially in South-East Asia. It present with a diverse clinical spectrum. Estimates suggest that annually over 50 million cases of dengue hemorrhagic fever (DHF) occur in Asian countries with a case fatality rate of less than 5%. Of those with DHF, at least 90% are children younger than 15 years old. In humans, dengue infection causes a spectrum of illness ranging from relatively mild, non-specific viral syndrome known as Dengue fever (DF) to severe hemorrhagic disease and death. Definitive early Dengue diagnosis requires laboratory tests and those suitable for use at this stage of illness are either costly, such as RT-PCR for Dengue; not sufficiently rapid, such as virus isolation. Currently test available are NS1 antigen detection and ELISA for dengue, IgM and IgG antibodies. Objective of this study is to study clinico-epidemiological and haematological features of Dengue infection.Methods: Prospective observational study involving initial 100 registered cases who were serologically confirmed dengue infection for a period of one year.Results: DF, DHF and DSS were found in 41%, 53% and 6% patients respectively. Most common presenting complaint and bleeding manifestation were fever and petechiae. Uncommonly altered sensorium and icterus were found in severe dengue infection. 6% patients had coagulopathy, 37 patients had hepatic involvement and 2 patients had deranged renal function who had DSS. Fever was present in (100%) cases of DF, DHF and DSS. 26% patients had their platelet count <50000/mm3.Conclusions: Dengue is a common disease in the India with wide spectrum of clinical presentations, affecting 5-15 years age group children commonly. It is one of the dreaded fevers but early diagnosis and management according to recent WHO guidelines can decrease case fatality rate significantly.

Clinical profile of Dengue fever in an urban tertiary care hospital in South India

Background: Dengue is among the most common flavivirus infections in the world. Today dengue ranks as the most important mosquito- borne viral disease in the world. Current estimates report that, at least 112 countries are endemic for Dengue and about 40% of the world populations (2.5-3 billion people) are at risk in tropics and subtropics. Annually 100 million cases of dengue fever and half a million cases of DHF occur worldwide. The clinical features are noted to be different in varying demographics of the world outlining the importance of bringing out data from different parts of the world, so clinicians are better equipped to anticipate the problems associated with clinical dengue.Methods: The study was conducted over a period of 2 years at a tertiary care hospital in urban Bengaluru, India. A cross sectional study of a total of 250 patients was done. They were diagnosed to be positive for dengue serology (NS1 or IgM) before including them in the study. Clinical features, haematological, biochemical and radiological parameters were assessed.Results: Out of 250 patients with dengue fever, the most common symptoms were fever (100%), headache (94.4%) and myalgia (97.2%). Bleeding manifestations were noted in 11.6% of the patients. Bradycardia was noted in 14.8% of the study population. Leukopenia was noted in 36% of the study population. Increased SGOT was seen in 59.6% and increased SGPT in 52.8% of the 250 subjects. The clinical outcome of the 250 patients of dengue fever was classical dengue fever in 86.8%, DHF in 11.6%, DSS in 0.8% and death in 0.8%.Conclusions: All patients with dengue fever present with fever. Other common features noted were headache, myalgia. Bleeding manifestations are to be looked out for. Rare but important features that a clinician must be vigilant to look for are bradycardia and leucopenia.

Immature platelet fraction in children infected with dengue fever

Background: Millions are infected with dengue every year.' Early diagnosis of dengue infection is important for proper treatment of DHF and DSS to avoid fatal outcome. Thrombocytopenia is a common hematological abnormality in dengue, which demands platelet transfusion in most of the severe dengue cases. Platelet transfusion though life-saving has its own hazards. Hence, we can use some new parameter like immature platelet fraction (IPF) which is a measure of reticulated platelets that reflects the rate of thrombopoiesis. The risk of platelet transfusion may be decreased by rapid identification of immature platelet fraction. This study was performed to establish reference of IPF values for the assessment of thrombopoiesis.Methods: Blood samples from 150 children were obtained on day of illness 3, 5 and 7. The IPF is identified by sysmex XE2100 hematology analyser in the reticulocyte channel using a fluorescent dye and a carefully designed gating system and counted by a special software termed IPF master7. IPF values against platelet count were assessed separately on day 3, 5 and 7.Results: The reference intervals of IPF > 8 % and IPF < 8 % were assessed against platelet count. Increase in IPF favored increase in platelet count on day 5 which was statistically significant with the p value <0.001.Conclusions: A rapid and inexpensive automated measurement of IPF can be integrated as a standard parameter to evaluate the thrombopoietic state of the bone marrow. From the study it can be concluded that IPF is an important predictor of increase in platelet count.' Increase in IPF>8 % suggests that platelet count will be increased in next 24 to 48hrs indicating that further blood transfusion will not be required.

Determinantes sociais da saúde mental do idoso / Social determinants of mental health of the elderlyPalavras-chave em inglêsMental Health

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

Mechanisms of Chinese Dragon’s Blood on alleviating colonic mucosal damage in mice with ulceratice colitis based on network pharmacology / 中草药

Objective: To investigate the effects of Chinese Dragon’s Blood (CDB) on DSS-induced ulcerative colitis (UC) in mice, and predict the potential main active ingredients, targets and signaling pathways of CDB by network pharmacology. Methods: Mouse UC model was induced by DSS. Balb/c mice were randomly divided into control group, UC group, CDB high, medium, and low dose group, mesalazine control group, 10 mice in each group. Except the control group, each group drank 3.0% DSS solution freely for seven consecutive days. The CDB group and mesalazine group were given corresponding medicines for gastric perfusion during the modeling period. The mice were weighed regularly every day to conduct occult blood test and observe the animals. The fecal traits were evaluated by DAI. At the end of the experiment, the mice were sacrificed and HE stained and scored. The “compound-compound target-disease target” network was constructed by online databases such as TCMSP, String, Cytoscape, etc, and the target targets of core compound targets and compounds were extracted, GO and KEGG enrichment analysis was performed on related targets. Treatment of biological processes and mechanisms of action that UC may regulate were analyzed. Results: Compared with the control group, the infiltration of inflammatory cells in the model group was obvious, and a large number of cup cells disappeared, and the degree of lesions spread to the muscle layer or even the whole layer; The cup cells in the CDB group re-grew, the extent of the lesion was limited to the mucosa, and the inflammation was alleviated. Through the network pharmacology, 112 target targets of CDB were screened, and 14 core compound targets such as ABL1, F2, and JAK2 could be applied to 11 disease targets such as ICAM1, IL-6, PTGS2, and MTOR. The GO analysis contained 415 enrichment pathways, including 389 biological processes, nine molecular functions, and 17 cell components. The KEGG database was used to enrich the relevant pathways, and 84 pathways such as PI3K-Akt were screened for UC. Conclusion: CDB can alleviate colonic mucosal injury induced by DSS in UC mice. It may regulate the expression of ABL1, F2, JAK2 and other target proteins through flavonoids, and then indirectly regulate the expression of IL-6, PTGS2 and other disease proteins. The JAK2/STAT3 and PI3K-Akt-mTOR pathways regulate the levels of inflammatory factors, inhibit the inflammatory response, and ultimately alleviate UC colonic mucosal damage.

Effect of Estradiol in an Azoxymethane/Dextran Sulfate Sodium-Treated Mouse Model of Colorectal Cancer: Implication for Sex Difference in Colorectal Cancer Development / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study demonstrates that estradiol downregulates inflammation and inhibits colorectal cancer (CRC) development in azoxymethane/dextran sulfate sodium (AOM/DSS) mouse model. MATERIALS AND METHODS: AOM/DSS-treated male and female mice were sacrificed at weeks 2, 10, and 16, to assess estrogen effects on colitis and carcinogenesis. Macroscopic and histologic severity of colitis and Western blot and quantitative real-time polymerase chain reaction were evaluated, to measure inflammatory mediators and cytokines. RESULTS: Compared with AOM/DSS-treated male mice (M-AOM/DSS group), AOM/DSS-treated male mice with estradiol administration (M-AOM/DSS+estr group) displayed at week 2 significantly decreased severity of colitis. At weeks 10 and 16, AOM/DSS-treated female mice (F-AOM/DSS group) and the M-AOM/DSS+estr group showed significantly lower tumor multiplicity compared with the M-AOM/DSS group. At week 2, F-AOM/DSS group had a lower level of nuclear factor-κB (NF-κB) expression and higher level of nuclear factor erythroid 2-related factor 2 (Nrf2) expression, compared to the M-AOM/DSS group. At week 2, expression levels of NF-κB and its related mediators decreased in the M-AOM/DSS+estr group, while levels of Nrf2 and Nrf2-related anti-oxidant enzymes increased. In addition, estradiol significantly increased Nod-like receptor protein 3 (NLRP3) inflammasome expressions in AOM/DSS-treated male mice. In contrast, at weeks 10 and 16, Nrf2 and its-related anti-oxidant enzymes and NLRP3 inflammasome were highly expressed in M-AOM/DSS group and in F-AOM/DSS group, who developed cancer. CONCLUSION: The data suggest that estradiol inhibits the initiation of CRC by regulating Nrf2-related pathways. Moreover, these imply the dual role of Nrf2 and NLRP3 inflammasome, including promotion of tumor progression upon tumor initiation.

The anti-colitic effect of specific Kvl. 3 blocker in its regulation of macrophage autophagy / 中国药理学通报

Aim To investigate the mechanism of the effect of a specific Kvl. 3 blocker PAP-1 on DSS-in-duced colitis. Methods C57BL/6 mice were divided into normal control group, PAP-1 control group, DSS model group and DSS + PAP-1 group. DSS-induced colitis model was constructed by adding DSS (final concentration of 5% ) to the drinking water of mice. PAP-1 (3 jxg • g~1, 3 times a day for 7 days) was adminis tered intraperitoneally, while an equal volume of solvent was intraperitoneally injected to normal control group and model group. The changes of body weight of mice and the inflammatory activity index (DAI) were recorded every day. After the experiment, the peritoneal macrophages, spleen and colon tissues of mice were collected. Some colon tissues were used for colonic HE staining , and the tissue homogenate was used to detect MPO activities and inflammatory factors. Immunofluorescence confocal microscopy was used to observe the exudation of colonic macrophages. Transmission e-lectron microscopy was used to observe the autophagy-related structures of macrophages, qPCR and Western blot were used to detect the expression of iNOS, IL-1 £ and autophagy-related markers LC3-II , p62, and Bec-lin-1 in mouse colon, peritoneal macrophages and spleen macrophages. Results The DSS-induced mouse colitis model was successfully constructed. PAP-1 reduced weight loss of DSS-induced colitis mice (P <0. 05) and decreased DAI score (P <0. 05) and colon HI score ( P < 0. 05). The MPO activity and the levels of IL-1, IL-6 and TNF-ot decreased in colon tissue of DSS + PAP-1 group compared to DSS model group (P <0. 05). The expression of F4/80 in DSS + PAP-1 group was significantly lower than that in DSS model group based on immunofluorescence microscopic observation. Under the electron microscope, the autophagic bubbles in peritoneal macrophages and spleen macrophages in DSS + PAP-1 group increased compared with those in DSS model group. qPCR and West-em blot showed that in DSS + PAP-1 group, compared with DSS model group, the expression ofiNOS, IL-lfJ and p62 significantly decreased, while the expression of LC3-H and Beclin-1 markedly increased in colon, peritoneal macrophages and spleen macrophages ( P < 0. 05). Conclusions PAP-1 reduces the impaired autophagy of macrophages in mice with colitis, further decreases inflammatory cytokine production, and ultimately ameliorates the immunoinflammatory damage of colitis.

T Cell-Specific Knockout of STAT3 Ameliorates Dextran Sulfate Sodium-Induced Colitis by Reducing the Inflammatory Response

Signal transducer and activator of transcription 3 (STAT3) has a crucial role in various autoimmune disorders including, inflammatory bowel disease (IBD). Our previous study demonstrated that STAT3 activation by IL-6 in colonic epithelial cells exacerbates experimental ulcerative colitis. Activated T lymphocytes are also found in ulcerative colitis patients with intestinal inflammation, but the role of STAT3 in T cells remains elusive. To determine the STAT3 function of T cells in intestinal inflammation, we generated T cell-specific STAT3 knockout (KO) mice and used dextran sulfate sodium (DSS) to induce colitis. In this study, we demonstrated that T cell-specific STAT3 deletion alleviated DSS-induced colitis in mice, resulting in reduced histological scores and myeloperoxidase (MPO) activity. Importantly, the population of T cells in the spleen and lymph nodes was significantly decreased in the control and DSS-induced groups of STAT3 KO mice. In addition, STAT3 deficiency in T cells markedly reduced the production of interferon (IFN)-γ, IL-6, and IL-17A, whereas IL-10 secretion was increased. Collectively, the results suggest that STAT3 in T cells may be a therapeutic target in ulcerative colitis by balancing the immune response through T cell homeostasis.

Effects of 17β-Estradiol on Colonic Permeability and Inflammation in an Azoxymethane/Dextran Sulfate Sodium-Induced Colitis Mouse Model

BACKGROUND/AIMS: Intestinal barrier dysfunction is a hallmark of inflammatory bowel diseases (IBDs) such as ulcerative colitis. This dysfunction is caused by increased permeability and the loss of tight junctions in intestinal epithelial cells. The aim of this study was to investigate whether estradiol treatment reduces colonic permeability, tight junction disruption, and inflammation in an azoxymethane (AOM)/dextran sodium sulfate (DSS) colon cancer mouse model. METHODS: The effects of 17β-estradiol (E2) were evaluated in ICR male mice 4 weeks after AOM/DSS treatment. Histological damage was scored by hematoxylin and eosin staining and the levels of the colonic mucosal cytokine myeloperoxidase (MPO) were assessed by enzyme-linked immunosorbent assay (ELISA). To evaluate the effects of E2 on intestinal permeability, tight junctions, and inflammation, we performed quantitative real-time polymerase chain reaction and Western blot analysis. Furthermore, the expression levels of mucin 2 (MUC2) and mucin 4 (MUC4) were measured as target genes for intestinal permeability, whereas zonula occludens 1 (ZO-1), occludin (OCLN), and claudin 4 (CLDN4) served as target genes for the tight junctions. RESULTS: The colitis-mediated induced damage score and MPO activity were reduced by E2 treatment (p < 0.05). In addition, the mRNA expression levels of intestinal barrier-related molecules (i.e., MUC2, ZO-1, OCLN, and CLDN4) were decreased by AOM/DSS-treatment; furthermore, this inhibition was rescued by E2 supplementation. The mRNA and protein expression of inflammation-related genes (i.e., KLF4, NF-κB, iNOS, and COX-2) was increased by AOM/DSS-treatment and ameliorated by E2. CONCLUSIONS: E2 acts through the estrogen receptor β signaling pathway to elicit anti-inflammatory effects on intestinal barrier by inducing the expression of MUC2 and tight junction molecules and inhibiting pro-inflammatory cytokines.

Effects of CHL1 deficiency,a cell adhesion molecule,on the inflammatory bowel disease / 中国应用生理学杂志

OBJECTIVE@#To investigate the effects of deficiency of CHL1 in inflammatory bowel disease (IBD).@*METHODS@#Dextran Sulfate Sodium (DSS)-induced colitis model was used to study the effects of deficiency of CHL1 on the development of IBD. Ten CHL1(+/+) mice in C57/BL6 background were randomly divided into CHL1(+/+) group and DSS-induced CHL1(+/+) group. Ten CHL1(-/-) mice in C57/BL6 background were randomly divided into CHL1(-/-) group and DSS-induced CHL1(-/-) group. DSS-induced CHL1(+/+) group and DSS-induced CHL1(-/-)group were fed with 1.5% DSS for 7 days, and then drinking distilled water for 2 days. CHL1(+/+) group and CHL1(-/-) group as control group were fed with distilled water for 9 days. The changes of weight, survival, fecal blood and the change of colon length in this study were observed.@*RESULTS@#On the 7 day, the weight of DSS-induced CHL1(-/-) group were reduced significantly, and DSS-induced CHL1(-/-) group had extreme mortality on the 9th day. The fecal blood of DSS-induced CHL1(-/-) group also had higher score than that of DSS-induced CHL1(+/+) group. In the DSS-induced CHL1(-/-) group,the length of colon was shortened obviously.@*CONCLUSIONS@#The loss of CHL1 aggravates the development of IBD.