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OBJECTIVE: Chronic graft-versus-host disease (cGVHD) is a significant complication following allogenic hematopoietic stem cell transplantation, often necessitating therapeutic interventions such as rituximab (RTX) and cyclosporin A (CsA). This study aims to elucidate the mechanisms by which RTX and CsA jointly address B-cell dysregulation in cGVHD, providing a theoretical foundation and scientific rationale for the treatment and prognostic evaluation of this condition. METHODS: A total of 30 cGVHD mouse models were established by subjecting recipient mice to total body irradiation followed by injection of a mixed suspension of bone marrow cells and splenocytes from donor mice. From Day 2 to Day 29 post-model establishment, the mice received subcutaneous administration of RTX and CsA. Throughout the study, body weight, clinical cGVHD scores, and survival rates were monitored. Blood samples were collected via the orbital venous plexus. Serum levels of B-cell activating factor (BAFF) and pro-inflammatory factors were measured using enzyme-linked immunosorbent assay (ELISA), and the ratio of regulatory B cells (Bregs) in the blood sample was assessed via flow cytometry. RESULTS: Mice with cGVHD exhibited a 14.5% decrease in body weight, elevated clinical scores, and more severe symptoms compared to the control group. Notably, all mice in both the cGVHD and control groups survived until the conclusion of the study. Induction of cGVHD resulted in B-cell dysregulation, evidenced by elevated serum BAFF levels and a decreased proportion of Bregs. However, treatment with RTX combined with CsA ameliorated B-cell dysregulation and significantly reduced serum levels of pro-inflammatory factors in cGVHD mice, with decreases of 39.78% in TNF-α and 37.89% in IL-6. CONCLUSION: The combination of RTX and CsA effectively mitigates B-cell dysregulation in cGVHD, thereby reducing the severity and progression of the disease.
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SUMMARY: The 12C6+ heavy ion beam irradiation can cause bystander effects. The inflammatory cytokines, endocrine hormones and apoptotic proteins may be involved in 12C6+ irradiation-induced bystander effects. This study characterized the protective effects and mechanisms of Huangqi decoction (HQD) against 12C6+ radiation induced bystander effects. Wistar rats were randomly divided into control, 12C6+ heavy ion irradiation model, and high-dose/medium-dose/low-dose HQD groups. HE staining assessed the pathological changes of brain and kidney. Peripheral blood chemical indicators as well as inflammatory factors and endocrine hormones were detected. Apoptosis was measured with TUNEL. Proliferating cell nuclear antigen (PCNA) expression was determined with real-time PCR and Western blot.Irradiation induced pathological damage to the brain and kidney tissues. After irradiation, the numbers of white blood cells (WBC) and monocyte, and the expression of interleukin (IL)-2, corticotropin-releasing hormone (CRH) and PCNA decreased. The damage was accompanied by increased expression of IL-1β, IL-6, corticosterone (CORT) and adrenocorticotropic hormone (ACTH) as well as increased neuronal apoptosis. These effects were indicative of radiation-induced bystander effects. Administration of HQD attenuated the pathological damage to brain and kidney tissues, and increased the numbers of WBC, neutrophils, lymphocyte and monocytes, as well as the expression of IL-2, CRH and PCNA. It also decreased the expression of IL-1β, IL-6, CORT and ACTH as well as neuronal apoptosis. HQD exhibits protective effects against 12C6+ radiation-induced bystander effects. The underlying mechanism may involve the promotion of the production of peripheral blood cells, inhibition of inflammatory factors and apoptosis, and regulation of endocrine hormones.
La irradiación con haz de iones pesados 12C6+ puede provocar efectos secundarios. Las citoquinas inflamatorias, las hormonas endocrinas y las proteínas apoptóticas pueden estar involucradas en los efectos secundarios inducidos por la irradiación 12C6+. Este estudio caracterizó los efectos y mecanismos protectores de la decocción de Huangqi (HQD) contra los efectos externos inducidos por la radiación 12C6+. Las ratas Wistar se dividieron aleatoriamente en grupos control, modelo de irradiación de iones pesados 12C6+ y grupos de dosis alta/media/baja de HQD. La tinción con HE evaluó los cambios patológicos del cerebro y el riñón. Se detectaron indicadores químicos de sangre periférica, así como factores inflamatorios y hormonas endocrinas. La apoptosis se midió con TUNEL. La expresión del antígeno nuclear de células en proliferación (PCNA) se determinó mediante PCR en tiempo real y transferencia Western blot. La irradiación indujo daños patológicos en los tejidos cerebrales y renales. Después de la irradiación, disminuyó el número de glóbulos blancos (WBC) y monocitos, y la expresión de interleucina (IL)-2, hormona liberadora de corticotropina (CRH) y PCNA. El daño estuvo acompañado por una mayor expresión de IL-1β, IL-6, corticosterona (CORT) y hormona adrenocorticotrópica (ACTH), así como un aumento de la apoptosis neuronal. Estas alteraciones fueron indicativas de efectos inducidos por la radiación. La administración de HQD atenuó el daño patológico a los tejidos cerebrales y renales, y aumentó el número de leucocitos y monocitos, así como la expresión de IL-2, CRH y PCNA. También disminuyó la expresión de IL-1β, IL-6, CORT y ACTH, así como la apoptosis neuronal. HQD exhibe mecanismos protectores contra los efectos externos inducidos por la radiación 12C6+. El mecanismo subyacente puede implicar la promoción de la producción de células sanguíneas periféricas, la inhibición de factores inflamatorios y la apoptosis y la regulación de hormonas endocrinas.
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Animais , Feminino , Ratos , Medicamentos de Ervas Chinesas , Substâncias Protetoras/administração & dosagem , Íons Pesados/efeitos adversos , Scutellaria baicalensis/química , Encéfalo/efeitos dos fármacos , Encéfalo/efeitos da radiação , Hormônio Liberador da Corticotropina , Ensaio de Imunoadsorção Enzimática , Ratos Wistar , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Hormônio Adrenocorticotrópico , Antígeno Nuclear de Célula em Proliferação , Sistema Endócrino/efeitos dos fármacos , Sistema Endócrino/efeitos da radiação , Fatores Imunológicos/antagonistas & inibidores , Rim/efeitos dos fármacos , Rim/efeitos da radiaçãoRESUMO
The high rate of deaths around the world from noncommunicable diseases (NCDs) (70%) is a consequence of a poor diet lacking in nutrients and is linked to lifestyle and environmental conditions that together trigger predisposing factors. NCDs have increased 9.8% of public health spending worldwide, which has been increasing since 2000. Hence, international organizations such as the WHO, the Pan American Health Organization, and the Food and Agriculture Organization of the United Nations have been developing strategic plans to implement government and economic policies to strengthen programs in favor of food security and nutrition. A systematic review is presented to document an analysis of the origin and characteristics of obesity, cardiovascular disease, chronic respiratory diseases, diabetes, and cancers affecting a large part of the world's population. This review proposes a scientifically based report of functional foods including fruits, vegetables, grains, and plants, and how their bioactive compounds called nutraceuticals-when consumed as part of a diet-benefit in the prevention and treatment of NCDs from an early age. Multifactorial aspects of NCDs, such as culture and eating habits, are limitations to consider from the clinical, nutritional, and biochemical points of view of everyone who suffers from them.
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BACKGROUND: Deeper understanding on the risk factors and seeking potential predicted biomarkers for prognosis of total hip arthroplasty (THA) patients are of great significance. Limited researches focused the correlation between high mobility group box protein-1 (HMGB1) and the prognosis of THA patients. OBJECTIVE: The objective of this study was to investigate the role of HMGB1 and inflammatory factors in patients underwent total hip arthroplasty (THA). METHODS: The present prospective study enrolled 208 THA patients who went to our hospital during January 2020 to January 2022. Serum levels of HMGB1, C-reactive protein (CRP), interleukin-1b (IL-1ß), and IL-6 were detected at the admission, 1 day, 3 days, 7 days, 30 days, and 90 days after surgery. The levels of Harris score, Fugl-Meyer, 36-item short-form health survey (SF-36), and Pittsburgh sleep quality index (PSQI) were detected on 90 days after surgery in two groups. Receiver operating characteristic curve (ROC) was performed for analyzing the diagnostic value of HMGB1 and logistic regression model was used for identifying the risk factor for poor prognosis of THA patients. RESULTS: Serum levels of HMGB1 and inflammatory factors increased after surgery compared with the baselines. A positive correlation was found between HMGB1 and CRP on 1 day after surgery, and positive correlations were found among HMGB1, IL-1ß, and IL-6 on 3 day after surgery. Besides, low HMGB1 reduced the incidence of post-operative complications and improved prognosis of THA patients. CONCLUSION: Serum HMGB1 was correlated with inflammatory factors and the prognosis of THA patients.
OBJETIVO: Profundizar la comprensión de los factores de riesgo y buscar predecir biomarcadores potenciales para el pronóstico de pacientes con reemplazo total de cadera es de gran importancia. Los estudios limitados se han centrado en la correlación entre la nhigh mobility group box 1 protein (HMGB1) y el pronóstico en pacientes con artroplastia total de cadera. Investigar el papel de la HMGB1 sérica y los factores inflamatorios en pacientes sometidos a artroplastia total de cadera. MÉTODO: Estudio prospectivo que incluyó 208 pacientes con artroplastia total de cadera que acudieron a nuestro hospital. Los niveles de puntuación de Harris, Fugl-Meyer, encuesta de salud de formato corto de 36 ítems (SF-36) e índice de calidad del sueño de Pittsburgh (PSQI) se determinaron 90 días después de la cirugía en dos grupos. Se realizó la curva característica operativa del receptor (ROC) para analizar el valor diagnóstico de HMGB1 y se utilizó un modelo de regresión logística para identificar el factor de riesgo para mal pronóstico de los pacientes con artroplastia total de cadera. RESULTADOS: Las concentraciones séricas de HMGB1 y los factores inflamatorios aumentaron después de la cirugía en comparación con los valores iniciales. Se encontró una correlación positiva entre la HMGB1 y la proteína C reactiva 1 día después de la cirugía, y correlaciones positivas entre la HMGB1 y las interleucinas 1b y 6 a los 3 días de la cirugía. CONCLUSIONES: La HMGB1 sérica se correlacionó con los factores inflamatorios y con el pronóstico de los pacientes con artroplastia total de cadera.
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Artroplastia de Quadril , Proteína HMGB1 , Humanos , Interleucina-6 , Estudos Prospectivos , Proteína C-ReativaRESUMO
OBJECTIVES: This study aimed to investigate the efficacy of ultrasound-guided Percutaneous Transhepatic Biliary Drainage (PTCD) for the treatment of Acute Obstructive Suppurative Cholangitis (AOSC) combined with septic shock due to choledocholithiasis, and its effect on inflammatory factors. METHODS: Clinical data of 86 patients with AOSC and septic shock admitted to our hospital between January 2019 and May 2021 were retrospectively analyzed and grouped according to different treatment methods. Among them, 43 patients who underwent Endoscopic Retrograde Cholangiopancreatography (ERCP) and Endoscopic Nasobiliary Drainage (ENBD) were included in the Control Group (CNG), and 43 patients who underwent ultrasound-guided PTCD were included in the Study Group (SG). RESULTS: The total effective rate in the SG (88.37%) was higher than that in the CNG (69.77%) (p < 0.05); after surgery, the serum inflammatory factors PCT, IL-6, TNF-α, CRP levels, liver function indicators such as TBIL, DBIL, AST, ALT levels, and stress response indicators including NPY, PGE2, 5-HT levels were reduced, and were lower in the SG than in the CNG (p < 0.05); postoperatively, CD3+, CD4+, and CD4+/CD8+ levels in the CNG were significantly lower than those before surgery (p < 0.05); Postoperatively, CD3+, CD4+, and CD4+/CD8+ levels in the SG were significantly higher than those in the CNG (p < 0.05); and the complication rate in the SG (6.98%) was lower than that in the CNG (25.58%) (p < 0.05). CONCLUSIONS: Ultrasound-guided PTCD for AOSC combined with septic shock can facilitate the recovery of liver and immune functions with a low complication rate.
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Colangite , Choque Séptico , Humanos , Choque Séptico/complicações , Choque Séptico/terapia , Estudos Retrospectivos , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Colangite/cirurgia , Colangite/complicações , Supuração/complicações , Drenagem/efeitos adversos , Drenagem/métodos , Ultrassonografia de IntervençãoRESUMO
Abstract Objectives This study aimed to investigate the efficacy of ultrasound-guided Percutaneous Transhepatic Biliary Drainage (PTCD) for the treatment of Acute Obstructive Suppurative Cholangitis (AOSC) combined with septic shock due to choledocholithiasis, and its effect on inflammatory factors. Methods Clinical data of 86 patients with AOSC and septic shock admitted to our hospital between January 2019 and May 2021 were retrospectively analyzed and grouped according to different treatment methods. Among them, 43 patients who underwent Endoscopic Retrograde Cholangiopancreatography (ERCP) and Endoscopic Nasobiliary Drainage (ENBD) were included in the Control Group (CNG), and 43 patients who underwent ultrasound-guided PTCD were included in the Study Group (SG). Results The total effective rate in the SG (88.37%) was higher than that in the CNG (69.77%) (p <0.05); after surgery, the serum inflammatory factors PCT, IL-6, TNF-α, CRP levels, liver function indicators such as TBIL, DBIL, AST, ALT levels, and stress response indicators including NPY, PGE2, 5-HT levels were reduced, and were lower in the SG than in the CNG (p <0.05); postoperatively, CD3+, CD4+, and CD4+/CD8+ levels in the CNG were significantly lower than those before surgery (p <0.05); Postoperatively, CD3+, CD4+, and CD4+/CD8+ levels in the SG were significantly higher than those in the CNG (p <0.05); and the complication rate in the SG (6.98%) was lower than that in the CNG (25.58%) (p <0.05). Conclusions Ultrasound-guided PTCD for AOSC combined with septic shock can facilitate the recovery of liver and immune functions with a low complication rate.
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Abstract The present study was aimed to investigate the clinical significance of methyl-CpG binding protein 2 (MECP2) in patients with postherpetic neuralgia (PHN). This prospective case control study enrolled 319 cases of PHN patients from April 2017~December 2019. The patients' sleep quality and quality of life were evaluated using the Pittsburgh sleep quality score and the SF- 36 scale, respectively. The serum levels of MECP2, CRP, IL -6 and TNF-α were tested using enzyme linked immunosorbent assay (ELISA). The pain condition of the patients was evaluated using the visual analogue scale (VAS). The levels of MECP2 were significantly increased in PHN patients compared with the patients without PHN. Serum MECP2 levels were the highest in patients with severe pain, and were the lowest in patients with mild pain. Similarly, the frequency of severe pain in patients with low expression of MECP2 was significantly lower than the patients with higher MECP2 expression. Besides, serum levels of inflammatory factors CRP, IL -6 and TNF-α were markedly increased in PHN patients, which were also increased with the increase of the severity of pain. CRP, IL -6 and TNF-α were positively correlated with serum levels of MECP2 in PHN patients. Before the study, patients with lower MECP2 levels showed a significantly higher SF-36 score and lower Pittsburgh and VAS scores than patients with higher levels of MECP2. However, after one month, no significant difference was found between the patients. ROC curve showed MECP2 had the potential as a diagnostic biomarker for PHN. In conclusion, higher serum MECP2 levels are associated with a more severe pain condition and increased release of inflammatory factors.
Resumen El objetivo de este estudio fue investigar la importancia clínica de la MECP2 en pacientes con neuralgia posherpética (NPH). Este estudio observacional prospectivo incluyó 319 pacientes con NPH entre abril de 2017 y diciembre de 2019. La calidad del sueño y la calidad de vida de los pacientes se evaluaron con la escala de calidad del sueño de Pittsburgh y la escala SF - 36, respectivamente. Los niveles séricos de MECP2, PCR, IL -6 y TNF-α fueron determinados por ELISA. Se utilizó la escala visual analógica (EVA) para evaluar la intensidad del dolor. Los niveles de MECP2 en pacientes con NPH aumentaron significativamente en comparación con los pacientes sin NPH. El nivel sérico de MECP2 fue más alto en pacientes con dolor grave y el más bajo en pacientes con dolor leve. Además, la incidencia de dolor grave en pacientes con baja expresión de MECP2 fue significativamente menor que en pacientes con alta expresión de MECP2. Además, los niveles séricos de PCR, IL -6 y TNF-α aumentaron significativamente en pacientes con NPH, y se incrementaron con el aumento del grado de dolor. Los niveles séricos de PCR, IL -6 y TNF-α en pacientes con NPH se correlacionaron positivamente con los niveles séricos de MECP2. Antes del estudio, los pacientes con niveles más bajos de MECP2 tenían puntuaciones significativamente más altas de SF - 36, y puntuaciones más bajas de Pittsburgh y EVA que los pacientes con niveles más altos de MECP2. Sin embargo, no se encontraron diferencias significativas entre los pacientes un mes después. Las curvas ROC mostraron que la MECP2 podría ser un biomarcador de diagnóstico para la NPH. En general, los niveles séricos más altos de la MECP2 se asociaron con condiciones de dolor más graves y un aumento de la liberación de factores inflamatorios.
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BACKGROUND: Emerging evidence indicates the important role of herbal medicine for neuroinflammation, which is closely associated with neurodegenerative diseases. OBJECTIVE: To clarify the characteristics and primary mechanisms of action of the traditional herbal medicine Daphne kiusiana var. atrocaulis (Rehd.) F. Maekawa in neuroinflammation by phytochemistry and bioassays using both in vitro and in vivo assays. METHODS: The chemical composition of D. kiusiana var. atrocaulis was clarified using multiple chromatography technologies and spectroscopic analysis. The anti-neuroinflammatory effects of the identified components were evaluated in LPS-induced BV-2 cells by monitoring the production of nitric oxide. C57BL/6 mice were used to construct a neuroinflammatory model by injecting LPS into the lateral ventricle of the brain. The most promising component was evaluated in vivo by measuring the number of Iba-1 cells and expression of inflammatory factors. Furthermore, the anti-neuroinflammatory mechanism involved in the activation of the NF-κB pathway was investigated using western blot and immunofluorescence. RESULTS: Thirty-two constituents (1-32), including five new compounds, were successfully identified from D. kiusiana var. atrocaulis. Compounds 3, 5, 12-15, and 20 (IC50 values from 5.41 to 57.27 µM) could considerably inhibit the LPS-induced production of NO in BV-2 cells, displaying stronger anti-neuroinflammatory activities than that of minocycline (IC50 = 67.08 µM). The concentration of the most potential compound 13 (IC50 5.41 µM) was 5.4% of the ethyl acetate fraction. Acutissimalignan B (13) could reduce the mRNA expression of iNOs, TNF-α, IL-1ß, and IL-6, inhibit the phosphorylation of IκBα, and inhibit the nuclear translocation of NK-κB p65 in BV-2 cells induced by LPS. Moreover, in the LPS-induced mouse model, compound 13 was found to exert anti-neuroinflammatory activity by attenuating the activation of microglia in the cortex and hippocampus, repressing the phosphorylation of IκBα, inhibiting the nuclear translocation of NK-κB p65, and decreasing the mRNA expression of iNOs, TNF-α, IL-1ß, and IL-6 in the cortex. CONCLUSION: We found that D. kiusiana var. atrocaulis had an inhibitory activity on neuroinflammation. In addition, the main active component (-)-acutissimalignan B (13) showed anti-neuroinflammatory effects in both in vivo and in vitro assays. Its mechanism of action may be associated with the inhibition of the NF-κB signaling pathway. Our current findings provide new information on D. kiusiana var. atrocaulis in the treatment of neuroinflammation.
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Anti-Inflamatórios não Esteroides/farmacologia , Daphne/química , Inflamação/tratamento farmacológico , Lignanas/farmacologia , NF-kappa B/metabolismo , Animais , Anti-Inflamatórios não Esteroides/química , Avaliação Pré-Clínica de Medicamentos , Inflamação/metabolismo , Inflamação/patologia , Lignanas/química , Lipopolissacarídeos/toxicidade , Masculino , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/patologia , Inibidor de NF-kappaB alfa/genética , Inibidor de NF-kappaB alfa/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Preparações de Plantas/química , Preparações de Plantas/farmacologia , Transdução de Sinais/efeitos dos fármacosRESUMO
H1N1 virus-induced excessive inflammatory response contributes to severe disease and high mortality rates. There is currently no effective strategy against virus infection in lung. The present study evaluated the protective roles of a natural compound, lapiferin, in H1N1 virus-induced pulmonary inflammation in mice and in cultured human bronchial epithelial cells. Initially, Balb/C mice were grouped as Control, H1N1 infection (intranasally infected with 500 plaque-forming units of H1N1 virus), lapiferin (10 mg/kg), and H1N1+lapiferin (n=10/group). Lung histology, expression of inflammatory factors, and survival rates were assessed after 14 days of exposure. Administration of lapiferin significantly alleviated the virus-induced inflammatory infiltrate in lung tissues. Major pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, were decreased at both mRNA and protein levels by lapiferin administration in the lung homogenate. Lapiferin also reduced inflammatory cell numbers in bronchoalveolar fluid. Mechanistically, lapiferin suppressed the transcriptional activity and protein expression of NF-κB p65, causing inhibition on NF-κB signaling. Pre-incubation of human bronchial epithelial cells with an NF-κB signaling specific activator, ceruletide, significantly blunted lapiferin-mediated inhibition of pro-inflammatory cytokines secretion in an air-liquid-interface cell culture experiment. Activation of NF-κB signaling also blunted lapiferin-ameliorated inflammatory infiltrate in lungs. These results suggested that lapiferin was a potent natural compound that served as a therapeutic agent for virus infection in the lung.
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Humanos , Animais , Coelhos , Pneumonia , Sesquiterpenos/farmacologia , NF-kappa B/metabolismo , Substâncias Protetoras/farmacologia , Vírus da Influenza A Subtipo H1N1 , Transdução de Sinais , Citocinas , InflamaçãoRESUMO
INTRODUCTION AND OBJECTIVES: Acute liver failure (ALF) is a severe disease which is associated with a high mortality rate. As mild hypothermia has been shown to have protective effects on the brain, this study aimed to determine whether it also provides protection to the liver in rats with ALF and to explore its underlying mechanism. MATERIALS AND METHODS: In total, 72 rats were divided into 3 groups: control group (CG, treated with normal saline), normothermia group (NG, treated with d-galactosamine and lipopolysaccharide; d-GalN/LPS), and mild hypothermia group (MHG, treated with d-GalN/LPS and kept in a state of mild hypothermia, defined as an anal temperature of 32-35°C). The rats were examined at 4, 8, and 12h after treatment. RESULTS: Mild hypothermia treatment significantly reduced serum alanine transaminase and aspartate transaminase levels and improved the liver condition of rats with d-GalN/LPS-induced ALF at 12h. Serum tumor necrosis factor-alpha levels were significantly lower in the MHG than in the NG at 4h, but no significant differences were observed in the interleukin-10 levels between the NG and MHG at any time. The serum and hepatic levels of high mobility group box 1 were significantly lower in the MHG than in the NG at 8 and 12h. The protein expression levels of cytochrome C and cleaved-caspase 3 in hepatic tissues were significantly lower in the MHG than in the NG at 8h. CONCLUSION: Mild hypothermia improved the liver conditions of rats with ALF via its anti-inflammatory and anti-apoptotic effects.
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Hipotermia Induzida/métodos , Falência Hepática Aguda/terapia , Fígado/patologia , Alanina Transaminase/sangue , Animais , Apoptose , Aspartato Aminotransferases/sangue , Biomarcadores/metabolismo , Temperatura Corporal , Modelos Animais de Doenças , Feminino , Interleucinas/sangue , Fígado/metabolismo , Falência Hepática Aguda/metabolismo , Falência Hepática Aguda/patologia , Ratos , Ratos Sprague-DawleyRESUMO
Endometriosis is a gynecological disorder characterized by the growth of endometrial tissue (glands and stroma) outside the uterus, mainly in the peritoneal cavity, ovaries, and intestines. This condition shows estrogen dependency and progesterone resistance, and it has been associated with chronic inflammation, severe pain, and infertility, which negatively affect the quality of life in reproductive women. The molecular mechanisms involved in the pathogenesis of endometriosis are not completely understood; however, inflammation plays a key role in the pathophysiology of the disease, mainly by altering the function of immune cells (macrophages, natural killer, and T cells) and increasing levels of pro-inflammatory mediators in the peritoneal cavity, endometrium, and blood. These immune alterations inhibit apoptotic pathways and promote adhesion and proliferation of endometriotic cells, as well as angiogenesis and neurogenesis in endometriotic lesions. It has been demonstrated that hormonal alterations in endometriosis are related to the inflammatory unbalance in this disease. Particularly, steroid hormones (mainly estradiol) promote the expression and release of pro-inflammatory factors. Excessive inflammation in endometriosis contributes to changes of hormonal regulation by modulating sex steroid receptors expression and increasing aromatase activity. In addition, dysregulation of the inflammasome pathway, mediated by an alteration of cellular responses to steroid hormones, participates in disease progression through preventing cell death, promoting adhesion, invasion, and cell proliferation. Furthermore, inflammation is involved in endometriosis-associated infertility, which alters endometrium receptivity by impairing biochemical responses and decidualization. The purpose of this review is to present current research about the role of inflammasome in the pathogenesis of endometriosis as well as the molecular role of sex hormones in the inflammatory responses in endometriosis.
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OBJECTIVES: The aim of this study was to evaluate systemic inflammatory factors and their relation to success or failure in a spontaneous ventilation test. METHODS: This cross-sectional study included a sample of 54 adult patients. Demographic data and clinical parameters were collected, and blood samples were collected in the first minute of the spontaneous ventilation test to evaluate interleukin (IL)-1β, IL-6, IL-8, and IL-10, tumour necrosis factor alpha (TNFα) and C-reactive protein. RESULTS: Patients who experienced extubation failure presented a lower rapid shallow breathing index than those who passed, and these patients also showed a significant increase in C-reactive protein 48 hours after extubation. We observed, moreover, that each unit increase in inflammatory factors led to a higher risk of spontaneous ventilation test failure, with a risk of 2.27 (1.001 - 4.60, p=0.049) for TNFα, 2.23 (1.06 - 6.54, p=0.037) for IL-6, 2.66 (1.06 - 6.70, p=0.037) for IL-8 and 2.08 (1.01 - 4.31, p=0.04) for IL-10, and the rapid shallow breathing index was correlated with IL-1 (r=-0.51, p=0.04). CONCLUSIONS: C-reactive protein is increased in patients who fail the spontaneous ventilation test, and increased ILs are associated with a greater prevalence of failure in this process; the rapid shallow breathing index may not be effective in patients who present systemic inflammation.
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Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Desmame do Respirador , Inflamação/sangue , Testes de Função Respiratória , Estresse Fisiológico/fisiologia , Proteína C-Reativa/análise , Estudos Transversais , Estudos Prospectivos , Interleucinas/sangue , Fator de Necrose Tumoral alfa/sangueRESUMO
Multipotent mesenchymal stromal cells (MSC) are imbued with an immunosuppressive phenotype that extends to several immune system cells. In this study, we evaluated how distinct Toll-like receptor (TLR) agonists impact immunosuppressive properties of bone marrow (BM)-MSC and explored the potential mechanisms involved. We show that TLR4 stimulation by lipopolysaccharide (LPS) restricted the ability of MSC to suppress the proliferation of T lymphocytes, increasing the gene expression of interleukin (IL)-1ß and IL-6. In contrast, stimulation of TLR9 by DSP30 induced proliferation and the suppressive potential of BM-MSC, coinciding with reducing tumor necrosis factor (TNF)-α expression, increased expression of transforming growth factor (TGF)-ß1, increased percentages of BM-MSC double positive for the ectonucleotidases CD39+CD73+ and adenosine levels. Importantly, following simultaneous stimulation with LPS and DSP30, BM-MSC's ability to suppress T lymphocyte proliferation was comparable with that of non-stimulated BM-MSC levels. Moreover, stimulation of BM-MSC with LPS reduced significantly the gene expression levels, on co-cultured T lymphocyte, of IL-10 and interferon (IFN)γ, a cytokine with potential to enhance the immunosuppression mediated by MSC and ameliorate the clinical outcome of patients with graft-versus-host disease (GVHD). Altogether, our findings reiterate the harmful effects of LPS on MSC immunosuppression, besides indicating that DSP30 could provide a protective effect against LPS circulating in the blood of GVHD patients who receive BM-MSC infusions, ensuring a more predictable immunosuppressive effect. The novel effects and potential mechanisms following the stimulation of BM-MSC by DSP30 might impact their clinical use, by allowing the derivation of optimal "licensing" protocols for obtaining therapeutically efficient MSC.
Assuntos
Adenosina/farmacologia , Imunossupressores/farmacologia , Lipopolissacarídeos/farmacologia , Células-Tronco Mesenquimais/citologia , Antígenos CD/metabolismo , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Técnicas de Cocultura , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Terapia de Imunossupressão , Ligantes , Ativação Linfocitária/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Oligonucleotídeos/farmacologia , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Receptores Toll-Like/metabolismoRESUMO
We evaluated the effect of puerarin on spatial learning and memory ability of mice with chronic alcohol poisoning. A total of 30 male C57BL/6 mice were randomly divided into model, puerarin, and control groups (n=10 each). The model group received 60% (v/v) ethanol by intragastric administration followed by intraperitoneal injection of normal saline 30 min later. The puerarin group received intragastric 60% ethanol followed by intraperitoneal puerarin 30 min later, and the control group received intragastric saline followed by intraperitoneal saline. Six weeks after treatment, the Morris water maze and Tru Scan behavioral tests and immunofluorescence staining of cerebral cortex and hippocampal neurons (by Neu-N) and microglia (by Ib1) were conducted. Glutamic acid (Glu) and gamma amino butyric acid (GABA) in the cortex and hippocampus were assayed by high-performance liquid chromatography (HPLC), and tumor necrosis factor (TNF)-α and interleukin (IL)-1β were determined by ELISA. Compared with mice in the control group, escape latency and distance were prolonged, and spontaneous movement distance was shortened (P<0.05) by puerarin. The number of microglia was increased in both the cortex and hippocampal dentate gyrus (P<0.01), and neurons were reduced only in the hippocampal dentate gyrus (P<0.01) in puerarin-treated mice. In the model group, Glu and GABA levels decreased (P<0.05), and Glu/GABA, TNF-α, and IL-1β increased (P<0.01) with puerarin treatment, returning to near normal levels. In conclusion, puerarin protected against the effects of chronic alcohol poisoning on spatial learning and memory ability primarily because of anti-inflammatory activity and regulation of the balance of Glu and GABA.