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Apigenin is a flavonoid of low toxicity and multiple beneficial bioactivities, including the properties of antitumor, antioxidant, anti-inflammatory, and antiviral activities. However, the effects of Apigenin on influenza virus infection remain poorly understood. Thus, the aim of this study is to investigate the effect of Apigenin on influenza A virus (IAV)-induced inflammation and viral replication. This study demonstrated that Apigenin treatment significantly suppressed IAV-induced upregulation of retinoic acid-inducible gene-I (RIG-I) expression, as well as the production of proinflammatory cytokines and interferons (IFN-ß and IFN-λ1). Meanwhile, Apigenin also protected cells from IAV-induced cell death. In addition, Apigenin specifically inhibited the activation of RIG-I signaling via promoting the ubiquitin-mediated degradation of RIG-I, which may cause by the disrupting its interaction with heat shock protein 90α. Interestingly, instead of enhancing viral replication due to the inhibitory effects of Apigenin on the activation of RIG-I and expression of IFNs, Apigenin inhibited IAV replication in vitro. Further study demonstrated that Apigenin inhibited the influenza viral neuraminidase (NA) activity. Thus, Apigenin may serve as a promising supplementary approach for treatment of influenza because it protected cells from IAV-induced cell death and inhibited viral NA activity to suppress viral replication.
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Context: Oxymatrine (OMT) has various pharmacological effects, including immune reaction regulation, anti-inflammation and anti-hypersensitive reaction. Objective: This is the first report to investigate the molecular mechanism of OMT function in l-arginine (Arg)-induced acute pancreatitis (AP) involving intestinal injury. Materials and methods: Rat pancreatic AR42J and small intestinal IEC-6 cells were treated with Arg (200-800 µM) for 48 h plus OMT (4 mg/mL) treatment. Thirty adult Wistar rats were randomly assigned to control (saline), AP (i.p. of 250 mg/100 g body weight Arg) and OMT (i.p. injection of 50 mg/kg b.w. OMT every 6 h following Arg). Both cells and rats were harvested at 48 h. Results: Arg-induced cell proliferation in both rats AR42J (EC50 633.9 ± 31.4 µM) and IEC-6 cells (EC50 571.3 ± 40.4 µM) in a dose-dependent manner, which was significantly inhibited by OMT (4 mg/mL). Meanwhile, Arg (600 µM) induced expression of proinflammatory cytokines (TNF-α, IL-6, IL-1ß, NF-κB, IL-17A/IL-17F and IFN-γ) and activation of p-p38/p-ERK in vitro, which was reversed by OMT. In vivo, OMT (50 mg/kg) inhibited 250 mg/100 g of Arg-induced AP involving intestinal injury, including inhibiting Arg-induced inflammatory in pancreas and intestine, inhibiting Arg-induced increase of TNF-α, IL-6, IL-1ß, NF-κB and p-p38/p-ERK-MAPK signalling, and inhibiting Arg-induced increase of IL-17A/IL-17F, IFN-γ, ROR-γt and T-bet. Meanwhile, OMT inhibited Arg-induced expression of CD44 and CD55 in intestinal injury. Discussion and conclusions: OMT protects against Arg-induced AP involving intestinal injury via regulating Th1/Th17 cytokines and MAPK/NF-κB signalling, which is a promising therapeutic agent in clinics.
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Alcaloides/farmacología , Antiinflamatorios/farmacología , Íleon/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , FN-kappa B/metabolismo , Pancreatitis/prevención & control , Quinolizinas/farmacología , Células TH1/efectos de los fármacos , Células Th17/efectos de los fármacos , Enfermedad Aguda , Animales , Arginina , Línea Celular , Proliferación Celular/efectos de los fármacos , Citocinas/inmunología , Modelos Animales de Enfermedad , Íleon/inmunología , Íleon/patología , Masculino , Pancreatitis/inmunología , Pancreatitis/patología , Ratas Wistar , Células TH1/inmunología , Células Th17/inmunologíaRESUMEN
Matrine, one of the main active components of extracts from the dry roots of Sophora flavescens, has potent anti-tumor activity in vitro and in vivo. Here, we investigated the apoptosis in matrine-treated retinoblastoma cells. The results showed that matrine could inhibit cell proliferation and induce apoptosis in a dose- and time-dependent manner. Further investigation revealed that a disruption of mitochondrial transmembrane potential and an up-regulation of reactive oxygen species in matrine-treated cells. By western blot analysis, we found that the up-regulation of cleaved Apaf-1, cleaved caspase-3, cleaved caspase-9, cleaved caspase-7, Bax/Bcl-2, varying with different concentration of matrine. These protein interactions may play a pivotal role in the regulation of apoptosis. Taken together, these results overall indicate that matrine could be used as an effective anti-tumor agent in therapy of retinoblastoma targets the caspase-dependent signaling pathway.
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Alcaloides/farmacología , Apoptosis/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Quinolizinas/farmacología , Retinoblastoma/metabolismo , Transducción de Señal/efectos de los fármacos , Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Caspasas/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Retinoblastoma/genética , MatrinasRESUMEN
The objective of the present study was to explore the effects of maternal iodine excess during pregnancy on infants' neurodevelopment and physical development. A total of 143 mother-child pairs were enrolled in this cohort study. Maternal blood samples were collected during the obstetric examination. A mother-child questionnaire survey was conducted, and infants' blood samples were collected during the newborn physical examination. Infants' single-spot urine samples were collected, and intellectual, motor, and physical development were assessed at 2 months of age. The median (IQR) maternal serum iodine concentrations (SICs) in the first, second, and third trimesters of pregnancy were 91.2 (74.4, 102.2) µg/L, 81.2 (70.6, 94.8) µg/L, and 82.0 (68.9, 100.3) µg/L, respectively. In the first trimester of pregnancy, infants' psychomotor developmental index (PDI), body mass index (BMI) and weight-for-length Z score (WLZ) were higher with maternal suitable SIC (40 ~ 92 µg/L) than with maternal excess SIC (P < 0.05). Infants' PDI, BMI, weight-for-age Z score (WAZ) and WLZ were negatively correlated with maternal SIC (P < 0.05). Maternal excess SIC had a slightly negative effect on infants' MDI (OR = 1.304, P = 0.035, 95% CI = 1.019 ~ 1.668), PDI (OR = 1.124, P = 0.001, 95% CI = 1.052 ~ 1.200) and BMI (OR = 0.790, P = 0.005, 95% CI = 0.669 ~ 0.933). In the third trimester, infants' length-for-age Z score (LAZ) was higher with maternal high SIC (> 92 µg/L) (P = 0.015), and maternal SIC was positively correlated with infants' urine iodine concentration (UIC) (P = 0.026). Maternal iodine excess in the first trimester had a slightly negative effect on infants' intellectual, motor, and physical development. In the third trimester, maternal iodine excess only may have a positive impact on infants' height. Additionally, maternal iodine status was closely related to infants' iodine status.
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Yodo , Lactante , Embarazo , Recién Nacido , Femenino , Humanos , Estudios de Cohortes , Yodo/orina , Encuestas y Cuestionarios , Índice de Masa Corporal , Estado NutricionalRESUMEN
PURPOSE: We aimed to investigate the role of peripheral blood mononuclear cell transportation from mother to baby in hepatitis B virus (HBV) intrauterine infection. METHODS: Thirty HBsAg-positive pregnant women in the second trimester and their aborted fetuses were included in this study. Enzyme-linked-immunosorbent-assay was utilized to detect HBsAg in the peripheral blood of pregnant women and the femoral vein blood of their aborted fetuses. HBV-DNA in serum and peripheral blood mononuclear cells (PBMC) and GSTM1 alleles of pregnant women and their aborted fetuses were detected by nested polymerase chain reaction (PCR) and seminested PCR, respectively. We also examined the location of placenta HBsAg and HBcAb using immunohistochemical staining. The expression of placenta HBV-DNA was detected by in situ hybridization. RESULTS: For the 30 aborted fetuses, the HBV intrauterine infection rate was 43.33%. The HBV-positive rates of HBsAg in peripheral blood, serum, and PBMC were 10% (3/30), 23.33% (7/30), and 33.33% (10/30), respectively. Maternal-fetal PBMC transport was significantly positively correlated with fetal PBMC HBV-DNA (P = 0.004). Meanwhile, the rates of HBV infection gradually decreased from the maternal side to the fetus side of placenta (decidual cells > trophoblastic cells > villous mesenchymal cells > villous capillary endothelial cells). However, no significant correlation between placenta HBV infection and HBV intrauterine infection was observed (P = 0.410). CONCLUSIONS: HBV intrauterine infection was primarily due to peripheral blood mononuclear cell maternal-fetal transportation in the second trimester in pregnant women.
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Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/aislamiento & purificación , Hepatitis B/transmisión , Transmisión Vertical de Enfermedad Infecciosa , Leucocitos Mononucleares/virología , Placenta/virología , Complicaciones Infecciosas del Embarazo/virología , Feto Abortado , Adulto , ADN Viral/análisis , Ensayo de Inmunoadsorción Enzimática , Femenino , Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/análisis , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/inmunología , Humanos , Inmunohistoquímica , Lactante , Recién Nacido , Leucocitos Mononucleares/inmunología , Intercambio Materno-Fetal , Madres , Placenta/química , Reacción en Cadena de la Polimerasa , Embarazo , Complicaciones Infecciosas del Embarazo/sangre , Segundo Trimestre del EmbarazoRESUMEN
The rise of bioinformatics based on computer medicine provides a new method to reveal the complex biological data. This experiment is to explore the impacts of lipopolysaccharide on fetal lung developmental maturity and expressions of lung surfactant protein B (SP-B) and lung surfactant protein C (SP-C) in rats with gestational diabetes mellitus (GDM), thereby discussing the mechanism of developmental disorders in rats. Forty-eight conceived female rats were experimental subjects. Twenty-eight rats were randomly selected to construct the GDM models. All conceived rats underwent section on the 21st day of pregnancy. The ultrastructure of alveolar type II epithelial cells and the morphology of lung tissue were observed under a microscope. The protein localization and expression of SP-B and SP-C were determined by immunohistochemistry; the protein levels of SP-B and SP-C were determined by Western blot. Blood glucose and body weight of the GDM group were higher than those of the control group; the number of alveoli and alveolar area in the GDM group was lower than those in the control group; the alveolar interval in the GDM group was significantly higher than that in the control group (P < 0.05). The average absorbance of SP-B and SP-C in fetal lung tissue was significantly lower in the GDM group than that in the control group (P < 0.01). Changes in fetal lung tissue structure of rats were related to SP-B and SP-C, which was one of the main factors that affected the maturation of fetal lung tissue.
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Diabetes Gestacional/metabolismo , Lipopolisacáridos/efectos adversos , Pulmón/embriología , Pulmón/patología , Péptidos/metabolismo , Proteína B Asociada a Surfactante Pulmonar/metabolismo , Animales , Peso Corporal , Estudios de Casos y Controles , Diabetes Gestacional/sangre , Diabetes Gestacional/genética , Modelos Animales de Enfermedad , Femenino , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Pulmón/efectos de los fármacos , Pulmón/ultraestructura , Masculino , Péptidos/genética , Embarazo , Proteína B Asociada a Surfactante Pulmonar/genética , Distribución Aleatoria , RatasRESUMEN
BACKGROUND: Carboxypeptidase A4 (CPA4), as a novel tumor biomarker, is prevalently observed in various cancers. However, the potential role of CPA4 in pancreatic cancer (PC), to our knowledge, has not been fully clarified. MATERIALS AND METHODS: We systematically explored the detailed function of CPA4 in epithelial to mesenchymal transition (EMT) stimulated PC in human clinical samples and in vitro. RESULTS: CPA4 was overexpressed in clinical PC samples that was positively related with tumor size (P=0.026), T stage (P=0.011), lymph-node metastasis (P=0.026) and a worse prognosis for PC patients (P=0.001). Interestingly, CPA4 was inversely correlated with E-cadherin (r=-0.372, P=0.003) in clinical samples and PC cell lines which cooperatively contributed to a worse prognosis (P=0.005) for PC patients. CPA4 overexpression enhanced EMT in AsPC-1 and Capan-2 cells, which promoted EMT-like cellular morphology and cell invasion and migration. Meanwhile, CPA4 overexpression activated EMT and PI3K-AKT-mTOR signaling, following with the downregulation of E-cadherin and ß-catenin, and the upregulation of N-cadherin, vimentin, p-PI3K (Tyr458), p-AKT (Ser473) and p-mTOR (Ser2448). However, PI3K inhibitor LY294002 reversed CPA4 overexpression-stimulated EMT in vitro. Moreover, CPA4 was co-immunoprecipitated with AKT in two PC cells with CPA4 high expression. Conversely, CPA4 silencing inhibited EMT in PANC-1 cells. CPA4 overexpression or silencing promoted or inhibited cell proliferation and drug resistance in Capan-2 and PANC-1 cells via regulating Bcl2/Bax and cleaved-caspase3 signaling. However, LY294002 reversed CPA4 overexpression-stimulated cell proliferation and drug resistance in vitro in Bcl2/Bax and caspase3-dependent apoptosis. CONCLUSION: CPA4 overexpression contributes to aggressive clinical stage of PC patients and promotes EMT in vitro via activation of PI3K-AKT-mTOR signaling.
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Congenital thyroid hypofunction can cause a variety of developmental disorders. Hippocampus is an important structure participating in the cognitive activities. Neural function damage is able to induce hippocampal neuron apoptosis. As a miRNA expressed specifically and abundantly in brain tissue, miR-124 has protective effect to neuron apoptosis caused by cerebral apoplexy. However, its role in neuron apoptosis caused by thyroid hypofunction is still unclear. The rats were divided into four groups including normal group, thyroid hypofunction group, miR-124 negative control group, and miR-124 mimics group. Propylthiouracil (50 mg/d) was injected to the stomach to the rats with 15 d pregnancy till the newborn rats were born. Inducing the thyroid hypofunction rat model and then injecting miR-124 mimics to ventricle. Serum TSH, FT3 and FT4 were detected to confirm the model. Immunohistochemistry was carried out to calculate neuron number. Tunel assay was used to detect neuron apoptosis. Western blot was applied to detect apoptosis related protein Caspase-3, Bcl-2 and Bax expression. After brain injection miR-124 mimics, hippocampal neuron number and morphology both improved in 15 d newborn mice compared with thyroid hypofunction group. Tunel staining found positive neurons reduced, which indicated that miR-124 can inhibit hippocampal neuron apoptosis in thyroid hypofunction rats. Further Western blot results revealed that apoptosis inhibition might be related to down-regulating activated Caspase-3 and Bax levels, and up-regulating tumor-suppressor gene Bcl-2 expression. MiR-124 can protect neuron apoptosis in thyroid hypofunction rat.
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Apoptosis , Hipotiroidismo Congénito/metabolismo , Hipocampo/metabolismo , MicroARNs/metabolismo , Neuronas/metabolismo , Animales , Animales Recién Nacidos , Proteínas Reguladoras de la Apoptosis/metabolismo , Hipotiroidismo Congénito/inducido químicamente , Hipotiroidismo Congénito/genética , Hipotiroidismo Congénito/patología , Modelos Animales de Enfermedad , Femenino , Edad Gestacional , Hipocampo/patología , MicroARNs/genética , Neuronas/patología , Embarazo , Efectos Tardíos de la Exposición Prenatal , Propiltiouracilo , Ratas Sprague-Dawley , Transducción de Señal , Hormonas Tiroideas/sangreRESUMEN
BACKGROUND: The human heart consists of several cell types with distinct lineage origins. Interactions between these cardiac progenitors are very important for heart formation. The muscle segment homeobox gene family plays a key role in the cell morphogenesis and growth, controlled cellular proliferation, differentiation, and apoptosis, but the relationships between the genetic abnormalities and CHD phenotypes still remain largely unknown. The aim of this work was to evaluate variations in MSX1 and MSX2 for their possible associations with CHD. METHODS: We sequenced the MSX1 and MSX2 genes for 300 Chinese Han CHD patients and 400 normal controls and identified the variations. The statistical analyses were conducted using Chi-Square Tests as implemented in SPSS (version 19.0). The Hardy-Weinberg equilibrium test of the population was carried out using the online software OEGE. RESULTS: Six variations rs4647952, rs2048152, rs4242182, rs61739543, rs111542301 and rs3087539 were identified in the MSX2 gene, but the genetic heterozygosity of those SNPs was very low. In contrast, the genetic heterozygosity of two variations rs3821949 near the 5'UTR and rs12532 within 3'UTR of the MSX1 gene was considerably high. Statistical analyses showed that rs3821949 and rs12532 were associated with the risk of CHD (specifically VSD). CONCLUSIONS: The SNPs rs3821949 and rs12532 in the MSX1 gene were associated with CHD in Chinese Han populations.
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Cardiopatías Congénitas/genética , Factor de Transcripción MSX1/genética , Polimorfismo de Nucleótido Simple , Adolescente , Adulto , Diferenciación Celular/genética , Niño , Preescolar , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Proteínas de Homeodominio/genética , Humanos , Lactante , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
The expression of major histocompatibility complex (MHC) on human neural stem cells (hNSCs) is tightly related to the fate of these cells in transplantation, therefore strategies to relieve rejection and promote graft survival are necessary to be applied. This study investigated the effect of carbamylated erythropoietin (CEPO) on MHC expression and differentiation of hNSCs with or without IFN-gamma incubation. Results showed that low levels of MHC molecules were expressed on hNSCs and increased by IFN-gamma. CEPO enhanced MHC-I antigens in both proliferative and differentiated hNSCs, but decreased MHC-II antigens in differentiated hNSCs and those cells exposed to IFN-gamma. Furthermore, CEPO promoted neural differentiation of hNSCs and outgrowth of neurites. Western blot analysis revealed activation of Stat3, Stat5 and Akt during these processes. These results suggest that CEPO may have immunoregulatory function in hNSCs besides its neuroprotection.