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BACKGROUND: Scutellarein, a widely studied ingredient of scutellaria herbs, has higher bioavailability and solubility than that of scutellarin. Although the scutellarein had been reported to modulate numerous biological functions, its ability in suppressing cardiac hypertrophy remains unclear. Hence, the present study attempted to investigate whether scutellarein played critical roles in preventing phenylephrine (PE)-induced cardiac hypertrophy. METHODS AND RESULTS: Immunocytochemistry (ICC) was employed for evaluating the morphology of the treated cardiomyocytes. Real-time PCR and western blot were respectively applied to assess the mRNA levels and protein expression of the relevant molecules. Bioinformatics analyses were carried out to investigate the potential mechanisms by which scutellarein modulated the PE-induced cardiac hypertrophy. The results showed that Scutellarein treatment significantly inhibited PE-induced increase in H9c2 and AC16 cardiomyocyte size. Besides, scutellarein treatment also dramatically suppressed the expression of the cardiac hypertrophic markers: ANP, BNP and ß-MHC. Furthermore, the effects of scutellarein on attenuating the cardiac hypertrophy might be mediated by suppressing the activity of TRAF2/NF-κB signaling pathway. CONCLUSIONS: Collectively, our data indicated that scutellarein could protect against PE-induced cardiac hypertrophy via regulating TRAF2/NF-κB signaling pathway using in vitro experiments.
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Apigenina , Cardiomegalia , FN-kappa B , Apigenina/farmacología , Cardiomegalia/tratamiento farmacológico , Cardiomegalia/metabolismo , Humanos , Miocitos Cardíacos/metabolismo , FN-kappa B/metabolismo , Transducción de Señal , Factor 2 Asociado a Receptor de TNF/metabolismo , Factor 2 Asociado a Receptor de TNF/farmacologíaRESUMEN
Angiotensin II (AII) has been well known to induce cardiomyocyte hypertrophy. Epigallocatechin-3-gallate (EGCG) is the main active component of green tea and it has been shown to exhibit strong cardioprotective potential, although the underlying molecular mechanisms remain unclear. In this study, we investigated the role and mechanism of EGCG in preventing AII-induced cardiomyocyte hypertrophy using rat H9c2 cardiomyocytes cells. Reactive oxygen species assay, cell size, and mRNA expression of cardiac hypertrophy markers ANP and BNP were assessed in response to AII treatment. In addition, expression of proteins involved in Hippo signaling pathway were determined by western blot analysis. We found that AII treatment resulted in significant upregulation of ANP and BNP expression levels and increase in H9c2 cell size, which were markedly attenuated by EGCG treatment. Furthermore, our results suggested that EGCG inhibited AII-induced cardiac hypertrophy via regulating the Hippo signaling pathway. Therefore, EGCG may be an effective agent for preventing cardiac hypertrophy.
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Cardiomegalia/prevención & control , Catequina/análogos & derivados , Miocitos Cardíacos/efectos de los fármacos , Proteínas Serina-Treonina Quinasas/metabolismo , Transducción de Señal/efectos de los fármacos , Angiotensina II , Animales , Factor Natriurético Atrial/genética , Factor Natriurético Atrial/metabolismo , Cardiomegalia/inducido químicamente , Cardiomegalia/genética , Catequina/química , Catequina/farmacología , Línea Celular , Regulación de la Expresión Génica/efectos de los fármacos , Estructura Molecular , Miocitos Cardíacos/citología , Miocitos Cardíacos/metabolismo , Péptido Natriurético Encefálico/genética , Péptido Natriurético Encefálico/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Ratas , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/genéticaRESUMEN
To provide theoretical support for the safety control of rectangular pipe jacking tunnels crossing an existing expressway, a method for predicting the surface settlement of a rectangular pipe jacking tunnel is proposed in this study. Therefore, based on the high approximation of the BP neural network to any function under the multiparameter input, the PSO-BP mixed prediction model of the ground subsidence of the ultrashallow buried large section rectangular pipe jacking tunnel is established by taking into account the adaptive mutation method, adopting the improved particle swarm optimization (IPSO) algorithm with adaptive inertia weight and mutation particles in the later stage to determine the optimal hyperparameters of the prediction model. Through the case study of an ultrashallow large cross-section rectangular pipe jacking tunnel, this algorithm is compared with the traditional algorithm and combined with field monitoring data for analysis and prediction. The prediction results show that compared with the traditional BP neural network prediction model, AWPSO-BP model and PWPSO-BP model, the improved PSO-BP mixed prediction model shows a more stable prediction effect when the change in surface subsidence is gentle and the concavity and convexity are large. The predicted subsidence value is close to the actual value, and the accuracy and robustness of the prediction are significantly improved.
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Irritable bowel syndrome (IBS) is a functional intestinal disorder without clear pathological mechanisms. Classical treatments for IBS are not always effective and are usually accompanied by side effects. Selenium-enriched Bifidobacterium longum DD98 (Se-B. longum DD98) is a selenized probiotic strain which has shown many beneficial effects on the gastrointestinal tract, but its effects on IBS and the underlying mechanism are unclear. This study aims to investigate the relieving effects of Se-B. longum DD98 on chronic unpredictable mild stress (CUMS)-induced IBS in mice. The model mice were treated with saline, B. longum DD98, or Se-B. longum DD98 while receiving CUMS. The results suggest that Se-B. longum DD98 significantly relieved the intestinal symptoms of IBS mice and reduced intestinal permeability and inflammation. The depression and anxiety-like behaviors of IBS mice were also improved by Se-B. longum DD98. In addition, the expression of serotonin (5-HT), γ-aminobutyric acid (GABA), neuropeptide Y (NPY), and brain-derived neurotrophic factor (BDNF), which are indicators closely related to mood and brain-gut axis, were up-regulated in mice treated with Se-B. longum DD98. Furthermore, the 16S rRNA sequencing study showed that Se-B. longum DD98 effectively restored the relative abundance of intestinal microbes (e.g., Lactobacillus, Desulfovibrio, Akkermansia) and regulated the impaired diversity of gut microbiota in IBS mice. These results suggest that Se-B. longum DD98 positively acts on the brain-gut axis by improving intestinal functions and regulating mood-associated behaviors and indicators of IBS mice. Therefore, this Se-enriched probiotic strain could be considered a promising candidate for the alleviation of CUMS-induced IBS.
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Bifidobacterium longum , Síndrome del Colon Irritable , Probióticos , Selenio , Ratones , Animales , Síndrome del Colon Irritable/microbiología , Bifidobacterium longum/metabolismo , Selenio/metabolismo , ARN Ribosómico 16S/metabolismo , Intestinos , Probióticos/farmacologíaRESUMEN
Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), is characterized as a chronic and recurrent inflammatory disease whose pathogenesis is still elusive. The gut microbiota exerts important and diverse effects on host physiology through maintaining immune balance and generating health-benefiting metabolites. Many studies have demonstrated that IBD is associated with disturbances in the composition and function of the gut microbiota. Both the abundance and diversity of gut microbiota are dramatically decreased in IBD patients. Furthermore, some particular classes of microbiota-derived metabolites, principally short-chain fatty acids, tryptophan, and its metabolites, and bile acids have also been implicated in the pathogenesis of IBD. In this review, we aim to define the disturbance of gut microbiota and the key classes of microbiota-derived metabolites in IBD pathogenesis. In addition, we also focus on scientific evidence on probiotics, not only on the molecular mechanisms underlying the beneficial effects of probiotics on IBD but also the challenges it faces in safe and appropriate application.
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Enfermedad de Crohn , Microbioma Gastrointestinal , Enfermedades Inflamatorias del Intestino , Microbiota , Probióticos , Humanos , Enfermedades Inflamatorias del Intestino/metabolismo , Microbioma Gastrointestinal/fisiología , Probióticos/uso terapéuticoRESUMEN
The pathogenesis of ulcerative colitis (UC) is complicated with impaired intestinal epithelial barrier and imbalanced gut microbiota. Both selenium and probiotics have shown effects in regulating intestinal flora and ameliorating UC. The objective of this study is to investigate the alleviating effects of Selenium-enriched Bifidobacterium longum DD98 (Se-B. longum DD98) on dextran sulfate sodium (DSS)-induced colitis in mice and explore the underlying mechanism. After treatment of B. longum DD98, Se-B. longum DD98, and sulfasalazine for 3 weeks, the disease severity of UC mice was decreased, with colon lengthened and pathological phenotype improved. The expression of pro-inflammatory cytokines and oxidative stress parameters were also decreased. Thus, Se-B. longum DD98 showed a stronger effect on relieving the aforementioned symptoms caused by DSS-induced colitis. Exploration of the potential mechanism demonstrated that Se-B. longum DD98 showed higher activities to suppress the inflammatory response by inhibiting the activation of the toll-like receptor 4 (TLR4), compared to B. longum DD98 and sulfasalazine. Se-B. longum DD98 also significantly improved the intestinal barrier integrity by increasing the expression of tight junction proteins including ZO-1 and occludin. 16S rDNA sequencing analyses showed that Se-B. longum DD98 improved the diversity of the intestinal flora and promoted the abundance of health-benefiting taxa including Lachnospiraceae, Lactobacillaceae, and Prevotellaceae in family level. In conclusion, compared to B. longum DD98 and sulfasalazine, Se-B. longum DD98 showed stronger therapeutic effects on DSS-induced colitis in mice and might be a promising candidate for the treatment of UC.
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AIMS: The aims of this study were to explore factors that associated with gestational diabetes mellitus (GDM), and to determine the relationship between early maternal HbA1c levels and adverse fetal or neonatal events, and to determine an optimal maternal glucose testing method in order to decrease the potential health risk for their offspring. METHODS: From December 2015 to May 2016, a total of 6744 pregnant women were enrolled from Shanghai First Maternal and Infant Hospital affiliated to Tongji University prospectively in the nested case-control study. Each GDM case was matched with a healthy pregnant woman and followed up. Outcome analyses were conducted between GDM case and control groups, as well as elevated and normal maternal HbA1c levels, respectively. RESULTS: A total of 1836 women were included in the adverse fetal and neonatal events examination. For pregnant women with early HbA1câ¯≥â¯5.2%, the adjusted risk ratios (RR) of respiratory distress syndrome (RDS), pneumonia and jaundice were 4.37 (95%CI 1.54-12.35), 2.03 (95%CI 1.24-3.33) and 1.49 (95%CI 1.01-2.20), respectively. After treatments, the frequency for the majority of events in GDM group was similar to that of healthy pregnant women. Moreover, the area under the curve (AUC) of early maternal HbA1c in predicting potential RDS is 0.734. HbA1câ¯≤â¯4.9% excluded for RDS. CONCLUSIONS: Compared with women with normal HbA1c, those with an early elevated HbA1c level were more likely to develop adverse events, including RDS, pneumonia and jaundice. Early HbA1c testing can be used as an auxiliary method identifying potential RDS.
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Diabetes Gestacional/sangre , Enfermedades Fetales/etiología , Hemoglobina Glucada/metabolismo , Síndrome de Dificultad Respiratoria del Recién Nacido/etiología , Adulto , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Enfermedades Fetales/sangre , Humanos , Recién Nacido , EmbarazoRESUMEN
AIM: Glioma, with fast growth and progression features, is the most common and aggressive tumor in the central nervous system and is essentially incurable. This study is aimed at inducing neuronal differentiation to suppress glioma cell growth with a single transcription factor. METHODS: Overexpression of transcription factor SRY (sex determining region Y)-box 11 (SOX11) and Zic family member 1 (ZIC1) was, respectively, performed in glioma cells with lentivirus infection. CRISPR/Cas9 technology was used to knock out ZIC1 in U87 cells, and knockout efficiency was identified by Western blotting and Sanger sequencing. Cell cycle and apoptosis were detected by flow cytometry. The downstream targets of SOX11 were analyzed by Affymetrix GeneChip microarrays. qRT-PCR and immunofluorescence technique were used to verify gene targets of genetically modified U87 cells. All the cells were imaged by a fluorescence microscope. Gene expression correlation analysis and overall survival analysis based on TCGA dataset are performed by GEPIA. RESULTS: We induced glioma cells into neuron-like cells to suppress cell growth using a single transcription factor, SOX11 or ZIC1. Besides, we proved that there is a strong correlation between SOX11 and ZIC1. Our study revealed that SOX11 upregulates ZIC1 expression by binding with ZIC1 promoter, and ZIC1 partially mediates SOX11-induced neuronal differentiation in U87 cells. However, SOX11 expression is not regulated by ZIC1. Moreover, high MAP2 expression means better overall survival in TCGA lower grade glioma. CONCLUSION: This study revealed that glioma cells can be reprogrammed into neuron-like cells using a single factor ZIC1, which may be a potential tumor suppressor gene for gliomas treatment.
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Diferenciación Celular/fisiología , Glioma/metabolismo , Glioma/prevención & control , Neuronas/fisiología , Factores de Transcripción/biosíntesis , Línea Celular Tumoral , Técnicas de Reprogramación Celular/métodos , Genes Supresores de Tumor/fisiología , Glioma/genética , Células HEK293 , Humanos , Factores de Transcripción/genéticaRESUMEN
Epigallocatechin-3-gallate (EGCG) is one of the major polyphenolic compounds present in green tea extracts and has been used as a potential drug for the treatment of numerous diseases. The present study aimed to elucidate the role and mechanism of EGCG in protecting against H2O2-induced apoptosis in mouse vascular smooth muscle cells (VSMCs). VSMCs were pretreated with various concentrations of EGCG for 2 hours prior to treatment with H2O2. Treatment with H2O2 significantly decreased the cell viability and induced apoptosis of VSMCs, which were attenuated by pretreatment with EGCG. In particular, EGCG pretreatment significantly inhibited the H2O2-induced upregulation of cleaved forms of caspase-3, caspase-8, and caspase-9, Bax, CathepsinD, and downregulation of Bcl-2. Moreover, the antioxidation effect of EGCG on VSMCs was determined to be associated with the 67kD laminin receptor (67LR). Our results demonstrated that EGCG improved cell viability and protected VSMCs against oxidative stress through both extrinsic and intrinsic pathways, while 67LR is likely to be an active and key receptor of EGCG. These findings provide a novel molecular mechanism of EGCG in inhibiting H2O2-induced apoptosis in VSMCs, as well as its function in preventing the development of atherosclerosis.