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BACKGROUND: Myocardial injury is a major complication of sepsis and a key factor affecting prognosis. Therefore, early and accurate diagnosis and timely management of sepsis-induced cardiomyopathy (SICM) are of great significance for the prevention and treatment of sepsis. The gut microbiota has been shown to be closely associated with sepsis or myocardial injury, but the association between the gut microbiota and SICM is not fully understood. This study aimed to explore the link between gut microbiota composition and SICM. METHODS: A case-control and single-center study of clinical features and gut microbiota profiles by Metagenome and Virome was conducted in SICM patients (n = 15) and sepsis-uninduced cardiomyopathy patients (SNICM, n = 16). RESULTS: Compared with SNICM patients, SICM patients showed significant myocardial injury and higher 28-day mortality, SOFA scores, lactate levels, and infection levels on admission. Meanwhile, differences in the composition of gut bacteria, archaea, fungi, and viruses were analyzed between the two groups. Differential gut bacteria or viruses were found to have a good predictive effect on SICM. Furthermore, gut bacteria and viruses that differed between the two groups were strongly related. The abundance of Cronobacter and Cronobacter phage was higher in the SICM group than in the SNICM group, and the receiver operating characteristic curve showed that Cronobacter and Cronobacter phage both had a good predictive effect on SICM. CONCLUSIONS: SICM patients may have specific gut microbiota signatures, and Cronobacter and Cronobacter phages have a good ability to identify and diagnose SICM.
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Bacteriófagos , Cardiomiopatías , Microbioma Gastrointestinal , Sepsis , Humanos , Estudios de Casos y Controles , Disbiosis/complicaciones , Cardiomiopatías/etiología , Bacterias/genética , Sepsis/complicacionesRESUMEN
RNF2 (also known as ding, Ring1B or Ring2) is a member of the Ring finger protein family, which functions as E3 ubiquitin ligase for monoubiquitination of histone H2A at lysine 119 (H2AK119ub). RNF2 gene is located at the 1q25.3 site of human chromosome and the coding region is composed of 9 exons, encoding 336 amino acids in total. Many studies have demonstrated that overexpressed RNF2 was involved in the pathological progression of multiple cancers and has an impact on their clinical features. For instance, the upregulated expression level of RNF2 is positively correlated with the occurrence and progression of hepatocellular carcinoma, melanoma, prostate cancer, breast cancer, pancreatic cancer, gastric cancer, and bladder urothelial carcinoma, as well as with the radioresistance of lung cancer and chemoresistance of ovarian cancer. This review provides an up-to-date perspective on the relationship between RNF2 and several cancers and highlights recent studies on RNF2 regulation. In particular, the relevant cellular signaling pathways and potential clinical value of RNF2 in cancers are also discussed, suggesting its potential as an epigenetic biomarker and therapeutic target for these cancers.
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Carcinoma de Células Transicionales/genética , Regulación Neoplásica de la Expresión Génica/genética , Complejo Represivo Polycomb 1/metabolismo , Neoplasias de la Vejiga Urinaria/genética , Carcinoma de Células Transicionales/metabolismo , Carcinoma de Células Transicionales/patología , Histonas/metabolismo , Humanos , Ubiquitinación , Neoplasias de la Vejiga Urinaria/metabolismoRESUMEN
BACKGROUND: Alzheimer's disease (AD) is clinically characterized as a progressive cognitive impairment and behavioral disorder. Pathological hallmarks of AD include extracellular senile plaques (SPs), intracellular neurofibrillary tangles (NFTs) and massive neuronal loss. Although the exact cause of AD is not well understood, a mounting body of evidence has demonstrated that the pathogenesis of AD is associated with oxidative stress, neu-roinflammation, and amyloid beta (Aß) induced neural apoptosis. Moreover, overexpression of ß-secretase 1 (BACE1), Aß, mammalian target of rapamycin (mTOR), and Tau proteins are closely related to cognitive symptoms in AD. Studies have demonstrated that artemether, an antimalarial drug with acceptable side effects, possesses protective effects against neuroinflammation and oxidative stress. Importantly, artemether can easily penetrate the blood brain barrier, thereby representing an ideal drug candidate for AD treatment. METHODS: The effect of artemether on memory protection and the associated molecular mechanisms were investigated in an Aß25-35 induced cognitive impairments rat model. RESULTS: Results of the in vivo study showed that oral administration of artemether significantly attenuated Aß25-35-induced cognitive impairment in rats. Results of the in vitro study revealed that artemether significantly downregulated the endogenous expression of Aß, BACE1, mTOR, and Tau proteins in N2a cells. CONCLUSIONS: The beneficial effect of artemether against Aß 25-35-induced cognitive impairments was attributable to the downregulation of the expression of Aß, BACE1, mTOR, and Tau proteins, suggesting the potential of artemether as an effective, neuronal protective, and multi-targeted drug candidate for AD treatment.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/genética , Secretasas de la Proteína Precursora del Amiloide/genética , Péptidos beta-Amiloides , Animales , Arteméter , Ácido Aspártico Endopeptidasas/genética , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/tratamiento farmacológico , Fragmentos de Péptidos , Ratas , Serina-Treonina Quinasas TOR , Proteínas tauRESUMEN
OBJECTIVE: There is little evidence that adjuvant therapy after radical surgical resection of hepatocellular carcinoma (HCC) improves recurrence-free survival (RFS) or overall survival (OS). We conducted a multicentre, randomised, controlled, phase IV trial evaluating the benefit of an aqueous extract of Trametes robinophila Murr (Huaier granule) to address this unmet need. DESIGN AND RESULTS: A total of 1044 patients were randomised in 2:1 ratio to receive either Huaier or no further treatment (controls) for a maximum of 96 weeks. The primary endpoint was RFS. Secondary endpoints included OS and tumour extrahepatic recurrence rate (ERR). The Huaier (n=686) and control groups (n=316) had a mean RFS of 75.5 weeks and 68.5 weeks, respectively (HR 0.67; 95% CI 0.55 to 0.81). The difference in the RFS rate between Huaier and control groups was 62.39% and 49.05% (95% CI 6.74 to 19.94; p=0.0001); this led to an OS rate in the Huaier and control groups of 95.19% and 91.46%, respectively (95% CI 0.26 to 7.21; p=0.0207). The tumour ERR between Huaier and control groups was 8.60% and 13.61% (95% CI -12.59 to -2.50; p=0.0018), respectively. CONCLUSIONS: This is the first nationwide multicentre study, involving 39 centres and 1044 patients, to prove the effectiveness of Huaier granule as adjuvant therapy for HCC after curative liver resection. It demonstrated a significant prolongation of RFS and reduced extrahepatic recurrence in Huaier group. TRIAL REGISTRATION: NCT01770431; Post-results.
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Carcinoma Hepatocelular/tratamiento farmacológico , Mezclas Complejas/uso terapéutico , Hepatectomía/efectos adversos , Neoplasias Hepáticas/tratamiento farmacológico , Anciano , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/cirugía , Quimioterapia Adyuvante , Mezclas Complejas/efectos adversos , Femenino , Humanos , Hígado/patología , Hígado/cirugía , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Análisis de Supervivencia , Trametes , Resultado del TratamientoRESUMEN
Metal-organic frameworks (MOFs) with tunable compositions and morphologies are recognized as efficient self-sacrificial templates to achieve function-oriented nanostructured materials. Moreover, it is urgently needed to develop highly efficient noble metal-free oxygen evolution reaction (OER) electrocatalysts to accelerate the development of overall water splitting green energy conversion systems. Herein, a facile and cost-efficient strategy to synthesize Co9 S8 nanoparticles-embedded N/S-codoped carbon nanofibers (Co9 S8 /NSCNFs) as highly active OER catalyst is developed. The hybrid precursor of core-shell ZIF-wrapped CdS nanowires is first prepared and then leads to the formation of uniformly dispersed Co9 S8 /N, S-codoped carbon nanocomposites through a one-step calcination reaction. The optimal Co9 S8 /NSCNFs-850 is demonstrated to possess excellent electrocatalytic performance for OER in 1.0 m KOH solution, affording a low overpotential of 302 mV to reach the current density of 10 mA cm-2 , a small Tafel slope of 54 mV dec-1 , and superior long-term stability for 1000 cyclic voltammetry cycles. The favorable results raise a concept of exploring more MOF-based nanohybrids as precursors to induce the synthesis of novel porous nanomaterials as non-noble-metal electrocatalysts for sustainable energy conversion.
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Mitochondrial dysfunction causes renal tubular epithelial cell injury and promotes cell apoptosis and renal tubulointerstitial fibrosis (TIF) progression. TNF receptor-associated protein 1 (TRAP1) is a molecular chaperone protein that is localized in mitochondria. It plays an important role in cell apoptosis; however, its functional mechanism in TIF remains unclear. In this study, we observed the effects of TRAP1 in renal tubular epithelial cell mitochondria in mice with unilateral ureteral obstruction and its function in cell apoptosis and TIF. Results show that TRAP1 could protect the mitochondrial structure in renal tubular epithelial cells; maintain the levels of mitochondrial membrane potential, ATP, and mitochondrial DNA copy number; inhibit reactive oxygen species production; stabilize the expression of the mitochondrial inner membrane protein mitofilin; reduce renal tubular epithelial cell apoptosis; and inhibit TIF. These results provide new theoretical foundations for additional understanding of the antifibrotic mechanism of TRAP1 in the kidney.-Chen, J.-F., Wu, Q.-S., Xie, Y.-X., Si, B.-L., Yang, P.-P., Wang, W.-Y., Hua, Q., He, Q. TRAP1 ameliorates renal tubulointerstitial fibrosis in mice with unilateral ureteral obstruction by protecting renal tubular epithelial cell mitochondria.
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Células Epiteliales/metabolismo , Proteínas HSP90 de Choque Térmico/metabolismo , Túbulos Renales/metabolismo , Mitocondrias/metabolismo , Obstrucción Ureteral/metabolismo , Animales , Células Epiteliales/efectos de los fármacos , Fibrosis/tratamiento farmacológico , Fibrosis/metabolismo , Túbulos Renales/efectos de los fármacos , Túbulos Renales/patología , Masculino , Ratones Endogámicos C57BL , Sustancias Protectoras/farmacología , Especies Reactivas de Oxígeno/metabolismo , Obstrucción Ureteral/patologíaRESUMEN
Bracovirus is one of the two polydnavirus genera. Here, we used a cryo-EM analysis to reveal the near-native morphology of two nucleocapsid-containing model bracoviruses: Microplitis bicoloratus bracovirus (MbBV) and Microplitis mediator bracovirus (MmBV). MbBV and MmBV nucleocapsids have discernable cap structures in two distal regions with relatively high electron density. Adjacent to the end-cap structures are two electron-lucent rings. Some nucleocapsids were uniformly electron-dense and had a distinctive "helix-tail-like structure". Cryo-EM revealed inconsistent nucleocapsid diameters of 34-69.9 nm in MbBV and 46-69.9 nm in MmBV, and the largest observed cylindrical area length was expanded to 126 nm.
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Nucleocápside/ultraestructura , Polydnaviridae/ultraestructura , Avispas/virología , Animales , Microscopía por Crioelectrón , Nucleocápside/química , Nucleocápside/aislamiento & purificación , Polydnaviridae/química , Virión/química , Virión/aislamiento & purificación , Virión/ultraestructuraRESUMEN
Left ventricular hypertrophy (LVH) is a common abnormality in hemodialysis (HD) patients. Mitochondrial dysfunction contributes to the progression of LVH. As an inner mitochondrial membrane structural protein, mitofilin plays a key role in maintaining mitochondrial structure and function. The aim of this study was to investigate the relationship between mitofilin and LVH in HD patients. A total of 98 HD patients and 32 healthy controls were included in the study. Serum N-terminal proBNP (NT-proBNP), endothelin-1 (ET-1), and atrial natriuretic peptide (ANP) were examined. The protein level of mitofilin and the mitochondrial DNA (mtDNA) copy number were estimated in peripheral blood mononuclear cells (PBMCs). The left ventricle mass index (LVMI) was evaluated in all participants, and the interaction between these variables and the LVMI was assessed. The LVMI was positively correlated with the NT-proBNP, ET-1, and ANP levels, and it was negatively correlated with mtDNA copy number and mitofilin levels. Multiple regression analysis showed that the NT-proBNP, ET-1, and ANP levels as well as mitofilin levels and mtDNA copy number were associated with the LVMI. Although further research of these associations is needed, this result suggests that LVH may affect the levels of mitofilin in HD patients.
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Hipertrofia Ventricular Izquierda/sangre , Fallo Renal Crónico/terapia , Proteínas Mitocondriales/sangre , Proteínas Musculares/sangre , Diálisis Renal/efectos adversos , Adulto , Factor Natriurético Atrial/sangre , Biomarcadores/sangre , Estudios Transversales , ADN Mitocondrial/sangre , Ecocardiografía , Endotelina-1/sangre , Femenino , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/patología , Humanos , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Hipertrofia Ventricular Izquierda/etiología , Fallo Renal Crónico/sangre , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Factores de RiesgoRESUMEN
BACKGROUND: Cognitive and neuroimaging changes under chronic high-altitude exposure have never been followed up and dynamically assessed. OBJECTIVES: To investigate the cognitive and brain structural/functional alterations associated with chronic high-altitude exposure. METHODS: Sixty-nine college freshmen that were immigrating to Tibet were enrolled and followed up for two years. Neuropsychological tests, including verbal/visual memory and simple/recognition reaction time, were utilized to determine whether the subjects' cognitive function had changed in response to chronic high-altitude exposure. Structural magnetic resonance imaging (MRI) and resting-state functional MRI (rs-fMRI) were used to quantify brain gray matter (GM) volumes, regional homogeneity (ReHo) and functional connectivity (FC) alterations before and after exposure. Areas with changes in both GM and ReHo were used as seeds in the inter-regional FC analysis. RESULTS: The subjects showed significantly lower accuracy in memory tests and longer reaction times after exposure, and neuroimaging analysis showed markedly decreased GM volumes and ReHo in the left putamen. FC analysis seeding of the left putamen showed significantly weakened FC with the superior temporal gyrus, anterior/middle cingulate gyrus and other brain regions. In addition, decreased ReHo was found in the superior temporal gyrus, superior parietal lobule, anterior cingulate gyrus and medial frontal gyrus, while increased ReHo was found in the hippocampus. Differences in ReHo/FC before and after high-altitude exposure in multiple regions were significantly correlated with the cognitive changes. CONCLUSION: Cognitive functions such as working memory and psychomotor function are impaired during chronic high-altitude exposure. The putamen may play an important role in chronic hypoxia-induced cognitive impairment. Hum Brain Mapp 38:3865-3877, 2017. © 2017 Wiley Periodicals, Inc.
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Adaptación Fisiológica , Altitud , Encéfalo/fisiología , Cognición/fisiología , Adolescente , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Emigrantes e Inmigrantes , Femenino , Estudios de Seguimiento , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/fisiología , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Memoria/fisiología , Pruebas Neuropsicológicas , Tamaño de los Órganos , Tiempo de Reacción/fisiología , Descanso , Adulto JovenRESUMEN
Metal-organic frameworks (MOFs) featuring versatile topological architectures are considered to be efficient self-sacrificial templates to achieve mesoporous nanostructured materials. A facile and cost-efficient strategy is developed to scalably fabricate binary metal oxides with complex hollow interior structures and tunable compositions. Bimetal-organic frameworks of Ni-Co-BTC solid microspheres with diverse Ni/Co ratios are readily prepared by solvothermal method to induce the Ni x Co3-x O4 multishelled hollow microspheres through a morphology-inherited annealing treatment. The obtained mixed metal oxides are demonstrated to be composed of nanometer-sized subunits in the shells and large void spaces left between adjacent shells. When evaluated as anode materials for lithium-ion batteries, Ni x Co3-x O4 -0.1 multishelled hollow microspheres deliver a high reversible capacity of 1109.8 mAh g-1 after 100 cycles at a current density of 100 mA g-1 with an excellent high-rate capability. Appropriate capacities of 832 and 673 mAh g-1 could also be retained after 300 cycles at large currents of 1 and 2 A g-1 , respectively. These prominent electrochemical properties raise a concept of synthesizing MOFs-derived mixed metal oxides with multishelled hollow structures for progressive lithium-ion batteries.
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OBJECTIVE: To provide a feasible and cost-effective next-generation sequencing (NGS) method for accurate identification of viral pathogens in clinical specimens, because enormous limitations impede the clinical use of common NGS, such as high cost, complicated procedures, tremendous data analysis, and high background noise in clinical samples. METHODS: Viruses from cell culture materials or clinical specimens were identified following an improved NGS procedure: reduction of background noise by sample preprocessing, viral enrichment by barcoded oligonucleotide (random hexamer or non-ribosomal hexanucleotide) primer-based amplification, fragmentation-free library construction and sequencing of one-tube mixtures, as well as rapid data analysis using an in-house pipeline. RESULTS: NGS data demonstrated that both barcoded primer sets were useful to simultaneously capture multiple viral pathogens in cell culture materials or clinical specimens and verified that hexanucleotide primers captured as many viral sequences as hexamers did. Moreover, direct testing of clinical specimens using this improved hexanucleotide primer-based NGS approach provided further detailed genotypes of enteroviruses causing hand, foot, and mouth disease (HFMD) and identified other potential viruses or differentiated misdiagnosis events. CONCLUSION: The improved barcoded oligonucleotide primer-based NGS approach is simplified, time saving, cost effective, and appropriate for direct identification of viral pathogens in clinical practice.
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Enterovirus/clasificación , Herpesvirus Humano 4/aislamiento & purificación , Virus de la Influenza B/aislamiento & purificación , Análisis de Secuencia de ADN/métodos , Análisis de Secuencia de ARN/métodos , Técnicas de Laboratorio Clínico , Código de Barras del ADN Taxonómico , Cartilla de ADN , Enterovirus/genética , Enterovirus/aislamiento & purificación , Herpesvirus Humano 4/genética , Humanos , Virus de la Influenza B/genética , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
BACKGROUND AND AIM: Long non-coding RNAs have been confirmed to play a critical role in various cancers. In the present study, the effect of long non-coding RNA (lncRNA) CCAT1 on glioma cell proliferation and its potential mechanism were investigated. METHODS AND RESULTS: Real-time PCR results showed that lncRNA-CCAT1 expression was significantly upregulated in glioma cancer tissues and cell lines compared with controls. After inhibiting CCAT1 expression in glioma cell line U251 with siRNA-CCAT1 (si-CCAT1), the cell viability and cell colony formation were decreased, the cell cycle was arrested in G1 phase, and the cell apoptosis was increased. As reported in bioinformatics software starbase2.0, a total of 22 microRNAs were potentially targeted by CCAT1. It was confirmed that miR-410 was altered most by si-CCAT1. After up-regulating CCAT1 expression in U251 cells, miR-410 level was decreased. Luciferase reporter assay confirmed that CCAT1 targeted miR-410. Correlation analysis showed that CCAT1 expression was negatively related to miR-410 expression in glioma cancer tissues. In addition, down-regulation of miR-410 reversed the inhibitory effect of si-CCAT1 on glioma proliferation. CONCLUSION: These data demonstrated that lncRNA-CCAT1 promoted glioma cell proliferation via inhibiting miR-410, providing a new insight about the pathogenesis of glioma proliferation.
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Regulación Neoplásica de la Expresión Génica/genética , Glioma/genética , Glioma/patología , MicroARNs/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Proliferación Celular/genética , Humanos , Células Tumorales CultivadasRESUMEN
Official guidelines group together all cases of solitary hepatocellular carcinoma (HCC) without macroscopic vascular invasion, regardless of tumor size. Here, we examined whether this is justified based on overall survival (OS) after hepatic resection (HR). Patients with newly diagnosed solitary HCC treated by initial HR from January 2004 to October 2013 were classified into six groups based on tumor size (in 2-cm increments). Combining adjacent categories with similar OS led to three groups: ≤5 cm (n = 426), >5 and ≤8 cm (n = 229), and >8 cm (n = 202). Among all patients, median survival time was 62 months, and OS was 95 % at 1 year, 73 % at 3 years, and 54 % at 5 years. Patients in the ≤5 cm group showed significantly higher OS (P < 0.001) and lower tumor recurrence (P = 0.004) than those in the >5 and ≤8 cm group, who in turn showed significantly higher OS (P = 0.003) and lower tumor recurrence (P = 0.021) than those in the >8 cm group. Our results suggest that patients with solitary HCC should be subclassified based on tumor size for more accurate prognosis. We propose defining solitary HCC tumors >5 and ≤8 cm as "large" and tumors >8 cm as "huge".
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Carcinoma Hepatocelular/cirugía , Hepatectomía , Neoplasias Hepáticas/cirugía , Tumores Fibrosos Solitarios/cirugía , Adulto , Anciano , Carcinoma Hepatocelular/patología , Femenino , Humanos , Hígado/patología , Hígado/cirugía , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/patología , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/patología , Periodo Posoperatorio , Pronóstico , Tumores Fibrosos Solitarios/patología , Análisis de Supervivencia , Resultado del Tratamiento , Carga TumoralRESUMEN
Transforming growth factors ß (TGF-ß) pathway has been proven to play important roles in oncogenesis and angiogenesis of gliomas. MiR-132 might be related to TGF-ß signaling pathway and high miR-132 expression was reported to be a biomarker of poor prognosis in patients diagnosed with glioma. However, the expression regulation way involved in TGF-ß pathway and clinical significance of miR-132 have not been investigated in glioma cells. Here we reported that the mRNA level of miR-132 and TGF-ß concentration were both increased in patients with brain glioma. Correlation analysis revealed that TGF-ß concentration was positively correlated with mRNA level of miR-132. In addition, the mRNA level of miR-132 was up-regulated by TGF-ß in a concentration-dependent and time-dependent manner. Furthermore, we found that miR-132 was involved in modulation of the TGF-ß signaling pathway and down-regulation of SMAD7 expression by directly targeting the SMAD7 3'-UTR. MiR-132 was negatively correlated with SMAD7 in patients with brain glioma. Taken together, our results suggest that miR-132 could be stimulated by TGF-ß and might enhance the activation of TGF-ß signaling through inhibiting SMAD7 expression in glioma cells. These findings contribute to a better understanding of the mechanism of the activation of TGF-ß signaling by miR-132.
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Neoplasias Encefálicas/genética , Regulación Neoplásica de la Expresión Génica , Glioma/genética , MicroARNs/genética , Proteína smad7/genética , Factor de Crecimiento Transformador beta/metabolismo , Encéfalo/metabolismo , Neoplasias Encefálicas/metabolismo , Línea Celular , Femenino , Glioma/metabolismo , Humanos , Masculino , MicroARNs/metabolismo , Transducción de SeñalRESUMEN
Heart disease is among the leading causes of death worldwide, and the limited proliferation of mammalian cardiomyocytes prevents heart regeneration in response to injury. Bone morphogenetic protein-10 (BMP10) exerts multiple roles in various developmental events; however, the effect of BMP10 and the underlying mechanism involved in cardiac repair remains unclear. After stimulation with the recombinant BMP10, an obvious dose-dependent cardiomyocyte proliferation and reentry of differentiated mammalian cardiomyocytes into the cell cycle was observed. Furthermore, BMP10 stimulation strikingly enhanced Tbx20 expression. Further analysis demonstrated that T-box 20 (Tbx20) was involved in BMP10-induced proliferation of differentiated cardiomyocytes as preconditioning with Tbx20 siRNA significantly attenuated BMP10-induced DNA synthesis. In vivo, BMP10 induced rat cardiomyocyte DNA synthesis and cytokinesis. After myocardial infarction (MI), BMP10 stimulated cardiomyocyte cell-cycle reentry and mitosis, resulting in the decrease of infarct size and improvement of cardiac repair. Taken together, these data indicated that BMP10 stimulated cardiomyocyte proliferation and repaired cardiac function after heart injury. Consequently, BMP10 may be a potential target for innovative strategies against heart failure.
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Proteína Morfogenética Ósea 1/metabolismo , Proteínas Morfogenéticas Óseas/metabolismo , Corazón/fisiopatología , Infarto del Miocardio/terapia , Miocitos Cardíacos/citología , Proteínas de Dominio T Box/metabolismo , Animales , Ciclo Celular , Diferenciación Celular , Proliferación Celular , Terapia Genética , Pruebas de Función Cardíaca , Masculino , Infarto del Miocardio/metabolismo , Infarto del Miocardio/fisiopatología , Ratas , Ratas Endogámicas Lew , Proteínas Recombinantes/administración & dosificación , Proteínas de Dominio T Box/genéticaRESUMEN
BACKGROUND: Diabetic kidney disease (DKD) is a major complication of diabetes mellitus. Renal tubular epithelial cell (TEC) damage, which is strongly associated with the inflammatory response and mesenchymal trans-differentiation, plays a significant role in DKD; However, the precise molecular mechanism is unknown. The recently identified microRNA-630 (miR-630) has been hypothesized to be closely associated with cell migration, apoptosis, and autophagy. However, the association between miR-630 and DKD and the underlying mechanism remain unknown. AIM: To investigate how miR-630 affects TEC injury and the inflammatory response in DKD rats. METHODS: Streptozotocin was administered to six-week-old male rats to create a hyperglycemic diabetic model. In the second week of modeling, the rats were divided into control, DKD, negative control of lentivirus, and miR-630 overexpression groups. After 8 wk, urine and blood samples were collected for the kidney injury assays, and renal tissues were removed for further molecular assays. The target gene for miR-630 was predicted using bioinformatics, and the association between miR-630 and toll-like receptor 4 (TLR4) was confirmed using in vitro investigations and double luciferase reporter gene assays. Overexpression of miR-630 in DKD rats led to changes in body weight, renal weight index, basic blood parameters and histopathological changes. RESULTS: The expression level of miR-630 was reduced in the kidney tissue of rats with DKD (P < 0.05). The miR-630 and TLR4 expressions in rat renal TECs (NRK-52E) were measured using quantitative reverse transcription polymerase chain reaction. The mRNA expression level of miR-630 was significantly lower in the high-glucose (HG) and HG + mimic negative control (NC) groups than in the normal glucose (NG) group (P < 0.05). In contrast, the mRNA expression level of TLR4 was significantly higher in these groups (P < 0.05). However, miR-630 mRNA expression increased and TLR4 mRNA expression significantly decreased in the HG + miR-630 mimic group than in the HG + mimic NC group (P < 0.05). Furthermore, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), and IL-6 were significantly higher in the HG and HG + mimic NC groups than in NG group (P < 0.05). However, the levels of these cytokines were significantly lower in the HG + miR-630 mimic group than in the HG + mimic NC group (P < 0.05). Notably, changes in protein expression were observed. The HG and HG + mimic NC groups showed a significant decrease in E-cadherin protein expression, whereas TLR4, α-smooth muscle actin (SMA), and collagen IV protein expression increased (P < 0.05). Conversely, the HG + miR-630 mimic group exhibited a significant increase in E-cadherin protein expression and a notable decrease in TLR4, α-SMA, and collagen IV protein expression than in the HG + mimic NC group (P < 0.05). The miR-630 targets TLR4 gene expression. In vivo experiments demonstrated that DKD rats treated with miR-630 agomir exhibited significantly higher miR-630 mRNA expression than DKD rats injected with agomir NC. Additionally, rats treated with miR-630 agomir showed significant reductions in urinary albumin, blood glucose, TLR4, and proinflammatory markers (TNF-α, IL-1ß, and IL-6) expression levels (P < 0.05). Moreover, these rats exhibited fewer kidney lesions and reduced infiltration of inflammatory cells. CONCLUSION: MiR-630 may inhibit the inflammatory reaction of DKD by targeting TLR4, and has a protective effect on DKD.
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High suicide risk represents a serious problem in patients with major depressive disorder (MDD), yet treatment options that could safely and rapidly ameliorate suicidal ideation remain elusive. Here, we tested the feasibility and preliminary efficacy of the Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) in reducing suicidal ideation in patients with MDD. Thirty-two MDD patients with moderate to severe suicidal ideation participated in the current study. Suicidal ideation and depression symptoms were assessed before and after 5 days of open-label SAINT. The neural pathways supporting rapid-acting antidepressant and suicide prevention effects were identified with dynamic causal modelling based on resting-state functional magnetic resonance imaging. We found that 5 days of SAINT effectively alleviated suicidal ideation in patients with MDD with a high response rate of 65.63%. Moreover, the response rates achieved 78.13% and 90.63% with 2 weeks and 4 weeks after SAINT, respectively. In addition, we found that the suicide prevention effects of SAINT were associated with the effective connectivity involving the insula and hippocampus, while the antidepressant effects were related to connections of the subgenual anterior cingulate cortex (sgACC). These results show that SAINT is a rapid-acting and effective way to reduce suicidal ideation. Our findings further suggest that distinct neural mechanisms may contribute to the rapid-acting effects on the relief of suicidal ideation and depression, respectively.
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Trastorno Depresivo Mayor , Humanos , Trastorno Depresivo Mayor/diagnóstico por imagen , Trastorno Depresivo Mayor/terapia , Ideación Suicida , Hipocampo , Imagen por Resonancia Magnética , Antidepresivos/uso terapéuticoRESUMEN
Cadmium (Cd) removal from soil is crucial as Cd enters the food chain and affect food safety, thus impose severe threaten to human health. We developed PPC@PC-Fe, a dual-functional core-shell sphere for efficient soil Cd reduction. The shell (PPC) was composed of encapsulated citric acid (CA) in a polylactic acid (PLA) and polyethylene glycol (PEG) network, which endows a function of activating Cd; and the core (PC-Fe) consisted of a polyacrylic acid/carboxymethyl chitosan (PAA/CMC) hydrogel with Fe3O4 nanoparticles to adsorb adjacent activated Cd. Upon water contact, the shell dissolved, releasing CA to activate soil Cd. Simultaneously, the swellable PC-Fe core absorbed water and expanded in size, promoting the disintegration of PLA in the shell, which triggered the automatic separation of core from shell, enabling the exposed PC-Fe core to rapidly adsorb Cd. Furthermore, the PC-Fe core can be magnetically removed after adsorption of Cd. Soil culture tests showed that 2 % PPC@PC-Fe reduced soil Cd from 6.009 mg/kg to 4.834 mg/kg in 10 days, with the acid-soluble Cd being the predominantly target to be activated and remove. This study demonstrates an effective stepwise activation and adsorption mechanism by a single carrier, with simple magnetic collection minimizing secondary pollution. It offers an innovative approach to the remediation of cadmium-contaminated sites in the field.
RESUMEN
A Gram-negative, aerobic, rod-shaped, motile, non-spore-forming bacterial strain, designated 13-Q(T), was isolated from seaside soil under the stacks of the red algae in Hainan province in China. Identification was carried out on the basis of polyphasic taxonomy. Phylogenetic analysis of 16S rRNA gene sequences showed that strain 13-Q(T) belonged to the genus Pedobacter, and the highest similarity was 94.4 % with Pedobacter terricola KCTC 12876(T). Strain 13-Q(T) was able to grow at 10-40 °C, in pH 5.0-10.0, in the presence of 0-2.0 % NaCl. The major fatty acids were iso-C(15:0) (40.4 %), summed feature 3 (comprising iso-C(15:0) 2-OH and/or C(16:1) ω7c) (18.9 %) and iso-C(17:0) 3-OH (18.4 %). The predominant menaquinone was MK-7. The G+C content of the genomic DNA was 42.7 mol%. Strain 13-Q(T) could be distinguished from the nearest phylogenetic neighbors by various chemotaxonomic and phenotypic properties. The results of the polyphasic analyses suggested that strain 13-Q(T) should be considered to represent a novel species of the genus Pedobacter, for which the name Pedobacter hainanensis sp. nov. is proposed. The type strain is 13-Q(T) (=CCTCC AB 2012076(T) = NRRL B-59850(T)).
Asunto(s)
Pedobacter/clasificación , Microbiología del Suelo , Ácidos Grasos/química , Datos de Secuencia Molecular , Pedobacter/química , Pedobacter/genética , Filogenia , ARN Ribosómico 16S/genéticaRESUMEN
BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD), an emerging technique originated from Japan, has been introduced into China in recent years. The aim of this study was to evaluate the efficacy and safety of ESD in the treatment of gastrointestinal (GI) neoplasms. METHODOLOGY: Early GI neoplasms (n=41) in 40 patients from local Eastern China were treated with ESD at Zhejiang Provincial People's Hospital and followed-up from January 2009 to December 2011. Postoperative pathology, complications and therapeutic outcomes were retrospectively analyzed. RESULTS: Mean size of the resected lesions was 2.2±0.81cm (1.2-6.0cm) and mean operation time was 77±28 minutes (20-150 minutes). The rates for successful resection, en bloc resection and complications were 90.2% (37/41), 83.8% (31/37) and 9.8% (4/41), respectively. The postoperative pathology showed 4 cases of early esophageal cancer, 6 of early gastric cancer or high-grade intraepithelial neoplastic changes, 5 of rectal laterally spreading tumor, 5 of esophageal or gastric leiomyoma, 2 of gastric heterotopic pancreas, and 18 of esophageal and gastric flat lesions with low-grade intraepithelial neoplastic changes. Tumor residue or recurrence was not been detected in all 40 patients during follow-up. CONCLUSIONS: According to our experience in local Eastern China, ESD is a feasible technique for the treatment of GI neoplasms. Even though it has promising resection rate and acceptable complication rate, the indication of ESD should be selected strictly and the operators need to be well-trained.