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AIM: This study aimed to evaluate the prognostic value of the Naples Prognostic Score (NPS) for predicting mortality in patients with nonalcoholic fatty liver disease (NAFLD) and compare its performance with established non-invasive fibrosis scores, including the fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS). METHODS: Data from 10,035 NAFLD patients identified within the 1999-2018 National Health and Nutrition Examination Survey (NHANES) were analyzed. Cox regression models assessed the association between NPS and all-cause mortality, while time-dependent ROC analysis compared its predictive accuracy with FIB-4 and NFS. Mediation analysis explored the role of phenotypic age acceleration (PhenoAgeAccel). RESULTS: NPS was significantly associated with all-cause mortality, with each point increase corresponding to a 26 % increased risk (HR = 1.26, 95 % CI: 1.19-1.34). NPS demonstrated comparable predictive performance to FIB-4 and NFS, with further improvement when combined with either score (HRs of 2.03 and 2.11 for NPS + FIB-4 and NPS + NFS, respectively). PhenoAgeAccel mediated 31.5 % of the effect of NPS on mortality. CONCLUSIONS: This study found that NPS has the potential to be an independent, cost-effective, and reliable novel prognostic indicator for NAFLD that may complement existing tools and help improve risk stratification and management strategies for NAFLD, thereby preventing adverse outcomes.
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Inflamación , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/mortalidad , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Femenino , Masculino , Pronóstico , Persona de Mediana Edad , Adulto , Envejecimiento/fisiología , Encuestas Nutricionales , Estado Nutricional , Anciano , Índice de Severidad de la Enfermedad , Cirrosis Hepática/mortalidad , Cirrosis Hepática/diagnóstico , Factores de RiesgoRESUMEN
BACKGROUND: Fibrodysplasia ossificans progressiva (FOP) is an ultrarare and disabling genetic disorder of connective tissue characterized by congenital malformation of the great toes, and progressive heterotopic ossification (HO) in soft connective tissues. A gain-of-function mutation of activin A receptor type I (ACVR1) enables ACVR1 to recognize activin A as an agonist with bone morphogenetic protein (BMP) signalling that leads to HO. Previous studies confirmed that activin A stimulates BMP signalling in vitro and drives HO in mouse models of FOP. However, the roles for BMP4 and BMP6 in FOP are supported only by correlative evidence in vitro. Thus, it remains unclear whether the circulating levels of activin A, BMP4 and BMP6 correlate with flare-ups in FOP patients. Hence, we investigated the protein levels of activin A, BMP4 and BMP6 in the serum of FOP patients. RESULTS: We recruited 16 untreated FOP patients and 16 age- and sex- matched healthy control subjects in this study. The 16 FOP patients were retrospectively divided into the flare-up group (n = 8) and remission group (n = 8) depending on whether they had flare-ups or worsening of any joint movement in the last 6 months. The serum activin A, BMP4 and BMP6 levels were detected by enzyme-linked immunosorbent assay. The serum activin A, BMP4 and BMP6 levels were slightly higher in FOP patients (median: 434.05 pg/mL, 459.48 pg/mL and 67.84 pg/mL) versus healthy control subjects (median: 364.14 pg/mL, 450.39 pg/mL and 55.36 pg/mL). However, there were no statistically significant differences between the two groups (p > 0.05 for all items), nor were there significant differences between the flare-up and remission groups of FOP (p > 0.05 for all items). Univariate and multivariate logistic regression analyses showed that age, sex, and serum activin A, BMP4 and BMP6 levels were not related to flare-up in FOP patients. CONCLUSIONS: There were no significant differences in the serum levels of activin A, BMP4 and BMP6 in FOP patients compared with healthy control subjects. Serum activin A, BMP4 and BMP6 proteins might not be the stimulators for FOP flare-up, and may not be biomarkers for FOP diagnosis.
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Miositis Osificante , Osificación Heterotópica , Ratones , Animales , Miositis Osificante/genética , Estudios Retrospectivos , Mutación , Osificación Heterotópica/genética , Proteínas Morfogenéticas Óseas/genética , Proteínas Morfogenéticas Óseas/metabolismo , Receptores de Activinas Tipo I/genética , Receptores de Activinas Tipo I/metabolismoRESUMEN
PURPOSE: The aim of this study was to investigate the microRNA (miRNA) expression profile in peripheral blood mononuclear cells (PBMC) of thyroid-associated ophthalmopathy (TAO) patients and to explore the molecular mechanisms of MicroRNA-376b (miR-376b) in the pathogenesis of TAO. METHODS: PBMCs from TAO patients and healthy controls were analyzed by miRNA microarray to screen for the significantly differentially expressed miRNAs. The miR-376b expression in PBMCs were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). The downstream target of miR-376b was screened by online bioinformatics, and detected by qRT-PCR and Western blotting. RESULTS: Compared with normal controls, 26 miRNAs were significantly different in PBMCs of TAO patients (14 miRNAs were down-regulated and 12 miRNAs were up-regulated). Among them, miR-376b expression was significantly decreased in PBMCs from TAO patients compared to healthy controls. Spearman correlation analysis revealed that miR-376b expression in PBMCs was significantly negatively correlated with free triiodothyronine (FT3), and positively correlated with thyroid-stimulating hormone (TSH). MiR-376b expression was obviously reduced in 6T-CEM cells after triiodothyronine (T3) stimulation compared to controls. MiR-376b mimics significantly decreased hyaluronan synthase 2 (HAS2) protein expression and the mRNA expression of intercellular cell adhesion molecule-1 (ICAM1) and tumor necrosis factor-α (TNF-α) in 6T-CEM cells, whereas miR-376b inhibitors markedly elevated HAS2 protein expression and gene expression of ICAM1 and TNF-α. CONCLUSIONS: MiR-376b expression in PBMCs was significantly decreased in PBMCs from TAO patients compared with the healthy controls. MiR-376b, regulated by T3, could modulate the expression of HAS2 and inflammatory factors. We speculate that miR-376b may be involved in the pathogenesis of TAO patients by regulating the expression of HAS2 and inflammatory factors.
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Oftalmopatía de Graves , MicroARNs , Humanos , Leucocitos Mononucleares/metabolismo , Hialuronano Sintasas/metabolismo , Oftalmopatía de Graves/genética , Oftalmopatía de Graves/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Triyodotironina/metabolismo , MicroARNs/metabolismoRESUMEN
Background and objective: The diagnostic value of lipid and lipoprotein ratios for NAFLD in newly diagnosed T2DM remains unclear. This study aimed to investigate the relationships between lipid and lipoprotein ratios and the risk of NAFLD in subjects with newly diagnosed T2DM. Methods: A total of 371 newly diagnosed T2DM patients with NAFLD and 360 newly diagnosed T2DM without NAFLD were enrolled in the study. Demographics variables, clinical history and serum biochemical indicators of the subjects were collected. Six lipid and lipoprotein ratios, including triglycerides to high-density lipoprotein-cholesterol (TG/HDL-C) ratio, cholesterol to HDL-C (TC/HDL-C) ratio, free fatty acid to HDL-C (FFA/HDL-C) ratio, uric acid to HDL-C (UA/HDL-C) ratio, low-density lipoprotein-cholesterol to HDL-C (LDL-C/HDL-C) ratio, apolipoprotein B to apolipoprotein A1 (APOB/A1) ratio, were calculated. We compared the differences in lipid and lipoprotein ratios between NAFLD group and non-NAFLD group, and further analyzed the correlation and diagnostic value of these ratios with the risk of NAFLD in the newly diagnosed T2DM patients. Results: The proportion of NAFLD in patients with newly diagnosed T2DM increased progressively over the range Q1 to Q4 of six lipid ratios, including the TG/HDL-C ratio, TC/HDL-C ratio, FFA/HDL-C ratio, UA/HDL-C ratio, LDL-C/HDL-C ratio, and APOB/A1 ratio. After adjusting for multiple confounders, TG/HDL-C, TC/HDL-C, UA/HDL-C, LDL-C/HDL-C and APOB/A1 were all strongly correlated with the risk of NAFLD in patients with newly diagnosed T2DM. In patients with newly-onset T2DM, the TG/HDL-C ratio was the most powerful indicator for the diagnosis of NAFLD among all six indicators, with an area under the curve (AUC) of 0.732 (95% CI 0.696-0.769). In addition, TG/HDL-C ratio>1.405, with a sensitivity of 73.8% and specificity of 60.1%, had a good diagnostic ability for NAFLD in patients with newly diagnosed T2DM. Conclusions: The TG/HDL-C ratio may be an effective marker to help identify the risk of NAFLD in patients with newly diagnosed T2DM.
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Diabetes Mellitus Tipo 2 , Enfermedad del Hígado Graso no Alcohólico , Humanos , Estudios Retrospectivos , LDL-Colesterol , Apolipoproteínas B , HDL-Colesterol , Ácidos Grasos no Esterificados , Lipoproteínas , TriglicéridosRESUMEN
Purpose: Our aims were to investigate the pathogenesis of diabetic cardiomyopathy (DCM) and to explore the protective effect of glucagon-like peptide-1 receptor agonist (GLP-1RA) on DCM. Methods: After 12 weeks of treatment with exenatide-loaded microspheres, a long-acting GLP-1RA, in DCM mice, cardiac structure and function were evaluated by plasma B-type natriuretic peptide (BNP), echocardiography, H&E, oil red and Sirius staining. The expression of glucagon-like peptide-1 receptor in mouse heart tissue was determined by immunofluorescence staining. The label-free proteomic analysis of cardiac proteins was conducted among control, DCM and DM+GLP-1RA groups. Then, quantitative real-time PCR, Western blotting and dual-luciferase reporter assay were performed to verify the regulation of target protein by the upstream microRNA (miRNA). Results: GLP-1RA treatment obviously improved serum BNP, myocardial fibrosis, lipid deposition of the myocardium and echocardiography parameters in DCM mice. Sarcolemmal membrane-associated protein (SLMAP) was one of 61 differentially expressed cardiac proteins found in three groups by proteomic analysis. Up-regulation of microRNA-29b-3p (miR-29b-3p) and down-regulation of SLMAP were found in the ventricular myocardium of GLP-1RA-treated DCM mice. SLMAP was a target of miR-29b-3p, while GLP-1RA regulated SLMAP expression through miR-29b-3p. Furthermore, inhibition of glucagon-like peptide-1 receptor (GLP-1R) in cardiomyocytes reversed the effects of GLP-1RA on miR-29b/SLMAP. Conclusion: SLMAP may play roles in the pathogenesis of DCM and may be a target of GLP-1RA in protecting against DCM. After binding to myocardial GLP-1R, GLP-1RA can regulate the expression of myocardial SLMAP through miR-29b-3p.
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Diabetes Mellitus , Cardiomiopatías Diabéticas , Receptor del Péptido 1 Similar al Glucagón , Proteínas de la Membrana , MicroARNs , Animales , Ratones , Cardiomiopatías Diabéticas/tratamiento farmacológico , Cardiomiopatías Diabéticas/prevención & control , Cardiomiopatías Diabéticas/metabolismo , Receptor del Péptido 1 Similar al Glucagón/agonistas , MicroARNs/genética , MicroARNs/metabolismo , Miocitos Cardíacos/metabolismo , Proteómica , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismoRESUMEN
African swine fever (ASF) is a highly contagious disease of domestic and wild pigs caused by the African swine fever virus (ASFV). The current research on ASF vaccines focuses on the development of naturally attenuated, isolated, or genetically engineered live viruses that have been demonstrated to produce reliable immunity. As a result, a genetically engineered virus containing five genes deletion was synthesized based on ASFV Chinese strain GZ201801, named ASFV-GZΔI177LΔCD2vΔMGF. The five-gene-deleted ASFV was safe and fully attenuated in pigs and provides reliable protection against the parental ASFV strain challenge. This indicates that the five-gene-deleted ASFV is a potential candidate for a live attenuated vaccine that could control the spread of ASFV.
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Virus de la Fiebre Porcina Africana , Fiebre Porcina Africana , Vacunas Virales , Porcinos , Animales , Fiebre Porcina Africana/prevención & control , Vacunas Atenuadas/genética , Vacunas Virales/genética , Proteínas Virales/genética , VirulenciaRESUMEN
Oral microbial dysbiosis contributes to the development of oral squamous cell carcinoma (OSCC). Numerous studies have focused on variations in the oral bacterial microbiota of patients with OSCC. However, similar studies on fungal microbiota, another integral component of the oral microbiota, are scarce. Moreover, there is an evidence gap regarding the role that microecosystems play in different niches of the oral cavity at different stages of oral carcinogenesis. Here, we catalogued the microbial communities in the human oral cavity by profiling saliva, gingival plaque, and mucosal samples at different stages of oral carcinogenesis. We analyzed the oral bacteriome and mycobiome along the health-premalignancy-carcinoma sequence. Some species, including Prevotella intermedia, Porphyromonas endodontalis, Acremonium exuviarum, and Aspergillus fumigatus, were enriched, whereas others, such as Streptococcus salivarius subsp. salivarius, Scapharca broughtonii, Mortierella echinula, and Morchella septimelata, were depleted in OSCC. These findings suggest that an array of signature species, including bacteria and fungi, are closely associated with oral carcinogenesis. OSCC-associated diversity differences, species distinction, and functional alterations were most remarkable in mucosal samples, not in gingival plaque or saliva samples, suggesting an urgent need to define oral carcinogenesis-associated microbial dysbiosis based on the spatial microbiome. IMPORTANCE Abundant oral microorganisms constitute a complex microecosystem within the oral environment of the host, which plays a critical role in the adjustment of various physiological and pathological states of the oral cavity. In this study, we demonstrated that variations in the "core microbiome" may be used to predict carcinogenesis. In addition, sample data collected from multiple oral sites along the health-premalignancy-carcinoma sequence increase our understanding of the microecosystems of different oral niches and their specific changes during oral carcinogenesis. This work provides insight into the roles of bacteria and fungi in OSCC and may contribute to the development of early diagnostic assays and novel treatments.
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Carcinoma de Células Escamosas , Neoplasias de la Boca , Micobioma , Humanos , Neoplasias de la Boca/complicaciones , Neoplasias de la Boca/microbiología , Carcinoma de Células Escamosas/complicaciones , Carcinoma de Células Escamosas/microbiología , Disbiosis/microbiología , Bacterias/genética , Hongos/genéticaRESUMEN
Objective: Although the pathogenesis of non-alcoholic fatty liver disease (NAFLD) has been extensively studied, the role of its underlying pathogenesis remains unclear, and there is currently no approved therapeutic strategy for NAFLD. The purpose of this study was to observe the beneficial effects of Semaglutide on NAFLD in vivo and in vitro, as well as its potential molecular mechanisms. Methods: Semaglutide was used to treat type 2 diabetes mellitus (T2DM) combined with NAFLD mice for 12 weeks. Hepatic function and structure were evaluated by liver function, blood lipids, liver lipids, H&E staining, oil red staining and Sirius staining. The expression of α/ß hydrolase domain-6 (ABHD6) was measured by qPCR and Western blotting in vivo and in vitro. Then, dual-luciferase reporter assay was performed to verify the regulation of the upstream miR-5120 on ABHD6. Results: Our data revealed that Semaglutide administration significantly improved liver function and hepatic steatosis in T2DM combined with NAFLD mice. Furthermore, compared with controls, up-regulation of ABHD6 and down-regulation of miR-5120 were found in the liver of T2DM+NAFLD mice and HG+FFA-stimulated Hepa 1-6 hepatocytes. Interestingly, after Semaglutide intervention, ABHD6 expression was significantly decreased in the liver of T2DM+NAFLD mice and in HG+FFA-stimulated Hepa 1-6 hepatocytes, while miR-5120 expression was increased. We also found that miR-5120 could regulate the expression of ABHD6 in hepatocytes, while Semaglutide could modulate the expression of ABHD6 through miR-5120. In addition, GLP-1R was widely expressed in mouse liver tissues and Hepa 1-6 cells. Semaglutide could regulate miR-5120/ABHD6 expression through GLP-1R. Conclusion: Our data revealed the underlying mechanism by which Semaglutide improves hepatic steatosis in T2DM+NAFLD, and might shed new light on the pathological role of miR-5120/ABHD6 in the pathogenesis of T2DM+NAFLD.
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Diabetes Mellitus Tipo 2 , MicroARNs , Enfermedad del Hígado Graso no Alcohólico , Animales , Diabetes Mellitus Tipo 2/metabolismo , Péptidos Similares al Glucagón , Hígado/metabolismo , Ratones , Ratones Endogámicos C57BL , MicroARNs/genética , MicroARNs/metabolismo , Monoacilglicerol Lipasas/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismoRESUMEN
Purpose: This study aims to investigate the renal protective effect of glucagon-like peptide 1 receptor agonist (GLP-1RA) on improving renal tubular damage in diabetic kidney disease (DKD) and to explore the potential mechanism of GLP-1RA on renal tubular protection. Methods: Long-acting GLP-1RA was used to treat DKD mice for 12 weeks. The label-free quantitative proteomic analysis of renal proteins was conducted to explore the differentially expressed proteins (DEPs) in the renal tissues of the control, DKD and GLP-1RA groups. The DEPs and markers of renal tubular injury were verified by qPCR in vivo and in vitro. The expression of glucagon-likepeptide-1 receptor (GLP-1R) in renal tubules was determined by immunofluorescence staining. Results: GLP-1RA treatment significantly improved the tubular damages in kidney tissues of DKD mice and mTEC cells stimulated by high glucose (HG). Proteomics analysis revealed that 30 proteins in kidney tissue were differentially expressed among three groups. Seminal vesicle secretory protein 6 (SVS6) was the most differentially expressed protein in kidney tissues among three groups of mice. The expression changes of Svs6 mRNA in vitro and in vivo detected by qPCR were consistent with the results of proteomic analysis. Furthermore, reduction of Svs6 expression by SVS6 siRNA could attenuate HG-stimulated tubular injury in mTEC cells. Immunofluorescence staining also found that GLP-1R was widely expressed in renal tubules in vitro and in vivo. Conclusion: GLP-1RA significantly improved renal tubular damage in DKD mice. SVS6 may be a potential therapeutic target for GLP-1RA in the treatment of DKD.
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OBJECTIVE: Branched-chain amino acids (BCAAs) are essential AAs which are widely used as antioxidants in patients with liver and kidney dysfunction. However, BCAAs are strongly correlated with insulin resistance (IR) and diabetes. This study aimed to evaluate the relationship among BCAAs, oxidative stress, and type 2 diabetes mellitus (T2DM) in a Chinese population. METHODS: Anthropometric and biochemical examinations were performed in 816 individuals who participated in the Huai'an Diabetes Prevention Program. Serum BCAAs concentrations were measured by hydrophilic interaction chromatography-tandem mass spectrometric method. Oxidative stress was evaluated by malondialdehyde (MDA) as an index of lipid peroxidation and the superoxide dismutase (SOD) activity. RESULTS: A total of 816 participants were divided into three groups: normal glucose metabolism (NGM), prediabetes, and newly-diagnosed diabetes mellitus (NDM). Subjects in NDM group show higher MDA and lower SOD levels than subjects in other groups. L-Val levels positively correlated with MDA levels and negatively with SOD in NDM groups. After adjusting for T2DM risk factors, high L-Val levels were significantly associated with higher BMI, WC, FPG, increased LnTG and decreased HDL-C. L-Val was also independently associated with NDM (OR 1.06, 95% CI 1.02-1.10; P = 0.005). Furthermore, the odds ratios for NDM among participants with high L-Val (≥35.25µg/mL) levels showed a 2.25-fold (95% CI 1.11-4.57; P = 0.024) increase compared to participants with low L-Val (<27.26 µg/mL) levels after adjusting for MDA and confounding factors. CONCLUSION: High serum L-Val levels are independently associated with oxidative stress, thus promoting IR and NDM. Further study should be done to clarify the mechanism.
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Gouty arthritis is a common inflammatory disease characterized by monosodium urate (MSU) crystal-induced nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome activation with upregulated caspase 1 protease and IL-1ß in macrophages. Cucurbitacin B (CuB) is a tetracyclic triterpene that possesses a potential anti-inflammatory activity. However, the immunomodulatory and anti-inflammatory effects of CuB on gout have not been well characterized. Therefore, the purpose of the present study was to determine whether CuB exhibits anti-inflammatory effects on gout and to analyze the underlying molecular mechanism. We examined the effects of CuB on various stimuli-activated bone marrow-derived macrophages (BMDMs) and in a mouse model with MSU-induced acute gouty arthritis. Our results demonstrated that CuB effectively suppressed multiple stimuli-activated IL-1ß secretion by interrupting NLRP3 inflammasome complex formation, inhibiting NLRP3 inflammasome activation and suppressing key enzymes of glycolysis in macrophages. Consistent with this, CuB pretreatment also ameliorated MSU-induced arthritis in vivo models of gout arthritis, manifested by reduced foot swelling and inflammatory cell infiltration. Taken together, our data provide the evidence that CuB is an NLRP3 inflammasome inhibitor with therapeutic potential for treating NLRP3 inflammasome-mediated diseases, especially gouty arthritis.
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Artritis Gotosa/metabolismo , Inflamasomas/antagonistas & inhibidores , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Triterpenos/farmacología , Adenosina Trifosfato/metabolismo , Animales , Artritis Gotosa/tratamiento farmacológico , Artritis Gotosa/etiología , Artritis Gotosa/patología , Biomarcadores , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Glucólisis , Gota/tratamiento farmacológico , Gota/etiología , Gota/metabolismo , Gota/patología , Interleucina-1beta/metabolismo , Lipopolisacáridos/efectos adversos , Activación de Macrófagos/efectos de los fármacos , Activación de Macrófagos/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/metabolismo , Masculino , Ratones , Receptor Toll-Like 4/metabolismoRESUMEN
Strains of avian pathogenic Escherichia coli (APEC), the common pathogen of avian colibacillosis, encounter reactive oxygen species (ROS) during the infection process. Superoxide dismutases (SODs), acting as antioxidant factors, can protect against ROS-mediated host defenses. Our previous reports showed that the sodA gene (encoding a Mn-cofactor-containing SOD [MnSOD]) is highly expressed during the septicemic infection process of APEC. sodA has been proven to be a virulence factor of certain pathogens, but its role in the pathogenicity of APEC has not been fully identified. In this study, we deleted the sodA gene from the virulent APEC O2 strain E058 and examined the in vitro and in vivo phenotypes of the mutant. The sodA mutant was more sensitive to hydrogen peroxide in terms of both its growth and viability than was the wild type. The ability to form a biofilm was weakened in the sodA mutant. The sodA mutant was significantly more easily phagocytosed by chicken macrophages than was the wild-type strain. Chicken infection assays revealed significantly attenuated virulence of the sodA mutant compared with the wild type at 24 h postinfection. The virulence phenotype was restored by complementation of the sodA gene. Quantitative real-time reverse transcription-PCR revealed that the inactivation of sodA reduced the expression of oxidative stress response genes katE, perR, and osmC but did not affect the expression of sodB and sodC Taken together, our studies indicate that SodA is important for oxidative resistance and virulence of APEC E058.IMPORTANCE Avian colibacillosis, caused by strains of avian pathogenic Escherichia coli, is a major bacterial disease of severe economic significance to the poultry industry worldwide. The virulence mechanisms of APEC are not completely understood. This study investigated the influence of an antioxidant protein, SodA, on the phenotype and pathogenicity of APEC O2 strain E058. This is the first report demonstrating that SodA plays an important role in protecting a specific APEC strain against hydrogen peroxide-induced oxidative stress and contributes to the virulence of this pathotype strain. Identification of this virulence factor will enhance our knowledge of APEC pathogenic mechanisms, which is crucial for designing successful strategies against associated infections and transmission.
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Proteínas Bacterianas/metabolismo , Infecciones por Escherichia coli/veterinaria , Escherichia coli/patogenicidad , Enfermedades de las Aves de Corral/patología , Superóxido Dismutasa/metabolismo , Factores de Virulencia/metabolismo , Animales , Biopelículas/crecimiento & desarrollo , Pollos , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Infecciones por Escherichia coli/microbiología , Infecciones por Escherichia coli/patología , Eliminación de Gen , Perfilación de la Expresión Génica , Prueba de Complementación Genética , Peróxido de Hidrógeno/toxicidad , Pruebas de Sensibilidad Microbiana , Viabilidad Microbiana/efectos de los fármacos , Estrés Oxidativo , Fagocitosis , Enfermedades de las Aves de Corral/microbiología , Reacción en Cadena en Tiempo Real de la Polimerasa , Estrés Fisiológico , Superóxido Dismutasa/deficienciaRESUMEN
In this paper, a series of poly ammonium shale inhibitors were prepared from diethylamine, epichlorohydrin, and melamine (DEM) and their inhibition to shale were evaluated by bentonite linear expansion test, anti-swelling experiments, and mud ball experiments. Additionally, other properties of drilling fluid treated by poly ammonium were evaluated. Anti-swelling results showed that anti-swelling rate of DEM-8 reaches up to 97.8% when its concentration reaches to 0.8%. Mud ball experiment and drilling fluid evaluation showed DEM-8 has strong inhibitive capability to bentonite hydration swelling and controlling the particle size of bentonite in a large scale. The inhibition mechanism of DEM-8 was studied by thermogravimetric analysis and scanning electron microscope. The results demonstrate that DEM-8 can be adsorbed on clay surface through electrostatic interaction and hydrogen bonds by an anchoring effect and a hydrophobic effect.
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CONTEXT: Thyroid stimulating hormone (TSH) has received increasing attention as being closely associated with increased low-density lipoprotein cholesterol (LDL-c) level and higher atherosclerotic risks. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is known for increasing circulating LDL-c level by inducing LDL receptor degradation. However, whether TSH influences hepatic PCSK9 expression and LDL-c metabolism remains unclear. METHODS: First, the correlation between TSH and lipid profiles were investigated in euthyroid population and in subclinical hypothyroidism patients. Then, an in vitro study was conducted to validate the effects of TSH on hepatic PCSK9 expression in HepG2 cells. RESULTS: Serum TSH concentrations positively correlated with LDL-c levels in euthyroid subjects. Subclinical hypothyroidism patients with higher serum TSH levels showed significantly increased serum PCSK9 levels than the matched euthyroid participants (151.29 (89.51-293.03) vs. 84.70 (34.98-141.72) ng/ml, P<0.001), along with increased LDL-c concentrations. In HepG2 cells, LDLR expression on the plasma membrane was decreased, and PCSK9 mRNA and protein levels were synchronously upregulated after recombinant human TSH (rhTSH) treatment, while the effects could be blocked by TSH receptor blocking antibody K1-70. Sterol regulatory element binding protein (SREBP) 1c and SREBP2 mRNA expressions were enhanced after rhTSH treatment, and specific siRNAs significantly inhibited the effects of rhTSH. Furthermore, there was a noticeable induction of PCSK9 expression by rhTSH even though HMGCR gene expression was silenced. CONCLUSION: We conclude a regulating role of TSH on hepatic PCSK9 expression, which further contributing to a higher LDL-c level.
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Hipotiroidismo/sangre , Lípidos/sangre , Lipoproteínas LDL/sangre , Hígado/efectos de los fármacos , Proproteína Convertasa 9/metabolismo , Tirotropina/sangre , Estudios Transversales , Femenino , Células Hep G2 , Humanos , Hipotiroidismo/diagnóstico , Hígado/metabolismo , Masculino , Persona de Mediana Edad , Proproteína Convertasa 9/sangre , Proproteína Convertasa 9/genética , Índice de Severidad de la Enfermedad , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Proteína 2 de Unión a Elementos Reguladores de Esteroles/genética , Proteína 2 de Unión a Elementos Reguladores de Esteroles/metabolismo , Tirotropina/farmacología , Regulación hacia ArribaRESUMEN
Urinary tract infections (UTIs) are among the most common human diseases worldwide. This study aimed to collect uropathogenic Escherichia coli (UPEC) isolates from Jiangsu Province and obtain insights into the molecular epidemiology of UPEC in this region. The O serotypes, phylogenetic groups, and virulence factors of 183 UPEC isolates were determined. In this study, we isolated 51 UPEC isolates with common O serotypes including O1, O2, O4, O6, O7, O16, O18 and O75, as well as 35 of those with uncommonly encountered O serotypes including O8, O12, O15, O26, and O74. Groups B2 and D were the most prevalent phylogenetic groups and accounted for 29.5% and 41% of the isolates, respectively. In the tested 13 virulence genes (VGs), tonB and dsdA possessed the highest prevalence rate, followed by fimH, degP and ompR. Several other virulence genes such as fliC, neuC, ireA, and vat had prevalence less than 23%. Moreover, representative isolates belonging to common or uncommon O serotypes with different numbers of VGs were chosen for the pathogenic analyses. Based on the results of 1-day-old chick lethality assay and UTI ascending mouse infection model, our study suggested that the virulence of UPEC isolates for chicks and/or mice depended on both the number of VGs expressed and the O serotypes.
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Infecciones por Escherichia coli/microbiología , Genotipo , Antígenos O/análisis , Serogrupo , Infecciones Urinarias/microbiología , Escherichia coli Uropatógena/clasificación , Factores de Virulencia/análisis , Animales , Animales Recién Nacidos , Pollos , China , Modelos Animales de Enfermedad , Infecciones por Escherichia coli/epidemiología , Humanos , Ratones Endogámicos BALB C , Epidemiología Molecular , Filogenia , Análisis de Supervivencia , Infecciones Urinarias/epidemiología , Escherichia coli Uropatógena/genética , Escherichia coli Uropatógena/aislamiento & purificación , Escherichia coli Uropatógena/patogenicidad , Factores de Virulencia/genéticaRESUMEN
BACKGROUND Clinical cases of nonmedullary thyroid carcinoma (NMTC) in combination with primary hyperparathyroidism (PHPT) have been reported occasionally. However, the clinical characteristics and risk factors of concomitant NMTC in PHPT patients remain unclear. This study aimed to assess the association between PHPT and NMTC, and evaluate the clinical characteristics and risk factors of NMTC in Chinese patients with PHPT. MATERIAL AND METHODS This was a retrospective cohort analysis. We reviewed the medical records of 155 patients who underwent surgery for PHPT in two large medical centers in China between 2009 and 2014. The clinical manifestations, biochemical abnormalities, and histological characteristics of PHPT patients were analyzed. RESULTS Of the 155 patients with PHPT, 58 patients (37.4%) had thyroid nodules and 12 patients (7.7%) were ill with concomitant NMTC. PHPT patients with NMTC demonstrated significantly lower preoperative serum calcium levels compared to PHPT patients with benign thyroid nodules (p<0.05). A significantly negative association between preoperative serum calcium levels and the presence of NMTC was found in PHPT patients (p<0.05). Furthermore, ROC analysis revealed that albumin-corrected serum calcium levels <2.67 mmol/L had good capacity to differentiate the PHPT patients with NMTC from those with benign thyroid nodules. CONCLUSIONS Compared with the reported much lower prevalence of thyroid carcinoma in the general population, our results suggest that PHPT might be a risk factor for the malignancy of thyroid nodules; a lower level of serum calcium may predict the existence of NMTC in PHPT patients with thyroid nodules.
Asunto(s)
Calcio/sangre , Hiperparatiroidismo Primario/sangre , Neoplasias de la Tiroides/sangre , Adolescente , Adulto , Anciano , Biomarcadores de Tumor/sangre , China , Estudios de Cohortes , Femenino , Humanos , Hiperparatiroidismo Primario/cirugía , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Neoplasias de la Tiroides/patología , Adulto JovenRESUMEN
Objective. This study aimed to evaluate the relationship between branched-chain amino acids (BCAAs), metabolic syndrome (MS), and other cardiovascular (CV) risk factors in middle-aged and elderly Chinese population at high risk for the development of cardiovascular disease (CVD). Methods. 1302 subjects were enrolled from the Huai'an Diabetes Prevention Program. Results. BCAAs levels were positively correlated with MS, its components, and CV risk profile. The odds ratio (OR) for MS among subjects in the fourth quartile of BCAAs levels showed a 2.17-fold increase compared with those in the first quartile. BCAAs were independently associated with high Framingham risk score even after adjusting for MS and its components (P < 0.0001). Additionally, the OR for high CV risk was 3.20-fold (P < 0.0001) in participants in the fourth BCAAs quartile with MS compared with participants in the first BCAAs quartile without MS. Conclusions. Increased BCAAs levels are independent risk factors of MS and CVD in addition to the traditional factors in middle-aged and elderly Chinese population. The development of CVD in MS patients with high level BCAAs is accelerated. Intervention studies are needed to investigate whether the strategy of BCAAs reduction has impacts on endpoints in patients with higher CV risk. This study is registered with ChiCTR-TRC-14005029.
RESUMEN
Certain strains of avian pathogenic Escherichia coli (APEC) cause severe extraintestinal infections in poultry, including acute fatal septicemia, subacute pericarditis, and airsacculitis. These bacteria contain an RstA/RstB regulatory system, a two-component system that may help APEC strains adapt to the extra-intestinal environment and survive under stressful conditions. Whether RstA correlates with APEC pathogenesis or acts as an APEC virulence factor has not been established. Here we provide the first evidence for an important role of rstA in APEC virulence. We generated an rstA-deficient mutant from the highly virulent APEC strain E058. Virulence of the mutant strain was evaluated in vivo and in vitro through bird infection assays, a cytotoxicity assay on chicken macrophage cell line HD-11, and a bactericidal assay to serum complement. Based on lethality assays in 1-day-old birds, rstA deletion from APEC E058 reduced the bacterial virulence in birds. The deletion also deeply impaired the capacity of APEC E058 to colonize deeper tissues of 5-week-old specific pathogen free chickens. No obvious gross or histopathological lesions were observed in the visceral organs of chickens challenged with the rstA-deficient strain. Also, rstA inactivation reduced the survival of APEC E058 within chicken macrophages. However, no significant differences were observed between the mutant and the wild-type strain in resistance to serum. Our data collectively show that the rstA gene functions in the pathogenesis of diseases caused by avian pathogenic E. coli.
Asunto(s)
Pollos/microbiología , Proteínas de Escherichia coli/metabolismo , Escherichia coli/patogenicidad , Factores de Virulencia/metabolismo , Animales , Escherichia coli/genética , Infecciones por Escherichia coli/microbiología , Infecciones por Escherichia coli/patología , Infecciones por Escherichia coli/veterinaria , Proteínas de Escherichia coli/genética , Corazón/virología , Mutación INDEL , Hígado/virología , Pulmón/virología , Enfermedades de las Aves de Corral/microbiología , Enfermedades de las Aves de Corral/patología , Factores de Virulencia/genéticaRESUMEN
Avian pathogenic Escherichia coli (APEC) infection causes avian colibacillosis, which refers to any localized or systemic infection, such as acute fatal septicemia or subacute pericarditis and airsacculitis. The RfaH transcriptional regulator in E. coli is known to regulate a number of phenotypic traits. The direct effect of RfaH on the virulence of APEC has not been investigated yet. Our results showed that the inactivation of rfaH significantly decreased the virulence of APEC E058. The attenuation was assessed by in vivo and in vitro assays, including chicken infection assays, an ingestion and intracellular survival assay, and a bactericidal assay with serum complement. The virulence phenotype was restored to resemble that of the wild type by complementation of the rfaH gene in trans. The results of the quantitative real-time reverse transcription-PCR (qRT-PCR) analysis and animal system infection experiments indicated that the deletion of rfaH correlated with decreased virulence of the APEC E058 strain.
Asunto(s)
Pollos , Infecciones por Escherichia coli/veterinaria , Proteínas de Escherichia coli/genética , Escherichia coli/genética , Factores de Elongación de Péptidos/genética , Enfermedades de las Aves de Corral/microbiología , Transactivadores/genética , Animales , Coinfección , Cartilla de ADN/genética , Resistencia a la Enfermedad , Escherichia coli/crecimiento & desarrollo , Escherichia coli/patogenicidad , Infecciones por Escherichia coli/inmunología , Infecciones por Escherichia coli/microbiología , Proteínas de Escherichia coli/metabolismo , Prueba de Complementación Genética , Macrófagos/microbiología , Factores de Elongación de Péptidos/metabolismo , Fenotipo , Enfermedades de las Aves de Corral/inmunología , Eliminación de Secuencia , Organismos Libres de Patógenos Específicos , Transactivadores/metabolismo , Virulencia , Factores de Virulencia/genética , Factores de Virulencia/metabolismoRESUMEN
BACKGROUND: Steroid 11beta-hydroxylase deficiency (11beta-OHD), an autosomal recessive inherited disease, accounts for 5% - 8% of congenital adrenal hyperplasia. It was scarcely reported in China. This article reports two Chinese girls with 11beta-OHD. METHODS: The two patients were sisters and presented with hypertrichosis, skin pigmentation, laryngeal prominence and virilization of external genitalia. The patients were followed up for their clinical symptoms and signs, hormone profile, and adrenal image. The genomic deoxyribonucleic acids of the patients and their parents were isolated. 11beta-hydroxylase gene (CYP11B1) was amplified by polymerase chain reaction and directly sequenced. RESULTS: Hormone tests showed that serum cortisol was in the low limit of normal range, whereas the concentrations of adrenocorticotropic hormone, testosterone and progesterone were much higher than those of normal adult females. There were obvious adrenal hyperplasia and advance of bone age. After 11 months of treatment with dexamethasone, the skin pigment became regressed; the breast, uterus and ovary gradually developed and normal menstrual cycle started while the manifestations of virilization did not change. A single point mutation of CYP11B1 (R454C, GGC --> TGC) in all the members of this family was detected. The sisters were homozygous and their parents were heterozygous. CONCLUSIONS: The clinical manifestation of 11beta-OHD is complicated. The manifestation of virilization could not regress after treatment with dexamethasone. The novel missense mutation of CYP11B1 (R454C, GGC --> TGC) is the pathogenesis of 11beta-OHD at least in some Chinese patients.