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BACKGROUND: Neonatal Intrahepatic Cholestasis (NICCD), as the early-age stage of Citrin deficiency involving liver dysfunction, lacks efficient diagnostic markers. Procalcitonin (PCT) has been identified as a biomarker for infection as well as various organ damage. This study aimed to explore the potential of PCT as a biomarker for NICCD. METHODS: In a single-center retrospective case-control study. Serum PCT concentrations before and after treatment of 120 NICCD patients, as the study group, were compared to the same number of cholestatic hepatitis patients, as the control group. The potential value of PCT to discriminate NICCD from control disease was further explored using Receiver Operating Characteristic (ROC) curve analysis and compared to those of other inflammatory markers. RESULTS: There was a significantly higher level of PCT in NICCD patients than in the control group. PCT concentrations were only weakly correlated with neutrophil counts and CRP levels (p Ë 0.05). At a cut-off value of 0.495 ng/mL, PCT exhibited a significantly higher diagnostic value compared to other inflammatory markers for discriminating NICCD from the control, with a sensitivity of 90.8 % and specificity of 98.3 %. CONCLUSION: PCT might be used as an initial biomarker to discriminate children with NICCD from another hepatitis disease.
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Biomarcadores , Colestasis Intrahepática , Citrulinemia , Polipéptido alfa Relacionado con Calcitonina , Curva ROC , Humanos , Polipéptido alfa Relacionado con Calcitonina/sangre , Biomarcadores/sangre , Estudios Retrospectivos , Masculino , Femenino , Estudios de Casos y Controles , Colestasis Intrahepática/sangre , Colestasis Intrahepática/diagnóstico , Citrulinemia/sangre , Citrulinemia/complicaciones , Citrulinemia/diagnóstico , Lactante , Recién Nacido , Sensibilidad y Especificidad , Proteína C-Reactiva/análisis , Valores de ReferenciaRESUMEN
OBJECTIVE: To explore the characteristics of SLCO1B1/SLCO1B3 gene variants among children with Rotor syndrome (RS). METHODS: Four children who were admitted to the Department of Hepatology of Hunan Children's Hospital between January 2019 and January 2022 were selected as the study subjects. Trio-whole exome sequencing was carried out for the four families, and gel electrophoresis was used to verify an insertional variant of long-interspersed element-1 (LINE-1). RESULTS: Genetic testing has identified three variants of the SLCO1B1 gene, including c.1738C>T (p.R580*), c.757C>T (p.R253*) and c.1622A>C (p.Q541P), and two variants of the SLCO1B3 gene, including c.481+22insLINE-1 and c.1747+1G>A among the children. Three of them were found to harbor homozygous variants of the SLCO1B1/SLCO1B3 genes, and one has harbored compound heterozygous variants. Sanger sequencing confirmed the existence of all variants, and gel electrophoresis has confirmed the existence of the LINE-1 insertional variant of about 6 kb within intron 6 of the SLCO1B3 gene in all children. CONCLUSION: The pathogenesis of the RS among the four children may be attributed to the variants of the SLCO1B1/SLCO1B3 genes. The LINE-1 insertion variant of the SLCO1B3 gene may be common among Chinese RS patients.
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Pruebas Genéticas , Miembro 1B3 de la Familia de los Transportadores de Solutos de Aniones Orgánicos , Humanos , Masculino , Femenino , Niño , Miembro 1B3 de la Familia de los Transportadores de Solutos de Aniones Orgánicos/genética , Preescolar , Pruebas Genéticas/métodos , Transportador 1 de Anión Orgánico Específico del Hígado/genética , Secuenciación del Exoma , Lactante , MutaciónRESUMEN
PURPOSE: This study utilized intelligent devices to remotely monitor patients with chronic obstructive pulmonary disease (COPD), aiming to construct and evaluate machine learning (ML) models that predict the probability of acute exacerbations of COPD (AECOPD). METHODS: Patients diagnosed with COPD Group C/D at our hospital between March 2019 and June 2021 were enrolled in this study. The diagnosis of COPD Group C/D and AECOPD was based on the GOLD 2018 guidelines. We developed a series of machine learning (ML)-based models, including XGBoost, LightGBM, and CatBoost, to predict AECOPD events. These models utilized data collected from portable spirometers and electronic stethoscopes within a five-day time window. The area under the ROC curve (AUC) was used to assess the effectiveness of the models. RESULTS: A total of 66 patients were enrolled in COPD groups C/D, with 32 in group C and 34 in group D. Using observational data within a five-day time window, the ML models effectively predict AECOPD events, achieving high AUC scores. Among these models, the CatBoost model exhibited superior performance, boasting the highest AUC score (0.9721, 95 % CI: 0.9623-0.9810). Notably, the boosting tree methods significantly outperformed the time-series based methods, thanks to our feature engineering efforts. A post-hoc analysis of the CatBoost model reveals that features extracted from the electronic stethoscope (e.g., max/min vibration energy) hold more importance than those from the portable spirometer. CONCLUSIONS: The tree-based boosting models prove to be effective in predicting AECOPD events in our study. Consequently, these models have the potential to enhance remote monitoring, enable early risk assessment, and inform treatment decisions for homebound patients with chronic COPD.
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Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Medición de Riesgo , Aprendizaje Automático , Progresión de la EnfermedadRESUMEN
Abstract Background Neonatal Intrahepatic Cholestasis (NICCD), as the early-age stage of Citrin deficiency involving liver dysfunction, lacks efficient diagnostic markers. Procalcitonin (PCT) has been identified as a biomarker for infection as well as various organ damage. This study aimed to explore the potential of PCT as a biomarker for NICCD. Methods In a single-center retrospective case-control study. Serum PCT concentrations before and after treatment of 120 NICCD patients, as the study group, were compared to the same number of cholestatic hepatitis patients, as the control group. The potential value of PCT to discriminate NICCD from control disease was further explored using Receiver Operating Characteristic (ROC) curve analysis and compared to those of other inflammatory markers. Results There was a significantly higher level of PCT in NICCD patients than in the control group. PCT concentrations were only weakly correlated with neutrophil counts and CRP levels (p ˂ 0.05). At a cut-off value of 0.495 ng/mL, PCT exhibited a significantly higher diagnostic value compared to other inflammatory markers for discriminating NICCD from the control, with a sensitivity of 90.8 % and specificity of 98.3 %. Conclusion PCT might be used as an initial biomarker to discriminate children with NICCD from another hepatitis disease.
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Coriolus versicolor, a popular traditional Chinese medicinal herb, is widely used in China to treat spleen and liver diseases; however, the beneficial effects of C. versicolor polysaccharides (CVPs) on nonalcoholic fatty liver disease (NAFLD) remain elusive. Herein we isolated and purified a novel CVP (molecular weight, 17,478 Da) from fermented mycelium powder. This CVP was composed of mannose, galacturonic acid, glucose, galactose, xylose, and fucose at a molar ratio of 22:1:8:15:10:3. Methylation, gas chromatography-mass spectrometry, and nuclear magnetic resonance analyses indicated that the CVP backbone consisted of â1)-ß-D-Man-(6,4â1)-α-D-Gal-(3â1)-α-D-Man-(4â1)-α-D-Gal-(6â, with branches of â1)-α-D-Glc-(6â1)-α-D-Man-(4,3â1)-ß-D-Xyl-(2â1)-ß-D-Glc on the O-6 position of â1)-ß-D-Man-(6,4â of the main chain. The secondary branches linked to the O-4 position of â1)-α-D-Man-(4,3â with the chain of â1)-α-D-Fuc-(4â1)-α-D-Man. Further, CVP treatment alleviated the symptoms of NAFLD in an HFD-induced mice model. CVP altered gut microbiota, predominantly suppressing microbes associated with bile acids both in the serum and cecal contents. In vitro data showed that CVP reduced HFD-induced hyperlipidemia via farnesoid X receptor. Our results improve our understanding of the mechanisms underlying the cholesterol- and lipid-lowering effects of CVP and indicate that CVP is a promising candidate for NAFLD therapy.
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Enfermedad del Hígado Graso no Alcohólico , Polyporaceae , Humanos , Animales , Ratones , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Polisacáridos/farmacología , Polisacáridos/uso terapéutico , Polisacáridos/química , Micelio/químicaRESUMEN
Cs2SnI6 powder is, for the first time, solution-prepared via the formula CsI + SnI2 + I2 â Cs2SnI6. The product is highly pure and air/thermal stable. It is found that N,N-dimethylformamide (DMF) and methanol induce severe Cs2SnI6 deterioration with the appearance of a CsI phase in film preparation from Cs2SnI6 powder, while solvents of γ-butyrolactone (GBL) and ethylene glycol methyl ether (EGME) (Film-EGME) give better results. Then, by introducing EGME solvent, in situ preparation of Cs2SnI6 films (Film-1 to Film-4) is realized under solution reaction, which is found to be dominated by thermal dynamic process, i.e., highly pure/oriented Film-4 is obtained under the maximum reagent-concentration. Besides, for good reaction, the solubility of solvent should be balanced among all the reagents and products. Solid-state dye sensitized solar cells (ss-DSSCs) comprising a Cs2SnI6 electrolyte are investigated. The power conversion efficiencies (PCEs) of the ss-DSSCs based on solution-casted Film-EGME and the in situ-prepared Film-4 are 1.81% and 3.30%, respectively. Particularly, with the in situ prepared Cs2SnI6 films, it is found that the open circuit voltages of the ss-DSSCs are closely related to their gap states. When additive is added in Cs2SnI6 electrolyte, a PCE of 6.14% is obtained in an ss-DSSC. Our work highlights the importance of solvent in film preparation and the role of Cs2SnI6 gap states in device performance.
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BACKGROUND: Progressive familial intrahepatic cholestasis type 3 (PFIC3) is an autosomal recessive disease caused by pathogenic variants of the gene ABCB4. This study aimed to investigate the ABCB4 genotypic and the clinical phenotypic features of PFIC3 patients. METHODS: The clinical and molecular genetic data of 13 new pediatric patients with PFIC3 as well as 82 reported ones in the PubMed and CNKI databases were collected and analyzed. RESULTS: The 13 new PFIC3 patients included six females and seven males, and the main presentations were hepatomegaly, splenomegaly, jaundice, and pruritus, as well as increased levels of gamma-glutamyl transpeptidase (GGT). Fourteen new ABCB4 variants were detected, including eight diagnosed to be likely-pathogenic and six, pathogenic. Among all the 95 PFIC3 cases, hepatomegaly was observed in 85.3% (81/95), pruritus in 67.4% (64/95), splenomegaly in 52.6% (50/95), jaundice in 48.4% (46/95), portal hypertension in 34.7% (33/95) and GGT elevation in 100% (88/88) of the patients. Positive responses at varied degrees to oral ursodeoxycholic acid (UDCA) treatment were observed in 66.1% (39/59) of the patients, among whom 38.5% (15/39) fully recovered in terms of the laboratory changes. Although the condition remained stable in 53 patients (58.9%, 53/90), the clinical outcomes were not promising in the rest 37 cases (41.1%, 37/90), including 7 died, 27 having undergone while another 3 waiting for liver transplantation. A total of 96 ABCB4 variants were detected in the 95 patients. PFIC3 patients with biallelic null variants exhibited earlier onset ages [10.5 (2, 18) vs. 19 (8, 60) months, p = 0.007], lower UDCA response rate [18.2% (2/11) vs. 77.1% (37/48), p = 0.001], and more unpromising clinical outcomes [80% (12/15) vs. 33.3% (25/75), p = 0.001], compared with those with non-biallelic null variants. CONCLUSIONS: PFIC3 presented with hepatomegaly, pruritus, splenomegaly and jaundice with increased serum GGT level as a biochemistry hallmark. Although varying degrees of improvement in response to UDCA therapy were observed, 41.1% of PFIC3 patients exhibited unfavorable prognosis. ABCB4 genotypes of biallelic null variants were associated with severer PFIC3 phenotypes. Moreover, the 14 novel variants in this study expanded the ABCB4 mutation spectrum, and provided novel molecular biomarkers for diagnosis of PFIC3 patients.
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Colestasis Intrahepática , Ictericia , Masculino , Femenino , Humanos , Hepatomegalia/genética , Hepatomegalia/tratamiento farmacológico , Esplenomegalia/tratamiento farmacológico , Colestasis Intrahepática/tratamiento farmacológico , Colestasis Intrahepática/genética , Colestasis Intrahepática/diagnóstico , Ácido Ursodesoxicólico/uso terapéutico , Ictericia/tratamiento farmacológico , Prurito/tratamiento farmacológicoRESUMEN
OBJECTIVE: This study aimed to compare the diagnostic value of the single or combined applications of transient elastography (TE) and multivariate indicators with biopsy for the detection of liver fibrosis in children caused by chronic hepatitis B (CHB). METHODS: This study included 148 CHB children treated at Hunan Children's Hospital from January 1st 2015 to December 31st 2018, aged from 0.83 to 14.58 years old. All patients underwent liver biopsy (LB), of which 43 patients underwent TE. Multiple clinical data, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), Platelet (PLT), and HBV-deoxyribonucleic acid (HBV DNA) of all patients were collected. The diagnostic values for CHB of TE and its combinations with these indicators were measured. The patients were classified in two ways: no hepatic fibrosis group (F0) versus fibrosis group (F ≥ 1), and no significant hepatic fibrosis group (F < 2) versus significant hepatic fibrosis group (F ≥ 2). The statistical assessment was performed between groups within each classification to compare the diagnostic value of different parameters. RESULTS: The operating characteristic area under curve (AUC) of liver fibrosis diagnosed by liver stiffness measurement (LSM) which obtained by TE, AST-to-PLT ratio index (APRI), and fibrosis-4 index (FIB-4) were 0.740, 0.701, and 0.651, while the corresponding cut-off values were 5.9 kPa, 0.50, and 0.10, respectively. The AUC of significant liver fibrosis diagnosed by LSM, APRI and FIB-4 were 0.849, 0.701, and 0.509, while the corresponding cut-off values were 8.4 kPa, 0.76, and 0.08, respectively. While with the combinations of LSM and APRI, LSM and FIB-4, LSM and APRI and FIB-4, APRI and FIB-4, the AUC of significant liver fibrosis were 0.866, 0.855, 0.869, and 0.684, respectively. The AUC of significant liver fibrosis diagnosed by the LSM was significantly higher than APRI and FIB-4. CONCLUSIONS: The diagnostic value of transient elastography was better than that of APRI and FIB-4 for CHB children with significant liver fibrosis. In addition, TE also has relatively high application values on the diagnosis of patients with different degrees of liver fibrosis caused by CHB.
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Diagnóstico por Imagen de Elasticidad , Hepatitis B Crónica , Adolescente , Aspartato Aminotransferasas , Biomarcadores , Biopsia/efectos adversos , Niño , Preescolar , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/diagnóstico por imagen , Hepatitis B Crónica/patología , Humanos , Lactante , Hígado/diagnóstico por imagen , Hígado/patología , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/etiología , Curva ROCRESUMEN
OBJECTIVE: To explore the genetic basis for a child with infantile liver failure syndrome type 2 (ILFS type 2). METHODS: Clinical features of the child were analyzed. Next generation sequencing was also carried out for him. RESULTS: The child was found to harbor compound heterozygous variants of the NBAS gene, which included a novel nonsense c.2746A>T (p.R916X, 1456) variant in exon 24 and a missense c.3596G>A (p.C1199Y) mutation in exon 31, which has been associated with ILFS type 2. The two variants were respectively inherited from his father and mother. CONCLUSION: The compound heterozygous variants of c.3596G>A and c.2746A>T of the NBAS gene probably underlay the ILFS type 2 in this child.
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Pruebas Genéticas , Fallo Hepático , Niño , Exones/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , MutaciónRESUMEN
Introduction: Transient infantile hypertriglyceridemia (HTGTI) is a rare autosomal recessive disease. At present, only 20 cases of HTGTI have been reported worldwide. Hence, it is necessary to further assess the phenotypic and genetic variation spectra of HTGTI. Case Presentation: A 10-month-old male infant was diagnosed with hypertriglyceridemia, hepatomegaly, liver injury, fasting hypoglycemia, and insulin resistance. Trio-whole exome sequencing (trio-WES) was performed on the patient and his parents. Bioinformatics software was used to analyze the suspected genes and potential pathogenicity of the resulting mutant proteins. The results of trio-WES demonstrated that the patient was homozygous for a novel mutation in the GPD1 gene (NM_005276.3; c.805C>T/p.Arg269Trp), whereas his parents were heterozygous for the same mutation. Bioinformatics prediction results demonstrated that the mutation might affect the protein function, and crystal simulation results showed that the mutation might affect the protein-binding ability of the enzyme. Conclusion: Our results indicated that the novel homozygous mutation in GPD1 could be the pathogenic factor in the patient. Our report highlights the value of genome sequencing in the diagnosis of infant liver disease with low phenotypic heterogeneity.
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We explore the role of miR-125b in septic cardiomyopathy, focusing on miR-125b/STAT3/HMGB1 axis. CLP mouse model and LPS-stimulated primary rat cardiomyocytes (CMs) and H9C2 cell were used as in vivo and in vitro models of septic cardiomyopathy, respectively. qRT-PCR and western blot were performed to measure expression levels of miR-125b, STAT3, HMGB1, and autophagy-related proteins. MTT assay was employed to examine LPS toxicity. Dual luciferase activity assay and CHIP were performed to validate interactions of miR-125b/STAT3 and STAT3/HMGB1 promoter. Immunostaining was used to assess the level of autophagic flux. ROS level was measured by fluorescence assay. Heart functions were examined via intracoronary Doppler ultrasound. miR-125b was diminished while STAT3 and HMGB1 were elevated in the heart tissue following CLP surgery and in LPS-treated H9C2 cells. LPS treatment up-regulated ROS generation and suppressed autophagic flux. Overexpression of miR-125b mimics or knockdown of STAT3 or HMGB1 alleviated LPS-induced hindrance of autophagic flux and ROS production. miR-125b directly targeted STAT3 mRNA and STAT3 bound with HMGB1 promoter. Overexpression of miR-125b mitigated myocardial dysfunction induced by CLP in vivo. Hyperactivation of STAT3/HMGB1 caused by reduced miR-125b contributes to ROS generation and the hindrance of autophagic flux during septic cardiomyopathy, leading to myocardial dysfunction.
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Autofagia , Cardiomiopatías/prevención & control , Proteína HMGB1/antagonistas & inhibidores , MicroARNs/genética , Factor de Transcripción STAT3/antagonistas & inhibidores , Sepsis/complicaciones , Animales , Apoptosis , Cardiomiopatías/etiología , Cardiomiopatías/metabolismo , Cardiomiopatías/patología , Proliferación Celular , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Ratones , Ratas , Ratas Sprague-Dawley , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Transducción de SeñalRESUMEN
Nuclear receptor coactivator 5 (NCOA5) has been reported to be involved in the regulation of several malignancies; however, to the best of our knowledge, its role in breast cancer is still unknown. The present study aimed to reveal the biological function of NCOA5 in breast cancer cells. NCOA5 expression in breast cancer tissues and cell lines was examined using reverse transcription-quantitative PCR and western blotting. Small interfering RNA (siRNA) against NCOA5 (siNCOA5) was transfected into MDA-MB-453 and MCF-7 cells to knock down NCOA5. MTT, transwell migration and cell adhesion assays were performed to determine cell viability, migration and adhesion abilities of breast cancer cells, respectively. In addition, the expression levels of N-cadherin, Vimentin and E-cadherin were examined by western blotting. It was revealed that NCOA5 expression was significantly increased in breast cancer tissues and cell lines. Knockdown of NCOA5 suppressed breast cancer cell viability and migration, and induced cell adhesion. Compared with those in cells transfected with non-targeting negative control siRNA, the protein expression levels of N-cadherin and Vimentin were significantly decreased, whereas the protein expression levels of E-cadherin were significantly increased in cells transfected with siNCOA5. The present study demonstrated that knockdown of NCOA5 suppressed cell viability and migration, induced cell adhesion, and inhibited epithelial-mesenchymal transition of breast cancer cells, indicating that NCOA5 may serve a tumor-promoting role in breast cancer.
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INTRODUCTION: Septic cardiomyopathy is a common complication of sepsis with high morbidity and mortality, but lacks specific therapy. This study aimed to reveal the role of circTLK1 and its potential mechanisms in septic cardiomyopathy. MATERIALS AND METHODS: The in vitro and in vivo models of septic cardiomyopathy were established. Cell viability and apoptosis were detected by CCK8, TUNEL and flow cytometry, respectively. LDH, CK, SOD, MDA, ATP, 8-OHdG, NAD+/NADH ratio, ROS level, mitochondrial membrane potential and cytochrome C distribution were evaluated using commercial kits. qRT-PCR and western blotting were performed to detect RNA and protein levels. Mitochondrial DNA (mtDNA) copy number and transcription were assessed by quantitative PCR. Dual-luciferase assay, RNA immunoprecipitation and co-immunoprecipitation were performed to verify the interaction between circTLK1/PARP1 and miR-17-5p. RESULTS: CircTLK1, PARP1 and HMGB1 were up-regulated in the in vitro and in vivo models of septic cardiomyopathy. CircTLK1 inhibition restrained LPS-induced up-regulation of PARP1 and HMGB1. Moreover, circTLK1 knockdown repressed sepsis-induced mtDNA oxidative damage, mitochondrial dysfunction and consequent cardiomyocyte apoptosis by inhibiting PARP1/HMGB1 axis in vitro and in vivo. In addition, circTLK1 enhanced PARP1 expression via sponging miR-17-5p. Inhibition of miR-17-5p abolished the protective effects of circTLK1 silencing on oxidative mtDNA damage and cardiomyocyte apoptosis. CONCLUSION: CircTLK1 sponged miR-17-5p to aggravate mtDNA oxidative damage, mitochondrial dysfunction and cardiomyocyte apoptosis via activating PARP1/HMGB1 axis during sepsis, indicating that circTLK1 may be a putative therapeutic target for septic cardiomyopathy.
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Cardiomiopatías/metabolismo , ADN Circular/fisiología , ADN Mitocondrial/fisiología , Proteínas Serina-Treonina Quinasas , Sepsis/metabolismo , Animales , Línea Celular , Proteína HMGB1/metabolismo , Humanos , Masculino , MicroARNs/metabolismo , Miocitos Cardíacos , Poli(ADP-Ribosa) Polimerasa-1/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/fisiología , Ratas , Ratas Sprague-DawleyRESUMEN
Butyrate has been shown to be effective in ulcerative colitis (UC). However, its oral administration is rare due to its rancid odour and unpleasant taste. In this study, the effect of a butyrate-releasing polysaccharide derivative, xylan butyrate ester (XylB), was evaluated in a dextran sodium sulphate (DSS)-induced UC model in C57BL/6 mice. Linear xylan was extracted from corn cobs. The C-2 and C-3 positions of the linear xylan were esterified with butyrate, forming XylB. The protective and therapeutic effects of XylB against UC were determined in a DSS-induced mouse model. The results showed that XylB treatments reversed the imbalance between pro- and anti-inflammatory cytokines. Moreover, XylB rebalanced the gut microbiota that interfered with DSS treatment and significantly decreased the relative abundance of the genera Oscillibacter, Ruminococcaceae UCG-009, Erysipelatoclostridium, and Defluviitaleaceae UCG-01. XylB increased butyrate content in the colon, upregulated G-protein coupled receptor 109A protein expression, inhibited histone deacetylase (HDAC) activity, and exerted anti-inflammatory activity through autophagy pathway activation and nuclear factor-κB (NF-κB) inhibition. XylB reduces inflammatory intestinal damage in mice, suggesting that it would be a potential drug for the treatment of UC and could be used to overcome the limitations of the oral administration of sodium butyrate.
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Antiinflamatorios/administración & dosificación , Antiinflamatorios/farmacología , Butiratos/metabolismo , Colitis/tratamiento farmacológico , Sulfato de Dextran/efectos adversos , Xilanos/administración & dosificación , Xilanos/farmacología , Administración Oral , Animales , Antiinflamatorios/química , Antiinflamatorios/uso terapéutico , Autofagia/efectos de los fármacos , Secuencia de Carbohidratos , Colitis/inmunología , Colitis/metabolismo , Colon/efectos de los fármacos , Colon/inmunología , Colon/metabolismo , Ratones , Ratones Endogámicos C57BL , Linfocitos T Reguladores/efectos de los fármacos , Células Th17/efectos de los fármacos , Xilanos/química , Xilanos/uso terapéuticoRESUMEN
OBJECTIVE: To evaluate the effect of transcutaneous neuromuscular electrical stimulation on prevention of intensive care unit-acquired weakness (ICU-AW) in chronic obstructive pulmonary disease (COPD) patients with mechanical ventilation. METHODS: A prospective randomized controlled study was conducted. Sixty COPD patients aged 18-85 years old who were accepted mechanical ventilation therapy admitted to general intensive care unit (ICU) of the First Affiliated Hospital of Hunan University of Medicine from October 2017 to October 2018 were enrolled. Patients were divided into control group (n = 30) and intervention group (n = 30) by random number table method. All patients were accepted routine treatment, and on this basis, the intervention group was applied transcutaneous neuromuscular electrical stimulation on the extremities (twice a day, 30 minutes each time) after 24 hours of admission until ICU discharge. The Medical Research Council muscle strength score (MRC-Score), grip strength, incidence of ICU-AW on the 7th day after admission and on the day of ICU discharge; modified Barthel index score on the day of ICU discharge; and duration of mechanical ventilation, the length of ICU stay, and the length of hospital stay were compared between the two groups. RESULTS: Twenty-nine and 27 patients in the control group and the intervention group respectively finally completed the study in dividually. There was no significant difference in gender, age, Barthel index score before 2 weeks of ICU admission, body mass index or acute physiology and chronic health evaluation (APACHE) in ICU between the two groups. There was no significant difference in the MRC-Score, grip strength or incidence of ICU-AW on the 7th day after ICU admission between the two groups. Compared to the control group, the MRC-Score, grip strength and Barthel index score in the intervention group were significantly increased [MRC-Score: 55.97±8.43 vs. 46.32±7.36, grip strength (kg): 33.46±11.62 vs. 27.42±9.64, Barthel index score: 46.04±5.46 vs. 42.13±3.32, all P < 0.05], the incidence rate of ICU-AW was significantly decreased [7.4% (2/27) vs. 31.0% (9/29), P < 0.05], and duration of mechanical ventilation, the length of ICU stay, the length of hospital stay were significantly shortened [duration of mechanical ventilation (days): 5.12±2.01 vs. 7.24±4.35, the length of ICU stay (days): 8.34±2.36 vs. 10.45±2.62, the length of hospital stay (days): 13.21±2.21 vs. 15.38±3.67, all P < 0.05]. CONCLUSIONS: Transcutaneous neuromuscular electrical stimulation can effectively improve the muscle strength of COPD patients with mechanical ventilation and reduce the incidence of ICU-AW.
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Debilidad Muscular/prevención & control , Enfermedad Pulmonar Obstructiva Crónica/terapia , Respiración Artificial , Estimulación Eléctrica Transcutánea del Nervio , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Unidades de Cuidados Intensivos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To investigate role of ß-catenin and lncRNA MALAT1/miR-217 axis to converge into the regulation of ZEB-1 in hepatocyte growth factor (HGF)-induced hepatocytes differentiated from bone marrow mesenchymal stem cells (BM-MSCs). METHODS: BM-MSCs were isolated and HGF was used to induce the differentiation of BM-MSCs into hepatocytes. HSC-T6 cells, BRL-3 A cells and differentiated BM-MSCs were treated by lipopolysaccharide(LPS). shRNAs were used to silence ß-catenin and recombinant plasmids were used to over-express ZEB1. Measurement of cell viability was conducted using MTT assay and Hoechst 33342 staining. RNA immunoprecipitation (RIP) assay was used to determine binding of miR-217-3p and MALAT1. RESULTS: BM-MSCs successfully differentiated into hepatocytes by HGF treatment. Expression of ß-catenin, ZEB-1 and TERT was up-regulated to a higher level in hepatocytes differentiated from BM-MSCs than HSC-T6 cells and BRL-3 A cells after LPS stimulation. When ß-catenin was knocked down in all cell lines, expression of ß-catenin, ZEB-1 and TERT was significantly decreased as well as telomerase activity. While when ZEB1 was over-expressed, expression of TERT and telomerase activity was all significantly up-regulated. In hepatocytes differentiated from BM-MSCs, miR-217 was down-regulated and lncRNA MALAT1 was up-regulated. RIP analysis showed MALAT1 was physically associated with miR-217 and might function in the regulation of ZEB-1, further enhancing the expression of TERT so as to augment telomerase activity. CONCLUSION: We successfully used HGF to mediate differentiation of BM-MSCs into hepatocytes, and found that ß-catenin-coordinated MALAT1/miR-217 axis could up-regulate expression of ZEB-1 and further enhanced the telomerase activity through regulation of TERT in BM-MSCs differentiating into hepatocytes.
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Diferenciación Celular/fisiología , Hepatocitos/citología , Células Madre Mesenquimatosas/citología , Telomerasa/metabolismo , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/biosíntesis , Animales , Células de la Médula Ósea/citología , Células de la Médula Ósea/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Femenino , Factor de Crecimiento de Hepatocito/farmacología , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Células Madre Mesenquimatosas/efectos de los fármacos , ARN Largo no Codificante/biosíntesis , Ratas , Ratas Sprague-Dawley , Regulación hacia Arriba , beta Catenina/metabolismoAsunto(s)
Broncoscopía/métodos , Disnea/diagnóstico , Broncoscopía/efectos adversos , Disnea/terapia , Femenino , Humanos , Lactante , Recién Nacido , MasculinoRESUMEN
Telomeres located at the ends of chromosomes are involved in genomic stability and play a key role in various cancers and age-related diseases. Age-related macular degeneration (AMD) is a late-onset, age-associated progressive neurodegenerative disease, which includes the geographic atrophy (GA) subtype and the choroidal neovascularization (CNV) subtype. To better understand how leukocyte telomere length (LTL) is related to AMD, we conducted an association study in 197 AMD patients and 259 healthy controls using the established quantitative PCR technique. Logistic regression was performed to evaluate the association of LTL and AMD with the age-adjusted ratio of the telomere length to the copy number of a single-copy gene (T/S). Notably, we found a significant association between AMD and LTL (OR=2.24; 95% CI=1.68-3.07; P=0.0001) after adjusting for age and sex. Furthermore, the results showed a strongly significant association between the GA subtype and the LTL (OR=4.81; 95% CI=3.15-7.82; P=0.0001) after adjusting for age and sex. Our findings provide evidence of the role that LTL plays in the pathological mechanisms of AMD, mainly in the GA subgroup but not the CNV subgroup.
Asunto(s)
Envejecimiento , Atrofia Geográfica , Leucocitos/fisiología , Degeneración Macular , Telómero/fisiología , Anciano , Envejecimiento/patología , Envejecimiento/fisiología , Estudios de Casos y Controles , China/epidemiología , Femenino , Inestabilidad Genómica/fisiología , Atrofia Geográfica/sangre , Atrofia Geográfica/etiología , Atrofia Geográfica/patología , Humanos , Degeneración Macular/sangre , Degeneración Macular/complicaciones , Degeneración Macular/epidemiología , Degeneración Macular/patología , Masculino , Persona de Mediana Edad , Estadística como AsuntoRESUMEN
Epidermal growth factor receptor (EGFR) is a member of the receptor tyrosine kinases ErbB family and it is found to be overexpressed in gastric cancer. However, the mechanism of the regulation of the EGFR expression is still unknown. We used the Sequenom EpiTYPER assay to detect the methylation status of the EGFR promoter in normal and tumour tissues of 30 patients with gastric cancer. We also carried out quantitative real time PCR (qPCR) to detect the expression level of EGFR in our 30 patients. Notably, increased methylation level at EGFR promoter was found in tumour tissues than the corresponding adjacent noncancerous. In both Region I DMR and Region II DMR detected in our study, tumor tissues were significantly hypermethylated (P=2.7743E-10 and 2.1703E-05, respectively). Region I_â¿CpG_2 was also found to be associated with the presence of distant metastasis (P=0.0323). Furthermore, the results showed a strongly significant association between the relative EGFR expression and the EGFR methylation changes in both Region I and Region II (P=0.0004 and 0.0001, respectively). Our findings help to indicate the hypermethylation at EGFR promoter in gastric cancer and it could be a potential epigenetic biomarker for gastric cancer status and progression.
Asunto(s)
Metilación de ADN/genética , Receptores ErbB/genética , Regiones Promotoras Genéticas , Neoplasias Gástricas/genética , Adulto , Anciano , Anciano de 80 o más Años , Receptores ErbB/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Gástricas/patologíaRESUMEN
OBJECTIVE: To investigate the changes in peripheral blood Th17 and CD4(+)CD25(+) regulatory T (Treg) cells and their significance among children with hand, foot and mouth disease (HFMD). METHODS: Eighty-nine children with HFMD, including 55 cases of common HFMD and 34 cases of severe HFMD, were included in the study; and 30 healthy children were selected as the control group. The percentages of Th17 and CD4(+)CD25(+) Treg cells in CD4(+) T cells in peripheral blood were determined by flow cytometry. The expression levels of interleukin (IL)-10, transforming growth factor-ß (TGF-ß), and IL-17 were measured by enzyme-linked immunosorbent assay. RESULTS: Compared with the control group, the cases of common HFMD and severe HFMD had significantly increased levels of Th17 cells and IL-17 (P<0.05) but significantly decreased levels of CD4(+)CD25(+) Treg cells, IL-10, and TGF-ß (P<0.05). The severity of the HFMD was positively correlated with the levels of Th17 cells and IL-17 in peripheral blood but negatively correlated with the levels of CD4(+)CD25(+) Treg cells, IL-10, and TGF-ß. CONCLUSIONS: Children with HFMD have increased response of Th17 cells but decreased response of CD4(+)CD25(+) Treg cells in peripheral blood. Th17/CD4(+)CD25(+) Treg cell imbalance may play an important role in the pathogenesis of HFMD.