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1.
Adv Mater ; : e2404774, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38721927

RESUMO

Green ammonia synthesis through electrocatalytic nitrate reduction reaction (eNO3RR) can serve as an effective alternative to the traditional energy-intensive Haber-Bosch process. However, achieving high Faradaic efficiency (FE) at industrially relevant current density in neutral medium poses significant challenges in eNO3RR. Herein, with the guidance of theoretical calculation, a metallic CoNi-terminated catalyst is successfully designed and constructed on copper foam, which achieves an ammonia FE of up to 100% under industrial-level current density and very low overpotential (-0.15 V versus reversible hydrogen electrode) in a neutral medium. Multiple characterization results have confirmed that the maintained metal atom-terminated surface through interaction with copper atoms plays a crucial role in reducing overpotential and achieving high current density. By constructing a homemade gas stripping and absorption device, the complete conversion process for high-purity ammonium nitrate products is demonstrated, displaying the potential for practical application. This work suggests a sustainable and promising process toward directly converting nitrate-containing pollutant solutions into practical nitrogen fertilizers.

2.
Sci Adv ; 10(18): eadn7556, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38691609

RESUMO

Atomically precise metal nanoclusters (NCs) are emerging as idealized model catalysts for imprecise metal nanoparticles to unveil their structure-activity relationship. However, the directional synthesis of robust metal NCs with accessible catalytic active sites remains a great challenge. In this work, we achieved bulky carboranealkynyl-protected copper NCs, the monomer Cu13·3PF6 and nido-carboranealkynyl bridged dimer Cu26·4PF6, with fair stability as well as accessible open metal sites step by step through external ligand shell modification and metal-core evolution. Both Cu13·3PF6 and Cu26·4PF6 demonstrate remarkable catalytic activity and selectivity in electrocatalytic nitrate (NO3-) reduction to NH3 reaction, with the dimer Cu26·4PF6 displaying superior performance. The mechanism of this catalytic reaction was elucidated through theoretical computations in conjunction with in situ FTIR spectra. This study not only provides strategies for accessing desired copper NC catalysts but also establishes a platform to uncover the structure-activity relationship of copper NCs.

3.
Angew Chem Int Ed Engl ; 63(8): e202316910, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38179795

RESUMO

Electrocatalytic reduction of nitrate (NO3 RR) to synthesize ammonia (NH3 ) provides a competitive manner for carbon neutrality and decentralized NH3 synthesis. Atomically precise nanoclusters, as an advantageous platform for investigating the NO3 RR mechanisms and actual active sites, remain largely underexplored due to the poor stability. Herein, we report a (NH4 )9 [Ag9 (mba)9 ] nanoclusters (Ag9 NCs) loaded on Ti3 C2 MXene (Ag9 /MXene) for highly efficient NO3 RR performance towards ambient NH3 synthesis with improved stability in neutral medium. The composite structure of MXene and Ag9 NCs enables a tandem catalysis process for nitrate reduction, significantly increasing the selectivity and FE of NH3 . Besides, compared with individual Ag9 NCs, Ag9 /MXene has better stability with the current density performed no decay after 108 hours of reaction. This work provides a strategy for improving the catalytic activity and stability of atomically precise metal NCs, expanding the mechanism research and application of metal NCs.

4.
PeerJ ; 10: e13828, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35959480

RESUMO

Background: The gender differences in demographic and clinical characteristics were examined in patients with hepatitis B virus (HBV)-related liver diseases. Methods: Overall, 634 patients (44.7 ± 13.8 years) were consecutively included. Data of demographic and clinical characteristics were collected during an assessment interview. Comparisons between male and female patients in terms of demographic and clinical data were carried out using univariate analyses. The independent associations between the demographic and clinical variables and gender were examined with either logistic regression or analysis of covariance as appropriate. Results: The study sample consisted of 452 male and 182 female patients. Multiple logistic regression analyses revealed that being employed (OR = 3.4), personal monthly income <3,000 yuan (OR = 0.3), being current alcohol users (OR = 6.4), Cirrhosis (OR = 5.9), Hepatocellular Carcinoma (HCC) (OR = 8.5) and having less severe insomnia (OR = 0.6) were independently associated with male gender. The analysis of covariance revealed that after controlling for other potential confounding variables, later onset of HBV-related diseases (F = 4.5, p = 0.03) and older age (F = 6.7, p = 0.009) were independently associated with male gender. Conclusions: Given the significant clinical differences in male and female patients with HBV-related liver diseases, more attention should be given to gender-specific treatment and prevention for this population.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Masculino , Feminino , Carcinoma Hepatocelular/epidemiologia , Vírus da Hepatite B , Neoplasias Hepáticas/epidemiologia , Fatores Sexuais , Demografia
5.
BMC Gastroenterol ; 21(1): 490, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34930143

RESUMO

BACKGROUND: To assess the association of HSD17B13 rs72613567:TA allelic variant with liver disease, we performed the current review and meta-analysis. METHODS: Seven studies were identified by a search of CNKI,CBM,MEDLINE, PubMed, EMBASE, and CENTRAL databases from inception to November 2021. Odds ratios (ORs) with 95% confidence interval (CI) were calculated using random effects model or fixed effects model based on the between-study heterogeneity. The Stata 14.0 software was employed for data analysis. RESULTS: Statistical analysis showed that the HSD17B13 rs72613567:TA allelic variant can decrease the risk of hepatocellular carcinoma(HCC) in nonalcoholic fatty liver disease (NAFLD) patients, alcoholic fatty liver disease (ALD) patients and viral hepatitis patients (TA vs T OR = 0.766, 95% CI = 0.682-0.860, P = 0.000; TATA + TAT vs TT OR = 0.755, 95% CI = 0.645-0.885, P = 0.001) or healthy controls(TA vs T OR = 0.649, 95% CI = 0.431-0.977, P = 0.038). Besides, the HSD17B13 rs72613567:TA allelic variant can also provide protection from nonalcoholic fatty liver disease (NAFLD) not only in entire population (TA vs T OR = 0.669, 95% CI = 0.524-0.856, P = 0.001) but also in healthy people (TA vs T OR = 0.600, 95% CI = 0.464-0.777, P = 0.000). No significant publication bias found in this airticle. CONCLUSION: The present findings suggest HSD17B13 rs72613567:TA allelic variant can reduce the risk of HCC and NAFLD in the entire population studied.


Assuntos
17-Hidroxiesteroide Desidrogenases/genética , Carcinoma Hepatocelular , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Alelos , Carcinoma Hepatocelular/genética , Humanos , Neoplasias Hepáticas/genética , Hepatopatia Gordurosa não Alcoólica/genética , Razão de Chances
6.
Front Oncol ; 11: 733680, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722278

RESUMO

Hepatocellular carcinoma (HCC) is a common malignancy worldwide. Alpha-fetoprotein (AFP) is still the only serum biomarker widely used in clinical settings. However, approximately 40% of HCC patients exhibit normal AFP levels, including very early HCC and AFP-negative HCC; for these patients, serum AFP is not applicable as a biomarker of early detection. Thus, there is an urgent need to identify novel biomarkers for patients for whom disease cannot be diagnosed early. In this study, we screened and identified novel proteins in AFP-negative HCC and evaluated the feasibility of using autoantibodies to those protein to predict hepatocarcinogenesis. First, we screened and identified differentially expressed proteins between AFP-negative HCC tissue and adjacent non-tumor liver tissue using SWATH-MS proteome technology. In total, 2,506 proteins were identified with a global false discovery rate of 1%, of which 592 proteins were expressed differentially with 175 upregulated and 417 downregulated (adjusted p-value <0.05, fold-change FC ≥1.5 or ≤0.67) between the tumor and matched benign samples, including 14-3-3 zeta protein. For further serological verification, autoantibodies against 14-3-3 zeta in serum were evaluated using enzyme-linked immunosorbent, Western blotting, and indirect immunofluorescence assays. Five serial serum samples from one patient with AFP-negative HCC showed anti-14-3-3 zeta autoantibody in sera 9 months before the diagnosis of HCC, which gradually increased with an increase in the size of the nodule. Based on these findings, we detected the prevalence of serum anti-14-3-3 zeta autoantibody in liver cirrhosis (LC) patients, which is commonly considered a premalignant liver disease of HCC. We found that the prevalence of autoantibodies against 14-3-3 zeta protein was 16.1% (15/93) in LC patient sera, which was significantly higher than that in patients with chronic hepatitis (0/75, p = 0.000) and normal human sera (1/60, 1.7%, p = 0.01). Therefore, we suggest that anti-14-3-3 zeta autoantibody might be a biomarker for predicting hepatocarcinogenesis. Further follow-up and research of patients with positive autoantibodies will be continued to confirm the relationship between anti-14-3-3 zeta autoantibody and hepatocarcinogenesis.

7.
PeerJ ; 9: e10956, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33717693

RESUMO

OBJECTIVE: This study aimed to describe the one-month prevalence of insomnia symptoms (insomnia hereafter) and the demographic and clinical correlates, and its association with quality of life (QOL) in Chinese patients with HBV-related liver disease. METHOD: A total of 689 patients with HBV-related liver disease in Beijing, China formed the study sample. Three forms of insomnia including difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS) and early morning awakening (EMA) were assessed using standardized questions. QOL was measured using the Medical Outcomes Study Short Form 12 (SF-12). RESULTS: The one-month prevalence of at least one type of insomnia was 69.5%, while DIS, DMS and EMA were 60.4%, 54.7% and 50.9%, respectively. Only 4.8% of patients suffering from insomnia received treatment. Multiple logistic regression analyses revealed that pre-existing medical conditions were positively associated with DIS and EMA; patients with more severe depressive symptoms were more likely to have DIS, DMS and EMA; local residents were less likely to have DIS; and those who were married and older were more likely to have DMS. Insomnia was not independently associated with QOL. CONCLUSIONS: Insomnia is common in Chinese patients with HBV-related liver disease with a very low rate of treatment. Greater attention should be given to identify and treat insomnia in this patient population.

8.
J Dig Dis ; 22(3): 136-142, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33421264

RESUMO

The liver is an important immune organ. Hepatocellular injury can be caused by many factors, which further leads to chronic liver diseases by activating the immune system. Multiple immune cells, such as T lymphocytes, B lymphocytes, natural killer cells (NKs), natural killer T cells (NKTs), and γδT cells, accumulate and participate in the immune regulation of the liver. NKTs are an indispensable component of immune cells in the liver, and invariant natural killer T cells (iNKTs) are the main subpopulation of NKTs. iNKTs activated by glycolipid antigen presented on CD1d secrete a series of cytokines and also act on other immune cells through cell-to-cell contact. Studies on the relationship between iNKTs and liver immunity have provided clues to uncover the pathogenesis of liver diseases and develop a promising strategy for the diagnosis and treatment of liver diseases.


Assuntos
Doenças do Sistema Digestório , Hepatopatias , Células T Matadoras Naturais , Citocinas/imunologia , Humanos , Ativação Linfocitária/fisiologia , Células T Matadoras Naturais/imunologia
9.
Acta Biochim Pol ; 68(1): 33-39, 2020 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-33355876

RESUMO

The cell membrane, which is lipid-rich, is not only a simple mechanical barrier but also an important and complex component of the cell. It also communicates with the external environment. Sphingomyelin is an important class of phospholipids in the membrane that performs many functions. Interest in sphingomyelin-based liposomes, which are a critical component of cell membranes, have become the focus of intense study in recent years. Through additional research, the function of sphingomyelin and its derivatives in diseases can be gradually elucidated. Sphingomyelin consists of ceramide and its derivatives including ceramide-1-phosphate glucosylceramide and sphingosine-1-phosphate. The metabolism of glucosylceramide is regulated by glucosylceramide synthase (EC: 2.4.1.80) which is the key enzyme in the glycosylation of ceramide. The activity of glucosylceramide synthase directly affects the level of glucosylceramide in cells which in turn affects the function of cells and may eventually lead to diseases. Recently, the relationship between glucosylceramide and its metabolic enzymes, with diseases has become a relatively new area of study. The purpose of this paper is to address the relationship between glucosylceramide, glucosylceramide synthase, and their possible association with liver diseases at the theoretical level.


Assuntos
Carcinoma Hepatocelular/metabolismo , Glucosilceramidas/metabolismo , Glucosiltransferases/metabolismo , Cirrose Hepática/metabolismo , Neoplasias Hepáticas/metabolismo , Lesão Pulmonar/metabolismo , Apoptose , Membrana Celular/metabolismo , Ceramidas/metabolismo , Glucosilceramidas/química , Glucosiltransferases/química , Hepatócitos/metabolismo , Humanos , Lisofosfolipídeos/metabolismo , Esfingomielinas/metabolismo , Esfingosina/análogos & derivados , Esfingosina/metabolismo
10.
Clin Lab ; 66(8)2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32776747

RESUMO

BACKGROUND: The relationship between non-cholestatic liver disease and total bile acid (TBA) remains obscure. The present study aimed to verify this relationship in patients with non-cholestatic chronic hepatitis B virus (HBV) infection. METHODS: A total of 922 consecutive chronic HBV infected patients with alkaline phosphatase (ALP) ≤ 1.5 upper limit of normal (ULN) and gamma-glutamyl transferase (GGT) ≤ 3 ULN were rigorously included in this cross-sectional study. Liver biopsy was performed in 53 patients and Scheuer scoring system was used to evaluate inflammation grade. G3/G4 or Child-Pugh B/C were considered to be significant liver injury. RESULTS: Compared to Child-Pugh A, TBA, total bilirubin (TBIL), ALP, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and AST to ALT ratio (AST/ALT) were significantly higher in Child-Pugh B/C, while TBIL to TBA ratio (TBIL/TBA) was significantly lower (all p < 0.001). In multivariate analysis, TBA and AST/ALT were independently correlated with Child-Pugh B/C [odds ratio (OR) = 1.04, p < 0.001; OR = 1.79, p < 0.001, respectively]. The area under the curve (AUC) of TBA (0.82) was significantly higher than that of AST (0.73, p < 0.001) and ALT (0.63, p < 0.001). Furthermore, in patients with liver biopsy, TBA was also significantly higher in G3/G4 while TBIL/TBA was significantly lower (p < 0.05). After adjusting the factors related to bile excretion, TBIL/TBA was independently associated with G3/G4 (OR = 0.89, p = 0.037). CONCLUSIONS: Serum TBA shows a close relationship with significant liver injury in chronic HBV infected patients without cholestasis. Assessment of TBA, especially in combination with TBIL/TBA, may serve as a non-invasive marker for the diagnosis of non-cholestatic hepatic damage.


Assuntos
Colestase , Hepatite B Crônica , Alanina Transaminase , Ácidos e Sais Biliares , Estudos Transversais , Hepatite B Crônica/diagnóstico , Humanos , Fígado
11.
Exp Ther Med ; 20(1): 243-250, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32550883

RESUMO

Although the platelet count may provide clues regarding the severity of liver disease, there are currently no available data supporting the utility of the platelet count to evaluate the degree of liver injury in patients with chronic hepatitis B virus (HBV) infection. The present study aimed to determine the association between the platelet count and the severity of liver injury in patients with chronic HBV infection. A total of 941 patients were included and were stratified into a Child-Turcotte-Pugh (CTP) class A group and a CTP class B/C group using the CTP scoring system. A total of 53 patients underwent liver biopsy. The pathological stage F4 was defined as cirrhosis based on the METAVIR scoring system. Compared with that in patients with CTP class A, the platelet count in patients with CTP class B/C was lower (P<0.001). Similarly, for patients with normal alanine aminotransferase (ALT) levels, the platelet count was significantly different between the CTP class B/C and A groups (P<0.001). The platelet count was inversely correlated with the CTP score (r=-0.420, P<0.001) and independently associated with CTP grade B/C [odds ratio (OR), 0.994; 95% CI, 0.990-0.999; P=0.009]. The area under the receiver operating characteristic curve (AUC) of the platelet count to distinguish CTP grade B/C from A was 0.712 and 0.791, respectively, in all patients with HBV infection and the subset with normal ALT levels. In addition, compared to patients with chronic hepatitis B, patients with cirrhosis had a lower platelet count and higher aspartate transaminase-to-platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4) (P<0.001). The platelet count was inversely correlated with FIB-4 (r=-0.855, P<0.001) and APRI (r=-0.741, P<0.001). The AUC for the platelet count to distinguish cirrhosis from chronic hepatitis B was 0.927 (sensitivity, 78.76%; specificity, 92.22%). Among patients who underwent liver biopsy, the platelet count in those with F4 was lower compared with that in patients with ≤F3 (P=0.013). The platelet count was inversely correlated with the pathological stage (r=-0.295, P=0.032) and was independently associated with F4 (OR, 0.978; 95% CI, 0.960-0.997; P=0.026). The AUC of the platelet count to distinguish F4 from patients with ≤F3 was 0.761. In conclusion, the platelet count may be used as a non-invasive marker to assess the severity of liver injury and of liver fibrosis in patients with chronic HBV infection.

12.
Int J Clin Exp Pathol ; 12(3): 1035-1040, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31933916

RESUMO

Idiopathic portal hypertension (IPH) is a rare disease, and its etiology and pathogenesis have not yet been fully clarified. The main clinical manifestations are non-cirrhotic intrahepatic portal hypertension, accompanied by splenomegaly, thrombocytopenia, and recurrent upper gastrointestinal bleeding. The liver histopathologic changes are diverse. Splenectomy is considered an effective treatment for hypersplenism. We report a patient who presented with splenomegaly, then underwent splenectomy to relieve thrombocytopenia based on routine treatment strategies. However, multiple space-occupying lesions were found in the liver about one year later. Thereafter, the lesions were confirmed as nodular regenerative hyperplasia (NRH) by liver biopsy, the patient was finally diagnosed with IPH. We consider that although splenectomy is generally recommended for IPH, under certain circumstances splenectomy may disturb blood flow in the liver, leading to the formation of NRH. Therefore, splenectomy in IPH patients should be chosen carefully.

13.
Mol Med Rep ; 16(5): 7355-7360, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28944894

RESUMO

Our previous study found that glucosylceramide, a type of sphingolipids, was associated with liver inflammation and fibrosis. Glucosylceramide is generated by glucosylceramide synthase (GCS), which is encoded by the UDP­glucose ceramide glucosyltransferase (UGCG) gene. GCS is a key enzyme to regulate the physiological activity of cells. However, the role of GCS in hepatic cells remains unclear. The aim of the present study was to explore the mechanism of GCS in the proliferation and apoptosis of liver cells. Following the interference of expression of GCS in vitro by UGCG small interfering (si)RNA, the MTT method was performed to detect the proliferation of HL­7702 hepatocytes, and ELISA was used to determine the concentration of tumor necrosis factor (TNF) α and cytochrome c in the supernatant of culture system. Fluorescence microscopy was used to observe the apoptosis of liver cells stained by Annexin V­fluorescein isothiocyanate/propidium iodide. Reverse transcription­quantitative polymerase chain reaction was used to detect the gene expression apoptosis regulator Bcl­2 (Bcl­2), apoptosis regulator Bax (Bax) and caspase-3. Western blot analysis was used to detect the expression of caspase-3 protein in the liver cells. Following treatment with UGCG siRNA for 24 h, the proliferation of HL­7702 hepatocytes was significantly inhibited when compared with the transfection reagent group. Furthermore, the early and advanced apoptosis of liver cells showed an increasing trend. Additionally, concentrations of TNF α and cytochrome c showed no significant difference between the UGCG siRNA and transfection reagent groups. Compared with the transfection reagent group, Bcl­2 mRNA expression decreased, and Bax and caspase-3 mRNA expression increased in the UGCG siRNA transfection group. The protein expression level of caspase-3 showed increased in hepatocytes following the treatment with UGCG siRNA. In conclusion, the metabolic changes of sphingolipids caused by the lack of GCS may be involved in the proliferation and apoptosis of liver cells through the Bcl­2/Bax signaling pathway.


Assuntos
Apoptose , Proliferação de Células , Glucosiltransferases/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismo , Linhagem Celular , Citocromos c/análise , Glucosiltransferases/antagonistas & inibidores , Glucosiltransferases/genética , Hepatócitos/citologia , Hepatócitos/metabolismo , Humanos , Plasmídeos/genética , Plasmídeos/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Transfecção , Fator de Necrose Tumoral alfa/análise
14.
Medicine (Baltimore) ; 96(34): e7885, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28834904

RESUMO

Chronic hepatitis C virus (HCV) infection is a serious public health problem worldwide. China, as the country with the largest number of HCV infections in the world, plays a significant role in eliminating hepatitis C. Due to different financial situations and education background, hepatitis C patients take different actions for their disease treatment and management. Therefore, antiviral treatment status should be attached great importance to learn the medical demand of patients. A nationwide, multicenter survey was conducted from July 2015 to June 2016. Of 1798 inpatients and outpatients with chronic HCV from 56 hospitals participated in the survey. Each patient completed the questionnaire with questions about his/her antiviral therapy status, perception of treatment barriers, and expectations for future treatment. In total 1622 patients, including 1241 with chronic hepatitis C, 344 with cirrhosis, and 37 patients with hepatocellular carcinoma, fulfilled data collection requirements and finally were included in analysis. Overall, up to 30.7% of the patients had not or currently does not intend to receive antiviral therapy. The main reason was expecting more potent and well-tolerance medication (31.5%), followed by the fear of interferon related side effects (27.5%). Multiple regression analysis showed that the patient's annual income, the severity of HCV, and comorbidity were independent predictors of not receiving antiviral therapy. The whole patients were expecting more potent and well tolerance medication available soon. In summary, Peg-IFN/RBV treatment regimen cannot meet the need of patients well, and safe and efficient direct-acting antivirals are urgently needed in mainland China.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Ribavirina/uso terapêutico , Adulto , Fatores Etários , Antivirais/administração & dosagem , Antivirais/efeitos adversos , China , Estudos Transversais , Quimioterapia Combinada , Uso de Medicamentos/estatística & dados numéricos , Honorários Farmacêuticos , Genótipo , Hepatite C Crônica/epidemiologia , Humanos , Interferon-alfa/administração & dosagem , Interferon-alfa/efeitos adversos , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/epidemiologia , Pessoa de Meia-Idade , Polietilenoglicóis , Ribavirina/administração & dosagem , Ribavirina/efeitos adversos , Índice de Gravidade de Doença , Fatores Sexuais , Fatores Socioeconômicos , Adulto Jovem
15.
World J Gastroenterol ; 23(20): 3655-3663, 2017 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-28611518

RESUMO

AIM: To investigate the mechanism of hepatoprotection conferred by liver fibrosis through evaluating the activation phenotype of kupffer cells. METHODS: Control and fibrotic mice were challenged with a lethal dose of D-GalN/lipopolysaccharide (LPS), and hepatic damage was assessed by histology, serum alanine transferase (ALT) levels, and hepatic expression of HMGB1, a potent pro-inflammatory mediator. The localization of F4/80 (a surrogate marker of KCs), HMGB1, and type I collagen (Col-1) was determined by immunofluorescence staining. The phenotype of KCs was characterized by real-time PCR. KCs isolated from control or fibrotic mice were challenged with LPS or HMGB1 peptide, and HMGB1 translocation was analyzed. RESULTS: Liver fibrosis protected mice against D-GalN/LPS challenge, as shown by improved hepatic histology and reduced elevation of ALT compared with the normal mice treated in the same way. This hepatoprotection was also accompanied by inhibition of HMGB1 expression in the liver. Co-localization of F4/80, HMGB1, and Col-1 was found in fibrotic livers, indicating the close relationship between KCs, HMGB1 and liver fibrosis. KCs isolated from fibrotic mice predominantly exhibited an M2-like phenotype. In vitro experiments showed that HMGB1 was localized in the nucleus of the majority of M2-like KCs and that the translocation of HMGB1 was inhibited following stimulation with LPS or HMGB1 peptide, while both LPS and HMGB1 peptide elicited translocation of intranuclear HMGB1 in KCs isolated from the control mice. CONCLUSION: M2-like Kupffer cells in fibrotic liver may exert a protective effect against acute insult by inhibiting the translocation of HMGB1.


Assuntos
Células de Kupffer/citologia , Cirrose Hepática/fisiopatologia , Fígado/fisiopatologia , Macrófagos/citologia , Animais , Colágeno Tipo I/metabolismo , Galactosamina , Proteína HMGB1/metabolismo , Inflamação , Lipopolissacarídeos , Cirrose Hepática/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Microscopia de Fluorescência , Fenótipo , Transporte Proteico , Reação em Cadeia da Polimerase em Tempo Real
16.
World J Gastroenterol ; 23(19): 3496-3504, 2017 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-28596685

RESUMO

AIM: To determine the prevalence and diagnostic value of autoantibodies in α-fetoprotein (AFP)-negative hepatocellular carcinoma (HCC). METHODS: Fifty-six serum samples from AFP-negative HCC cases, 86 from AFP-positive HCC cases, 168 from chronic liver disease cases, and 59 from normal human controls were included in this study. Autoantibodies to nucleophosmin (NPM)1, 14-3-3zeta and mouse double minute 2 homolog (MDM2) proteins in AFP-negative HCC serum were evaluated by enzyme-linked immunosorbent assay. Partially positive sera were further evaluated by western blotting. Immunohistochemistry was used to detect the expression of three tumor-associated antigens (TAAs) in AFP-negative HCC and normal control tissues. RESULTS: The frequency of autoantibodies to the three TAAs in AFP-negative HCC sera was 21.4%, 19.6% and 19.6%, which was significantly higher than in the chronic liver disease cases and normal human controls (P < 0.01) as well as AFP-positive HCC cases. The sensitivity of the three autoantibodies for diagnosis of AFP-negative HCC ranged from 19.6% to 21.4%, and the specificity was approximately 95%. When the three autoantibodies were combined, the sensitivity reached 30.4% and the specificity reached 91.6%. CONCLUSION: Autoantibodies to NPM1, 14-3-3zeta and MDM2 may be useful biomarkers for immunodiagnosis of AFP-negative HCC.


Assuntos
Autoanticorpos/sangue , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , alfa-Fetoproteínas/metabolismo , Proteínas 14-3-3/imunologia , Proteínas 14-3-3/metabolismo , Idoso , Autoanticorpos/imunologia , Carcinoma Hepatocelular/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imuno-Histoquímica , Testes Imunológicos , Hepatopatias/metabolismo , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/imunologia , Proteínas Nucleares/metabolismo , Nucleofosmina , Proteínas Proto-Oncogênicas c-mdm2/imunologia , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteínas Recombinantes/metabolismo , Estudos Retrospectivos , alfa-Fetoproteínas/imunologia
17.
Arch Psychiatr Nurs ; 31(3): 287-290, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28499569

RESUMO

BACKGROUND: There are no data about the frequency of major depression in patients with liver disease related to Hepatitis B virus (HBV) in China. This study examined the prevalence of major depression and its clinical correlates and association with quality of life (QOL) in patients with HBV-related liver diseases. METHOD: Altogether 634 patients with HBV-related liver diseases met study entry criteria and completed the survey. The diagnosis of major depression was established with the Mini International Neuropsychiatric Interview (MINI). Socio-demographic and clinical characteristics, Global Assessment of Functioning (GAF) and QOL were measured. RESULTS: The prevalence of major depression was 6.4%. Multivariable logistic regression analyses revealed that insomnia (P=0.01, OR=5.5, 95%CI=1.4-21.6) and global functioning (P<0.001, OR=0.6, 95% CI=0.5-0.7) were independently associated with major depression. Major depression was associated with both poor physical (F (1, 634)=4.0, P=0.04) and mental QOL (F (1, 634)=26.2, P<0.001). CONCLUSIONS: Given the negative impact of depression on patients' QOL, more attempts should be made to identify and treat it in HBV-related diseases.


Assuntos
Transtorno Depressivo Maior/epidemiologia , Vírus da Hepatite B , Hepatopatias , Qualidade de Vida , Adulto , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Inquéritos e Questionários
18.
Medicine (Baltimore) ; 95(23): e3773, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27281078

RESUMO

The aim of the present study was to explore the relationship between plasma sphingolipids and hepatitis C virus (HCV) replication in chronic hepatitis C (CHC) patients.A cohort of 120 treatment-naïve CHC patients was included. Liver biopsies and the Scheuer scoring system were used to assess hepatic inflammatory activity. Blood biochemical indicators, HCV-RNA load, and immunological markers were also measured. Forty-four plasma sphingolipids were identified and quantified using high-performance liquid chromatography-tandem mass spectrometry.The hexosylceramide (HexCer) (d18:1/18:1) level was significantly different between patients with a low HCV load (<10 IU/mL) and a high HCV load (≥10 IU/mL), and it was positively correlated with the HCV-RNA load (r = 0.337, P = 0.001) in CHC patients. Additionally, the plasma HexCer (d18:1/18:1) level (odds ratio 1.302, 95% confidence interval 1.129-1.502) was an independent factor for a high HCV-RNA load. For patients with hepatic inflammation grade ≤2 or HCV genotype 2, HexCer (d18:1/18:1) was independently related to a high HCV-RNA load.Plasma HexCer (d18:1/18:1) might be involved in the high viral replication level in chronic HCV infection, especially for CHC patients with genotype 2.


Assuntos
Previsões , Hepacivirus/genética , Hepatite C Crônica/sangue , RNA Viral/genética , Esfingomielinas/sangue , Regulação para Cima , Carga Viral , Replicação Viral , Biomarcadores/sangue , Feminino , Seguimentos , Genótipo , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Esfingomielinas/biossíntese
19.
Medicine (Baltimore) ; 95(6): e2639, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26871786

RESUMO

Prompt and accurate prediction of the outcome is the key to make correct medical decision and to reduce the mortality in patients with HBV-related acute-on-chronic liver failure (ACLF). Increasing evidence have certified that small, noncoding microRNAs (miRNAs) play critically regulatory roles in the pathogenesis of liver diseases. However, it remains unclear whether and how miRNAs involve in the prognosis of ACLF.Microarray analysis was performed to characterize the miRNA expression profiles in liver tissues from 1 HBV-related ACLF patient and 1 matched healthy control. Nine miRNAs with at least 5 folds difference between these 2 persons were picked out. The present prospective study involving 39 HBV-related ACLF patients including 20 recovered and 19 nonrecovered patients, which include death (n = 9) and liver transplantation (n = 10). The serum expression of these miRNAs detected by quantitative real-time Polymerase Chain Reaction (qRT-RCR) was then compared between the 2 groups. Moreover, the correlation between the serum miRNAs and the prognostic indexes for ACLF was analyzed.The result of microarray analysis showed 9 miRNAs had different expression in liver tissues of ACLF patient compared with healthy control (upregulated: miRNA-130a, -21, -143, and -200a; downregulated: miRNA-486-5p, -192, -148a, -122, and -194). Unlike the expression profiles in liver tissue, 8 serum miRNAs except miRNA-194 were markedly upregulated in ACLF patients (P < 0.05). Remarkably, the serum expression of miRNA-130a and miRNA-486-5p was higher in recovered than nonrecovered ACLF patients (P < 0.05). Especially, the serum miRNA-130a was negatively correlated with international normalized ratio, prothrombin time, Model for End-Stage Liver Disease score, and positively correlated with prothrombin time activity. The AUC for recovered versus nonrecovered patients of miRNA-130a was 0.741 (P = 0.02).miRNA-130a might be a useful prognosis biomarker in patients with HBV-related ACLF.


Assuntos
Insuficiência Hepática Crônica Agudizada/genética , Insuficiência Hepática Crônica Agudizada/virologia , Hepatite B Crônica/complicações , MicroRNAs/genética , Insuficiência Hepática Crônica Agudizada/sangue , Insuficiência Hepática Crônica Agudizada/mortalidade , Adulto , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , MicroRNAs/sangue , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Regulação para Cima
20.
Eur J Gastroenterol Hepatol ; 28(4): 444-8, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26649802

RESUMO

OBJECTIVE: Various methods, including the indocyanine green (ICG) clearance test, the Child-Turcotte-Pugh score (CTP), model for end-stage liver disease (MELD), and MELD combined with serum sodium concentration (MELD-Na), have been used widely in liver function evaluation in patients with end-stage liver disease. In this study, we compared the ability of these methods to predict mortality in patients with decompensated hepatitis B cirrhosis. METHODS: A total of 98 patients with decompensated hepatitis B cirrhosis were included in this study and followed up for 12 months. The ICG-derived measurements (ICG-PDR, ICG-R15, EHBF), CTP, MELD, and MELD-Na were obtained within 2 days after patients' admission and patients' survival at 1, 3, 6, and 12 months was recorded. Receiver operating curve was used to evaluate the ability of these methods to predict mortality in these patients with decompensated hepatitis B cirrhosis. RESULTS: At 1 month, 3 months, 6 months and 12 months, the cumulative number of deaths and liver transplant recipients was 12 (12.2%), 17 (17.3%), 21 (21.4%) and 25 (25.5%), respectively. The ICG-derived measurements, CTP, MELD, and MELD-Na of nonsurvivors were significantly different compared with that in survivors. All methods yielded viable values in predicting short-term and medium-term prognosis for patients with decompensated hepatitis B cirrhosis, with most area under the curve exceeding 0.8. Moreover, the ICG-derived measurements showed a significant correlation with that of CTP, MELD, and MELD-Na. CONCLUSION: All four methods, ICG clearance test, CTP, MELD, and MELD-Na, provided reliable prediction of mortality in patients with decompensated hepatitis B cirrhosis for both short-term and medium-term prognosis.


Assuntos
Corantes/administração & dosagem , Técnicas de Apoio para a Decisão , Hepatite B/diagnóstico , Hepatite B/mortalidade , Verde de Indocianina/administração & dosagem , Cirrose Hepática/diagnóstico , Cirrose Hepática/mortalidade , Testes de Função Hepática/métodos , Sódio/sangue , Idoso , Área Sob a Curva , Biomarcadores/sangue , Feminino , Hepatite B/complicações , Humanos , Cirrose Hepática/cirurgia , Cirrose Hepática/virologia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Curva ROC , Reprodutibilidade dos Testes , Fatores de Risco
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