Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 47
Filtrar
2.
BMJ Open ; 11(8): e048410, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34408049

RESUMO

INTRODUCTION: The current clinical guidelines do not recommend antiviral therapy for subjects with positive hepatitis B virus (HBV)-DNA and normal alanine transaminase (ALT). In this study, we will assess the safety and efficacy of tenofovir alafenamide fumarate (TAF) in the treatment of adults with positive HBV-DNA and normal ALT, including long-term prognosis. METHODS AND ANALYSIS: This study is a non-double-blind randomised controlled trial. Study participants will be randomised into the treatment group and the control group. In the treatment group, subjects will receive TAF monotherapy, while those in the control group will receive no antiviral treatment. Subjects will be followed up at the beginning of the study and every 12 or 24 weeks thereafter for review of laboratory findings and to record adverse events. The primary endpoint is the proportion of patients with serum hepatitis B surface antigen loss. ETHICS AND DISSEMINATION: This study protocol was approved by the Ethics Committee of the Third Affiliated Hospital of Sun Yat-Sen University for Human Study (reference number [2019]02-599-01). The results of this study will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04231565.


Assuntos
DNA Viral , Fumaratos , Adulto , Alanina , Alanina Transaminase , Método Duplo-Cego , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Tenofovir/análogos & derivados , Tenofovir/uso terapêutico
3.
J Clin Transl Hepatol ; 9(4): 503-513, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34447679

RESUMO

Background and Aims: The safety and efficacy of mesenchymal stem cells (MSCs) in the treatment of acute-on-chronic liver failure (ACLF) have been validated. However, the impact of the pathological ACLF microenvironment on MSCs is less well understood. This study was designed to explore the changes in the functional properties of MSCs exposed to ACLF serum. Methods: MSCs were cultured in the presence of 10%, 30% and 50% serum concentrations from ACLF patients and healthy volunteers. Then, the cell morphology, phenotype, apoptosis and proliferation of MSCs were evaluated, including the immunosuppressive effects. Subsequently, mRNA sequencing analysis was used to identify the molecules and pathways involved in MSC functional changes in the context of ACLF. Results: In the presence of ACLF serum, MSC morphology significantly changed but phenotype did not. Besides, MSC proliferation activity was weakened, while the apoptosis rate was lightly increased. Most importantly, the immunosuppressive function of MSCs was enhanced in a low-concentration serum environment but transformed into a proinflammatory response in a high-concentration serum environment. RNA sequencing indicated that 10% serum concentration from ACLF patients mediated the PI3K-Akt pathway to enhance the anti-inflammatory effect of MSCs, while the 50% serum concentration from ACLF patients promoted the conversion of MSCs into a proinflammatory function by affecting the cell cycle. Conclusions: The 50% ACLF serum concentration is more similar to the environment in the human body, which means that direct peripheral blood intravenous infusion of MSCs may reduce the effect of transplantation. Combining treatments of plasma exchange to reduce harmful substances in serum may promote MSCs to exert a stronger anti-inflammatory effect.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34197929

RESUMO

OBJECTIVES: Hepatitis B virus infection is an important public health problem. We analysed the cost-effectiveness of the first-line therapies, including nucleotide analogues (namely tenofovir alafenamide fumarate (TAF), tenofovir disoproxil fumarate (TDF) and entecavir) and pegylated interferon (Peg-IFN) for patients with chronic hepatitis B (CHB) in China. METHODS: A Markov model describing CHB disease progression was constructed to compare the cost-effectiveness of the first-line therapies, considering both satisfactory (HBeAg seroconversion) and optimal (HBsAg seroclearance) treatment goals. We examined the main outcomes, including cumulative lifetime cost per patient, incremental quality-adjusted life years (QALYs), incremental cost-effectiveness ratio and net monetary benefit. Uncertainty analysis was conducted to identify key influential parameters. RESULTS: Compared with the baseline strategy, Peg-IFN had the highest QALY gain for HBeAg-positive (HBeAg+) CHB patients achieving a satisfactory goal and an optimal goal (3.19 and 6.32 respectively), and TDF was the most cost-effective therapy for HBeAg-negative CHB patients ($1418/QALY) achieving a satisfactory goal. Among nucleotide analogues, TAF was the most-effective strategy and had higher acceptability to achieve an optimal goal in the Eastern region of China (under 1 x GDP per capita threshold). CONCLUSIONS: Among nucleotide analogues, TDF was the most cost-effective treatment in China for CHB patients to achieve satisfactory and optimal treatment goals, whereas TAF was cost-effective and more effective in the wealthier region. Peg-IFN was most cost-effective among HBeAg+ CHB patients to achieve both goals, with better clinical outcomes. Our findings also indicate the importance of regular monitoring during and after CHB treatment, and could inform treatment strategies in China and other countries.

5.
Front Pharmacol ; 12: 616858, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33716744

RESUMO

Sodium taurocholate cotransporting polypeptide (NTCP) acts as a cellular receptor for the hepatitis B virus infection of host hepatocytes. Previously, many studies confirmed that the NTCP p.Ser267Phe variant was a protective factor against HBV-related disease progression. We therefore designed this study to investigate whether the NTCP p.Ser267Phe variant exerts an additive anti-HBV effect in chronic hepatitis B (CHB) patients on mainstream NAs treatment. After propensity score matching (PSM), a total of 136 CHB patients were included, among whom 68 were heterozygous carriers and 68 were wild-type controls. Proportions of primary nonresponse, partial virological response, virological breakthrough and hepatitis B reactivation and the HBV DNA clearance rate at each time point were compared using the chi-square test. Kaplan-Meier analysis and matched t-tests were also performed to estimate the speed of viral clearance and serum HBV DNA reduction, respectively. The proportion of primary nonresponse was significantly lower in heterozygous carriers than in wild-type controls (p < 0.001), especially in patients using entecavir (p = 0.013). Specifically, heterozygous carriers achieved HBV DNA clearance faster than wild-type controls (log-rank p = 0.0198). HBV DNA levels were reduced more in heterozygous carriers after 12 weeks (p < 0.001) and 24 weeks (p = 0.006) of treatment, especially among patients using ETV. Here, our study demonstrated that heterozygous mutations in rs2296651 enhanced the antiviral response of first-line NAs and helped to explore the possibility of combining NAs and NTCP blockers for a better anti-HBV effect.

7.
Aging (Albany NY) ; 13(6): 8563-8587, 2021 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-33714200

RESUMO

Tumor mutation burden (TMB) has been associated with prognosis in various malignancies, but it has yet to be elucidated in hepatocellular carcinoma (HCC). We aimed to investigate the prognostic effects of TMB and its relationship with immune infiltration through multiple databases and whole-exome sequencing, so as to establish a panel model capable of predicting prognosis. The results demonstrated that the prognosis of high TMB group was worse than that of low TMB group, with a cutoff TMB value of 4.9. Enrichment analysis demonstrated that differentially expressed genes were mainly related to T cell activation, cell membrane localization and matrix composition. Tumor immune infiltration analysis revealed the infiltrations of Th2, Th17, and Tgd were up-regulated in high TMB group, while those of Tr1, MAIT, and DC were up-regulated in low TMB group. TMB-Infiltration model fit well with the actual survival observation, with a C-index 0.785 (0.700-0.870), which verified in ICGC-LIRI-JP was 0.650 (0.553-0.747). Additionally, these screened immune genes performed well in predicting tumor vascular invasion with a C-index of 0.847 (0.778-0.916). Overall, these results indicated that patients with high mutation frequency of immune-related genes and high TMB were prone to have worse prognosis and relapse after radical treatment.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/imunologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/imunologia , Linfócitos do Interstício Tumoral/imunologia , Adulto , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico
8.
Adv Sci (Weinh) ; 8(4): 2001961, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33643786

RESUMO

The incidence of bone metastases in hepatocellular carcinoma (HCC) has increased prominently over the past decade owing to the prolonged overall survival of HCC patients. However, the mechanisms underlying HCC bone-metastasis remain largely unknown. In the current study, HCC-secreted lectin galactoside-binding soluble 3 (LGALS3) is found to be significantly upregulated and correlates with shorter bone-metastasis-free survival of HCC patients. Overexpression of LGALS3 enhances the metastatic capability of HCC cells to bone and induces skeletal-related events by forming a bone pre-metastatic niche via promoting osteoclast fusion and podosome formation. Mechanically, ubiquitin ligaseRNF219-meidated α-catenin degradation prompts YAP1/ß-catenin complex-dependent epigenetic modifications of LGALS3 promoter, resulting in LGALS3 upregulation and metastatic bone diseases. Importantly, treatment with verteporfin, a clinical drug for macular degeneration, decreases LGALS3 expression and effectively inhibits skeletal complications of HCC. These findings unveil a plausible role for HCC-secreted LGALS3 in pre-metastatic niche and can suggest a promising strategy for clinical intervention in HCC bone-metastasis.

9.
J Viral Hepat ; 28(4): 592-600, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33423348

RESUMO

Tenofovir alafenamide (TAF) has been available in China for a short time, little is known about its safety and efficacy in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (HBV-ACLF). We conducted this study to further verify the safety and efficacy of TAF in these patients. Eighty-eight eligible subjects were included and divided into three groups: TAF group, TDF group and ETV group. Clinical and laboratory test results were collected and the survival status, virus suppression status and liver and renal function improvement were observed during follow-up. No drug-related adverse events were observed within a 48-week observation period. At week 48, the survival rates of the three groups were 56.5%, 78.3% and 59.5% (p = 0.262). HBV DNA undetectable rates were similar (80.0% vs.75.0% vs.84.6%, respectively, p = 0.863). Liver function improved in all the three groups over time. Compared with the other two groups, patients in the TAF group had a greater decrease in serum creatinine (CR) and an increase in estimated glomerular filtration rate (eGFR), especially at week 12. At week 48, the median changes of CR were -0.7 (IQR -3.0, 13.0) vs. 15.0 (IQR -3.0, 21.0) vs. 5.0 (IQR -9.0, 14.0), respectively (p = 0.334), while the median changes of eGFR were -2.12 (IQR -13.87, 1.44) vs. -10.43 (IQR -20.21, 3.18) vs. -5.31 (IQR -14.72, 5.44) ml/min/1.73 m2 , respectively (p = 0.592). In this real-world clinical study, TAF is as effective as TDF and ETV, and may be more beneficial in protecting renal function in the early stages of antiviral therapy.


Assuntos
Insuficiência Hepática Crônica Agudizada , Hepatite B Crônica , Insuficiência Hepática Crônica Agudizada/tratamento farmacológico , Alanina , Antivirais/efeitos adversos , Guanina/uso terapêutico , Vírus da Hepatite B , Hepatite B Crônica/tratamento farmacológico , Humanos , Estudos Prospectivos , Tenofovir/análogos & derivados , Tenofovir/uso terapêutico , Resultado do Tratamento
10.
Cancer Nurs ; 44(3): 180-189, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-31651462

RESUMO

BACKGROUND: Cancer-related chronic pain is reported by many patients during treatment. There are very few Chinese tools for measuring psychological inflexibility caused by cancer pain, particularly with regard to psychological processes that might influence pain severity and function disorder during cancer treatment. OBJECTIVE: To culturally adapt the Psychological Inflexibility in Pain Scale (PIPS) to Chinese cancer patients experiencing chronic pain, including the determination of psychometric properties of the translated PIPS. METHODS: This cross-sectional study included 2 phases: (1) translation and cultural adaptation and (2) determination of psychometric properties of the translated PIPS. In total, 389 cancer patients with several types of cancer experiencing chronic pain enrolled from May to September 2018 at a tertiary cancer hospital in Yuelu District of Hunan Province, China. RESULTS: The Chinese PIPS version was semantically equivalent to the original. It had a 2-factor structure with satisfactory content validity (content validity index = 0.78-1.00), convergent and discriminant validity (composite reliability and average variance extracted at 0.41-0.89, P < .001), criterion-related validity (r = 0.54 and 0.41, P < .001), Cronbach's α coefficients (α = .87), and test-retest reliability (0.9 ≤ r ≤ 0.98). CONCLUSIONS: The Chinese PIPS version has been culturally adapted and has strong psychometric properties. The scale is a psychometrically sound assessment of psychological inflexibility that can be used for future studies of pain and pain management for cancer patients. IMPLICATIONS FOR PRACTICE: The study provides a vital tool for the psychological management of cancer patients with chronic pain.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33204296

RESUMO

Perimenopausal syndrome (PMS) has a high incidence rate and affects the physical and mental health of middle-aged and elderly women. The blockage of PMS is significant in improving the health of perimenopausal women. Currently, for PMS prevention and treatment, traditional Chinese medicine (TCM) has become an ideal choice because of its safety and effectiveness. This study aimed to explore the anti-PMS effects of Ziyin Bushen Decoction (DKTP) and the underlying mechanism. Thirty female Wistar rats were divided into 5 groups (n = 6): control group, low-dose DKTP group, medium-dose DKTP group, high-dose DKTP group, and nilestriol group. The estradiol (E2) level in rat peripheral blood was analyzed using an E2 Radioimmunoassay Kit, and uterine morphologic changes were examined by hematoxylin-eosin staining. Learning and memory ability of rats was assessed by Morris water maze (MWM) and novel object recognition (NOR) task. E2 synthesis, metabolism, and transport associated estrogen receptor-alpha (ERα), GnRHR, CYP17, CYP11A1, CYP19, 17ßHSD, STS, and SHGB were assessed to explore the E2-promoting mechanism of DKTP during PMS treatment. The loss of learning and memory, the decreased estrous and uterine coefficient, and the presence of histopathological changes suggests a successful establishment of rat PMS model. Following DKTP or nilestriol treatment, the above results were reversed. E2 level in serum, uterine, and ovarian tissues was upregulated upon different concentrations of DKTP treatment, indicating that DKTP promotes the E2 level in a dose-dependent manner. DKTP also increased the expression of ERα, CYP17, CYP11A1, CYP19, 17ßHSD, STS, and SHGB while decreased the GnRHR expression in uterine and ovarian tissues, revealing that these key molecules involved in estrogen synthesis, metabolism, and transport in PMS rats. We confirmed the anti-PMS effect of DKTP through enhancing E2 production. Exploring a novel drug based on improving E2 synthesis, metabolism, and transport may represent a novel strategy for PMS prevention and treatment.

12.
Biosci Rep ; 40(10)2020 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-32955083

RESUMO

OBJECTIVES: To identify the prognostic value of aberrantly methylated differentially expressed genes (DEGs) in hepatocellular carcinoma (HCC) and to explore the underlying mechanisms of tumorigenesis. METHODS: Gene expression profiles (GSE65372 and GSE37988) were analyzed using GEO2R to obtain aberrantly methylated DEGs. Functional enrichment analysis of screened genes was performed by the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Cytoscape software was used to analyze the PPI network and to select hub genes. Transcriptional and proteinic expression data of hub genes were obtained through UALCAN and the Human Protein Reference Database. Finally, we analyzed the prognostic value of hub genes with the Kaplan-Meier Plotter and MethSurv database. RESULTS: In total, 24 up-hypomethylated oncogenes and 37 down-hypermethylated tumor suppressor genes (TSGs) were identified, and 8 hub genes, including 4 up-hypomethylated oncogenes (CDC5L, MERTK, RHOA and YBX1) and 4 down-hypermethylated TSGs (BCR, DFFA, SCUBE2 and TP63), were selected by PPI. Higher expression of methylated CDC5L-cg05671347, MERTK-cg08279316, RHOA-cg05657651 and YBX1-cg16306148, and lower expression of methylated BCR-cg25410636, DFFA-cg20696875, SCUBE2-cg19000089 and TP63-cg06520450, were associated with better overall survival (OS) in HCC patients. Multivariate analysis also showed they were independent prognostic factors for OS of HCC patients. CONCLUSIONS: In summary, different expression of methylated genes above mentioned were associated with better prognosis in HCC patients. Altering the methylation status of these genes may be a therapeutic target for HCC, but it should be further evaluated in clinical studies.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Biologia Computacional , Metilação de DNA , Neoplasias Hepáticas/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Valor Preditivo dos Testes , Prognóstico , Mapas de Interação de Proteínas , Medição de Risco , Fatores de Risco , Transcrição Genética , Transcriptoma
13.
Biomed Res Int ; 2020: 3765937, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32626741

RESUMO

Background: Single nucleotide polymorphism (SNP) of complement component 2 (C2) has been found to be significantly associated with hepatocellular carcinoma (HCC). However, little is known about the role and mechanism of C2 in HCC. In the present study, we aimed to explore the prognostic value of C2 and its correlation with tumor-infiltrating immune cells in HCC. Materials and Methods: mRNA expression was downloaded from TCGA (365 HCC patients and 50 healthy controls), GSE14520 (220 HCC patients and 220 adjacent normal tissues), and ICGC HCC (232 HCC patients) cohorts. Unpaired Student's t-tests or ANOVA tests were used to evaluate differences of C2 expression. Univariate and multivariate analyses were used to analyze the prognostic value of C2. CIBERSORT was used to calculate the proportion of 22 kinds of tumor-infiltrating immune cells. Results: Significantly lower C2 expression was found at HCC compared to healthy controls, and C2 was associated with TNM stages. Higher C2 expression was significantly associated with better prognosis, and multivariate analysis showed that C2 was also an independent factor for the prognosis of HCC. Moreover, elevated CD4 T cells were found at HCC patients with higher C2 expression while the higher proportion of macrophage M0 cells was found in HCC patients with lower C2 expression. KEGG analysis showed that "cell cycle," "AMPK signaling pathway," and "PPAR signaling pathway" were enriched in HCC patients with higher C2 expression. Conclusion: C2 is a prognostic factor for HCC and may be used as a therapeutic target for future treatment of HCC.


Assuntos
Carcinoma Hepatocelular , Complemento C2 , Neoplasias Hepáticas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Complemento C2/genética , Complemento C2/metabolismo , Bases de Dados Genéticas , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Transdução de Sinais/genética , Transcriptoma/genética , Adulto Jovem
14.
J Viral Hepat ; 27(10): 1071-1081, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32384193

RESUMO

Previously, we identified rare missense mutations of complement component 2 (C2) to be associated with chronic hepatitis B (CHB) by exome sequencing. However, up to now, little is known about the role of C2 in CHB. In the present study, we aimed to perform preliminary exploration about the underlying role of C2 in CHB. Serum samples from 113 CHB patients and 30 healthy controls, and liver biopsy samples from 5 CHB patients and 3 healthy controls were obtained from the Third Affiliated Hospital of Sun Yat-sen University between January 2018 and January 2020. HepG2.2.15 and HepG2-NTCP cells infected with HBV were used to examine the influence of HBV infection on C2 expression. IFN-treated HepG2.2.15 cells were used to assess the effect of IFN on C2 expression. C2-overexpressing or C2-silencing HepG2.2.15 cells were constructed to evaluate the effect of C2 on HBV infection. Western blot and RT-qPCR were used to measure C2 expression in biopsy samples. HBeAg and HBsAg in culture medium and C2 of serum samples were measured by ELISA. HBV-DNA was measured by RT-qPCR. GSE84044, GSE54747 and GSE27555 were downloaded from GEO. C2 expression in liver tissue and serum was significantly lower in CHB patients compared to healthy controls, and significantly higher C2 expression was found in CHB patients with lower ALT, AST, Scheuer grade and stages compared to CHB patients with higher ALT, AST, Scheuer grades and Scheuer stage. Besides, HBV infection could decrease C2 expression by increasing expression of Sp1 and reducing expression of HDAC4. Moreover, C2 could enhance the anti-virus effect of IFN on HepG2.2.15 cells and also inhibit HBV replication in HepG2.2.15 cells by inhibition of p38-MAPK signalling pathway. In conclusion, HBV may promote viral persistence in CHB patients by inhibiting C2 expression.


Assuntos
Vírus da Hepatite B , Hepatite B Crônica , Complemento C2 , DNA Viral , Antígenos de Superfície da Hepatite B , Antígenos E da Hepatite B , Humanos
15.
J Exp Clin Cancer Res ; 38(1): 475, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31771611

RESUMO

BACKGROUND: Forkhead box G1 (FOXG1) is a member of the Fox transcription factor family involved in regulation of many cancers. However, the role of FOXG1 in hepatocellular carcinogenesisis largely unclear. The present study aimed at examining the biological function and underlying mechanism of FOXG1 on hepatocellular carcinoma (HCC) tumor metastasis as well as its clinical significance. METHODS: Levels of FOXG1 were determined by immunohistochemical and real-time PCR analysis in HCC cell lines and human HCC samples. The effect of FOXG1 on cancer cell invasion and metastasis was investigated in vitro and in vivo in either FOXG1-silenced or overexpressing human HCC cell lines. Immunoprecipitation and chromatin immunoprecipitation assays were performed to investigate the interaction of FOXG1, ß-catenin, TCF4 and the effect on Wnt target-gene promoters. RESULTS: In human HCC, the level of FOXG1 progressively increased from surrounding non tumorous livers to HCC, reaching the highest levels in metastatic HCC. Furthermore, expression levels of FOXG1 directly correlated with cancer cell epithelial-mesenchymal transition (EMT) phenotype. In FOXG1-overexpressing cells, FOXG1 promotes the stabilization and nuclear accumulation of ß-catenin by directly binding to ß-catenin and it associates with the lymphoid enhancer factor/T cell factor proteins (LEF/TCFs) on Wnt responsive enhancers (WREs) in chromatin. CONCLUSIONS: The results show that FOXG1 plays a key role in mediating cancer cell metastasis through the Wnt/ß-catenin pathway in HCC cells and predicts HCC prognosis after surgery. Targeting FOXG1 may provide a new approach for therapeutic treatment in the future.


Assuntos
Carcinoma Hepatocelular/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Via de Sinalização Wnt , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Fatores de Transcrição Forkhead/biossíntese , Fatores de Transcrição Forkhead/genética , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Metástase Neoplásica , Proteínas do Tecido Nervoso/biossíntese , Proteínas do Tecido Nervoso/genética , Prognóstico , Transdução de Sinais , Proteína 2 Semelhante ao Fator 7 de Transcrição/metabolismo , Regulação para Cima , beta Catenina/metabolismo
16.
Materials (Basel) ; 12(11)2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31159300

RESUMO

Zinc coatings and superhydrophobic surfaces have their own characteristics in terms of metal corrosion resistance. Herein, we have prepared a robust and repairable superhydrophobic zinc coating (SZC) based on a widely commercially available cold galvanized paint via a fast (within 10 min) and facile process for corrosion resistance. Specifically, the cold galvanized paint was sprayed onto the iron substrate, followed by acetic acid (HAc) etching and stearic acid (STA) hydrophobizing. The as-obtained sample was coded as Fe-Zn-HAc-STA and possessed an apparent contact angle of 168.4 ± 1.5° as well as a sliding angle of 3.5 ± 1.2°. The Fe-Zn-HAc-STA sample was mechanically durable and easily repairable. After being ultrasonicated in ethanol for 100 min, the superhydrophobicity was still retained. The Fe-Zn-HAc-STA sample lost its superhydrophobicity after being abraded against sandpaper with a load of 100 g and regained its superhydrophobicity after HAc etching and subsequent STA hydrophobizing. The corrosion resistance of the SZC was investigated by immersing the Fe-Zn-HAc-STA sample into the static or dynamic aqueous solution of NaCl (3.5 wt.%) and the lasting life of the entrapped underwater air layer (EUAL) was roughly determined by the turning point at the variation curve of surface wettability against immersion time. The lasting life of the EUAL iwas 8 to 10 days for the SZC in the static NaCl solution and it decreased sharply to 12 h in a dynamic one with the flow rate of 2 and 4 m/s. This suggests that the superhydrophobic surface provided extra corrosion protection of 8 to 10 days or 12 h to the zinc coating. We hope that the SZC may find its practical application due to the facile and fast fabrication procedure, the good mechanical durability, the easy repairability, and the good corrosion protection.

17.
J Immunol Res ; 2019: 1538439, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31198792

RESUMO

Background and Aims: Serum immunoglobulins are frequently increased in patients with chronic liver disease, but little is known about the role of serum immunoglobulins and their correlations with interleukin-27 (IL-27) in patients with HBV-related acute-on-chronic liver failure (HBV-ACLF). This study was aimed at determining the role of serum immunoglobulin (IgG, IgA, and IgM) levels and their associations with IL-27 in noncirrhotic patients with HBV-ACLF. Methods: Samples were assessed from thirty patients with HBV-ACLF, twenty-four chronic hepatitis B (CHB) subjects, and eighteen normal controls. Disease severity of HBV-ACLF was evaluated. Serum IL-27 levels were examined by enzyme-linked immunosorbent assay. Immunoglobulin levels were assessed using immunoturbidimetric assay. Correlations between immunoglobulin levels and IL-27 were analyzed. Receiver operating characteristic (ROC) curves were used to predict the 3-month mortality. Results: 25 (83.3%) HBV-ACLF patients had elevated serum IgG levels (>1 ULN), 14 (46.7%) patients had elevated IgA, and 15 (50%) had raised IgM. IgG, IgA, and IgM levels were higher in HBV-ACLF patients than in CHB patients and normal controls. Moreover, IgG, IgA, and IgM levels were positively correlated with Tbil levels but negatively correlated with prothrombin time activity (PTA) levels. Additionally, IgG levels were significantly increased in nonsurviving patients than in surviving HBV-ACLF patients (P = 0.007) and positively correlated with MELD score (r = 0.401, P = 0.028). Also, IgG levels were positively correlated with IL-27 levels in HBV-ACLF patients (r = 0.398, P = 0.029). Furthermore, ROC curve showed that IgG levels could predict the 3-month mortality in HBV-ACLF patients (the area under the ROC curve: 0.752, P = 0.005). Conclusions: Our findings demonstrated that serum immunoglobulins were preferentially elevated in HBV-ACLF patients. IgG levels were positively correlated with IL-27 and may predict prognosis in HBV-ACLF patients.


Assuntos
Insuficiência Hepática Crônica Agudizada/diagnóstico , Vírus da Hepatite B/fisiologia , Hepatite B/diagnóstico , Imunoglobulina G/sangue , Fígado/patologia , Doença Aguda , Insuficiência Hepática Crônica Agudizada/mortalidade , Adulto , Feminino , Hepatite B/imunologia , Hepatite B/mortalidade , Humanos , Interleucina-27/sangue , Masculino , Prognóstico , Estudos Prospectivos , Análise de Sobrevida , Regulação para Cima
18.
Materials (Basel) ; 12(11)2019 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-31181832

RESUMO

The main aim of this study is to evaluate the possibility of applying foundry dust (FD) derived filler for the preparation of natural rubber (NR) based composites by characterizing the mechanical properties. The as-received FD was processed via a simple and low-cost procedure, including sieving, deironing and milling using a variety of industrial equipment. FD powders before and after silane coupling agent (Si 69) modification were used as fillers for NR. NR composites inserted with different content of modified and unmodified FD up to 50 phr were prepared via dry-mixing method. Then, comprehensive mechanical performances were performed on the corresponding vulcanizates. It was demonstrated that NR composite filled with 50 phr of modified FD exhibited optimized comprehensive mechanical performance. Tear strength and hardness is increased by 21.3% and 12.8% than pure NR, respectively. Tensile strength is reduced by 21% and elongation at break remained nearly unchanged. Additionally, the composite showed a large increment of 50.9% for its wet grip property, while exhibited an increment of only 11.9% for its rolling resistance in comparison with the composite containing 10 phr of FD. The findings of this study may provide a new application area for the large amounts of utilization of foundry waste with a high level of value being added.

19.
Can J Gastroenterol Hepatol ; 2019: 9703907, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31058113

RESUMO

Research on effects of anti-hepatitis B virus (HBV) nucleoside analogs on male fertility and birth defects is limited and safety of nucleoside analogs in pregnancy is still a concern. Chronic hepatitis B (CHB) patients in Guangdong province were surveyed using a structured questionnaire. We collected data including medication type, fertility, and birth defects. Moreover, a survey of the knowledge of antiviral nucleoside analogs safety in fertility of male patients was conducted among physicians nationwide. Semen samples of 30 patients were collected. We screened 1050 HBV-positive male patients. Reasons for not receiving antivirals in 150 patients were "did not meet criteria for antiviral therapy," fertility, and financial. Furthermore, 900 participants received antivirals (85.71%, 900/1050), including 792 patients with children and 15.15% (120/792) took anti-HBV treatment when preparing for pregnancy. Based on whether they received antiviral therapy during conception or not, we divided patients into two groups. In the child-bearing age group, 88.33% (106/120) of patients received telbivudine (LDT), whereas the other group mainly received entecavir (ETV) (87.20%, 586/672). No significant difference occurred in birth defect incidence rates between both groups. Furthermore, 558 physicians completed questionnaires. Reasons that influenced drug selection were "patient's condition," "fertility demand," "financial condition," and "compliance." Telbivudine was the first-choice drug (32.80%, 183/558) while tenofovir (TDF) was the second (2.69%, 15/558). Additionally, 61.47% of physicians considered telbivudine or tenofovir as the first choice for male patients who met antiviral criteria, whereas 19% suggested delayed therapy and follow-up until childbirth. No significant changes occurred in semen volume, concentration, mobility, and percentage before and after administration of anti-HBV nucleoside analogs, which did not affect male fertility and birth defect incidence while the desire for pregnancy influenced drug selection and timing of administration. Further research on the effects of analogs on male fertility and fetal safety is required.


Assuntos
Antivirais/uso terapêutico , Pai , Fertilidade , Vírus da Hepatite B , Hepatite B Crônica/tratamento farmacológico , Tenofovir/uso terapêutico , Adulto , Antivirais/administração & dosagem , Feto/anormalidades , Humanos , Recém-Nascido , Masculino , Inquéritos e Questionários , Tenofovir/efeitos adversos , Carga Viral
20.
Cell Death Dis ; 10(5): 336, 2019 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-31000692

RESUMO

Mesenchymal stromal cells (MSCs) can differentiate to various cell types including osteoblasts, chondrocytes, and adipocytes. This cellular flexibility contributes to widespread clinical use of MSCs in tissue repair. However, challenges remain in efficient cellular expansion of MSCs for stem cell therapy. Current MSC culture methods have resulted in reduced self-renewal of MSCs and compromised therapeutic outcomes. This study identifies that nicotinamide mononucleotide (NMN), a key natural NAD+ intermediate, effectively encourages MSC expansion in vitro and in vivo. The in vitro expanded MSCs had heightened osteogenesis, but reduced adipogenesis. Furthermore, NMN supplementation stimulated osteogenesis of endogenous MSCs, and protected bone from aging and irradiation induced damage in mice. Mechanistically, we found that NMN treatment upregulated SIRT1. Genetically overexpressing SIRT1 in MSCs by using Prx1 cre; ColA1flox-stop-flox-SIRT1 mice promoted osteogenesis and reduced adipogenesis in aged mice. Overall, our data demonstrate that NMN promoted MSC self-renewal with strengthened osteogenesis and reduced adipogenesis via upregulating SIRT1 in aged mice.


Assuntos
Adipogenia/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Mononucleotídeo de Nicotinamida/farmacologia , Osteogênese/efeitos dos fármacos , Sirtuína 1/metabolismo , Envelhecimento , Animais , Células da Medula Óssea/citologia , Osso e Ossos/metabolismo , Autorrenovação Celular/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/efeitos da radiação , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Sirtuína 1/genética , Regulação para Cima/efeitos dos fármacos , Irradiação Corporal Total
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...