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1.
Antiviral Res ; 184: 104953, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33065138

RESUMO

BACKGROUND & AIMS: Normal/mildly elevated ALT (<2 × ULN) CHB patients are potentially at risk of progression to cirrhosis and/or hepatocellular carcinoma (HCC). We aimed to assess the outcomes of anti-viral therapy for normal/mild elevation of ALT CHB patients. METHODS: CHB patients (n = 432) who have had liver biopsied were determined. It was determined that the outcomes of anti-viral therapy in CHB patients with normal/mild elevation of ALT, in response to nucleoside/nucleotide analogues (NAs) (n = 190) and pegylated interferon (PEG-IFN) (n = 30) treatment for up to 72 weeks. Non-anti-viral treated patients were used as control (n = 40). RESULTS: There was about 50% of the CHB patients showed hepatic inflammatory necrosis ≥ G2 and/or fibrosis ≥ S2 among >30-years-old. The rate of undetectable HBV DNA in NAs and PEG-IFN groups was ~50%, ~80% or ~90% at week 24, 48 or 72, respectively. HBeAg clearance rate was lower in NAs treated than that in PEG-IFN group at week 48 (6% vs 20%, P < 0.05). ALT normalization rate was increased by 1.18-fold at week 72. HBsAg decline in HBeAg+ patients treated with NAs or PEG-IFN was 0.418 or 1.217 log IU/mL (P < 0.0001) at week 48; whereas HBsAg decline was 0.176 or 0.816 log IU/mL (P < 0.001) in HBeAg- patients. HBsAg at baseline and week 24 were strong predictors of "low HBsAg at week 48". CONCLUSION: Long term anti-viral therapy inhibits HBV replication effectively in ALT<2 × ULN CHB patients. PEG-IFN therapy is recommended for HBeAg+ patients with baseline HBsAg<4.37 log IU/ml and HBeAg- patients with baseline HBsAg<2.66 log IU/ml to achieve "low HBsAg at week 48".

2.
Microbiol Resour Announc ; 9(35)2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32855257

RESUMO

Bacteriophage OSY-STA is a new anti-Salmonella phage that was isolated from a chicken farm in Ohio. It is a promising candidate for food safety applications, considering its efficiency in infecting several Salmonella enterica serovars. The current work presents its genomic characteristics. Salmonella phage OSY-STA has a 111,039-bp genome and 166 open reading frames.

3.
Am J Gastroenterol ; 115(12): 2026-2035, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32858565

RESUMO

INTRODUCTION: Acute-on-chronic liver failure (ACLF) is defined by the European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) consortium and the North American Consortium for the Study of End-Stage Liver Disease (NACSELD) as an acute deterioration of cirrhosis with multiple organ failures and high short-term mortality. However, their diagnostic criteria differ. We aimed to compare these 2 criteria in the prediction of prognosis in hospitalized cirrhosis. METHODS: This was a prospective study of nonelectively hospitalized patients with cirrhosis (N = 468) from a single tertiary hospital between 2016 and 2018. Baseline characteristics, incidence, and types of organ failure and survival data at 7, 28, and 90 days were collected. Prognostic utilities of the 2 criteria were compared. RESULTS: One hundred thirty-seven of 468 patients (29.3%) had EASL-CLIF ACLF, and 35 of 468 (7.4%) had NACSELD ACLF. The 28-day transplant-free survival of ACLF was 58.4% using EASL-CLIF and 37.1% using the NACSELD criteria. In predicting 28-day mortality, the NACSELD criteria demonstrated significantly higher overall accuracy (92.0% vs 85.3%, P < 0.01), specificity (99.7% vs 84.0%, P < 0.001), and positive predictive value (97.1% vs 50.4%, P < 0.001) but lower sensitivity (49.3% vs 92.5%, P < 0.001) and negative predictive value (91.6% vs 98.5%, P < 0.001) than those of EASL-CLIF. The results were similar in predicting 7-day outcome. However, the overall accuracy became similar between NACSELD and EASL-CLIF ACLF criteria in predicting 90-day mortality (86.3% vs 88.7%, P = 0.27) because of the decrease of sensitivity and negative predictive value of NACSELD ACLF criteria. The prognostic performance of these 2 ACLF criteria was similar when applied to patients with or without hepatitis B virus infection as an etiology of cirrhosis. DISCUSSION: There are both caveats and utilities of NACSELD and EASL-CLIF ACLF criteria in prognosis prediction in patients with cirrhosis. NACSED criteria is highly accurate in predicting morality, whereas the EASL-CLIF criteria is more sensitive to identify patients who would benefit from liver transplantation.

5.
Front Pharmacol ; 11: 381, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32317964

RESUMO

Alzheimer's disease (AD) is a complex neurodegenerative disease characterized by cognitive dysfunction. Kai-Xin-San (KXS) is a traditional Chinese medicine (TCM) formula that has been used to treat AD patients for over a thousand years in China. However, the therapeutic mechanisms of KXS for treating AD have not been fully explored. Herein, we used a comprehensive network pharmacology approach to investigate the mechanism of action of KXS in the treatment of AD. This approach consists of construction of multiple networks and Gene Ontology enrichment and pathway analyses. Furthermore, animal experiments were performed to validate the predicted molecular mechanisms obtained from the systems pharmacology-based analysis. As a result, 50 chemicals in KXS and 39 AD-associated proteins were identified as major active compounds and targets, respectively. The therapeutic mechanisms of KXS in treating AD were primarily related to the regulation of four pathology modules, including amyloid beta metabolism, tau protein hyperphosphorylation process, cholinergic dysfunction, and inflammation. In scopolamine-induced cognitive dysfunction mice, we validated the anti-inflammatory effects of KXS on AD by determining the levels of inflammation cytokines including interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α. We also found cholinergic system dysfunction amelioration of KXS is correlated with upregulation of the cholinergic receptor CHRNB2. In conclusion, our work proposes a comprehensive systems pharmacology approach to explore the underlying therapeutic mechanism of KXS for the treatment of AD.

6.
Cancer Med ; 9(9): 3057-3069, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32150664

RESUMO

BACKGROUND: Alpha-fetoprotein (AFP), routinely used for diagnosis of hepatocellular carcinoma (HCC), is limited with relatively low sensitivity and high false positivity in HBV-related HCC (HBV-HCC). Thus, an alternative approach was explored to improve specificity/sensitivity for diagnosis of HBV-HCC, using the combination of AFP, inflammatory score, and liver function. METHODS: Chronic hepatitis B (CHB) (n = 510) and HBV-HCC (n = 473) patients were identified retrospectively for this study. The diagnostic value of single vs combined biomarkers for HBV-HCC was analyzed, using ROC curve. RESULTS: It was observed that elderliness, male sex, cirrhosis, HBeAg+ or no-antiviral therapy, and elevation of ALT, AST, neutrophil-lymphocyte ratio (NLR), and AFP were associated with developing HBV-HCC. However, the cut-off ALT defined by Chinese standard, but not by AASLD, was a risk factor. Interestingly, AFP of HBeAg- HBV-HCC patients without cirrhosis was significantly higher than that of the HBeAg+ patients. AUC values for AFP, ALT, AST, or NLR were 0.84 (95% CI: 0.815-0.862), 0.533 (95% CI: 0.501-0.565), 0.696 (95% CI: 0.666-0.725), or 0.684 (95% CI: 0.654-0.713) with optimal cut-off at 7.21 ng/mL, 43 IU/mL, 38 IU/mL, or 2.61, respectively. Combination of AFP with ALT, AST, and NLR improved the diagnostic performance for HBV-HCC, compared to any of the single biomarkers or any other combinations among these patients (except no-cirrhosis). CONCLUSIONS: Elderliness, male sex, elevated ALT, AST, NLR, AFP, cirrhosis, HBeAg+ , and no-antiviral treatment were independent risk factors for HBV-HCC. AASLD standard of ALT cut-off value may not be suitable for the Chinese population. Regular monitoring of HCC among HBeAg- patients with abnormal AFP may improve the management of HBV-HCC. The diagnostic performance of AFP combined with ALT, AST, and NLR for HBV-HCC was superior to single biomarker or any other combinations among these patients, and its diagnostic equation can be used as useful tool for differentiation of HBV-HCC from CHB.

7.
World J Gastroenterol ; 26(6): 645-656, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32103873

RESUMO

BACKGROUND: Reports on bacterial infection (BI) in decompensated cirrhosis (DC) is mainly from alcoholic cirrhosis. The role of BI as a trigger or complication of acute-on-chronic liver failure (ACLF) in patients with hepatitis B virus decompensated cirrhosis (HBV-DC) remains to be investigated. AIM: To investigate the impact of BI on the outcomes of the patients with HBV-DC admitted into the hospital with or without ACLF. METHODS: This retrospective study included patients with HBV-DC admitted to two tertiary centers in China. In-hospital overall survival, 90-d transplant-free survival, 5-year post-discharge survival, and cumulative incidence of ACLF were evaluated. Risk factors for death were analyzed considering liver transplantation as a competing event. RESULTS: A total of 1281 hospitalized HBV-DC patients were included; 284 had ACLF at admission. The overall prevalence of BI was 28.1%. The patients with BI had a significantly lower in-hospital survival and transplant-free 90-d survival than those without, in both the patients admitted with and without ACLF. The presence of BI significantly increased the risk of developing ACLF [sub-distribution hazard ratio (sHR) = 2.52, 95%CI: 1.75-3.61, P < 0.001] in the patients without ACLF. In the patients discharged alive, those who had an episode of BI had a significantly lower 5-year transplant-free survival. BI was an independent risk factor for death in the patients admitted without ACLF (sHR = 3.28, 95%CI: 1.93-5.57), while in ACLF admissions, the presence of pneumonia, but not other type of BI, independently increased the risk of death (sHR = 1.87, 95%CI: 1.24-2.82). CONCLUSION: BI triggers ACLF in patients with HBV-DC and significantly impairs short-term survival. HBV-DC patients should be monitored carefully for the development of BI, especially pneumonia, to avoid an adverse outcome.

8.
J Org Chem ; 85(6): 4354-4364, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32090568

RESUMO

An efficient approach to prepare trifluoromethyl-α-carbolines and ester group-substituted α-carbolines via the tandem cyclization reaction of 2-(2-aminophenyl)acetonitriles and trifluoromethyl 1,3-diones or ß,γ-unsaturated α-ketoesters was reported. The transformation proceeded smoothly in the presence of catalytic environmental-benign iron salts, which are used to prepare the desired products in moderate to good yields.

9.
J Pediatr Endocrinol Metab ; 32(7): 653-665, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31194681

RESUMO

Diabetic nephropathy (DN) is considered as one of the most popular microvascular complications of diabetes and the leading cause of death among diabetic patients. Currently, even though safflower yellow (SY) is widely adapted in the clinical treatment of DN, no meta-analysis can guarantee the safety of this treatment. This paper aims to evaluate the dominant method of SY on DN disease. The reliable source of information for randomized controlled trials (RCTs) and clinical research is listed as follows: the Chinese Biomedical Literature database, Chongqing VIP, Embase, the Cochrane Library and the China Academic Journals Full-text Database (CNKI). The CNKI search included Chinese journal articles, the full-text of important conferences and dissertations up to March 30, 2017. We picked out some particularly influential outcome variables including urinary albumin excretion rate (UAER), fasting blood sugar (FBG), blood urea nitrogen (BUN) and high-sensitivity C-reactive protein (hs-CRP) in each extracted study. In total, 1289 participants were included in this meta-analysis. The efficacy of SY alone or combined with Western medicine in the treatment of DN was better with statistically significant factors (odds ratio [OR] = 3.6, 95% confidence interval [CI] [2.37, 5.47], p < 0.00001). We found that SY lessened the UAER, heightened the proportion of blood sugar and beneficially improved other detective indicators related to DN. Therefore, SY used alone or in combination with Western medicine was significantly more efficacious with lower toxicity than Western medicine alone.


Assuntos
Chalcona/análogos & derivados , Diabetes Mellitus/fisiopatologia , Nefropatias Diabéticas/prevenção & controle , Chalcona/uso terapêutico , Nefropatias Diabéticas/epidemiologia , Humanos , Incidência , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
Biosci Trends ; 13(2): 130-135, 2019 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-30930359

RESUMO

Single nucleotide polymorphisms (SNP) influence the outcome of antiviral therapy in chronic hepatitis B patients. Interferon ß promoter stimulator 1 polymorphisms (IPS-1) regulate interferon (IFN) mediated viral clearance in hepatitis B virus (HBV) infection. In our study, HepG2 and HepG2.2.15 were transfected with different SNP genotype expression vectors of IPS-1 (wild-type, rs17857295, rs7262903 and rs7269320). The production of IPS-1 and IFN were evaluated in these transfected cells. IPS-1 in the HepG2.2.15 cells transfected with rs17857295 or rs7262903 was 37% or 31% lower than that with wild-type transfection (p < 0.001). IFN-ß in rs17857295 or rs7262903 transfected HepG2.2.15 cells was 5.4 or 3.7 fold higher than that of wild-type transfection (p < 0.0001). IPS-1 in rs7269320 SNP transfected HepG2.2.15 cells was 40% lower than that of wild-type transfection (p < 0.0001); no significantly different IFN-ß was observed between rs7269320 SNP and wild-type transfections. IFN-ß expression was > 2 fold higher in rs17857295 transfected HepG2.2.15 cells than HepG2 cells (p < 0.001). The data suggests that host HBV viral clearance is stronger in IPS-1 rs17857295 or rs7262903 SNP genotype patients than wild-type patients. Relatively weak inducible IFN-ß production in HBV infected patients with IPS-1 rs7269320 SNP or wild-type may contribute to chronic virus infection.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Hepatite B/genética , Interferon beta/metabolismo , Polimorfismo de Nucleotídeo Único/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Vetores Genéticos/metabolismo , Genótipo , Células HEK293 , Células Hep G2 , Humanos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
11.
Dig Liver Dis ; 51(9): 1323-1329, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30928419

RESUMO

BACKGROUND: The aim of this study was to compare the diagnostic accuracy of the FibroTouch and FibroScan in patients with chronic liver disease (CLD) for staging fibrosis. METHODS: A prospective study was conducted in 435 CLD patients between 2014 and 2017. Index tests (FibroTouch, FibroScan, APRI, and FIB-4 score) and a reference standard (liver biopsy) were performed within one week. RESULTS: The area under the receiver operating curve (AUROC) of the FibroTouch was similar with that of the FibroScan for the diagnosis of significant fibrosis, severe fibrosis, or cirrhosis; however, the AUROC of the FibroTouch was higher than that of APRI or FIB-4 (p < 0.001). There was a significant correlation (rho = 0.85, p < 0.001) between the FibroTouch and FibroScan for liver stiffness. The overall diagnostic accuracy of FibroTouch for significant fibrosis, severe fibrosis, or cirrhosis was 73.3%, 83.2%, or 84.1%, respectively. No significant differences between the FibroTouch and FibroScan were detected regarding the sensitivity, specificity, negative predictive value, positive predictive value, and accuracy. The optimal cut-off values for each stage of fibrosis were similar between the FibroTouch and FibroScan. CONCLUSION: The FibroTouch is a valuable diagnostic tool for diagnosing liver fibrosis with good diagnostic accuracy which was comparable with that of the FibroScan, but superior to that of the APRI and FIB-4.


Assuntos
Técnicas de Imagem por Elasticidade/instrumentação , Hepatopatias/patologia , Fígado/patologia , Adulto , Doença Crônica , Feminino , Fibrose , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC
12.
Neural Regen Res ; 14(5): 794-804, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30688265

RESUMO

Kai Xin San (KXS, containing ginseng, hoelen, polygala, and acorus), a traditional Chinese herbal compound, has been found to regulate cognitive dysfunction; however, its mechanism of action is still unclear. In this study, 72 specific-pathogen-free male Kunming mice aged 8 weeks were randomly divided into a vehicle control group, scopolamine group, low-dose KXS group, moderate-dose KXS group, high-dose KXS group, and positive control group. Except for the vehicle control group and scopolamine groups (which received physiological saline), the doses of KXS (0.7, 1.4 and 2.8 g/kg per day) and donepezil (3 mg/kg per day) were gastrointestinally administered once daily for 2 weeks. On day 8 after intragastric treatment, the behavioral tests were carried out. Scopolamine group and intervention groups received scopolamine 3 mg/kg per day through intraperitoneal injection. The effects of KXS on spatial learning and memory, pathological changes of brain tissue, expression of apoptosis factors, oxidative stress injury factors, synapse-associated protein, and cholinergic neurotransmitter were measured. The results confirmed the following. (1) KXS shortened the escape latency and increased residence time in the target quadrant and the number of platform crossings in the Morris water maze. (2) KXS increased the percentage of alternations between the labyrinth arms in the mice of KXS groups in the Y-maze. (3) Nissl and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining revealed that KXS promoted the production of Nissl bodies and inhibited the formation of apoptotic bodies. (4) Western blot assay showed that KXS up-regulated the expression of anti-apoptotic protein Bcl-2 and inhibited the expression of pro-apoptotic protein Bax. KXS up-regulated the expression of postsynaptic density 95, synaptophysin, and brain-derived neurotrophic factor in the cerebral cortex and hippocampus. (5) KXS increased the level and activity of choline acetyltransferase, acetylcholine, superoxide dismutase, and glutathione peroxidase, and reduced the level and activity of acetyl cholinesterase, reactive oxygen species, and malondialdehyde through acting on the cholinergic system and reducing oxidative stress damage. These results indicate that KXS plays a neuroprotective role and improves cognitive function through reducing apoptosis and oxidative stress, and regulating synapse-associated protein and cholinergic neurotransmitters.

13.
Front Physiol ; 10: 1503, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31920708

RESUMO

Background: Long non-coding RNAs (lncRNAs) have recently been tightly linked to plenty of human diseases. However, knowledge of acute-on-chronic liver failure (ACLF) related lncRNAs remains insufficient. In this work, we studied the role of the lncRNA nuclear enriched abundant transcript 1 (NEAT1) in the pathogenesis of ACLF. Methods: ACLF model was established by challenging D-galactosamine (D-GalN)/ lipopolysaccharide (LPS) i.p. in rats with cirrhosis. The serum levels of IL-1, IL-6, and HMGB1 were determined using ELISA. Quantitative real time-PCR and western blot were performed to evaluate RNA and protein levels of inflammatory response. RNA immunoprecipitation assay was performed to confirm protein that interacts with NEAT1. Findings: Over-expression of NEAT1 could interact with TRAF6 and decrease its ubiquitination level, and significantly reduced the expression levels of IL-6, IL-22. Importantly, in ACLF rat model, NEAT1 over-expression reduced several cytokines expression and alleviated the pathological status in contrast to the control group. Additionally, NEAT1 was increased and positively correlated with IL-22 and IL-6 levels in PBMCs from the ACLF patients. Interpretation: NEAT1 can suppress inflammatory response through blockade of TRAF6 ubiquitination in ACLF rat model, suggesting that lncRNA NEAT1 might play protective roles in the pathogenesis of ACLF and provide promising novel target for pharmacological intervention.

14.
Infect Drug Resist ; 11: 2001-2009, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30464542

RESUMO

Background and aims: Chronic hepatitis B (CHB) patients rarely achieve hepatitis B surface antigen (HBsAg) loss with nucleoside/nucleotide analog therapy. Methods: In this retrospective study, it was evaluated that the rate of HBsAg loss in the HBe antigen negative (HBeAg-) patients (n=101) treated with entecavir (ETV) for ≥24 weeks followed by switching to (n=22) or adding on (n=26) pegylated interferon (PEG-IFN), and continuing ETV (n=53). Results: HBsAg clearance rate at week 48 was 9% (2/22), 15% (4/26), and 0% (0/53) (P<0.05), in switch-to or add-on, or ETV monotherapy CHB patients, respectively. HBsAg reduction at week 48 was 1.182, 0.6614, or 0.056 log IU/mL, in switch-to, add-on, and ETV patients, respectively (P<0.001). The response rate (HBsAg reduction >1 log IU/mL at week 48) in the switch-to, add-on, and ETV monotherapy CHB patients was 60%, 40%, and 2%, respectively (P<0.001). In the switch-to and add-on patients, HBsAg reduction and clearance were associated with HBsAg titers at week 0 and HBsAg reduction at week 24. Furthermore, HBsAg reduction at week 24 was associated with the response rate at week 48 in the switch-to and add-on patients, showing that the area under the receiver operating characteristic curve was 0.904. Positive predictive value and negative predictive value for response rate was 70% and 100% with cut-off value 0.2 log IU/mL, respectively. Conclusion: In summary, we demonstrated that PEG-IFN enhanced HBsAg loss in HBeAg- CHB patients. High HBsAg clearance was achieved in the patients with HBsAg titers at baseline <1,000 IU/mL and HBsAg reduction >0.2 log IU/mL.

15.
Medicine (Baltimore) ; 97(43): e12967, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30412118

RESUMO

BACKGROUND: Xingnaojing injection (XNJ) sharpen the mind and induce consciousness and are widely used in acute phases of intracerebral hemorrhage (ICH). Naloxone hydrochloride injection (NX) performs equally well and replace the effects of morphine-like substances to promote conscious awareness. The applications of XNJ combined with NX for ICH show some advantages compared with NX applied individually. The aim of this systematic review is to evaluate the effectiveness and safety of XNJ combined with NX for ICH. METHODS: Comprehensive searches were conducted in 8 medical databases (PubMed, Cochrane Library, Web of Science, Embase, CNKI, VIP, CBM and Wanfang database) from inceptions to October 2017 for randomized controlled trials (RCTs) that compared the applications of XNJ and NX with NX applied individually in ICH. Literature screening, assessing risk of bias and data extraction were conducted by 2 reviewers independently. According to the Cochrane Collaboration's RevMan5.3 software to perform the data analysis. RESULTS: 32 RCTs (3068 cases) were selected and the quality of studies were low. All trials compared XNJ and NX with NX applied individually. The overall meta-analysis results showed that XNJ combined with NX have significant effect on clinical efficacy (OR 3.78, 95% CI: 3.03-4.73; P < .00001), GCS score (MD 3.86, 95% CI: 3.46-4.25; P < .00001), coma duration (MD -5.59, 95% CI: -6.96 to -4.22; P < .00001), NIHSS score (MD -6.24, 95% CI: -8.05 to -4.42; P < .00001), Barthel Index score (MD 14.12, 95% CI: 6.7-21.54; P < .0002), cerebral hematoma volume (MD -6.05, 95% CI: -6.85 to -5.24; P < .00001) than NX applied individually. Adverse events reported in 4 studies and included mild discomfort symptoms. CONCLUSION: The effectiveness and safety of XNJ combined with NX for ICH cannot be determined due to the low quality of literature, publication bias and heterogeneity. More rigorous RCTs are necessary to verify the role of XNJ combined with NX in the treatment of ICH.


Assuntos
Hemorragia Cerebral/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Naloxona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Quimioterapia Combinada , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Naloxona/efeitos adversos , Antagonistas de Entorpecentes/efeitos adversos , Fármacos Neuroprotetores/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
Expert Opin Biol Ther ; 18(10): 1085-1094, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30182763

RESUMO

BACKGROUND: The effect of nucleos(t)ide analogs (NAs) versus interferon (IFN) on the occurrence of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) is controversial. We assessed whether antiviral strategy affected HCC development in CHB patients at different HCC risks. METHODS: 1112 CHB patients with antiviral therapy were included in this retrospective study. Patients treated with NAs only were classified into NAs group (n = 682) while those received IFN treatment with or without NAs were defined as IFN group (n = 430). Propensity score matching (PSM) was applied to minimize baseline differences. RESULTS: Totally, 31 patients developed HCC during follow-up (median 5.41 years). The cumulative HCC incidence at 10 years was significantly lower in the IFN group than NAs group (2.7% vs 8.0%, p < 0.001). Similar results were obtained in the PSM-cohort. Patients with IFN-based treatment were less likely to develop HCC than those with NAs (Hazard ratio = 0.15; 95% CI 0.04-0.66; p = 0.012). Subgroup analyses demonstrated that this superiority of IFN in reducing HCC development was obvious in patients at high- but not low-risk of HCC. CONCLUSIONS: Reduction of HCC development was more significant in CHB patients at higher HCC risk with IFN-based therapy than NAs treatment.


Assuntos
Antivirais/administração & dosagem , Carcinoma Hepatocelular/prevenção & controle , Hepatite B Crônica/tratamento farmacológico , Interferons/administração & dosagem , Neoplasias Hepáticas/prevenção & controle , Nucleosídeos/uso terapêutico , Adulto , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/virologia , Estudos de Coortes , Quimioterapia Combinada , Feminino , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/fisiologia , Hepatite B Crônica/complicações , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/patologia , Humanos , Incidência , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Nucleosídeos/análogos & derivados , Estudos Retrospectivos , Fatores de Risco
17.
Biomed Res Int ; 2018: 3538763, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30050927

RESUMO

Cognitive dysfunction is characterized as the gradual loss of learning ability and cognitive function, as well as memory impairment. Jiao-tai-wan (JTW), a Chinese medicine prescription including Coptis chinensis and cinnamon, is mainly used for the treatment of insomnia, while the effect of JTW in improving cognitive function has not been reported. In this study, we employed a scopolamine- (SCOP-) treated learning and memory deficit model to explore whether JTW could alleviate cognitive dysfunction. In behavioral experiments, Morris water maze, Y-maze, fearing condition test, and novel object discrimination test were conducted. Results showed that oral administration of JTW (2.1 g/kg, 4.2 g/kg, and 8.4 g/kg) can effectively promote the ability of spatial recognition, learning and memory, and the memory ability of fresh things of SCOP-treated mice. In addition, the activity of acetylcholinesterase (AChE) was effectively decreased; the activity of choline acetyltransferase (ChAT) and concentration of acetylcholine (Ach) were improved after JTW treatment in both hippocampus and cortex of SCOP-treated mice. JTW effectively ameliorated oxidative stress because of decreased the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) and increased the activities of superoxide dismutase (SOD) and catalase (CAT) in hippocampus and cortex. Furthermore, JTW promotes the expressions of neurotrophic factors including postsynaptic density protein 95 (PSD95) and synaptophysin (SYN) and brain-derived neurotrophic factor (BDNF) in both hippocampus and cortex. Nissl's staining shows that the neuroprotective effect of JTW was very effective. To sum up, JTW might be a promising candidate for the treatment of cognitive dysfunction.


Assuntos
Colinérgicos/farmacologia , Disfunção Cognitiva/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Acetilcolinesterase , Animais , Hipocampo/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto , Camundongos , Coelhos , Escopolamina
18.
Rejuvenation Res ; 21(3): 200-209, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28782427

RESUMO

The association between diabetes and dementia has been well demonstrated by epidemiologic studies. Berberine (BBR) has been reported to ameliorate diabetes and diabetic encephalopathy (DE). However, the mechanism is still unknown. In this study, we employ a diabetic model, db/db mice, to explore whether BBR could protect DE through the SIRT1/endoplasmic reticulum (ER) stress pathway. Behavioral results (Morris water maze, Y-maze spontaneous alternation test, and fear conditioning test) showed that oral administration of BBR (50 mg/kg) improved the learning and memory ability. Furthermore, BBR promoted lipid metabolism and decreased fasting glucose in db/db mice. Moreover, western blot analysis revealed that BBR increased the synapse- and nerve-related protein expression (PSD95, SYN, and NGF) and decreased the protein expression of inflammatory factors (TNF-α and NF-κB) in the hippocampus of db/db mice. BBR also increased the protein expression of SIRT1 and downregulated ER stress-associated proteins (PERK, IRE-1α, eIF-2α, PDI, and CHOP) in the hippocampus of db/db mice. Taken together, the present results suggest that the SIRT1/ER stress pathway might be a crucial mechanism in the neuroprotective effect of BBR against DE.


Assuntos
Berberina/farmacologia , Encefalopatias/tratamento farmacológico , Diabetes Mellitus Experimental/complicações , Estresse do Retículo Endoplasmático , Sirtuína 1/metabolismo , Animais , Biomarcadores/sangue , Glicemia/metabolismo , Encefalopatias/complicações , Transtornos Cognitivos/sangue , Condicionamento Psicológico , Medo , Feminino , Teste de Tolerância a Glucose , Hipocampo/metabolismo , Inflamação , Insulina/sangue , Metabolismo dos Lipídeos , Aprendizagem em Labirinto , Memória , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacos
19.
Autophagy ; 14(6): 1072-1073, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28614034

RESUMO

The alterations in cellular ubiquitin (Ub) homeostasis, known as Ub stress, feature and affect cellular responses in multiple conditions, yet the underlying mechanisms are incompletely understood. We recently reported that the macroautophagy/autophagy receptor SQSTM1/p62, functions as a novel Ub sensor to activate autophagy upon Ub+ stress (upregulation of the Ub level). First, SQSTM1 was found to undergo extensive ubiquitination and activate autophagy under Ub+ stress induced by prolonged Bortezomib (BTZ) treatment, Ub overexpression or by heat shock. Mechanistically, Ubiquitination of SQSTM1 disrupts its dimerization of the UBA domain, switching it from an auto-inhibitory conformation to recognize poly-ubiquitinated cargoes, promoting autophagic flux. Interestingly, Ub+ stress-responsive SQSTM1 ubiquitination is mediated by Ub conjugating enzymes, UBE2D2/3, in a unique E2-dependent manner. Our work has thus revealed a novel mechanism for how SQSTM1 senses cellular Ub stress conditions and regulates selective autophagy in response to diverse intrinsic or extrinsic challenges.


Assuntos
Autofagia , Ubiquitina , Ligação Proteica , Domínios Proteicos , Proteína Sequestossoma-1 , Ubiquitinação
20.
Sci Total Environ ; 616-617: 90-96, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29107782

RESUMO

Flies can be transmission vehicles of Salmonella from cattle to humans. This study determined the prevalence of Salmonella in/on flies captured from 33 cattle farms, including 5 beef and 28 dairy farms, in Georgia, USA, and characterized antibiotic resistance profiles of the isolated Salmonella. Twenty-six out of the 33 cattle farms (79%) and 185 out of the 1650 flies (11%) tested positive for Salmonella in the study. The incidence of Salmonella-positive flies varied from farm to farm, ranging from 0 to 78%. Among the 185 Salmonella isolated from flies, 29% were resistant to ampicillin, 28% to tetracycline, 21% to amoxicillin/clavulanic acid, 20% to cefoxitin, and 12% to streptomycin. Incidences of resistance against other tested antibiotics were low, ranging from 0 to 3%. Furthermore, 28% of the Salmonella isolates were multidrug resistant, demonstrating resistance to 3 or more antibiotics. The minimal inhibitory concentrations of ampicillin, cefoxitin, streptomycin, and tetracycline against the Salmonella isolates ranged from 32 to >2048, 64 to 2048, 128 to 1024, and 32 to 1024µg/mL, respectively. These data suggest that flies could be effective vehicles of transmitting antibiotic resistant Salmonella and disseminating antibiotic resistance genes on cattle farms, posing risks to human and animal health.


Assuntos
Dípteros/microbiologia , Farmacorresistência Bacteriana Múltipla , Fazendas , Salmonella/isolamento & purificação , Animais , Antibacterianos , Bovinos , Georgia , Testes de Sensibilidade Microbiana
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