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1.
Cardiol Res Pract ; 2020: 4375651, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33282418

RESUMO

Background: Heart failure (HF) is the terminal stage of all cardiovascular events. Although implantable cardioverter defibrillator (ICD) therapies have reduced mortality among the high-risk HF population, it is necessary to determine whether certain factors can predict mortality even after cardiac device implantation. Growth stimulation expressed gene 2 (ST2) is an emerging biomarker for HF patient stratification in different clinical settings. Aims: This study aimed to investigate the relationship between baseline soluble ST2 (sST2) levels in serum and the clinical outcomes of high-risk HF patients with device implantation. Methods: Between January 2017 and August 2018, we prospectively recruited consecutive patients implanted with an ICD for heart failure, with LVEF ≤35% as recommended, and analyzed the basic characteristics, baseline serum sST2, and NT-proBNP levels, with at least 1-year follow-up. All-cause mortality was the primary endpoint. Results: During a 643-day follow-up, all-cause mortality occurred in 16 of 150 patients (10.67%). Incidence of all-cause mortality increased significantly in patients with sST2 levels above 34.98846 ng/ml (16.00% vs. 5.33%, P = 0.034). After adjusting the model (age, gender, device implantation, prevention of sudden death, LVEDD, LVEF, WBC and CLBBB, hsTNT, etiology, and eGFR) and the model combined with NT-proBNP, the risk of all-cause death was increased by 2.5% and 1.9%, respectively, per ng/ml of sST2. The best sST2 cutoff for predicting all-cause death was 43.42671 ng/ml (area under the curve: 0.72, sensitive: 0.69, and specificity: 0.69). Compared to patients with sST2 levels below 43.42671 ng/ml, the risk of all-cause mortality was higher in those with values above the threshold (5.1% vs. 21.2%, P = 0.002). ST2 level ≥43.42671 ng/ml was an independent predictor of all-cause mortality (HR: 3.30 [95% CI 1.02-10.67]). Age (HR: 1.06 [95% CI: 1.01-1.12]) and increased NT-proBNP per 100 (HR: 1.02 [95% CI: 1.01-1.03]) were also associated with all-cause mortality in ICD patients. Conclusions: sST2 level was associated with risk of all-cause mortality, and a threshold of 43.43 ng/ml showed good distinguishing performance to predict all-cause mortality in patients with severe heart failure, recommended for ICD implantation. Patients with sST2 levels more than 43.42671 ng/ml even after ICD implantation should therefore be monitored carefully.

2.
J Therm Biol ; 94: 102725, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33292981

RESUMO

Temperature is a key environmental factor, and understanding how its fluctuations affect physiological and metabolic processes is critical for fish. The present study characterizes the energy response and fatty acid metabolism in Onychostoma macrolepis exposed to low temperature (10 °C). The results demonstrated that cold stress remarkably disrupted the energy homeostasis of O. macrolepis, then the AMP-activated protein kinase (AMPK) could strategically mobilize carbohydrates and lipids. In particular, when the O. macrolepis were faced with cold stress, the lipolysis was stimulated along with the enhanced fatty acid ß-oxidation for energy, while the fatty acid synthesis was supressed in the early stage. Additionally, the fatty acid composition analysis suggested that saturated fatty acid (SFA) might accumulate while monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid (PUFA) in storage lipids (mainly containing non-polar lipid, NPL) could be utilized to supply energy during cold acclimation. Altogether, this study may provide some meritorious for understanding the cold-tolerant mechanism of fish in the viewpoint of energy balance combined with fatty acid metabolism, and thus to contribute to this species rearing in fish farms in the future.

3.
Clin Sci (Lond) ; 134(22): 3007-3022, 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33103728

RESUMO

Hepatitis B virus (HBV) infection remains a global public health problem. Nearly 257 million people worldwide have been infected with HBV, resulting in 887,000 people dying of cirrhosis or liver cancer caused by chronic hepatitis B (CHB) annually. Therefore, identification of new targets against HBV is urgently needed. Long noncoding RNAs (LncRNAs) have gained widespread attention in recent years due to their function in cancer, inflammation and other diseases. Notably, a growing number of lncRNAs have been found to play a role in HBV development. In the present study, we first identified a famous lncRNA, HOTAIR, which was significantly up-regulated in HBV-infected cells and PBMCs from CHB patients. Furthermore, we evaluated the clinical relevance of HOTAIR in 20 CHB patients and found that higher levels of HOTAIR expression were associated with higher ALT/AST levels and were positively correlated with HBsAg and HBV DNA levels. In addition, functional analysis showed that HOTAIR promoted HBV transcription and replication by elevating the activities of HBV promoters via modulation of the levels of cccDNA-bound SP1. In conclusion, our study reveals that HOTAIR expression is correlated with the clinicopathological and physiological characteristics of HBV. Thus, HOTAIR may serve as a novel HBV diagnostic and therapeutic biomarker based on its ability to facilitate HBV transcription and replication.

4.
Zhongguo Zhen Jiu ; 40(8): 877-9, 2020 Aug 12.
Artigo em Chinês | MEDLINE | ID: mdl-32869599

RESUMO

Started from the needs of clinical teaching and practice of acupuncture and moxibustion, based on the acupuncture Tongren education and assessment model, the virtual acupuncture teaching system was developed with the help of virtual reality (VR) technology, and applied to the course teaching of meridian and acupoint and needling and moxibustion method of Acupuncture Sciences. Compared with conventional teaching, this system can effectively improve practical operation test scores of students, meanwhile, it has higher interest, interactivity and helpfulness for knowledge learning, and improve independent learning ability, learning effect and memory depth, so student's satisfaction is higher.

5.
J Hepatol ; 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32987030

RESUMO

BACKGROUND: Current antiviral therapies help keep hepatitis B virus (HBV) under control, but they are not curative. A cure for chronic hepatitis B (CHB) is lacking due to the inability of current therapies to eliminate the intracellular viral replication intermediate termed covalently closed-circular DNA (cccDNA). Therefore, there is an urgent need to develop strategies to cure CHB. Functional silencing of cccDNA is a crucial curative strategy that may be achieved by targeting the viral protein HBx. METHODS: Here, we screened 2000 small-molecule compounds for their ability to inhibit HiBiT-tagged HBx (HiBiT-HBx) expression by using a HiBiT lytic detection system. The antiviral activity of a candidate compound and underlying mechanism of its effect on cccDNA transcription were evaluated in HBV-infected cells and a humanized liver mouse model. RESULTS: Dicoumarol, an inhibitor of NAD(P)H:quinone oxidoreductase (NQO1), significantly reduced HBx expression. Moreover, dicoumarol showed potent antiviral activity against HBV RNAs, HBV DNA, HBsAg and HBc protein in HBV-infected cells and a humanized liver mouse model. Mechanistic study found that endogenous NQO1 binds to and protects HBx protein from 20S proteasome-mediated degradation. NQO1 knockdown or dicoumarol treatment significantly reduced the recruitment of HBx to cccDNA and inhibited cccDNA transcription activity, which was correlated with establishment of a repressive chromatin state. The absence of HBx markedly blocked the antiviral effect induced by NQO1 knockdown or dicoumarol treatment in HBV-infected cells. CONCLUSIONS: This study reports a novel small molecule that targets HBx to combat chronic HBV infection and reveals a function of NQO1 in HBV replication through the regulation HBx protein stability.

6.
Phys Rev Lett ; 125(11): 111105, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32976017

RESUMO

Observations of ultradiffuse galaxies NGC 1052-DF2 and -DF4 show they may contain little dark matter, challenging our understanding of galaxy formation. Using controlled N-body simulations, we explore the possibility that their properties can be reproduced through tidal stripping from the elliptical galaxy NGC 1052, in both cold dark matter (CDM) and self-interacting dark matter (SIDM) scenarios. To explain the dark matter deficiency, we find that a CDM halo must have a very low concentration so that it can lose sufficient inner mass in the tidal field. In contrast, SIDM favors a higher and more reasonable concentration as core formation enhances tidal mass loss. Final stellar distributions in our SIDM benchmarks are more diffuse than the CDM one, and hence the former are in better agreement with the data. We further show that a cored CDM halo model modified by strong baryonic feedback is unlikely to reproduce the observations. Our results indicate that SIDM is more favorable for the formation of dark-matter-deficient galaxies.

7.
Medicine (Baltimore) ; 99(23): e20181, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32501970

RESUMO

BACKGROUND: This study will examine the effects of oxymatrine on the proliferation of human liver cancer Bel-7404 cells (HLCBC). METHODS: This study will search electronic bibliographic databases available in PUBMED, EMBASE, Cochrane Library, Scopus, Cumulative Index to Nursing and Allied Health Literature, China Biology Medicine, and China National Knowledge Infrastructure. We attempt to search case-controlled studies (CCSs) or randomized controlled studies (RCSs) pertaining to HLCBC from their inception to the February 29, 2020 without limitations of language and publication time. We will include any CCSs or RCSs on exploring oxymatrine on the proliferation of HLCBC. We will assess the methodological quality of CCSs by Newcastle-Ottawa Scale, and RCSs by Cochrane risk of bias tool. Review Manager 5.3 software will be utilized for statistical analysis. RESULTS: The current study will summarize most recent eligible studies to investigate the effects of oxymatrine on the proliferation of HLCBC. CONCLUSION: Its results may provide reliable scientific evidence on effects of oxymatrine on the proliferation of HLCBC. SYSTEMATIC REVIEW REGISTRATION: INPLASY202040026.


Assuntos
Alcaloides/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Quinolizinas/farmacologia , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Fator de Transcrição E2F1/biossíntese , Expressão Gênica , Genes myc/efeitos dos fármacos , Humanos , Reação em Cadeia da Polimerase em Tempo Real , Projetos de Pesquisa
8.
Medicine (Baltimore) ; 99(21): e19996, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32481264

RESUMO

BACKGROUND: This study will explore the association between Ki-67 expression and clinical pathological characteristics (CPC) of colorectal cancer (CC). METHODS: We will search relevant studies from electronic databases (Cochrane Library, PUBMED, EMBASE, Scopus, Cumulative Index to Nursing and Allied Health Literature, China Biology Medicine, and China National Knowledge Infrastructure) from beginning to April 1, 2020 without language and publication time limitations. We will consider all case-controlled studies (CCSs) or randomized controlled studies (RCSs) investigating the association between Ki-67 expression and CPC of CC. We will appraise study quality of CCSs by Newcastle-Ottawa Scale, and RCSs by Cochrane risk of bias tool. Statistical analysis will be carried out by Review Manager 5.3 software. RESULTS: The present study will explore the association between Ki-67 expression and CPC of CC. CONCLUSION: Its findings may summarize scientific evidence of the association between Ki-67 expression and CPC of CC, and may provide helpful evidence for clinical practice.Systematic review registration: PROSPERO CRD42020173795.


Assuntos
Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Antígeno Ki-67/biossíntese , Metanálise como Assunto , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Humanos
9.
Medicine (Baltimore) ; 99(26): e20854, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590784

RESUMO

INTRODUCTION: Although primary hepatic neuroendocrine carcinomas, whose prognostic mechanisms remain unclear, are rare, coexistence of neuroendocrine carcinomas and other tumors is rarer. In this report, we describe a unique case of coexistence between primary hepatic neuroendocrine carcinoma and a distal cholangiocarcinoma in the pancreas. PATIENT CONCERNS: A 64-year-old woman with a history of diabetes, but none of hepatitis, was admitted to hospital because of intermittent epigastric distension and pain discomfort for more than 1 month aggravated 1 day. A contrast-enhanced computed tomography (CT) scan of the upper abdomen and abdominal magnetic resonance imaging (MRI) revealed a thickening of the bile duct wall in the middle and lower segment of common bile duct and the corresponding lumen is narrow and low-density tumors with ring enhancement (1.83 cm × 1.9 cm) in lobi hepatis dexte. DIAGNOSIS: Primary neuroendocrine carcinoma of the liver was diagnosed to be coexisting with a distal cholangiocarcinoma, which had invaded the pancreas. Immunohistochemical examination revealed that the neoplastic cells strongly expressed chromogranin A, synaptophysin, and CD56 proteins. The tumor cells did not express HepPar-1, glypican-3, S-100, CK7, and CK19 in the liver tumor. A distal bile duct in pancreatic tissues shows the characteristics of typical bile duct carcinoma, as an invasion of carcinoma is also seen in the pancreatic tissues. Gastrointestinal endoscopy, chest and abdominal CT, abdominal MRI, and positron emission tomography (PET)-CT were used to exclude metastatic neuroendocrine tumors of the liver. INTERVENTIONS: Resection of the pancreas-duodenum, the right anterior lobe of the liver, and regional lymph nodes was performed in patients. OUTCOMES: The patient had survived for 5 months after the operation. CONCLUSION: A unique case of a coexistence of primary hepatic neuroendocrine carcinoma and a distal cholangiocarcinoma, which had invaded the pancreas. No treatment guidelines are established for the treatment of the unique case.


Assuntos
Carcinoma Neuroendócrino/diagnóstico , Colangiocarcinoma/diagnóstico , Fígado/anormalidades , Antígeno CD56/análise , Antígeno CD56/sangue , Carcinoma Neuroendócrino/patologia , Colangiocarcinoma/patologia , Cromogranina A/análise , Cromogranina A/sangue , Feminino , Humanos , Imuno-Histoquímica/métodos , Fígado/patologia , Fígado/fisiopatologia , Pessoa de Meia-Idade , Prognóstico , Sinaptofisina/análise , Sinaptofisina/sangue , Tomografia Computadorizada por Raios X/métodos
10.
Medicine (Baltimore) ; 99(20): e20136, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443327

RESUMO

BACKGROUND: This study will investigate the diagnostic accuracy of Ki67 expression in colorectal cancer (CC). METHODS: A comprehensive search in electronic bibliographic databases (MEDLINE, EMBASE, Cochrane Library, Web of Science, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure) will be performed from inception to the February 29, 2020 with no restrictions to the language and publication status. Two authors will examine the collected studies, extract essential data, and appraise study quality separately. If possible, we will estimate receiver operating characteristic (ROC), sensitivity and specificity by utilizing bivariate random effects and hierarchical summary ROC models. RESULTS: This study will summarize present evidence to explore the diagnostic accuracy of Ki67 expression in CC. CONCLUSION: The findings of this study will clarify the diagnostic accuracy of Ki67 expression in CC. SYSTEMATIC REVIEW REGISTRATION: INPLASY202030009.


Assuntos
Neoplasias do Colo/imunologia , Neoplasias Colorretais/imunologia , Antígeno Ki-67/metabolismo , Biomarcadores Tumorais/imunologia , Estudos de Casos e Controles , Neoplasias do Colo/patologia , Neoplasias Colorretais/patologia , Confiabilidade dos Dados , Humanos , Sensibilidade e Especificidade
11.
Medicine (Baltimore) ; 99(20): e20266, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443370

RESUMO

BACKGROUND: Previous reports found that cinnamaldehyde has effects on anti-respiratory syncytial virus (ARSV). However, their results are still contradictory. Therefore, this study will systematically address the effects of cinnamaldehyde on ARSV. METHODS: The following electronic bibliographic databases will be retrieved from their outset to the March 31, 2020: MEDLINE, EMBASE, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Technology Periodical Database, China Biology Medicine, and China National Knowledge Infrastructure. No language and publication time limitations will be exerted in this study. All relevant case-controlled studies or randomized controlled studies exploring the effects of cinnamaldehyde on ARSV will be included. Study quality of case-controlled studies will be assessed by Newcastle-Ottawa scale, and that of randomized controlled studies will be identified by Cochrane risk of bias tool. All data pooling and analysis will be performed using RevMan 5.3 software. RESULTS: This study will summarize the up-to-date high-quality evidence to synthesize outcome data on the effects of cinnamaldehyde on ARSV. CONCLUSION: Findings of this study may provide beneficial evidence for both clinicians and future studies regarding the effects of cinnamaldehyde on ARSV. SYSTEMATIC REVIEW REGISTRATION: INPLASY202040074.


Assuntos
Acroleína/análogos & derivados , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Acroleína/administração & dosagem , Acroleína/efeitos adversos , Acroleína/uso terapêutico , Apoptose , Western Blotting , Estudos de Casos e Controles , Relação Dose-Resposta a Droga , Células HeLa , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Vírus Sincicial Respiratório Humano/efeitos dos fármacos
12.
Medicine (Baltimore) ; 99(20): e20290, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443376

RESUMO

BACKGROUND: This study will examine the effects of artemisinin on proliferation and apoptosis of human liver cancer HepG2 cells (HLCHG-2C). METHODS: This study will systematically retrieve potential literatures in MEDLINE, Scopus, Web of Science, Cochrane Library, EMBASE, WANGFANG, and China National Knowledge Infrastructure from their initiation to the February 29, 2020. There are not limitations related to the language and publication time. All case-controlled studies (CCSs) or randomized controlled studies (RCSs) will be included in this study which investigated the effects of artemisinin on proliferation and apoptosis of HLCHG-2C. Two independent investigators will examine searched records, collect data from included studies, and will identify their methodological quality. Any divergences will be disentangled by discussion with another investigator. RevMan 5.3 software will be placed to pool the data and to carry out data analysis. RESULTS: This study will summarize all eligible studies to test the effects of artemisinin on proliferation and apoptosis of HLCHG-2C. CONCLUSION: The results of this study will exert evidence to examine the effects of artemisinin on proliferation and apoptosis of HLCHG-2C, and it may benefit further research, patients, and healthcare providers. SYSTEMATIC REVIEW REGISTRATION: INPLASY202040075.


Assuntos
Anti-Infecciosos/farmacologia , Apoptose/efeitos dos fármacos , Artemisininas/farmacologia , Proliferação de Células/efeitos dos fármacos , Neoplasias Hepáticas/tratamento farmacológico , Células Hep G2 , Humanos , Projetos de Pesquisa
13.
Phys Rev Lett ; 124(14): 141102, 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-32338958

RESUMO

We study evolution of self-interacting dark matter subhalos in the Milky Way tidal field. The interaction between the subhalos and the Milky Way's tides lead to more diverse dark matter distributions in the inner region, compared to their cold dark matter counterparts. We test this scenario with two Milky Way satellite galaxies, Draco and Fornax, opposite extremes in the inner dark matter content, and find that they can be accommodated within the self-interacting dark matter model proposed to explain the diverse rotation curves of spiral galaxies in the field.

14.
Microb Cell Fact ; 19(1): 39, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32070345

RESUMO

The efficiency of industrial fermentation process mainly depends on carbon yield, final titer and productivity. To improve the efficiency of L-lysine production from mixed sugar, we engineered carbohydrate metabolism systems to enhance the effective use of sugar in this study. A functional metabolic pathway of sucrose and fructose was engineered through introduction of fructokinase from Clostridium acetobutylicum. L-lysine production was further increased through replacement of phosphoenolpyruvate-dependent glucose and fructose uptake system (PTSGlc and PTSFru) by inositol permeases (IolT1 and IolT2) and ATP-dependent glucokinase (ATP-GlK). However, the shortage of intracellular ATP has a significantly negative impact on sugar consumption rate, cell growth and L-lysine production. To overcome this defect, the recombinant strain was modified to co-express bifunctional ADP-dependent glucokinase (ADP-GlK/PFK) and NADH dehydrogenase (NDH-2) as well as to inactivate SigmaH factor (SigH), thus reducing the consumption of ATP and increasing ATP regeneration. Combination of these genetic modifications resulted in an engineered C. glutamicum strain K-8 capable of producing 221.3 ± 17.6 g/L L-lysine with productivity of 5.53 g/L/h and carbon yield of 0.71 g/g glucose in fed-batch fermentation. As far as we know, this is the best efficiency of L-lysine production from mixed sugar. This is also the first report for improving the efficiency of L-lysine production by systematic modification of carbohydrate metabolism systems.


Assuntos
Corynebacterium glutamicum/metabolismo , Frutose/metabolismo , Lisina/biossíntese , Engenharia Metabólica , Sacarose/metabolismo , Proteínas de Bactérias/metabolismo , Corynebacterium glutamicum/crescimento & desenvolvimento , Fermentação
15.
Cell Commun Signal ; 17(1): 168, 2019 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-31842909

RESUMO

BACKGROUND: Our previous study has demonstrated that NAD(P)H: quinone oxidoreductase 1 (NQO1) is significantly upregulated in human liver cancer where it potentiates the apoptosis evasion of liver cancer cell. However, the underlying mechanisms of the oncogenic function of NQO1 in HCC have not been fully elucidated. METHODS: Expression of NQO1, SIRT6, AKT and X-linked inhibitor of apoptosis protein (XIAP) protein were measured by western blotting and immunohistochemistry. Additionally, the interaction between NQO1 and potential proteins were determined by immunoprecipitation assays. Furthermore, the effect of NQO1 and SIRT6 on tumor growth was determined in cell model and orthotopic tumor implantation model. RESULTS: We found that NQO1 overexpression in HCC enhanced SIRT6 protein stability via inhibiting ubiquitin-mediated 26S proteasome degradation. High level of SIRT6 reduced acetylation of AKT which resulted in increased phosphorylation and activity of AKT. Activated AKT subsequently phosphorylated anti-apoptotic protein XIAP at Ser87 which determined its protein stability. Reintroduction of SIRT6 or AKT efficiently rescued NQO1 knock-out-mediated inhibition of growth and induction of apoptosis. In orthotopic mouse model, NQO1 knock-out inhibited tumor growth and induced apoptosis while this effect was effectively rescued by SIRT6 overexpression or MG132 treatment partially. CONCLUSIONS: Collectively, these results reveal an oncogenic function of NQO1 in sustaining HCC cell proliferation through SIRT6/AKT/XIAP signaling pathway.


Assuntos
Apoptose , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , NAD(P)H Desidrogenase (Quinona)/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Sirtuínas/metabolismo , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Neoplasias Hepáticas/patologia , NAD(P)H Desidrogenase (Quinona)/deficiência , Fosforilação , Estabilidade Proteica , Transdução de Sinais , Regulação para Cima
16.
EBioMedicine ; 49: 232-246, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31680002

RESUMO

BACKGROUND: Hepatitis B surface antigen (HBsAg) is one of the important clinical indexes for hepatitis B virus (HBV) infection diagnosis and sustained seroconversion of HBsAg is an indicator for functional cure. However, the level of HBsAg could not be reduced by interferons and nucleoside analogs effectively. Therefore, identification of a new drug targeting HBsAg is urgently needed. METHODS: In this study, 6-AN was screened out from 1500 compounds due to its low cytotoxicity and high antiviral activity. The effect of 6-AN on HBV was examined in HepAD38, HepG2-NTCP and PHHs cells. In addition, the antivirus effect of 6-AN was also identified in mouse model. FINDINGS: 6-AN treatment resulted in a significant decrease of HBsAg and other viral markers both in vitro and in vivo. Furthermore, we found that 6-AN inhibited the activities of HBV SpI, SpII and core promoter by decreasing transcription factor PPARα, subsequently reduced HBV RNAs transcription and HBsAg production. INTERPRETATION: We have identified a novel small molecule to inhibit HBV core DNA, HBV RNAs, HBsAg production, as well as cccDNA to a minor degree both in vitro and in vivo. This study may shed light on the development of a novel class of anti-HBV agent.


Assuntos
6-Aminonicotinamida/farmacologia , Antígenos de Superfície da Hepatite B/metabolismo , Vírus da Hepatite B/fisiologia , Replicação Viral/efeitos dos fármacos , 6-Aminonicotinamida/química , Animais , Biomarcadores/sangue , Modelos Animais de Doenças , Células Hep G2 , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/genética , Humanos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Modelos Biológicos , Regiões Promotoras Genéticas/genética , Transcrição Genética/efeitos dos fármacos , Viremia/sangue
17.
Front Pharmacol ; 10: 1270, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31708789

RESUMO

Hepatitis B virus (HBV) is a major public health threat and anti-HBV drugs are limited to nucleos(t)ide analogs (NAs) and pegylated interferon alpha (Peg-IFNα). Toward identifying an effective compound for HBV treatment is important to suppress and eradicate HBV. In this study, we explored the anti-viral effect of Sirtuin 6 (SIRT6) inhibitor, OSS_128167, in HBV transcription and replication. Firstly, we found that OSS_128167 could decrease the level of HBV core deoxyribonucleic acid (DNA) and 3.5-Kb ribonucleic acid (RNA) in vitro. Furthermore, the level of HBV DNA and 3.5-Kb RNA were also markedly suppressed by OSS_128167 administration in HBV transgenic mice. In addition, we found that depletion of SIRT6 inhibited HBV transcription and replication in HepG2.2.15 and HBV-infected HepG2-sodium taurocholate cotransporting polypeptide cells, whereas overexpression of SIRT6 enhanced HBV transcription and replication. Importantly, the positive effect of SIRT6 overexpression on HBV transcription could be blocked by OSS_128167 treatment. Further mechanism studies showed that HBV core promoter was significantly activated by SIRT6 through upregulating peroxisome proliferator-activated receptors α (PPARα) expression. And ectopical expression of SIRT6 or PPARα relieved the restriction of HBV transcription mediated by OSS_128167. In summary, our results showed that OSS_128167 might serve as a potential antiviral agent for HBV therapy and SIRT6 played a pivotal role in HBV transcription and replication.

18.
Trials ; 20(1): 644, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31775839

RESUMO

BACKGROUND: Obesity has become a major public health hazard with epidemic proportions, affecting adults, adolescents, and children of both genders. Previous studies have suggested that acupoint catgut embedding (ACE) might be a potential therapeutic approach for obesity. The purpose of this study is to conduct a rigorous and normative trial to determine the efficacy of ACE for obesity. METHODS/DESIGN: A total of 99 eligible patients diagnosed with obesity will be recruited in this study. They will be randomly allocated to either the verum ACE group, sham ACE group, or waiting list (WL) group, with 33 patients in each group. Each patient in the two ACE-based groups will receive eight sessions of treatment, lasting over 8 weeks. The primary outcome is the reduction of body mass index (BMI) after treatment. Secondary outcomes will include waist circumference (WC), hip circumference (HC), waist:hip ratio, body fat percentage, blood lipid level, subcutaneous fat area, visceral fat area, and World Health Organization Quality of Life (WHOQOL). All the outcomes will be evaluated at baseline, at the end of the 8 weeks of treatments, and at 3 months of follow-up. The evaluators and data analyzers will be blinded to group allocation. DISCUSSION: The findings of this randomized, sham-, and WL-controlled trial will help to investigate the influence of ACE on clinical variables as well as visceral fat area of obesity, which will provide high-quality evidence on the efficacy of ACE for obesity. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800020248. Registered on December 21, 2018.


Assuntos
Pontos de Acupuntura , Terapia por Acupuntura/métodos , Categute , Obesidade/terapia , Perda de Peso , Terapia por Acupuntura/efeitos adversos , Adolescente , Adulto , Idoso , Categute/efeitos adversos , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Obesidade/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
19.
Phys Rev Lett ; 123(12): 121102, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31633968

RESUMO

We study the gravothermal evolution of dark matter halos in the presence of dissipative dark matter self-interactions. Dissipative interactions are present in many particle-physics realizations of the dark-sector paradigm and can significantly accelerate the gravothermal collapse of halos compared to purely elastic dark matter self-interactions. This is the case even when the dissipative interaction timescale is longer than the free-fall time of the halo. Using a semianalytical fluid model calibrated with isolated and cosmological N-body simulations, we calculate the evolution of the halo properties-including its density profile and velocity dispersion profile-as well as the core-collapse time as a function of the particle model parameters that describe the interactions. A key property is that the inner density profile at late times becomes cuspy again. Using 18 dwarf galaxies that exhibit a corelike dark matter density profile, we derive constraints on the strength of the dissipative interactions and the energy loss per collision.

20.
J Ind Microbiol Biotechnol ; 46(7): 937-949, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30937555

RESUMO

Traditional amino acid producers typically exhibit the low glucose uptake rate and growth deficiency, resulting in a long fermentation time because of the accumulation of side mutations in breeding of strains. In this study, we demonstrate that the efficiency of L-lysine production in traditional L-lysine producer Corynebacterium glutamicum ZL-9 can be improved by rationally engineering glucose uptake systems. To do this, different bypasses for glucose uptake were investigated to reveal the best glucose uptake system for L-lysine production in traditional L-lysine producer. This study showed that overexpression of the key genes in PTSGlc or non-PTSGlc increased the glucose consumption, growth rate, and L-lysine production. However, increasing the function of PTSGlc in glucose uptake led to the increase of by-products, especially for plasmid-mediated expression system. Increasing the participation of non-PTSGlc in glucose utilization showed the best glucose uptake system for L-lysine production. The final strain ZL-92 with increasing the expression level of iolT1, iolT2 and ppgK could produce 201.6 ± 13.8 g/L of L-lysine with a productivity of 5.04 g/L/h and carbon yield of 0.65 g/(g glucose) in fed-batch culture. This is the first report of a rational modification of glucose uptake systems that improve the efficiency of L-lysine production through increasing the participation of non-PTSGlc in glucose utilization in traditional L-lysine producer. Similar strategies can be also used for producing other amino acids or their derivatives.


Assuntos
Corynebacterium glutamicum/metabolismo , Glucose/metabolismo , Lisina/biossíntese , Técnicas de Cultura Celular por Lotes , Transporte Biológico , Corynebacterium glutamicum/genética , Engenharia Metabólica/métodos
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