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BACKGROUND: Traumatic aniridia occurs when the iris is extruded from the eye and is often accompanied by lens injuries. However, traumatic aniridia due to dislocation of the iris into the vitreous cavity without lens damage has never been reported. CASE PRESENTATION: A 30-year-old man presented with visual loss and pain for 6 h after a thin wire injured his right eyeball. Ophthalmologic examinations manifested a 2 mm full-thickness corneal laceration and total hyphema. An intact clear lens, healthy attached retina, and almost complete iris tissue in the vitreous cavity were found after resolution of hyphema the next day. Further examination revealed that the defect in the zonule below the corneal wound was the path for the iris to enter the vitreous cavity. The patient opted for nonsurgical treatment until pigment granules and opacity were observed in the vitreous cavity after 50 days. Vitrectomy was performed to remove the dislocated iris. CONCLUSIONS: The presentation of this unique case indicates that the torn iris was displaced to the vitreous cavity with an intact lens and missing local zonula instead of out the corneal laceration after a penetrating injury. The type of injury, mechanism, and force on the spot may contribute to the occurrence of this rare condition. Instead of artificial irises, tinted glasses were more appropriate treatment option for this patient. Peripheral retinal examination was essential in the management of this case. In such cases, the iris in the vitreous cavity should be resected to prevent complications.
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Lesões da Córnea , Lacerações , Cristalino , Masculino , Humanos , Adulto , Hifema , Cristalino/cirurgia , Iris/cirurgia , Lesões da Córnea/complicações , Lesões da Córnea/diagnóstico , Lesões da Córnea/cirurgiaRESUMO
The involvement of several microRNAs (miRs) in the initiation and development of tumors through the suppression of the target gene expression has been highlighted. The aberrant expression of miR-181d-5p and cyclin-dependent kinase inhibitor 3 (CDKN3) in non-small-cell lung cancer (NSCLC) was then screened by microarray analysis. In the present study, we performed a series of in vivo and in vitro experiments for the purpose of investigating their roles in NSCLC and the underlying mechanism. There was a high expression of CDKN3, whereas miR-181d-5p was downregulated in NSCLC. Quantitative RT-PCR, Western blot analysis, and dual-luciferase reporter gene assay further identified that CDKN3 could be negatively regulated by miR-181d-5p. Moreover, the upregulation of miR-181d-5p or silencing of CDKN3 could inactivate the Akt signaling pathway. A549 with the lowest miR-181d-5p and H1975 with the highest CDKN3 among the five NSCLC cell lines (H1299, A549, H1975, NCI-H157, and GLC-82) were adopted for in vitro experiments, in which expression of miR-181d-5p and CDKN3 was altered by transfection of miR-181d-5p mimic/inhibitor or siRNA-targeting CDKN3. Afterwards, cell proliferation, apoptosis, invasion, migration, and angiogenesis, as well as epithelial-mesenchymal transition (EMT), were evaluated, and tumorigenicity was assessed. In addition, an elevation in miR-181d-5p or depletion in CDKN3 led to significant reductions in proliferation, invasion, migration, angiogenesis, EMT, and tumorigenicity of NSCLC cells, coupling with increased cell apoptosis. In conclusion, this study highlights the tumor-suppressive effects of miR-181d-5p on NSCLC via Akt signaling pathway inactivation by suppressing CDKN3, thus providing a promising therapeutic strategy for the treatment of NSCLC.
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Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Proteínas Inibidoras de Quinase Dependente de Ciclina/metabolismo , Fosfatases de Especificidade Dupla/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Apoptose/genética , Apoptose/fisiologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Proliferação de Células/fisiologia , Proteínas Inibidoras de Quinase Dependente de Ciclina/antagonistas & inibidores , Proteínas Inibidoras de Quinase Dependente de Ciclina/genética , Fosfatases de Especificidade Dupla/antagonistas & inibidores , Fosfatases de Especificidade Dupla/genética , Transição Epitelial-Mesenquimal/genética , Transição Epitelial-Mesenquimal/fisiologia , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Xenoenxertos , Humanos , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Nus , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , Transdução de SinaisRESUMO
BACKGROUND: It has been reported that the emergence of HBV rtA181T/sW172* mutant could result in a dominant secretion defect of HBsAg and increase the risk of HCC development. This study was designed to reveal the role and possible pathogenic mechanism of truncated mutant HBsAg in tumorigenesis of HBV rtA181T/sW172* mutant. RESULTS: As compared to wide type or substituted mutant HBsAg, the ratio of cell clones was significant higher in L02 cells stable expressing truncated mutant HBsAg. Injection of L02 cells stable expressing truncated mutant HBsAg into the dorsal skin fold of nude mice resulted in increased primary tumor growth compared to L02 cells stable expressing wide-type and substituted mutant HBsAg. In HBV replication L02 cell lines, the key molecular involved in TGF-ß/Smad pathway was also investigated. We found that the mRNA and protein levels of Smad3/2, CREB and CyclinD1 were significantly higher and TGFBI level was significantly lower in cells stably expressing truncated mutant HBsAg as compared to cells stably expressing wide-type and substituted mutant HBsAg. Additionally, after administration of TGF-ß1 (increasing TGFBI level), the volume of tumor is obviously reduced in nude mice with injection of L02 cells stable expressing truncated HBsAg. CONCLUSIONS: The emergence of sW172* mutant may increase the tumorigenesis of HBV, and its mechanism may be associated with down-regulated expression of TGFBI in TGF-ß/Smad signaling pathway.
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Transformação Celular Neoplásica , Expressão Gênica , Antígenos de Superfície da Hepatite B/genética , Vírus da Hepatite B/genética , Hepatite B/metabolismo , Hepatite B/virologia , Mutação , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Animais , Linhagem Celular , Transformação Celular Viral , Modelos Animais de Doenças , Feminino , Hepatite B/complicações , Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Humanos , Camundongos , Camundongos Nus , Transdução de SinaisRESUMO
Various aerolysin-like pore-forming proteins have been identified from bacteria to vertebrates. However, the mechanism of receptor recognition and/or pore formation of the eukaryotic members remains unknown. Here, we present the first crystal and electron microscopy structures of a vertebrate aerolysin-like protein from Danio rerio, termed Dln1, before and after pore formation. Each subunit of Dln1 dimer comprises a ß-prism lectin module followed by an aerolysin module. Specific binding of the lectin module toward high-mannose glycans triggers drastic conformational changes of the aerolysin module in a pH-dependent manner, ultimately resulting in the formation of a membrane-bound octameric pore. Structural analyses combined with computational simulations and biochemical assays suggest a pore-forming process with an activation mechanism distinct from the previously characterized bacterial members. Moreover, Dln1 and its homologs are ubiquitously distributed in bony fishes and lamprey, suggesting a novel fish-specific defense molecule.
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Toxinas Bacterianas/química , Simulação de Dinâmica Molecular , Proteínas Citotóxicas Formadoras de Poros/química , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Proteínas de Peixe-Zebra/química , Sequência de Aminoácidos , Animais , Toxinas Bacterianas/metabolismo , Lectinas/química , Lectinas/metabolismo , Mananas/química , Mananas/metabolismo , Dados de Sequência Molecular , Proteínas Citotóxicas Formadoras de Poros/genética , Ligação Proteica , Estrutura Terciária de Proteína , Peixe-Zebra , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismoRESUMO
Soil quality (SQI) is a comprehensive indicator reflecting the agricultural productivity of soil, and soil ecosystem multifunctionality (performing multiple functions simultaneously; EMF) can reflect complex biogeochemical processes. However, the effects of enhanced efficiency nitrogen fertilizers (EENFs; urease inhibitors (NBPT), nitrification inhibitors (DCD), and coated controlled-release urea (RCN)) application on the SQI and soil EMF and their relationships are still unclear. Therefore, we conducted a field experiment to study the effects of different EENFs on the SQI, enzyme stoichiometry and soil EMF in semiarid areas of Northwest China (Gansu, Ningxia, Shaanxi, Shanxi). Across the four study sites, DCD and NBPT increased SQI by 7.61-16.80 % and 2.61 %-23.20 % compared to mineral fertilizer, respectively. N fertilizer application (N200 and EENFs) alleviated microbial N limitation, and EENFs alleviated microbial N and C limitations to a greater extent in Gansu and Shanxi. Moreover, nitrogen inhibitors (Nis; DCD and NBPT) improved the soil EMF to a greater extent than N200 and RCN, DCD increased by 205.82-340.00 % and 145.00-215.47 % in Gansu and Shanxi, respectively; NBPT increased by 332.75-778.59 % and 364.44-929.62 % in Ningxia and Shanxi, respectively. A random forest model showed that the microbial biomass carbon (MBC), microbial biomass nitrogen (MBN) and soil water content (SWC) of the SQI factors were the main driving forces of soil EMF. Moreover, SQI improvement could alleviate microbial C and N limitations and promote the improvement of soil EMF. It is worth noting that soil EMF was mainly affected by microbial N limitation rather than C limitation. Overall, NIs application is an effective way to improve the SQI and soil EMF in the semiarid region of Northwest China.
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Ecossistema , Solo , Solo/química , Nitrogênio/análise , Fertilizantes/análise , Urease , Microbiologia do Solo , CarbonoRESUMO
OBJECTIVES: Hepatocellular carcinoma (HCC) is a common indication for hepatectomy that is often complicated by postoperative complication. The authors sought to investigate the relationship between the open with laparoscopic approach of hepatectomy and incidences of postoperative infectious complications. PATIENTS AND METHODS: Using a multicenter database, HCC patients who underwent laparoscopic hepatectomy (LH) or open hepatectomy (OH) were reviewed and analyzed. Propensity score matching (PSM), inverse probability of treatment weight (IPTW), and multivariate logistic regression analyses were utilized to assess the association of the operative approach with postoperative infectious complications, including incisional surgical site infection (SSI), organ/space SSI, and remote infection (RI). RESULTS: Among 3876 patients, 845 (21.8%) and 3031 (78.2%) patients underwent LH and OH, respectively. The overall incidence of infection was 6.9 versus 14.6% among patients who underwent LH versus OH, respectively ( P <0.001). Of note, the incidences of incisional SSI (1.8 vs. 6.3%, P <0.001), organ/space SSI (1.8 vs. 4.6%, P <0.001), and RI (3.8 vs. 9.8%, P <0.001) were all significantly lower among patients who underwent LH versus OH. After PSM (6.9, 1.8, 1.8, and 3.8% vs. 18.5, 8.4, 5.2, and 12.8%, respectively) and IPTW (9.5, 2.3, 2.1, and 5.5% vs. 14.3, 6.3, 4.5, and 9.8%, respectively), LH remained associated with statistically lower incidences of all types of infectious complications. After adjustment for other confounding factors on multivariate analyses, LH remained independently associated with lower incidences of overall infection, incisional SSI, organ/space SSI, and RI in the overall, PSM, and IPTW cohorts, respectively. CONCLUSION: Compared with open approach, laparoscopic approach was independently associated with lower incidences of postoperative infectious complications following hepatectomy for HCC.
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Carcinoma Hepatocelular , Laparoscopia , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Pontuação de Propensão , Hepatectomia/efeitos adversos , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Laparoscopia/efeitos adversos , Tempo de Internação , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: To retrospectively analyze the cytomegalovirus (CMV) antigenemia test and re-test after antiviral chemotherapy in patients with autoimmune and non-autoimmune diseases. METHODS: CMV Brite kit and indirect immunofluorescence were used to detect CMVpp65 antigenemia in 6471 peripheral blood leukocyte specimens from 5325 clinic and hospitalized patients with clinically suspicious CMV infections from May 2008 to February 2012. And the positive results were defined as episodes of systemic CMV activity. RESULTS: In 6471 EDTA-treated peripheral blood specimens, 948 (14.6%) were found with positive CMV antigenemia. The average positive rate from 13 kinds of autoimmune diseases was 34.9% (670/1922) in which systemic lupus erythematosus patients had the highest (52.4%, 551/1052). Meanwhile, the average positive rate from 12 kinds of non-autoimmune diseases was only 6.1% (144/2367) in which it was 17.3% (27/156) in patients with respiratory/acute renal failure, acquired immunodeficiency syndrome (AIDS) and kidney transplant recipients. And 189 patients with positive antigenemia were re-tested after antiviral chemotherapy and only 64 (33.9%) were converted negatively. CONCLUSIONS: Patients with autoimmune diseases have replaced traditionally immunocompromised patients, e.g. AIDS and kidney transplant recipient, to become the highest risk group of systemic CMV activity. Negative conversion rate of CMV antigenemia is low after antiviral chemotherapy.
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Antígenos Virais/sangue , Doenças Autoimunes/complicações , Infecções por Citomegalovirus/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/uso terapêutico , Doenças Autoimunes/sangue , Doenças Autoimunes/tratamento farmacológico , Criança , Pré-Escolar , Citomegalovirus , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/tratamento farmacológico , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
Helicobacter pylori infections are threats to public health due to their high infection rate and drug resistance. Identification of single-nucleotide variants (SNVs) in H. pylori is crucial for both diagnosis and therapy. Yet the clinical testing of resistant H. pylori mutants is still facing some challenges, such as the selectivity is not good enough for SNVs in abundant wild-type DNA, the lack of clinical validation and the economical burden on patients. Herein, an X-shaped DNA probe with a toehold initiator was designed, which could specifically hybridize with certain genotype DNA due to the thermodynamically driven reaction. A competitive reaction was developed to amplify the thermodynamic difference between wild-type DNA and SNVs, diminishing the interference of wild-type DNA. By this means, multiple SNVs in H. pylori were successfully identified and two SNVs related to clarithromycin resistance are chosen as model targets. A paper strip was fabricated for visual, fast screening of SNVs. Furthermore, the approach was validated using clinical samples, and a point-of-care (POCT) testing diagnosis was executed on saliva samples, demonstrating its potential for the prevention and cure of H. pylori infections.
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Infecções por Helicobacter , Helicobacter pylori , Antibacterianos/farmacologia , Claritromicina/farmacologia , Claritromicina/uso terapêutico , Farmacorresistência Bacteriana/genética , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/genética , Humanos , Testes de Sensibilidade Microbiana , NucleotídeosRESUMO
AIM: To describe the clinical heterogeneity of patients with novel mutations in BEST1. METHODS: All the members in the two Chinese families underwent detailed clinical evaluations including best-corrected visual acuity, slit-lamp examination, applanation tonometry, and dilated fundus examination. Fundus autofluorescence, fundus fluorescein angiography, spectral-domain optical coherence tomography, electrooculography, and electroretinogram were also performed. Genomic DNA was extracted from venous blood for all the participants. The targeted next-generation sequencing of inherited retinal disease-associated genes was conducted to identify the causative mutation. RESULTS: A novel BEST1 missense mutation c.41T>C (p.Leu14Ser) was identified in Family 1. It was co-segregated with the phenotype of best vitelliform macular dystrophy (BVMD) and bioinformatics analysis confirmed it was harmful. Another novel BEST1 frameshift mutation c.345_346insGGCAAGGACG (p.Glu119Glyfs*116) and a novel USH2A missense mutation c.12560G>A, p.Arg4187His were identified in family 2 with retinitis pigmentosa (RP), which might interact and lead to the phenotype of RP. CONCLUSION: Two novel mutations in the BEST1 gene in two unrelated families with distinct phenotypes and BEST1 mutation accompanied with USH2A mutation would result in RP, which could be enormously helpful in understanding the pathogenesis of the inherited retinal disease caused by a BEST1 mutation.
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This study aims to explore the roles of fibroblast activation protein (FAP) and hepatocyte growth factor (HGF) expressions in the angiogenesis and metastasis of gastric cancer (GC). From May 2012 to December 2015, 110 GC patients who received surgical treatment in the First Hospital of Qinhuangdao were selected. The HGF and FAP expressions in 110 cases of GC, 130 cases of normal gastric mucosa and 115 cases of gastric ulcer were detected by streptavidin-perosidase (SP) method. Venous blood HGF level of GC patients was tested by enzyme-linked immunosorbent assay (ELISA). The micro-vessel number of the patients in the three groups were calculated and analyzed. In GC group, positive expression rates of FAP and HGF protein were 61.8% and 67.3% respectively, which were both higher than those in normal gastric mucosa and gastric ulcer groups. The micro-vessel numbers in patients of the normal gastric mucosa and gastric ulcer groups are far less than that in GC group. FAP, HGF and micro-vessel density (MVD) were significantly correlated with infiltration depth, tumor-node-metastasis (TNM) staging, lymph node metastasis (LNM) and distant metastasis. The results of ELISA showed that serum HGF level was related to tumor size, infiltration degree, TNM staging, LNM and distant metastasis. FAP and HGF expressions in GC were positively correlated with MVD, and the expressions of FAP and HGF in GC were in positive correlation. Our study provided evidence that high FAP and HGF expressions may be positively correlated with the angiogenesis and metastasis of GC.
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Adenocarcinoma/secundário , Biomarcadores Tumorais/metabolismo , Gelatinases/metabolismo , Fator de Crescimento de Hepatócito/metabolismo , Proteínas de Membrana/metabolismo , Neovascularização Patológica/patologia , Serina Endopeptidases/metabolismo , Neoplasias Gástricas/patologia , Adenocarcinoma/irrigação sanguínea , Adenocarcinoma/metabolismo , Endopeptidases , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neovascularização Patológica/metabolismo , Prognóstico , Neoplasias Gástricas/irrigação sanguínea , Neoplasias Gástricas/metabolismo , Taxa de SobrevidaRESUMO
AIM: To recombine the human alpha B-crystallin (αB-crystallin) using gene cloning technology and prokaryotic expression vector and confirm the biological activity of recombinant human αB-crystallin. METHODS: Cloning the human αB-crystallin cDNA according to the nucleotide sequence of the human αB-crystallin, constructing the pET-28/CRYAB prokaryotic expression plasmid by restriction enzyme digestion method, and stably expressing transformed into the Escherichia coli (E. coli) DH5 alpha. The recombinant human αB-crystallin was purified by Q sepharose. By enzyme digestion analysis, Western blotting and sequencing, the recombinant human αB-crystallin was identified and the activity of its molecular protein was detected. RESULTS: Compared with the gene bank (GeneBank), the cloned human sequence of human αB-crystallin cDNA has the same open reading frame. Identification and sequencing of the cloned human αB-crystallin cDNA in prokaryotic expression vector confirmed the full length sequence, and the vector was constructed successfully. The E. coli containing plasmid pET-28/CRYAB induced by isopropyl-ß-D-thiogalactoside successfully expressed the human αB-crystallin. Insulin confirmed that the recombinant human αB-crystallin has a molecular chaperone activity. CONCLUSION: The prokaryotic expression vector pET-28/CRYAB of recombinant human αB-crystallin is successfully constructed, and the recombinant human αB-crystallin with molecular chaperone activity is obtained, which lay a foundation for the research and application of the recombinant human αB-crystallin and its chaperone activity.
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Following the Aeromonas hydrophila aerolysin, various aerolysin-like pore-forming proteins have been identified from bacteria to vertebrates. We have recently reported the mechanism of receptor recognition and in vitro pore-formation of a zebrafish aerolysin-like protein Dln1/Aep1. However, the physiological function of Aep1 remains unknown. Here we detected that aep1 gene is constitutively expressed in various immune-related tissues of adult zebrafish; and moreover, its expression is significantly up-regulated upon bacterial challenge, indicating its involvement in antimicrobial infection. Pre-injection of recombinant Aep1 into the infected zebrafish greatly accelerated the clearance of bacteria, resulting in significantly increased survival rate. Meanwhile, the induced expression of cytokines such as interleukin IL-1ß and tumor necrosis factor TNF-α in zebrafish upon injection of recombinant Aep1 suggested that Aep1 may be a pro-inflammatory protein that triggers the antimicrobial immune responses. However, compared to the overproduction of these cytokines in the infected zebrafish, pre-injection of Aep1 could significantly reduce the expression level of these cytokines, accompanying with a reduced bacterial load. Moreover, the expression profiles through the developmental stages of zebrafish demonstrated that aep1 is activated at the very early stage prior to the maturation of adaptive immune system. Altogether, our findings proved that Aep1 is an innate immune molecule that prevents the bacterial infection.
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Toxinas Bacterianas/metabolismo , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Infecções Estafilocócicas/imunologia , Staphylococcus aureus/imunologia , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/imunologia , Imunidade Adaptativa/genética , Aeromonas hydrophila/genética , Animais , Toxinas Bacterianas/genética , Células Cultivadas , Regulação da Expressão Gênica no Desenvolvimento , Imunidade Inata , Mediadores da Inflamação/metabolismo , Interleucina-1beta/metabolismo , Filogenia , Proteínas Citotóxicas Formadoras de Poros/genética , Fator de Necrose Tumoral alfa/metabolismo , Proteínas de Peixe-Zebra/genéticaRESUMO
The hepatitis B virus(HBV) polymerase rtA181T mutation is selected during long-term antiviral therapy. As the polymerase gene completely overlaps with the envelope (S) gene, HBV rtA181T mutation also carries sW172 mutations. In this study, we investigated whether there were biological differences between rtA181T/sW172* (coding truncated HBsAg) and rtA181T/sW172L (coding substituted HBsAg) mutants. In cell experiments, a slight decline of viral replication was observed in both two mutants as compared to wild-type strains, but the levels of supernatant HBsAg and HBV DNA in rtA181T/sW172* were significantly lower than those in rtA181T/sW172L transfected cells. In animal experiments, we were amazed to find that viral replication in rtA181T/sW172* mutant increased and maintained significantly longer than that in rtA181T/sW172L mutant, while no significant difference was observed between rtA181T/sW172L and wild-type strains. Compared with wild-type strains, there were intracellular accumulations of HBsAg and HBcAg in rtA181/sW172* but none in rtA181/sW172L mutant strains. Importantly, we also found that truncated HBsAg could increase the activity of HBV core promoter, but substituted HBsAg could not. In summary, the characteristics of above two rtA181T mutants mentioned above were significantly different, and it is necessary and important for us to distinguish sW172* truncated mutation from sW172L substituted mutation.
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Antígenos de Superfície da Hepatite B/metabolismo , Vírus da Hepatite B/enzimologia , DNA Polimerase Dirigida por RNA/genética , Animais , DNA Viral/sangue , DNA Viral/metabolismo , Células Hep G2 , Antígenos do Núcleo do Vírus da Hepatite B/metabolismo , Antígenos de Superfície da Hepatite B/sangue , Antígenos de Superfície da Hepatite B/genética , Humanos , Fígado/metabolismo , Camundongos , Mutagênese Sítio-Dirigida , Regiões Promotoras Genéticas , DNA Polimerase Dirigida por RNA/metabolismo , Transfecção , Replicação ViralRESUMO
BACKGROUND AND AIMS: The aims of this study were to explore the correlation between chronic hepatitis B virus (HBV) drug-resistant mutation profiles and the efficacy of nucleoside analog rescue therapy in patients with initial antiviral treatment failure. PATIENTS AND METHODS: Patients with initial antiviral therapy failure were recruited between January 2011 and January 2013 from the Division of Infectious Disease, West China Hospital, Sichuan University, Chengdu, People's Republic of China. Following drug-resistant mutation testing, eligible patients received nucleoside analog rescue therapy for 24 weeks. The primary endpoint was rescue therapy efficacy, and the secondary endpoint was adverse events. RESULTS: We recruited 168 patients with chronic HBV infection who had initial antiviral treatment failure. Eighty-nine patients (52.98%) experienced virological breakthrough (group A); 79 patients (47.02%) had partial/null response (group B). Among the patients, 102 (102/168, 60.7%) carried at least one HBV drug resistance mutation. The prevalence of genotypic resistance was significantly higher in group A than in group B (P<0.001). In addition, 118 patients (118/168, 70.2%) achieved undetectable serum HBV DNA with the nucleoside analog rescue therapy. Rescue therapy (P=0.002) and no evidence of genotypic resistance (P=0.001) were related to a higher rate of virological response. CONCLUSION: These data indicate that patients with chronic HBV infection who have initial antiviral therapy failure with or without signs of genotypic resistance may still stand a chance of gaining therapeutic benefit with nucleoside analog rescue therapy.
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BACKGROUND: Compound anisodine (CA) is a compound preparation made from hydrobromide anisodine and procaine hydrochloride. The former is an M-choline receptor blocker with the function of regulating the vegetative nervous system, improving microcirculation, and so on. The latter is an antioxidant with the activities of neuroprotection. This study aimed to investigate the potential neuroprotection of CA, which affects the degeneration of the retinal ganglion cells (RGCs) in an animal model with chronic ocular hypertension. METHODS: Female C57BL/6J mice (n = 24) were divided randomly into four groups: normal control group without any treatment (Group A, n = 6); CA control group with feeding the CA solution (Group B, n = 6); microbeads (MBs) control group with injecting MB into the anterior chamber (Group C, n = 6); CA study group with MB injection and with feeding the CA solution (Group D, n = 6). Intraocular pressure (IOP) was measured every 3 days after MB injection. At the 21st day, neurons were retrograde-labeled by Fluoro-Gold (FG). Animals were sacrificed on the 27th day. Retinal flat mounts were stained immunohistologically by α2-III-tubulin. FG-retrograde-labeled RGCs, α2-III-tubulin-positive RGCs, and α2-III-tubulin-positive nerve fibers were quantified. RESULTS: Mice of Groups C and D expressed the incidence of consistent IOP elevation, which is above the IOP level of Group A with the normal one. There is no significant difference in IOP between Groups A and B (P > 0.05). On the 27th day, there were distinct loss in stained RGCs and nerve fibers from Groups C and D compared with Group A (allP < 0.001). The quantity was significantly higher in Group D as compared to Group C (allP < 0.001) but lower than Group A (allP > 0.001). There was no significant difference in the quantity of RGCs and nerve fibers between Groups A and B (allP > 0.05). CONCLUSIONS: These findings suggest that CA plays an importantly neuroprotective role on RGCs in a mouse model with chronic ocular hypertension.
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Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Hipertensão Ocular/tratamento farmacológico , Derivados da Escopolamina/farmacologia , Derivados da Escopolamina/uso terapêutico , Animais , Sobrevivência Celular/efeitos dos fármacos , Feminino , Imuno-Histoquímica , Pressão Intraocular/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória , Células Ganglionares da Retina/efeitos dos fármacosRESUMO
OBJECTIVE: This study aimed to assess risk factors for mother-to-child transmission (MTCT) of hepatitis B virus (HBV) after immunoprophylaxis. METHODS: Risk factors for MTCT were assessed using a multivariate logistic regression model. PATIENTS: We enrolled 256 mother-child pairs with positive maternal hepatitis B surface antigens (HBsAg) between January 2010 and June 2013. All children received passive-active immunization after birth. The children were tested for HBsAg at birth and 6-12 months and/or 1-3 years of age. RESULTS: Among 256 children, 10 (3.9%) developed HBV infection, all of whom were born to hepatitis B e antigen (HBeAg)-positive mothers with a high HBV DNA level (median, 7.36; range, 6.75-8.00 log10 IU/mL). A total of 20 mothers received antiviral treatment during pregnancy. The maternal viral load decreased from an average of 7.16 to 3.08 log10 IU/mL (p<0.0001) at delivery. The multivariate logistic regression analysis showed that a high maternal HBV DNA level [odds ratio (OR) for each log10 IU/mL increase, 2.44; 95% confidence interval (CI), 1.13-5.29, p=0.023] and vaginal delivery (OR=6.96, 95% CI, 1.80-26.93, p=0.005) were risk factors for HBV immunoprophylaxis failure. CONCLUSION: Additional treatment strategies should be considered in HBeAg-positive mothers with an HBV DNA level above 6-7 log10 IU/mL. In addition, our study supports the use of Cesarean section for infants born to HBsAg-positive mothers.
Assuntos
Antivirais/uso terapêutico , Hepatite B/prevenção & controle , Hepatite B/transmissão , Imunoglobulinas/uso terapêutico , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Complicações Infecciosas na Gravidez/prevenção & controle , Adulto , Pré-Escolar , Feminino , Seguimentos , Hepatite B/tratamento farmacológico , Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/imunologia , Humanos , Imunização Passiva , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Análise Multivariada , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/virologia , Fatores de Risco , Fatores de Tempo , Carga Viral , Adulto JovemRESUMO
BACKGROUND AND AIMS: To evaluate the antiviral response of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients who had baseline high viral load (HVL), defined as having hepatitis B virus (HBV) DNA>9log 10 copies/mL, after 96weeks of entecavir (ETV) treatment. METHODS: A total of 99 HBeAg-positive CHB patients (50 with HVL and 49 with non-HVL) were treated with ETV monotherapy for 96weeks. RESULTS: Virological response (VR) (HBVDNA<300copies/mL) was achieved in 42%, 62%, 68% of HVL patients and in 67.34%, 85.71%, 85.71% of non-HVL patients at weeks 48,72,96, respectively. The VR rates of the HVL group were lower than those of the non-HVL group (P=0.006, P=0.007, and P=0.037). In the HVL group, a total of 30 patients had HBV DNA<1000copies/mL at week 48 and those patients had a 93.3% chance of achieving VR at week 96, whereas the patients who had HBV DNA levels>1000copies/mL at week 48 only had a 30% chance to achieve VR at week 96. Among the 96weeks of treatment, one patient had virological breakthrough in the HVL group and this patient had HBVDNA>1000copies/mL at week48. The rates of biochemical responses (BR) and HBeAg seroconversion (SR) were similar between the HVL group and non-HVL group at weeks 48 and 96. CONCLUSION: The baseline HVL was a negative predictor of virological response in CHB patients with ETV monotherapy. For those HVL patients treated by ETV with poor VR, which defined as HBVDNA>1000copies/mL at week48, the treatment strategies need to be adjusted.
Assuntos
Antivirais/administração & dosagem , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Carga Viral/efeitos dos fármacos , Adulto , Antivirais/farmacologia , Feminino , Guanina/administração & dosagem , Guanina/farmacologia , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Nucleosídeos , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Scaffolds for bone tissue engineering applications should have suitable degradability in favor of new bone ingrowth after implantation into bone defects. In this study, degradation behavior of polyurethane composites composed of triblock copolymer poly(caprolactone)-poluronic-poly(caprolactone) (PCL-Pluronic-PCL, PCFC) and nanohydroxyapatite (n-HA) was investigated. The water contact angle and water absorption were measured to reveal the effect of n-HA content on the surface wettability and swelling behavior of the n-HA/PCFC composites, respectively. The weight loss in three degradation media with pH value of 4.0, 7.4, and 9.18 was also studied accordingly. Fourier transform infrared analysis, differential scanning calorimeter, X-ray diffraction, thermal-gravimetric analysis, and scanning electron microscopy were used to investigate the change of chemical structure and micromorphology after the n-HA/PCFC composite with 30% HA was degraded for different time intervals. Meanwhile, in vivo degradation was conducted by subcutaneous implantation. The weight loss and morphology change during observation periods were also studied.
Assuntos
Plásticos Biodegradáveis/química , Durapatita/química , Teste de Materiais , Poloxaleno/química , Poliuretanos/química , Animais , Concentração de Íons de Hidrogênio , RatosRESUMO
This study prepared a composite scaffold composed of curcumin and poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL, PCEC) copolymer using coelectrospinning technology. Incorporation of curcumin into the polymeric matrix had an obvious effect on the morphology and dimension of PCEC/curcumin fibers. The results of in vitro anti-oxidant tests and of the cytotoxicity assay demonstrated that the curcumin-loaded PCEC fibrous mats had significant anti-oxidant efficacy and low cytotoxicity. Curcumin could be sustainably released from the fibrous scaffolds. More importantly, in vivo efficacy in enhancing wound repair was also investigated based on a full-thickness dermal defect model for Wistar rats. The results indicated that the PCEC/curcumin fibrous mats had a significant advantage in promoting wound healing. At 21 days post-operation, the dermal defect was basically recovered to its normal condition. A percentage of wound closure reached up to 93.3 ± 5.6% compared with 76.9 ± 4.9% of the untreated control (p < 0.05). Therefore, the as-prepared PCEC/curcumin composite mats are a promising candidate for use as wound dressing.
Assuntos
Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Curcumina/química , Curcumina/farmacologia , Poliésteres/química , Poliésteres/farmacologia , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Alicerces Teciduais/química , Cicatrização/efeitos dos fármacos , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Feminino , Fibroblastos/efeitos dos fármacos , Camundongos , Microscopia Eletrônica de Varredura , Ratos , Ratos Wistar , Pele/patologia , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície , Engenharia Tecidual , Ferimentos e Lesões/tratamento farmacológico , Ferimentos e Lesões/patologiaRESUMO
BACKGROUND: Little is known about the duration of combination therapy for patients with chronic hepatitis B (CHB) and suboptimal response to nucleos(t)ide analogues(NAs) monotherapy. OBJECTIVES: This study aimed to assess whether monotherapy could be used for treatment of CHB patients, who poorly responded to Adefovir Dipivoxil (ADV) but obtained good responses after at least 12-month lamivudine (LAM) or telbivudine (LdT) add-on therapy. PATIENTS AND METHODS: Forty-five patients were enrolled, and the baseline time-point was determined according to enrollment data. Twenty-six patients chose to continue combination therapy (LAM+ADV or LdT+ADV, Group A) and 19 patients switched to single-drug maintenance therapy (LAM or LdT or ADV, Group B). RESULTS: There were no signiï¬cant differences between two groups in baseline characteristics (P > 0.05). At 12th month, sustained virological response rate was greater in group A compared to group B (96.2% vs. 47.4%, P < 0.001), and the rates of NAs-associated resistance were 0% in group A and 15.8% in group B. Alanine aminotransferase normalization rate was also signiï¬cantly higher in group A compared with group B (92.3% vs. 36.8%, P < 0.001). Among hepatitis positive patients with Be antigen (HBeAg)-, 40% (4/10) in group A and 9.1% (1/11) in group B achieved HBeAg seroconversion at the 12th month. Of patients in group B with positive-HBeAg before the previous combination therapy and detectable HBV DNA at 6 months of previous combination therapy were associated with high risks of viral relapse after switching to single-drug maintenance therapy. CONCLUSIONS: Prematurely switching to single-drug maintenance therapy would be resulted in viral relapse, and prolonged combination therapy was effective to maintain sustained responses for patients with initial suboptimal response to ADV.