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Primary liver cancer is one of the most common malignant tumors of the digestive system,of which hepatocellular carcinoma (HCC) accounts for more than 90% of the total cases.The patients with early HCC treated by surgical resection generally demonstrate good prognosis.However,due to the insidious onset,HCC in the vast majority of patients has progressed to the mid-to-late stage when being diagnosed.As a result,surgical treatment has unsatisfactory effects,and non-surgical treatment methods generally have severe side effects and low tumor selectivity.Nanoparticles (NP) with small sizes,large specific surface areas,and unique physical and chemical properties have become potential carriers for the delivery of therapeutic agents such as drugs,genes,and cytokines.The nano-delivery systems with NP as the carrier can regulate the metabolism and transformation of drugs,genes,and cytokines in vivo from time,space,and dose via functional modification,showing great potential in the treatment of HCC.This paper introduces the current status and advantages of several common nano-delivery systems,including organic nano-carriers,inorganic nano-carriers,and exosomes,in the treatment of HCC.Furthermore,this paper summarizes the mechanisms of NP-based nano-carriers in treating HCC and provides reference for the development of new nano-delivery systems.
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Carcinoma Hepatocelular , Sistemas de Liberação de Medicamentos , Neoplasias Hepáticas , Nanopartículas , Nanotecnologia , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/terapia , Nanopartículas/química , Nanotecnologia/métodos , Portadores de FármacosRESUMO
Histone methylation plays important roles in mediating the onset and progression of various cancers, and lysine-specific demethylase 5B (KDM5B), as a histone demethylase, is reported to be an oncogene in hepatocellular carcinoma (HCC). However, the mechanism underlying its tumorigenesis remains undefined. Hence, we explored the regulatory role of KDM5B in HCC cells, aiming to identify novel therapeutic targets for HCC. Gene Expression Omnibus database and StarBase were used to predict important regulatory pathways related to HCC. Then, the expression of KDM5B and microRNA-448 (miR-448) in HCC tissues was detected by RT-qPCR and Western blot analysis. The correlation between KDM5B and miR-448 expression was analysed by Pearson's correlation coefficient and ChIP experiments, and the targeting of YTH N6-methyladenosine RNA binding protein 3 (YTHDF3) by miR-448 was examined by luciferase assay. Additionally, the effect of KDM5B on the proliferation, migration, invasion and apoptosis as well as tumorigenicity of transfected cells was assessed using ectopic expression and depletion experiments. KDM5B was highly expressed in HCC cells and was inversely related to miR-448 expression. KDM5B demethylated H3K4me3 on the miR-448 promoter and thereby inhibited the expression of miR-448, which in turn targeted YTHDF3 and integrin subunit alpha 6 (ITGA6) to promote the malignant phenotype of HCC. Moreover, KDM5B accelerated HCC progression in nude mice via the miR-448/YTHDF3/ITGA6 axis. Our study uncovered that KDM5B regulates the YTHDF3/ITGA6 axis by inhibiting the expression of miR-448 to promote the occurrence of HCC.
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Hepatocellular carcinoma (HCC) occurs mainly in patients with chronic liver disease and cirrhosis. Increasing evidence has identified the involvement of microRNAs (miRNAs) acting as essential regulators in the progression of HCC. As predicted by microarray analysis, miR-448 might potentially affect HCC progression by regulating the melanoma-associated antigen (MAGEA). Therefore, the present investigation focused on exploring whether or not miR-448 and MAGEA6 were involved in the self-renewal and stemness maintenance of HCC stem cells. The interaction among miR-448, MAGEA6, and the AMPK signaling pathway was evaluated. It was noted that miR-448 targeted and downregulated MAGEA6, thus activating the AMP-activated protein kinase (AMPK) signaling pathway in HCC. Furthermore, for the purpose of exploring the functional relevance of MAGEA6 and miR-448 on the sphere formation, colony formation, and invasion and migration of HCC stem cells, the CD133+ CD44 + HCC stem cells were sorted and treated with the mimic or inhibitor of miR-448, small interfering RNA (siRNA) against MAGEA6 or an AMPK activator AICAR. MAGEA6 silencing or miR-448 overexpression was demonstrated to inhibit the abilities of sphere formation, colony formation, cell migration, and invasion of HCC cells. Afterwards, a rescue experiment was conducted and revealed that MAGEA6 silencing reversed the effects of miR-448 inhibitor on stemness maintenance and self-renewal of HCC stem cells. Finally, after the in vivo experiment was carried out, miR-448 was observed to restrain the tumor formation and stemness in vivo. Altogether, miR-448 activates the AMPK signaling pathway by downregulating MAGEA6, thus inhibiting the stemness maintenance and self-renewal of HCC stem cells, which identifies miR-448 as a new therapeutic strategy for HCC.
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Proteínas Quinases Ativadas por AMP/metabolismo , Antígenos de Neoplasias/metabolismo , Carcinoma Hepatocelular/enzimologia , Autorrenovação Celular , Neoplasias Hepáticas/enzimologia , MicroRNAs/metabolismo , Proteínas de Neoplasias/metabolismo , Células-Tronco Neoplásicas/enzimologia , Animais , Antígenos de Neoplasias/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Invasividade Neoplásica , Proteínas de Neoplasias/genética , Células-Tronco Neoplásicas/patologia , Transdução de SinaisRESUMO
Posttraumatic stress disorder (PTSD) is a psychiatric disorder that plagues trauma survivors. Evidence shows that brain-derived neurotrophic factor (BDNF) may be involved in the occurrence and development of PTSD. Here we tried to demonstrate whether BDNF gene polymorphisms are correlated with neurocognitive function following PTSD in patients with hepatocellular carcinoma (HCC). This study included 102 patients with HCC complicated with PTSD, 146 HCC patients, and 152 healthy volunteers. Initially, we evaluated the neurocognitive function of the study subjects. Next, we measured BDNF G11757C and rs6265 polymorphisms by polymerase chain reaction-restriction fragment length polymorphism. The correlation of BDNF polymorphisms and BDNF level with HCC complicated with PTSD was evaluated. The results revealed that HCC complicated with PTSD showed decreased serum BDNF level and Mini-mental state examination (MMSE) score. Serum BDNF level of HCC and HCC complicated with PTSD was positively correlated with MMSE score. GA + AA allele and A allele of rs6265 increased the risk of PTSD among patients with HCC. GA and AA genotypes of rs6265 were correlated with the decreased MMSE score of HCC complicated with PTSD. Haplotype GA of rs6265 and G11757C increased the risk of PTSD for HCC, while haplotype CG decreased this risk. Lastly, the logistic regression analysis suggested that low BDNF level was a contributor to HCC complicated with PTSD, while GG genotype of rs6265 served as a protective factor. Collectively, this study defines the GG genotype of BDNF rs6265 polymorphism as a protector to HCC complicated with PTSD. In addition, these results provided a promising target for PTSD prevention in patients with HCC.
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Povo Asiático/genética , Fator Neurotrófico Derivado do Encéfalo/genética , Carcinoma Hepatocelular/fisiopatologia , Disfunção Cognitiva/prevenção & controle , Polimorfismo de Nucleotídeo Único , Transtornos de Estresse Pós-Traumáticos/complicações , Adulto , Fator Neurotrófico Derivado do Encéfalo/sangue , Carcinoma Hepatocelular/psicologia , Estudos de Casos e Controles , China/epidemiologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/patologia , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Incidência , Neoplasias Hepáticas/fisiopatologia , Neoplasias Hepáticas/psicologia , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Transtornos de Estresse Pós-Traumáticos/epidemiologiaRESUMO
Radionuclide hypoxia imaging has become an indispensable core of tumor diagnosis. Nitroimidazole derivatives have been extensively used as the hypoxia imaging agents in preclinical and clinical research. It is the key to design the ideal structure for promising agents. The type and quantity of nitroimidazole, the linker structure and chiral may have an impact on the imaging results. The characteristics of the imaging agents including single electron reduction potential (SERP), oil-water partition coefficient (log P) and pharmacokinetics are also the key factors. In this review, we highlight the factors for hypoxia imaging, providing clues for the structure design of new agents.
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Hipóxia/diagnóstico por imagem , Neoplasias/diagnóstico por imagem , Nitroimidazóis/química , Cintilografia , Animais , HumanosRESUMO
Cyclin-dependent kinase-5(Cdk5) is a kind of Ser/Thr kinases in the signaling pathway, which regulates the neural development. The recent studies have confirmed that hyperactivation of Cdk5 is closely associated with the evolution, progression and apoptosis of tumors. The Cdk5 inhibitors have been extensively studied in the drug discovery against cancer. The structure features of these inhibitors and molecular mechanisms of their activities have provided clues for the drug development. In the second generation Cdk5 inhibitors, the ATP-binding pocket, a highly conserved site, has been targeted in the drug design in most cases. In addition, a growing number of peptides has been generated by targeting the protein/protein interfaces of Cdk5.
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Quinase 5 Dependente de Ciclina/antagonistas & inibidores , Desenho de Fármacos , Neoplasias/tratamento farmacológico , HumanosRESUMO
The dynamics of animal social structures are heavily influenced by environmental patterns of competition and cooperation. In folivorous colobine primates, prevailing theories suggest that larger group sizes should be favored in rainforests with a year-round abundance of food, thereby reducing feeding competition. Yet, paradoxically, larger groups are frequently found in high-altitude or high-latitude montane ecosystems characterized by a seasonal scarcity of leaves. This contradiction is posited to arise from cooperative benefits in heterogeneous environments. To investigate this hypothesis, we carried out a six-year field study on two neighboring groups of golden snub-nosed monkey ( Rhinopithecus roxellana), a species representing the northernmost distribution of colobine primates. Results showed that the groups adjusted their movement and habitat selection in response to fluctuating climates and spatiotemporal variability of resources, indicative of a dynamic foraging strategy. Notably, during the cold, resource-scarce conditions in winter, the large group occupied food-rich habitats but did not exhibit significantly longer daily travel distances than the smaller neighboring group. Subsequently, we compiled an eco-behavioral dataset of 52 colobine species to explore their evolutionary trajectories. Analysis of this dataset suggested that the increase in group size may have evolved via home range expansion in response to the cold and heterogeneous climates found at higher altitudes or latitudes. Hence, we developed a multi-benefits framework to interpret the formation of larger groups by integrating environmental heterogeneity. In cold and diverse environments, even smaller groups require larger home ranges to meet their dynamic survival needs. The spatiotemporal distribution of high-quality resources within these expanded home ranges facilitates more frequent interactions between groups, thereby encouraging social aggregation into larger groups. This process enhances the benefits of collaborative actions and reproductive opportunities, while simultaneously optimizing travel costs through a dynamic foraging strategy.
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Colobinae , Presbytini , Animais , Ecossistema , Colobinae/fisiologia , Clima , ChinaRESUMO
The aim of the present study is to investigate whether monocyte chemotactic protein-1 (MCP-1)-induced vascular smooth muscle cell (VSMC) proliferation is mediated via monocyte chemotactic protein-1 induced protein-1 (MCPIP1). MCPIP1 expressions in cultured VSMC were detected by real-time PCR and Western blot following MCP-1 incubation. After MCPIP1 was silenced by siRNA, cell number was counted by hemocytometer, VSMC activity was analyzed by CCK-8 kit, percentage of DNA synthesis was detected by EdU kit, percentage of S phase cell numbers were measured by flow cytometry, and c-fos mRNA expression induced by MCP-1 or platelet-derived growth factor (PDGF) was detected by real-time PCR. The results showed MCP-1 increased MCPIP1 mRNA and up-regulated MCPIP1 protein expression in dose- and time-dependent manners. Cell counts, cellular activity, the percentage of DNA synthesis, and the percentage of S phase cell numbers were remarkably decreased in MCPIP1 siRNA group, compared with those in MCP-1 group. The enhancing effect of MCP-1 or PDGF on c-fos mRNA expression was inhibited by MCPIP1 siRNA. These results suggest that MCP-1-induced VSMC proliferation is mediated via MCPIP1, and the underlying mechanism may involve c-fos expression up-regulation.
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Quimiocina CCL2/farmacologia , Miócitos de Músculo Liso/citologia , Ribonucleases/metabolismo , Fatores de Transcrição/metabolismo , Proliferação de Células , Células Cultivadas , Humanos , Músculo Liso Vascular/citologia , Fator de Crescimento Derivado de Plaquetas/farmacologia , Reação em Cadeia da Polimerase em Tempo Real , Regulação para CimaRESUMO
Increasing evidence has suggested the crucial role cyclin-dependent kinases (CDKs) in the biology of hepatocellular carcinoma (HCC), a lethal malignancy with high morbidity and mortality. Hence, this study explored the modulatory effect of the putative cyclin-dependent kinase 11B (CDK11B)-mediated ubiquitination on HCC stem cells. The expression of CDK11B, SAM pointed domain-containing ETS transcription factor (SPDEF) and DOT1-like histone lysine methyltransferase (DOT1L) was determined by RT-qPCR and western blot analysis in HCC tissues and cells. The interaction among CDK11B, SPDEF, miR-448, and DOT1L was analyzed by Co-IP, ubiquitination-IP and ChIP assays, whereas their effects on the biological characteristics of HCC stem cells were assessed by sphere formation and colony formation assays. An in vivo xenograft tumor model was developed for validating the regulation of CDK11B in oncogenicity of HCC stem cells. We characterized the aberrant upregulation of CDK11B and downregulation SPDEF in HCC tissues and cells. CDK11B degraded SPDEF through ubiquitin-proteasome pathway, whereas SPDEF could bind to the miR-448 promoter and inhibit the expression of DOT1L by activating miR-448, whereby promoting self-renewal of HCC stem cells. Knockdown of CDK11B attenuated the self-renewal capability of HCC stem cells and their oncogenicity in vivo. These findings highlighted that blocking the CDK11B-induced degradation of SPDEF and enhancing miR-448-dependent inhibition of DOT1L may delay the progression of HCC by restraining self-renewal capability of HCC stem cells, representing novel targets for HCC management.
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Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Proteínas Proto-Oncogênicas c-ets/metabolismo , Células-Tronco/metabolismo , Ubiquitinação/genética , Animais , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Pessoa de Meia-IdadeRESUMO
Due to heavy air pollutants and aerosols in our country, the model for simultaneous evaluation of aerosol parameters and trace gases based on differential optical absorption spectroscopy is developed in the present paper. The spectra were used to get the concentrations of many trace gases and mean geometrical diameter, total number concentration and total volume of aerosol simultaneously over the same air volume. Retrieval of aerosol parameters was performed by the "table look-up" method based on total extinction coefficient. Experimental results show that trace gases and aerosol parameters can be successfully retrieved using this model.
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Upregulated ubiquitin-conjugating enzyme E2M (UBE2M) is associated with poor prognosis in malignancies; However, the phenotype and mechanism of action of UBE2M in hepatocellular carcinoma (HCC) remain elusive. Here, we report that UBE2M is overexpressed and correlated with poor prognosis in HCC patients. The UBE2M level is an independent prognostic factor for HCC patients. UBE2M knockdown inhibits HCC cell proliferation, migration, and invasion, whereas its overexpression has an opposite effect. Mechanistically, upregulated UBE2M exerts oncogenic effects by translocation of accumulated ß-catenin from the cytoplasm to the nucleus, thus activating downstream ß-catenin/cyclin D1 signaling. In summary, our study demonstrates a notable role of UBE2M in promoting the growth of HCC, providing a novel strategy for HCC prevention and treatment.
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Carcinoma Hepatocelular/patologia , Ciclina D1/metabolismo , Neoplasias Hepáticas/patologia , Enzimas de Conjugação de Ubiquitina/metabolismo , beta Catenina/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/análise , Proliferação de Células/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Transdução de Sinais/fisiologiaRESUMO
Our study aimed to investigate the expression, functional significance, and related mechanism of long noncoding RNA CRNDE (colorectal neoplasia differentially expressed) in hepatocellular carcinoma (HCC) pathogenesis. The resulted revealed that CRNDE was significantly overexpressed in HCC tissues and cell lines, and was statistically correlated with poor clinical outcome. CRNDE knockdown markedly decreased HCC cell proliferation, migration, and chemoresistance. In addition, in vivo experiments confirmed the suppressive effect of CRNDE knockdown on HCC progression. Mechanically, CRNDE directly bound to EZH2 (enhancer of zeste homolog), SUZ12 (suppressor of zeste 12), SUV39H1, and mediated their inhibition of tumor suppressor genes, including CUGBP Elav-like family member 2 (CELF2) and large tumor suppressor 2 (LATS2). CELF2 exerted tumor suppressive effect in HCC and was involved in CRNDE-mediated oncogenic effect. In addition, the oncogenic effects of CRNDE on HCC proliferation, migration and tumorigenesis, as well as its inhibition of Hippo pathway were abolished by LATS2 overexpression. Together, our work demonstrated the importance of CRNDE in HCC progression and elucidated the underlying molecular mechanisms. These findings provided new insights into HCC pathogenesis and chemoresistance mediated by CRNDE.
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Carcinoma Hepatocelular/genética , RNA Longo não Codificante/genética , Proteínas CELF/metabolismo , Carcinogênese/genética , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , China , Neoplasias Colorretais/genética , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/genética , Epigênese Genética/genética , Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , MicroRNAs/genética , Proteínas do Tecido Nervoso/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , RNA Longo não Codificante/metabolismo , Transdução de Sinais/genética , Transcriptoma/genética , Proteínas Supressoras de Tumor/metabolismoRESUMO
For real-time and on-line monitoring DOAS (differential optical absorption spectroscopy) system, a model based on an improved Elman network for monitoring pollutant concentrations was proposed. In order to reduce the systematical complexity, the forecasting factors have been obtained based on the step-wise regression method. The forecasting factors were current concentrations, temperature and relative humidity, and wind speed and wind direction. The dynamic back propagation (BP) algorithm was used for creating training set. The experiment results show that the predicted value follows the real well. So the modified Elman network can meet the demand of DOAS system's real time forecasting.
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OBJECTIVE: To investigate the effect of plasma exchange (PE) combined with hemofiltration (HF) on liver failure. METHODS: Seventy-seven inpatients with liver failure admitted during January 2006 to August 2007 were randomly assigned to receive PE combined with HF (PE+HF group, 38 cases), or PE alone (PE group, 39 cases). Forty-one inpatients with liver failure who had not received artificial liver support treatment were assigned to serve as control group. The survival rates and biochemical parameters of three groups were compared. RESULTS: There was no significant difference in biochemical parameters before treatment among three groups. Compared with pre-treatment values, albumin (Alb), cholinesterase (ChE) and prothrombin activity (PTA) of both PE group and PE+HF group were significantly increased after treatment, and total bilirubin (TBIL), alanine transaminase (ALT), aspartate transaminase (AST) of both PE group and PE+HF group were significantly decreased after treatment (P<0.05 or P<0.01). The survival rate of PE group, PE+HF group and control group was 48.7% (19/39), 68.4% (26/38), and 29.3% (12/41) respectively. The survival rate of PE+HF group was significantly higher than that of control group (chi(2)=12.11, P<0.01). The rate of recovery of consciousness of patients with hepatic encephalopathy in PE+HF group was higher than that of PE group (42.8% vs. 0, P<0.05). Compared with PE alone, the result was better when it was combined with HF in correction of electrolyte disturbance and acid-base imbalance (19/23 vs. 0/21, P<0.05). CONCLUSION: Treatment of liver failure by PE combined with HF is safe and effective, and its efficacy is higher than PE alone.
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Hemofiltração , Falência Hepática/terapia , Troca Plasmática , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths, but its molecular mechanisms are not yet well characterized. Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis, including that of HCC. However, the role of homeobox A11 antisense (HOXA11-AS) in determining HCC stem cell characteristics remains to be explained; hence, this study aimed to investigate the effects of HOXA11-AS on HCC stem cell characteristics. Initially, the expression patterns of HOXA11-AS and HOXA11 in HCC tissues, cells, and stem cells were determined. HCC stem cells, successfully sorted from Hep3B and Huh7 cells, were transfected with short hairpin or overexpression plasmids for HOXA11-AS or HOXA11 overexpression and depletion, with an aim to study the influences of these mediators on the self-renewal, proliferation, migration, and tumorigenicity of HCC stem cells in vivo. Additionally, the potential relationship and the regulatory mechanisms that link HOXA11-AS, HOXA11, and the Wnt signaling pathway were explored through treatment with Dickkopf-1 (a Wnt signaling pathway inhibitor). HCC stem cells showed high expression of HOXA11-AS and low expression of HOXA11. Both HOXA11-AS silencing and HOXA11 overexpression suppressed the self-renewal, proliferation, migration, and tumorigenicity of HCC stem cells in vivo, as evidenced by the decreased expression of cancer stem cell surface markers (CD133 and CD44) and stemness-related transcription factors (Nanog, Sox2, and Oct4). Moreover, silencing HOXA11-AS inactivated the Wnt signaling pathway by decreasing the methylation level of the HOXA11 promoter, thereby inhibiting HCC stem cell characteristics. Collectively, this study suggested that HOXA11-AS silencing exerts an antitumor effect, suppressing HCC development via Wnt signaling pathway inactivation by decreasing the methylation level of the HOXA11 promoter.
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Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Proteínas de Homeodomínio/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , RNA Longo não Codificante/metabolismo , Antígeno AC133/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/fisiologia , Proteínas de Homeodomínio/genética , Humanos , Receptores de Hialuronatos/metabolismo , Neoplasias Hepáticas/patologia , Proteína Homeobox Nanog/genética , Proteína Homeobox Nanog/metabolismo , Fator 3 de Transcrição de Octâmero/genética , Fator 3 de Transcrição de Octâmero/metabolismo , RNA Longo não Codificante/genética , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo , Fatores de Transcrição , Via de Sinalização WntRESUMO
Chronic hepatitis B virus (HBV) infection is a serious problem because of its worldwide distribution and possible adverse sequelae, such as cirrhosis and hepatocellular carcinoma. Thymosin alpha-1 (Talpha1) is an immune modifier that has been shown to be effective for chronic hepatitis B (CHB) in some trials. But the trials comparing Talpha1 vs. interferon alpha (IFNalpha) treatment in CHB have been small and the results have been inconsistent. So we conducted a meta-analysis to compare the efficacy of Talpha1 and IFNalpha in the treatment of CHB. Generally, four randomized controlled trials including 199 CHB patients who received Talpha1 or IFNalpha treatment were identified through MEDLINE and EMBASE online search. Virological (for hepatitis B e antigen (HBeAg) positive patients, loss of HBV DNA and HBeAg; for HBeAg negative patients, loss of HBV DNA), biochemical (normalization of transaminases) and complete responses (fulfill criteria of biochemical and virological response simultaneously) were analyzed using the intention-to-treat method. The odds ratio (OR) was used to measure the magnitude of the efficacy. The ORs (95% confidence interval) of the virological response, biochemical response and complete response of Talpha1 over IFNalpha at the end of 6 months treatment were 0.62 (0.35, 1.10), 0.60 (0.34, 1.05) and 0.54 (0.30, 0.97), respectively. The ORs (95% confidence interval) of the virological response, biochemical response and complete response of Talpha1 over IFNalpha at the end of follow-up (6 months post-treatment) were 3.71 (2.05, 6.71), 3.12 (1.74, 5.62) and 2.69 (1.47, 4.91), respectively. These data showed that compared with IFNalpha, the benefit of Talpha1 was not immediately significant at the end of therapy, but virological, biochemical and complete response had a tendency to increase or accumulate gradually after the therapy. For three of the four trials that studied HBeAg-negative patients, the results are mostly applicable to HBeAg-negative CHB.
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Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Timosina/análogos & derivados , Adulto , Alanina Transaminase/sangue , DNA Viral/sangue , Feminino , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/genética , Humanos , Interferon-alfa/efeitos adversos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Ensaios Clínicos Controlados Aleatórios como Assunto , Timalfasina , Timosina/uso terapêutico , Resultado do Tratamento , Replicação Viral/efeitos dos fármacosRESUMO
BACKGROUND: A liver support therapy, named molecular adsorbents recirculating system (MARS), has been used for more than 700 liver failure patients in China. We made here a summary to evaluate the effects of MARS treatment in different applications with emphasis on hepatitis B virus (HBV) based liver failure. METHODS: This report analyzed data of 252 patients (mean age (44.9+/- 12.7) years) in three groups: acute severe hepatitis (ASH), subacute severe hepatitis (SSH) and chronic severe hepatitis (CSH). The largest group was CSH (156 patients, 61.9%), and 188 patients (74.6%, 188/252) were infected with HBV. RESULTS: MARS treatments were associated with significant reduction of albumin bound toxins and water-soluble toxins. Most of the patients showed a positive response with a significant improvement of multiple organ function substantiated by a significant increase in prothrombin time activity (PTA) and median arterial pressure (MAP). There was a decrease in hepatic encephalopathy (HE) grade and Child-Turcotte-Pugh (CTP) scale. Thirty-nine of 188 HBV patients (20.7%) dropped out of the commendatory consecutive therapy ending with lower survival of 43.6% while the rest of the 149 patients had a survival rate of 62.4%. Survival within the ASH and SSH groups were 81.2% and 75.0%, respectively. In the CSH group, end stage patients were predominant (65/151, 43%), whereas the early and middle stage patients had a better prognosis: early stage survival, including orthotopic liver transplantation (OLT) survival of 91.7%, middle stage survival of 75%, end stage survival of 33.8%. CONCLUSIONS: MARS continues to be the most favorable extracorporeal treatment for liver support therapy in China for a wide range of conditions, including the majority of hepatitis B related liver failure conditions. The appropriate application of MARS for the right indications and stage of hepatic failure, as well as the fulfillment of prescribed treatments, will lead to the optimal therapeutic result.
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Falência Hepática/terapia , Diálise Renal , Desintoxicação por Sorção/métodos , Humanos , Falência Hepática/mortalidade , Desintoxicação por Sorção/efeitos adversosRESUMO
The objective of this study was to investigate the effects of ultrasound-guided injection of ultrasound contrast agents (UCAs) and the p53 gene on the treatment of rats with breast cancer (BC). Assembly of the p53 expression vector as well as that of a rat model with BC consisted of 200 successfully modeled rats randomly divided into 5 groups: p53 gene introduction, p53 gene introduction + ultrasound irradiation, p53 gene introduction + UCAs, p53 gene introduction + UCA + ultrasound irradiation, and UCA + ultrasound irradiation groups. Expression of p53 was detected via quantitative real-time polymerase chain reaction (qRT-PCR), western blotting and immunohistochemical staining. In the p53 gene introduction + ultrasound irradiation group, we observed increased tumor volume with blood flow signals around and necrotic tumor tissues with an inhibition rate of 36.30%, as well as higher expression of p53 than that in the p53 gene introduction group and p53 gene introduction + UCA group. In the p53 gene introduction + UCA + ultrasound irradiation group, tumor volume increased slightly with reduced blood flow signals and massive degenerative necrosis of tumor cells was identified with inhibition rate of 62.62%, and expression of p53 was higher than that in the rest groups. Taken together, the key findings obtained from the present study elucidate that injection of p53 gene and UCA microbubbles guided by ultrasound could increase the expression of p53, thus inhibiting the tumor growth in rats with BC.
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Neoplasias da Mama/terapia , Proteína Supressora de Tumor p53/metabolismo , Ultrassonografia/métodos , Animais , Western Blotting , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Meios de Contraste , Humanos , Imuno-Histoquímica , Necrose/genética , Necrose/metabolismo , Necrose/terapia , Ratos , Proteína Supressora de Tumor p53/genéticaRESUMO
OBJECTIVE: To investigate the correlations of four genetic single nucleotide polymorphisms (SNPs) of brain-derived neurotrophic factor (BDNF) with posttraumatic stress disorder (PTSD). METHODS: A total of 300 patients with sporadic PTSD and 150 healthy subjects (the control group) were selected according to the diagnostic criteria of PTSD (DSM-IV), and the genotypes of the BDNF SNPs G-712A, C270T, rs6265, and rs7103411 were detected by polymerase chain reaction and direct DNA sequencing to determine intergroup differences in the genotypes and allele frequencies; the p values were corrected with the permutation test. RESULTS: The genotypes and allele frequencies of the SNPs G-712A, rs6265, and rs7103411 of BDNF showed no significant intergroup differences (p>0.05). However, the genotype and allele frequencies of C270T showed significant differences between the PTSD group and the control group (p<0.05). CONCLUSION: The SNP C270T of BDNF may be associated with PTSD. Individuals carrying the polymorphic T allele of C270T may be more likely to suffer from PTSD.
RESUMO
Posttraumatic stress disorder (PTSD) is a common response to traumatic events. Many PTSD patients recover in the next few months, but in a significant subgroup, the symptoms persist, often for years. The present study shows that brain-derived neurotrophic factor (BDNF) gene is related to the pathological mechanism of a variety of mental diseases. Here we investigate the effect of methylation of BDNF gene and different loci on the occurrence and development of PTSD. Initially, using case-control method, 322 PTSD patients as well as 215 normal controls were selected as the subjects. Following peripheral venous blood being collected from the subjects, genomic DNA was extracted. Methylation of the cytosine-guanine dinucleotide (CpG) island in BDNF gene promoter was then modified by bisulfite and detected through direct sequencing. Methylation of CpG in BDNF gene promoter was closely related to PTSD, and the methylation level of CpG in BDNF gene promoter may serve as a biomarker for PTSD diagnosis. Types of trauma of PTSD patients may have a certain effect on the methylation level of BDNF gene promoter. Methylation level of the BDNF promoter, depressive degree score, poor sleep quality score, early trauma score, mental stress score, and trauma type were closely related to the occurrence and development of PTSD. Taken together, our data support the notion that stressful life events may directly cause CpG methylation in the BDNF promoter of PTSD patients. Stress types may be associated with methylation levels of CpG1, CpG7, and CpG18 in the BDNF promoter of PTSD patients. These findings provide a new way for the diagnosis and treatment of PTSD.