The tremendous public health and economic impact of coronavirus disease 2019(COVID-19), caused by severe acute respiratory syndrome coronavirus 2(SARSCoV-2), has become a huge challenge globally. There is increasing e...The tremendous public health and economic impact of coronavirus disease 2019(COVID-19), caused by severe acute respiratory syndrome coronavirus 2(SARSCoV-2), has become a huge challenge globally. There is increasing evidence that SARS-CoV-2 induces intestinal infections. Type Ⅲ interferon(IFN-λ) has an antiviral role in intestinal infection, with focused, long-lasting, and non-inflammatory characteristics. This review presents a summary of the structure of SARSCoV-2, including its invasion and immune escape mechanisms. Emphasis was placed on the gastrointestinal impact of SARS-CoV-2, including changes to the intestinal microbiome, activation of immune cells, and inflammatory responses.We also describe the comprehensive functions of IFN-λ in anti-enteric SARS-CoV-2 infection, and discuss the potential application of IFN-λ as a therapeutic agent for COVID-19 with intestinal symptoms.展开更多
Purpose: Interferon-γ (INF-γ) is a cytokine that participates in the immune reaction of the body. Its level of secretion can reflect the immune response condition after the body is infected by pathogens, which is a ...Purpose: Interferon-γ (INF-γ) is a cytokine that participates in the immune reaction of the body. Its level of secretion can reflect the immune response condition after the body is infected by pathogens, which is a significant indication of clinically-related diseases. Therefore, it is of great significance in application to develop a fluorescence biosensor to inspect INF-γ with rapidness, high sensitivity and high practicability. Method: The fluorescence sensor is made on the basis of the two-dimensional nano-material namely Carbon Nitride Nanosheet (CNNS) and the Aptamer probe to identify INF-γ (Apt®INF-γ). CNNS can quickly quench the Cy5 fluorescent dye modified on the Apt®INF-γ probe due to the Photoinduced Electron Transfer (PET), but when the INF-γ exists, Apt®INF-γ specifically identifies and combines it. The complex of Apt®INF-γ and INF-γ is away from CNNS, which can effectively block the fluorescent signal of Apt?INF-γ being quenched by CNNS. Result: The sensitive detection of IFN-γ protein can be achieved through the application of CNNS/Apt®INF-γ fluorescence sensing platform. In this method, the intensity of the fluorescent signal is positively correlated with the concentration of IFN-γ, of which the liner response range is 0.5 - 100 ng/mL and the limit of detection is 0.303 ng/mL. In addition, this fluorescence sensing platform has the advantages of high specificity, simple operation and low costs. It can inspect the content of IFN-γ in clinical serum samples without interference. The actual recovery rate of serum samples is 97.11% - 106.96%. Conclusion: Therefore, the CNNS/Apt®INF-γ sensing platform is expected to be implemented in the actual clinical detection, also conducive to developing a universal fluorescence biosensor to inspect other target materials.展开更多
Background:Women are mostly affected by thyroid carcinoma(THCA),an endocrine system cancer.However,the biomarkers of interferon-gamma(IFN-γ)in THCA have not been identified,so this study aimed to investigate whether ...Background:Women are mostly affected by thyroid carcinoma(THCA),an endocrine system cancer.However,the biomarkers of interferon-gamma(IFN-γ)in THCA have not been identified,so this study aimed to investigate whether IFN-γ-related genes could predict the overall prognosis of THCA patients.Methods:Transcriptome-related expression data were obtained from The Cancer Genome Atlas database.Differential expression of IFN-γ-responsive genes(DE-IFN-γ)between THCA and normal samples was determined based on the“limma”package in R.The prognostic value of the model was determined by least absolute shrinkage and selection operator,univariate Cox,and multivariate Cox analyses,as well as Kaplan-Meier curves.A nomogram was created to predict the THCA survival probabilities by combining clinicopathological features and prognostic genetic features.High-risk and low-risk groups were examined THCA-related pathways using gene set enrichment analysis.Correlations between the two groups with different scores and the immune microenvironment and immunotherapy were also explored.Finally,we verified the expression levels using real-time PCR.Results:From 48 DE-IFN-γ,4 DE-IFN-γ(METTL7B,VAMP8,CFB,IFIT3)associated with good prognosis were selected by least absolute shrinkage and selection operator and Cox co-screening.Based on these four genes,THCA patients were divided into two groups,with the high-risk group having a poorer overall survival rate.The risk score,age,and staging were identified as independent prognostic factors.The low-scoring group had significantly enriched 13 signaling pathways,according to gene set enrichment analysis.Meanwhile,the two groups delineated according to the risk score differed in terms of the immune microenvironment and immune checkpoints.Finally,our real-time PCR results corroborated previous hypotheses.Conclusion:Researchers identified four DE-IFN-γbiomarker genes with promising prognostic value for THCA patients,which may help guide immunotherapy preference.Moreover,it may subsequently influence our THCA treatment decisions.展开更多
Gastroduodenal tuberculosis(GD-TB)is exceptionally rare.The clinical manifestations of gastrointestinal TB are diverse and non-specific,which makes diagnosis difficult,leading to delayed diagnosis and high mortality.A...Gastroduodenal tuberculosis(GD-TB)is exceptionally rare.The clinical manifestations of gastrointestinal TB are diverse and non-specific,which makes diagnosis difficult,leading to delayed diagnosis and high mortality.As a peer-reviewer of World Journal of Clinical Cases,I would like to share my opinion on the article published by this journal.The patient had no family history of TB or contact with people with TB.Primary GD-TB presenting as gastric outlet obstruction and normal findings of thoracic computed tomography increased the difficulty of diagnosis and treatment in this patient.The diagnosis and treatment scheme of this typical case have reference value for the clinical treatment of GD-TB.展开更多
INTRODUCTIONIn China ,the incidence and mortality of gastric cancer rank the second among all cancers. Recent development of cancer [1-20].The aim of this study was investigat the insight of apoptosis and bcl-2, p53 a...INTRODUCTIONIn China ,the incidence and mortality of gastric cancer rank the second among all cancers. Recent development of cancer [1-20].The aim of this study was investigat the insight of apoptosis and bcl-2, p53 and C-myc protein expression in the development of gastric cancer .展开更多
AIM:To investigate the effects of adeno-associated virus (AAV) mediated expression of human interferon-γ for gene therapy in experimental hepatic fibrosis in vitro and in vivo. METHODS: We constructed the recombinant...AIM:To investigate the effects of adeno-associated virus (AAV) mediated expression of human interferon-γ for gene therapy in experimental hepatic fibrosis in vitro and in vivo. METHODS: We constructed the recombinant AAV encoding human INF-γ (rAAV- INF-γ) and took the primary rat hepatic stellate cells and carbon tetrachloride induced rats as the experimental hepatic fibrosis model in vitro and in vivo. Immunocytochemistry analysis was used to reveal the expression of α-SMA, the marker protein expressed in hepatic stellate cells. The mRNA expression of TGF-β, TIMP-1, and MMP-13 were analyzed by RT-PCR method. In vivo study, the hydroxyproline content in liver and serum AST, ALT were also detected. RESULTS: In vitro study, AAV vector could mediated efficient expression of human INF-γ, which inhibit the activation of hepatic stellate cells, decrease the expression of α-SMA and mRNA of TIMP-1, TGF-β, with the MMP-13 unchanged. In vivo study, the histological examination revealed that rAAV- INF-γ could inhibit the progression of the hepatic fibrosis. In the rAAV-INF-γ induced group, the hydroxyproline content and serum AST, ALT level were decreased to 177±28 μg/g wet liver, 668.5±140.0, 458.4±123.5 U/L, compare with the fibrosis control group 236±31 μg/g wet liver, 1 019.1±276.3, 770.5±154.3 U/L, respectively (P<0.01). mRNA expression of TIMP-1 in the rAAV-INF-γ induced rat liver was decreased while no significant change was observed in TGF-β and MMP-13. CONCLUSION: All these results indicated that rAAV-INF-γ has potential effects for gene therapy of hepatic fibrosis, which could inhibit the progression of hepatic fibrosis.展开更多
AIM. To investigate the influence of HLA-DRB1 alleles and HBV genotypes on inberferon-α therapy for chronic hepatitis B. METHODS: HLA-DRBI*03, *07, *09,*12, *15 alleles were determined using polymerase chain re...AIM. To investigate the influence of HLA-DRB1 alleles and HBV genotypes on inberferon-α therapy for chronic hepatitis B. METHODS: HLA-DRBI*03, *07, *09,*12, *15 alleles were determined using polymerase chain reaction/sequence specific primer (PCR/SSP) technique in 126 patients with chronic hepatitis B and 76 normal control subjects in Shandong Province, and HBV genotypes were determined by nested-PCR analysis using type-specific primers in 126 patients. RESULTS: The positivity of HLA-DRB1*07 allele in chronic hepatitis B group was significantly higher than that in normal control group (X^2 = 6.33, P〈0.025, RR = 2.37). Among the 126 patients, genotype B was found in 38 (30.2%), genotype C in 69 (54.8%), and mixed genotype (B+C) in 19 (15.0%), genotypes D-F were not found. Among the 46 DRB1*07(+) patients, 7 were responders and 39 were non-responders among them (X^2 = 6.71, P〈0.05). The positivity of HLADRB1*07 and prevalence of HBV genotype C were significantly higher in non-responders than in responders. CONCLUSION: High positivities of HLA-DRB1 *07 allele and HBV genotype C are closely associated with the lower response to interferon-α therapy for chronic hepatitis B.展开更多
AIM: To evaluate the in vitro anti-HBV activity of recombinant human IFN-γ, alone and in combination with lamivudine. METHODS: A recombinant baculovirus-HBV/HepG2 culture system was developed which could support prod...AIM: To evaluate the in vitro anti-HBV activity of recombinant human IFN-γ, alone and in combination with lamivudine. METHODS: A recombinant baculovirus-HBV/HepG2 culture system was developed which could support productive HBV infection in vitro. Expression of HBsAg and HBeAg in infected HepG2 culture medium was detected by commercial enzyme immunoassays. HBV DNA replication intermediates were detected in infected cells by Southern hybridization and viral DNA load was determined by dot hybridization. RESULTS: IFN-γat 0.1 to 5μg/L efficiently down regulated HBsAg expression in transduced HepG2 cells. At 5μg/L, IFN-γalso suppressed HBV DNA replication in these cells. While treatment with a combination of lamivudine and IFN-γshowed no additive effect, sequential treatment first with lamivudine and then IFN-γwas found to be promising. In this culture system the best HBV suppression was observed with a pulse of 2μmol/L lamivudine for two days, followed by 1μg/L IFN-γfor another four days. Compared to treatment with lamivudine alone, the sequential use of 0.2μmol/L lamivudine for two days, followed by 5μg/L IFN-γfor six days showed a 72% reduction in HBV cccDNA pool. CONCLUSION: This in vitro study warrants further evaluation of a combination of IFN-γand lamivudine, especially in IFN-αnon-responder chronic hepatitis B patients. A reduced duration of lamivudine treatment would also restrict the emergence of drug-resistant HBV mutants.展开更多
Tumor necrosis factor α (TNF-α) and interferon-γ (IFN-γ) are cytokines with strong antitumor activities. They were reacted with a photoactive arylazide-4-azidobenzoic acid, resulting in photoactive TNF-α and ...Tumor necrosis factor α (TNF-α) and interferon-γ (IFN-γ) are cytokines with strong antitumor activities. They were reacted with a photoactive arylazide-4-azidobenzoic acid, resulting in photoactive TNF-α and IFN-γ. The infrared (IR) spectra of these products showed the characteristic absorption of an azido group at 2127 cm^-1. By photo-immobilization, this modified TNF-α and IFN-γ were immobilized on polystyrene membranes for cell culture to prepare biomaterials. The micro-morphology of photoactive cytokines was observed with a scanning electron microscope (SEM). The inhibitory effect on growth of Hela cells and inducing apoptosis activity of these two cytokines were analyzed by growth curve, transmission electron microscope (TEM) and fluorescence active cell sorter (FACS). The results showed that co-immobilization of IFN-γ and TNF-α had significant inhibitory effect on growth of Hela cells, inhibitory rate up to 82%, and IFN-γ had obviously synergistic action.展开更多
Chronic inflammation associated with hepatitis C virus(HCV) infection can lead to disabling liver diseases with progression to liver cirrhosis and hepatocellular carcinoma. Despite the recent availability of more effe...Chronic inflammation associated with hepatitis C virus(HCV) infection can lead to disabling liver diseases with progression to liver cirrhosis and hepatocellular carcinoma. Despite the recent availability of more effective and less toxic therapeutic options, in most parts of the world the standard treatment consists of a weekly injection of pegylated interferon α(IFN-α) together with a daily dose of ribavirin. HCV patients frequently present circulating non-organ-specific autoantibodies demonstrating a variety of staining patterns in the indirect immunofluorescence assay for antinuclear antibodies(ANA). Between 20% to 40% of HCV patients treated with IFN-α and ribavirin develop autoantibodies showing a peculiar ANA pattern characterized as rods and rings(RR) structures. The aim of this article is to review the recent reports regarding RR structures and anti-rods/rings(antiRR) autoantibody production by HCV patients after IFN-α/ribavirin treatment. Anti-RR autoantibodies first appear around the sixth month of treatment and reach a plateau around the twelfth month. After treatment completion, anti-RR titers decrease/disappear in half the patients and remain steady in the other half. Some studies have observed a higher frequency of anti-RR antibodies in relapsers, i.e., patients in which circulating virus reappears after initially successful therapy. The main target of anti-RR autoantibodies in HCV patients is inosine-5'-monophosphate dehydrogenase 2(IMPDH2), the rate-limiting enzyme involved in the guanosine triphosphate biosynthesis pathway. Ribavirin is a direct IMPDH2 inhibitor and is able to induce the formation of RR structures in vitro and in vivo. In conclusion, these observations led to the hypothesis that anti-RR autoantibody production is a human model of immunologic tolerance breakdown that allows us to explore the humoral autoimmune response from the beginning of the putative triggering event: exposure to ribavirin and interferon.展开更多
AIM:To establish a predictive algorithm which may serve for selecting optimal candidates for interferon-α(IFN-α) treatment.METHODS:A total of 474 IFN-α treated hepatitis B virus e antigen(HBeAg)-positive patients w...AIM:To establish a predictive algorithm which may serve for selecting optimal candidates for interferon-α(IFN-α) treatment.METHODS:A total of 474 IFN-α treated hepatitis B virus e antigen(HBeAg)-positive patients were enrolled in the present study.The patients' baseline characteristics,such as age,gender,blood tests,activity grading(G) of intrahepatic inflammation,score(S) of liver fibrosis,hepatitis B virus(HBV) DNA and genotype were evaluated;therapy duration and response of each patient at the 24th wk after cessation of IFN-α treatment were also recorded.A predictive algorithm and scoring system for a sustained combined response(CR) to IFN-α therapy were established.About 10% of the patients were randomly drawn as the test set.Responses to IFN-α therapy were divided into CR,partial response(PR) and non-response(NR).The mixed set of PR and NR was recorded as PR+NR.RESULTS:Stratified by therapy duration,the most significant baseline predictive factors were alanine aminotransferase(ALT),HBV DNA level,aspartate aminotransferase(AST),HBV genotype,S,G,age and gender.According to the established model,the accuracies for sustained CR and PR+NR,respectively,were 86.4% and 93.0% for the training set,81.5% and 91.0% for the test set.For the scoring system,the sensitivity and specificity were 78.8% and 80.6%,respectively.There were positive correlations between ALT and AST,and G and S,respectively.CONCLUSION:With these models,practitioners may be able to propose individualized decisions that have an integrated foundation on both evidence-based medicine and personal characteristics.展开更多
AIM: To evaluate the effects of interferon-α-2b (IFN- α-2b) on expression of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) in human hepatocellular carcinoma (HCC) inoculated in nude...AIM: To evaluate the effects of interferon-α-2b (IFN- α-2b) on expression of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) in human hepatocellular carcinoma (HCC) inoculated in nude mice and to study the underlying mechanism of IFN-α- 2b against HCC growth. METHODS: Thirb/-two nude mice bearing human HCC were randomly divided into four groups (n = 8). On the 10th day after implantation of HCC cells, the mice in test groups (groups A, B and C) received IFN-α- 2b at a serial dose (10000 IU for group A, 20000 IU for group B, 40000 IU for group C sc daily) for 35 d. The mice in control group received normal saline (NS). The growth conditions of transplanted tumors were observed. Both genes and proteins of COX-2 and VEGF were detected by RT-PCR and Western blot. Apoptosis of tumor cells in nude mice was detected by TUNEL assay after treatment with IFN-α-2b. RESULTS: Tumors were significantly smaller and had a lower weight in the IFN-α-2b treatment groups than those in the control group (P 〈 0.01), and the tumor growth inhibition rate in groups A, B and C was 27.78%, 65.22% and 49.64%, respectively. The expression levels of both genes and proteins of COX-2 and VEGF were much lower in the IFN-α-2b treatment groups than in the control group (P 〈 0.01). The apoptosis index (AI) of tumor cells in the IFN-α-2b treatment groups was markedly higher than that in the control group (P 〈 0.01). Group B had a higher inhibition rate of tumor growth, a lower expression level of COX-2 and VEGF and a higher AI than groups A and C (P 〈 0.05), but there was no significant difference between groups A and C. CONCLUSION: The inhibitory effects of IFN-α-2b on implanted tumor growth and apoptosis may be associated with the down-regulation of COX-2 and VEGF expression. There is a dose-effect relationship. The medium dose of IFN-α-2b for inhibiting tumor growth is 20 000 IU/d.展开更多
In order to investigate the clinical value of vascular endothelial growth factor (VEGF) combined with interferon-γ (IFN-γ) in diagnosing malignant pleural effusion and tuberculous pleural effusion, 42 cases of m...In order to investigate the clinical value of vascular endothelial growth factor (VEGF) combined with interferon-γ (IFN-γ) in diagnosing malignant pleural effusion and tuberculous pleural effusion, 42 cases of malignant pleural effusion and 45 cases of tuberculous pleural effusion in Tongji Hospital, from March 2004 to May 2005, were included, The carcinoembryonic antigen (CEA), VEGF and IFN-γ levels of pleural effusion were detected by using ELISA, and adenosine deaminase (ADA) activity was determined by using enzyme kinetic analytical method. The sensitivity, specificity, accuracy and area under the curve (AUCR^ROC) of CEA and VEGF, VEGF/IFN-γ ratio, ADA and IFN-γ were measured by receiver operating characteristic curve (ROC), The results showed that CEA, VEGF levels and VEGF/IFN-γ ratio were significantly higher and the ADA and IFN-γ levels were significantly lower in malignant group than those in tuberculous group (P〈0,01), The sensitivity, specificity, accuracy and AUCR^ROC of VEGF/IFN-γ ratio (88,7%, 99,8%, 94,4%, 0.96 respectively) were higher than those of CEA (67.8%, 96.1%, 82,4%, 0.78 respectively) and VEGF (81,5%, 84,3%, 82.9%, 0.79 respectively). The sensitivity, specificity, accuracy and AUCR^ROC of IFN-γ (85.7%, 96,4%, 90.9%, 0.94 respectively) were higher than those of ADA (80,2%, 87,6%, 83.8%, 0,81 respectively). It was concluded that VEGF/IFN-γ ratio and IFN-γ could be used as valuable parameters for the differential diagnosis of malignant pleural effusion and tuberculous pleural effusion.展开更多
AIM To investigate the association between interferoninduced protein with tetratricopeptide repeats 1(IFIT1) polymorphisms and interferon-α(IFNα) treatment efficiency among Chinese hepatitis B virus(HBV) infection p...AIM To investigate the association between interferoninduced protein with tetratricopeptide repeats 1(IFIT1) polymorphisms and interferon-α(IFNα) treatment efficiency among Chinese hepatitis B virus(HBV) infection patients.METHODS Two hundred and twenty five newly diagnosed chronichepatitis B(CHB) patients were enrolled in the study. All of these patients received IFNα treatment for a course of 48 wk, and were followed up for 24 wk after the treatment was end. Clinical information about virological response, hepatitis B e antigen(HBe Ag) seroconversion rate and combined response at the end of the treatment, as well as the sustained response by the time of following up 24 wk after the treatment, was collected. Four tag-single nucleotide polymorphisms(SNPs) of IFIT1 were selected and assessed for their association with these clinical outcomes.RESULTS At the end of the treatment, HBe Ag seroconversion was observed in 27.1% patients. Thirty-six point nine percent patients achieved virological response, and 15.6% patients exhibited combined response. Sustained response was obtained in 26.2% patients. The main HBV genotype of the study was genotype B. Patients who infected with HBV genotype B or C showed better treatment efficiency, no matter which clinical outcome was considered. Among the four SNPs assessed, rs303218(A > G) was found to be significantly associated with the end point virological response when assuming additive model [OR = 0.64(95%CI: 0.42-0.96), P = 0.032]. Patients who carried rs303218 GG genotype had a rather higher rate of achieving virological response(response rate: 52%, OR = 0.40, 95%CI: 0.18-0.91; P = 0.028) when compared to those had AA genotype(response rate: 27%). The most significant interaction was observed in patients who had relative lower baseline aspartate transaminase. No association between SNPs and HBe Ag seroconversion, combined response or sustained response was observed.CONCLUSION IFIT1 involves in the regulation of IFNα treatment for CHB and its polymorphism rs303218 can predict the end point virological response. The finding requires further validation.展开更多
BACKGROUND: Studies have demonstrated that experimental autoimmune encephalomyelitis (EAE) onset correlates with increased interferon-v (IFN-γ) and tumor necrosis factor-α (TNF-α) expression. Oxymatrine (OM...BACKGROUND: Studies have demonstrated that experimental autoimmune encephalomyelitis (EAE) onset correlates with increased interferon-v (IFN-γ) and tumor necrosis factor-α (TNF-α) expression. Oxymatrine (OM) has been shown to inhibit autoimmune responses, but there are no reports showing that it could prevent the development of EAE. OBJECTIVE: To observe the effect of OM on serum levels of IFN-γ and TNF-α in a rat model of EAE.DESIGN, TIME AND SETTING: A randomized, controlled, animal study was performed at the Experimental Animal Center of Henan Academy of Chinese Medicine and at the Key Disciplines Laboratory Clinical Medicine of Henan Province between July and December 2008. MATERIALS: OM was purchased from Chia-tai Tianqing Pharmaceutical, China; complete Freund's adjuvant was purchased from Sigma, USA. METHODS: Forty female Wistar rats were randomly assigned to four groups: EAE model (M), low-dose OM treatment (OM-L), high-dose OM treatment (OM-H), and normal control (N, no immunization), with 10 rats in each group. EAE was established in the M, OM-L, and OM-H groups following immunization with Guinea pig spinal cord homogenate and complete Freund's adjuvant. The M and N groups were intraperitoneally injected with normal saline (6.7 mL/kg per day), the OM-L group received an intraperitoneal injection of OM (100 mg/kg per day), and the OM-H group received OM (150 mg/kg per day). MAIN OUTCOME MEASURES: At 16 days after immunization, the degree of histopathological changes in the spinal cord was assessed by hematoxylin-eosin stanining. Enzyme-linked immunosorbent assay was used to detect serum levels of IFN-γ, and radioimmunoassay was utilized to determine serum TNF-α level. Neurological scores were measured on a daily basis according to a 0-5 scale. RESULTS: Daily injections of OM, both high and low doses, resulted in decreased neurological scores in EAE rats (P〈0.01), as well as reduced cellular infiltration in the spinal cord and decreased levels of serum IFN-γ and TNF-α (P〈 0.01). CONCLUSION: OM reduced the onset and severity of EAE, which correlated with decreased IFN-γ and TNF-α expression.展开更多
AIM:To investigate the possibility of shortening the duration of peginterferon(Peg-IFN)plus ribavirin(RBV) combination therapy by incorporating interferon-β (IFN-β)induction therapy. METHODS:A one treatment arm,coho...AIM:To investigate the possibility of shortening the duration of peginterferon(Peg-IFN)plus ribavirin(RBV) combination therapy by incorporating interferon-β (IFN-β)induction therapy. METHODS:A one treatment arm,cohort prospective study was conducted on seventy one patients.The patients were Japanese adults with genotype 1b chronic hepatitis C,HCV-RNA levels of≥5.0 Log IU/mL or 100 KIU/mL,and platelet counts of≥90 000/μL.The treatment regimen consisted of a 2 wk course of twicedaily administration of IFN-βfollowed by 24 wk PegIFN plus RBV combination therapy.We prolonged the duration of the Peg-IFN plus RBV therapy to 48 wk if the patient requested it. RESULTS:The patients,including 44%males,were characterized by an median age of 63 years(range: 32-78 years),an median platelet count of 13.9(range: 9.1-30.6)×10 4 /μL,62%IFN-na?ve,and median HCV- RNA of 6.1(range:5.1-7.2)Log IU/mL.The sustained virologic response(SVR)rates were 34%(Peg-IFN:1-24 wk,n=61,95%confidence interval(CI): 24%-47%)and 55%(Peg-IFN:20-24 wk,n=31,95% CI:38%-71%,P<0.001;vs Peg-IFN:1-19 wk).TheSVR rate when the administration was discontinued early was 13%(Peg-IFN:1-19 wk,n=30,95%CI: 5%-30%),and that when the administration was prolonged was 50%(Peg-IFN:25-48 wk,n=10,95% CI:24%-76%,P<0.05;vs Peg-IFN:1-19 wk).In the patients who received 20-24 wk of Peg-IFN plus RBV,only the higher platelet count(≥130 000/μL) was significantly correlated with the SVR(odds ratio: 11.680,95%CI:2.3064-79.474,P=0.0024).In 45% (14/31)of the patients with a higher platelet count (≥130000/μL)before therapy,the HCV-RNA level decreased to below 3.3 Log IU/mL at the completion of IFN-β,and their SVR rate was 93%(13/14)after 20-24 wk administration of Peg-IFN plus RBV. CONCLUSION:These results suggest the possibilities of shortening the duration of Peg-IFN plus RBV combination therapy by actively reducing HCV-RNA levels using the IFN-βinduction regimen.展开更多
Atherosclerosis is a chronic inflammatory disorder of the vasculature and is the primary cause of cardiovascular disease(CVD). CVD is currently the world's leading cause of death and the numbers are predicted to r...Atherosclerosis is a chronic inflammatory disorder of the vasculature and is the primary cause of cardiovascular disease(CVD). CVD is currently the world's leading cause of death and the numbers are predicted to rise further because of a global increase in risk factors such as diabetes and obesity. Current therapies such as statins have had a major impact in reducing mortality from CVD. However, there is a marked residual CVD risk in patients on statin therapy. It is therefore important to understand the molecular basis of this disease in detail and to develop alternative novel therapeutics. Interferon-γ(IFN-γ) is a pro-inflammatory cytokine that is often regarded as a master regulator of atherosclerosis development. IFN-γ is able to influence several key steps during atherosclerosis development, including pro-inflammatory gene expression, the recruitment of monocytes from the blood to the activated arterial endothelium and plaque stability. This central role of IFN-γ makes it a promising therapeutic target. The purpose of this editorial is to describe the key role IFN-γ plays during atherosclerosis development, as well as discuss potential strategies to target it therapeutically.展开更多
We report a case of severe thrombocytopenia following pegylated interferon-α 2a(Peg-IFN-α 2a)treatment of hepatitis C virus infection and summarize the clinical characteristics of 16 cases of IFN-α induced severe t...We report a case of severe thrombocytopenia following pegylated interferon-α 2a(Peg-IFN-α 2a)treatment of hepatitis C virus infection and summarize the clinical characteristics of 16 cases of IFN-α induced severe thrombocytopenia and its immune-mediated mechanism.Discontinuation of IFN-α and early administration of immunosuppressants are the effective therapy for IFN-αinduced severe thrombocytopenia.展开更多
基金Supported by National Natural Science Foundation of China(to M.Y.),No.81970468.
文摘The tremendous public health and economic impact of coronavirus disease 2019(COVID-19), caused by severe acute respiratory syndrome coronavirus 2(SARSCoV-2), has become a huge challenge globally. There is increasing evidence that SARS-CoV-2 induces intestinal infections. Type Ⅲ interferon(IFN-λ) has an antiviral role in intestinal infection, with focused, long-lasting, and non-inflammatory characteristics. This review presents a summary of the structure of SARSCoV-2, including its invasion and immune escape mechanisms. Emphasis was placed on the gastrointestinal impact of SARS-CoV-2, including changes to the intestinal microbiome, activation of immune cells, and inflammatory responses.We also describe the comprehensive functions of IFN-λ in anti-enteric SARS-CoV-2 infection, and discuss the potential application of IFN-λ as a therapeutic agent for COVID-19 with intestinal symptoms.
文摘Purpose: Interferon-γ (INF-γ) is a cytokine that participates in the immune reaction of the body. Its level of secretion can reflect the immune response condition after the body is infected by pathogens, which is a significant indication of clinically-related diseases. Therefore, it is of great significance in application to develop a fluorescence biosensor to inspect INF-γ with rapidness, high sensitivity and high practicability. Method: The fluorescence sensor is made on the basis of the two-dimensional nano-material namely Carbon Nitride Nanosheet (CNNS) and the Aptamer probe to identify INF-γ (Apt®INF-γ). CNNS can quickly quench the Cy5 fluorescent dye modified on the Apt®INF-γ probe due to the Photoinduced Electron Transfer (PET), but when the INF-γ exists, Apt®INF-γ specifically identifies and combines it. The complex of Apt®INF-γ and INF-γ is away from CNNS, which can effectively block the fluorescent signal of Apt?INF-γ being quenched by CNNS. Result: The sensitive detection of IFN-γ protein can be achieved through the application of CNNS/Apt®INF-γ fluorescence sensing platform. In this method, the intensity of the fluorescent signal is positively correlated with the concentration of IFN-γ, of which the liner response range is 0.5 - 100 ng/mL and the limit of detection is 0.303 ng/mL. In addition, this fluorescence sensing platform has the advantages of high specificity, simple operation and low costs. It can inspect the content of IFN-γ in clinical serum samples without interference. The actual recovery rate of serum samples is 97.11% - 106.96%. Conclusion: Therefore, the CNNS/Apt®INF-γ sensing platform is expected to be implemented in the actual clinical detection, also conducive to developing a universal fluorescence biosensor to inspect other target materials.
基金supported by National Natural Science Foundation,Regional Science Foundation Project(NO.81960322,82160343)Medical Reserve Personnel Training Program of Yunnan Provincial Health Commission(NO.H-2018097)Joint Program of Applied Basic Research of Yunnan Provincial Department of Science and Technology-Kunming Medical University(NO.202101AY070001-158).
文摘Background:Women are mostly affected by thyroid carcinoma(THCA),an endocrine system cancer.However,the biomarkers of interferon-gamma(IFN-γ)in THCA have not been identified,so this study aimed to investigate whether IFN-γ-related genes could predict the overall prognosis of THCA patients.Methods:Transcriptome-related expression data were obtained from The Cancer Genome Atlas database.Differential expression of IFN-γ-responsive genes(DE-IFN-γ)between THCA and normal samples was determined based on the“limma”package in R.The prognostic value of the model was determined by least absolute shrinkage and selection operator,univariate Cox,and multivariate Cox analyses,as well as Kaplan-Meier curves.A nomogram was created to predict the THCA survival probabilities by combining clinicopathological features and prognostic genetic features.High-risk and low-risk groups were examined THCA-related pathways using gene set enrichment analysis.Correlations between the two groups with different scores and the immune microenvironment and immunotherapy were also explored.Finally,we verified the expression levels using real-time PCR.Results:From 48 DE-IFN-γ,4 DE-IFN-γ(METTL7B,VAMP8,CFB,IFIT3)associated with good prognosis were selected by least absolute shrinkage and selection operator and Cox co-screening.Based on these four genes,THCA patients were divided into two groups,with the high-risk group having a poorer overall survival rate.The risk score,age,and staging were identified as independent prognostic factors.The low-scoring group had significantly enriched 13 signaling pathways,according to gene set enrichment analysis.Meanwhile,the two groups delineated according to the risk score differed in terms of the immune microenvironment and immune checkpoints.Finally,our real-time PCR results corroborated previous hypotheses.Conclusion:Researchers identified four DE-IFN-γbiomarker genes with promising prognostic value for THCA patients,which may help guide immunotherapy preference.Moreover,it may subsequently influence our THCA treatment decisions.
基金Supported by Shenyang Science and Technology Plan Project,No.23-408-3-01The Natural Science Foundation of Liaoning Province,No.2022-MS-435.
文摘Gastroduodenal tuberculosis(GD-TB)is exceptionally rare.The clinical manifestations of gastrointestinal TB are diverse and non-specific,which makes diagnosis difficult,leading to delayed diagnosis and high mortality.As a peer-reviewer of World Journal of Clinical Cases,I would like to share my opinion on the article published by this journal.The patient had no family history of TB or contact with people with TB.Primary GD-TB presenting as gastric outlet obstruction and normal findings of thoracic computed tomography increased the difficulty of diagnosis and treatment in this patient.The diagnosis and treatment scheme of this typical case have reference value for the clinical treatment of GD-TB.
文摘INTRODUCTIONIn China ,the incidence and mortality of gastric cancer rank the second among all cancers. Recent development of cancer [1-20].The aim of this study was investigat the insight of apoptosis and bcl-2, p53 and C-myc protein expression in the development of gastric cancer .
基金Supported by the National High Technology Research and Development Program of China, 863 Program, No. 2003AA2Z347A
文摘AIM:To investigate the effects of adeno-associated virus (AAV) mediated expression of human interferon-γ for gene therapy in experimental hepatic fibrosis in vitro and in vivo. METHODS: We constructed the recombinant AAV encoding human INF-γ (rAAV- INF-γ) and took the primary rat hepatic stellate cells and carbon tetrachloride induced rats as the experimental hepatic fibrosis model in vitro and in vivo. Immunocytochemistry analysis was used to reveal the expression of α-SMA, the marker protein expressed in hepatic stellate cells. The mRNA expression of TGF-β, TIMP-1, and MMP-13 were analyzed by RT-PCR method. In vivo study, the hydroxyproline content in liver and serum AST, ALT were also detected. RESULTS: In vitro study, AAV vector could mediated efficient expression of human INF-γ, which inhibit the activation of hepatic stellate cells, decrease the expression of α-SMA and mRNA of TIMP-1, TGF-β, with the MMP-13 unchanged. In vivo study, the histological examination revealed that rAAV- INF-γ could inhibit the progression of the hepatic fibrosis. In the rAAV-INF-γ induced group, the hydroxyproline content and serum AST, ALT level were decreased to 177±28 μg/g wet liver, 668.5±140.0, 458.4±123.5 U/L, compare with the fibrosis control group 236±31 μg/g wet liver, 1 019.1±276.3, 770.5±154.3 U/L, respectively (P<0.01). mRNA expression of TIMP-1 in the rAAV-INF-γ induced rat liver was decreased while no significant change was observed in TGF-β and MMP-13. CONCLUSION: All these results indicated that rAAV-INF-γ has potential effects for gene therapy of hepatic fibrosis, which could inhibit the progression of hepatic fibrosis.
文摘AIM. To investigate the influence of HLA-DRB1 alleles and HBV genotypes on inberferon-α therapy for chronic hepatitis B. METHODS: HLA-DRBI*03, *07, *09,*12, *15 alleles were determined using polymerase chain reaction/sequence specific primer (PCR/SSP) technique in 126 patients with chronic hepatitis B and 76 normal control subjects in Shandong Province, and HBV genotypes were determined by nested-PCR analysis using type-specific primers in 126 patients. RESULTS: The positivity of HLA-DRB1*07 allele in chronic hepatitis B group was significantly higher than that in normal control group (X^2 = 6.33, P〈0.025, RR = 2.37). Among the 126 patients, genotype B was found in 38 (30.2%), genotype C in 69 (54.8%), and mixed genotype (B+C) in 19 (15.0%), genotypes D-F were not found. Among the 46 DRB1*07(+) patients, 7 were responders and 39 were non-responders among them (X^2 = 6.71, P〈0.05). The positivity of HLADRB1*07 and prevalence of HBV genotype C were significantly higher in non-responders than in responders. CONCLUSION: High positivities of HLA-DRB1 *07 allele and HBV genotype C are closely associated with the lower response to interferon-α therapy for chronic hepatitis B.
基金Supported by a grant from the Dabur Research Foundation, India and a Senior Research Fellowship of the CSIR, Gov. of India (to MKP)
文摘AIM: To evaluate the in vitro anti-HBV activity of recombinant human IFN-γ, alone and in combination with lamivudine. METHODS: A recombinant baculovirus-HBV/HepG2 culture system was developed which could support productive HBV infection in vitro. Expression of HBsAg and HBeAg in infected HepG2 culture medium was detected by commercial enzyme immunoassays. HBV DNA replication intermediates were detected in infected cells by Southern hybridization and viral DNA load was determined by dot hybridization. RESULTS: IFN-γat 0.1 to 5μg/L efficiently down regulated HBsAg expression in transduced HepG2 cells. At 5μg/L, IFN-γalso suppressed HBV DNA replication in these cells. While treatment with a combination of lamivudine and IFN-γshowed no additive effect, sequential treatment first with lamivudine and then IFN-γwas found to be promising. In this culture system the best HBV suppression was observed with a pulse of 2μmol/L lamivudine for two days, followed by 1μg/L IFN-γfor another four days. Compared to treatment with lamivudine alone, the sequential use of 0.2μmol/L lamivudine for two days, followed by 5μg/L IFN-γfor six days showed a 72% reduction in HBV cccDNA pool. CONCLUSION: This in vitro study warrants further evaluation of a combination of IFN-γand lamivudine, especially in IFN-αnon-responder chronic hepatitis B patients. A reduced duration of lamivudine treatment would also restrict the emergence of drug-resistant HBV mutants.
基金This work was supported by the China Postdoctoral Science Foundation under grant No.2004035588.
文摘Tumor necrosis factor α (TNF-α) and interferon-γ (IFN-γ) are cytokines with strong antitumor activities. They were reacted with a photoactive arylazide-4-azidobenzoic acid, resulting in photoactive TNF-α and IFN-γ. The infrared (IR) spectra of these products showed the characteristic absorption of an azido group at 2127 cm^-1. By photo-immobilization, this modified TNF-α and IFN-γ were immobilized on polystyrene membranes for cell culture to prepare biomaterials. The micro-morphology of photoactive cytokines was observed with a scanning electron microscope (SEM). The inhibitory effect on growth of Hela cells and inducing apoptosis activity of these two cytokines were analyzed by growth curve, transmission electron microscope (TEM) and fluorescence active cell sorter (FACS). The results showed that co-immobilization of IFN-γ and TNF-α had significant inhibitory effect on growth of Hela cells, inhibitory rate up to 82%, and IFN-γ had obviously synergistic action.
基金Supported by Brazilian government research foundations National Council for Research and Technology and Coordination for the Improvement of Higher Education Personnel with research grant and scholarships processNo.9028-11-0+2 种基金No.305064/2011-8 and No.232711/2014-3Sao Paulo Government agency Sao Paulo State Research Foundation withprocess No.2011/12448-0both granted to Andrade LEC and Keppeke GD
文摘Chronic inflammation associated with hepatitis C virus(HCV) infection can lead to disabling liver diseases with progression to liver cirrhosis and hepatocellular carcinoma. Despite the recent availability of more effective and less toxic therapeutic options, in most parts of the world the standard treatment consists of a weekly injection of pegylated interferon α(IFN-α) together with a daily dose of ribavirin. HCV patients frequently present circulating non-organ-specific autoantibodies demonstrating a variety of staining patterns in the indirect immunofluorescence assay for antinuclear antibodies(ANA). Between 20% to 40% of HCV patients treated with IFN-α and ribavirin develop autoantibodies showing a peculiar ANA pattern characterized as rods and rings(RR) structures. The aim of this article is to review the recent reports regarding RR structures and anti-rods/rings(antiRR) autoantibody production by HCV patients after IFN-α/ribavirin treatment. Anti-RR autoantibodies first appear around the sixth month of treatment and reach a plateau around the twelfth month. After treatment completion, anti-RR titers decrease/disappear in half the patients and remain steady in the other half. Some studies have observed a higher frequency of anti-RR antibodies in relapsers, i.e., patients in which circulating virus reappears after initially successful therapy. The main target of anti-RR autoantibodies in HCV patients is inosine-5'-monophosphate dehydrogenase 2(IMPDH2), the rate-limiting enzyme involved in the guanosine triphosphate biosynthesis pathway. Ribavirin is a direct IMPDH2 inhibitor and is able to induce the formation of RR structures in vitro and in vivo. In conclusion, these observations led to the hypothesis that anti-RR autoantibody production is a human model of immunologic tolerance breakdown that allows us to explore the humoral autoimmune response from the beginning of the putative triggering event: exposure to ribavirin and interferon.
文摘AIM:To establish a predictive algorithm which may serve for selecting optimal candidates for interferon-α(IFN-α) treatment.METHODS:A total of 474 IFN-α treated hepatitis B virus e antigen(HBeAg)-positive patients were enrolled in the present study.The patients' baseline characteristics,such as age,gender,blood tests,activity grading(G) of intrahepatic inflammation,score(S) of liver fibrosis,hepatitis B virus(HBV) DNA and genotype were evaluated;therapy duration and response of each patient at the 24th wk after cessation of IFN-α treatment were also recorded.A predictive algorithm and scoring system for a sustained combined response(CR) to IFN-α therapy were established.About 10% of the patients were randomly drawn as the test set.Responses to IFN-α therapy were divided into CR,partial response(PR) and non-response(NR).The mixed set of PR and NR was recorded as PR+NR.RESULTS:Stratified by therapy duration,the most significant baseline predictive factors were alanine aminotransferase(ALT),HBV DNA level,aspartate aminotransferase(AST),HBV genotype,S,G,age and gender.According to the established model,the accuracies for sustained CR and PR+NR,respectively,were 86.4% and 93.0% for the training set,81.5% and 91.0% for the test set.For the scoring system,the sensitivity and specificity were 78.8% and 80.6%,respectively.There were positive correlations between ALT and AST,and G and S,respectively.CONCLUSION:With these models,practitioners may be able to propose individualized decisions that have an integrated foundation on both evidence-based medicine and personal characteristics.
基金Supported by Clinical Key Program Point Subject Foundation of Ministry of Public Health, No. 20012434
文摘AIM: To evaluate the effects of interferon-α-2b (IFN- α-2b) on expression of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) in human hepatocellular carcinoma (HCC) inoculated in nude mice and to study the underlying mechanism of IFN-α- 2b against HCC growth. METHODS: Thirb/-two nude mice bearing human HCC were randomly divided into four groups (n = 8). On the 10th day after implantation of HCC cells, the mice in test groups (groups A, B and C) received IFN-α- 2b at a serial dose (10000 IU for group A, 20000 IU for group B, 40000 IU for group C sc daily) for 35 d. The mice in control group received normal saline (NS). The growth conditions of transplanted tumors were observed. Both genes and proteins of COX-2 and VEGF were detected by RT-PCR and Western blot. Apoptosis of tumor cells in nude mice was detected by TUNEL assay after treatment with IFN-α-2b. RESULTS: Tumors were significantly smaller and had a lower weight in the IFN-α-2b treatment groups than those in the control group (P 〈 0.01), and the tumor growth inhibition rate in groups A, B and C was 27.78%, 65.22% and 49.64%, respectively. The expression levels of both genes and proteins of COX-2 and VEGF were much lower in the IFN-α-2b treatment groups than in the control group (P 〈 0.01). The apoptosis index (AI) of tumor cells in the IFN-α-2b treatment groups was markedly higher than that in the control group (P 〈 0.01). Group B had a higher inhibition rate of tumor growth, a lower expression level of COX-2 and VEGF and a higher AI than groups A and C (P 〈 0.05), but there was no significant difference between groups A and C. CONCLUSION: The inhibitory effects of IFN-α-2b on implanted tumor growth and apoptosis may be associated with the down-regulation of COX-2 and VEGF expression. There is a dose-effect relationship. The medium dose of IFN-α-2b for inhibiting tumor growth is 20 000 IU/d.
基金This project was supported by a grant from the Science and Technology Foundation of Hubei Province (2003AA301C10)
文摘In order to investigate the clinical value of vascular endothelial growth factor (VEGF) combined with interferon-γ (IFN-γ) in diagnosing malignant pleural effusion and tuberculous pleural effusion, 42 cases of malignant pleural effusion and 45 cases of tuberculous pleural effusion in Tongji Hospital, from March 2004 to May 2005, were included, The carcinoembryonic antigen (CEA), VEGF and IFN-γ levels of pleural effusion were detected by using ELISA, and adenosine deaminase (ADA) activity was determined by using enzyme kinetic analytical method. The sensitivity, specificity, accuracy and area under the curve (AUCR^ROC) of CEA and VEGF, VEGF/IFN-γ ratio, ADA and IFN-γ were measured by receiver operating characteristic curve (ROC), The results showed that CEA, VEGF levels and VEGF/IFN-γ ratio were significantly higher and the ADA and IFN-γ levels were significantly lower in malignant group than those in tuberculous group (P〈0,01), The sensitivity, specificity, accuracy and AUCR^ROC of VEGF/IFN-γ ratio (88,7%, 99,8%, 94,4%, 0.96 respectively) were higher than those of CEA (67.8%, 96.1%, 82,4%, 0.78 respectively) and VEGF (81,5%, 84,3%, 82.9%, 0.79 respectively). The sensitivity, specificity, accuracy and AUCR^ROC of IFN-γ (85.7%, 96,4%, 90.9%, 0.94 respectively) were higher than those of ADA (80,2%, 87,6%, 83.8%, 0,81 respectively). It was concluded that VEGF/IFN-γ ratio and IFN-γ could be used as valuable parameters for the differential diagnosis of malignant pleural effusion and tuberculous pleural effusion.
文摘AIM To investigate the association between interferoninduced protein with tetratricopeptide repeats 1(IFIT1) polymorphisms and interferon-α(IFNα) treatment efficiency among Chinese hepatitis B virus(HBV) infection patients.METHODS Two hundred and twenty five newly diagnosed chronichepatitis B(CHB) patients were enrolled in the study. All of these patients received IFNα treatment for a course of 48 wk, and were followed up for 24 wk after the treatment was end. Clinical information about virological response, hepatitis B e antigen(HBe Ag) seroconversion rate and combined response at the end of the treatment, as well as the sustained response by the time of following up 24 wk after the treatment, was collected. Four tag-single nucleotide polymorphisms(SNPs) of IFIT1 were selected and assessed for their association with these clinical outcomes.RESULTS At the end of the treatment, HBe Ag seroconversion was observed in 27.1% patients. Thirty-six point nine percent patients achieved virological response, and 15.6% patients exhibited combined response. Sustained response was obtained in 26.2% patients. The main HBV genotype of the study was genotype B. Patients who infected with HBV genotype B or C showed better treatment efficiency, no matter which clinical outcome was considered. Among the four SNPs assessed, rs303218(A > G) was found to be significantly associated with the end point virological response when assuming additive model [OR = 0.64(95%CI: 0.42-0.96), P = 0.032]. Patients who carried rs303218 GG genotype had a rather higher rate of achieving virological response(response rate: 52%, OR = 0.40, 95%CI: 0.18-0.91; P = 0.028) when compared to those had AA genotype(response rate: 27%). The most significant interaction was observed in patients who had relative lower baseline aspartate transaminase. No association between SNPs and HBe Ag seroconversion, combined response or sustained response was observed.CONCLUSION IFIT1 involves in the regulation of IFNα treatment for CHB and its polymorphism rs303218 can predict the end point virological response. The finding requires further validation.
基金a Grant from the Natural Scientific Research Project of the Education Department of Henan Province,No. 2009A350009
文摘BACKGROUND: Studies have demonstrated that experimental autoimmune encephalomyelitis (EAE) onset correlates with increased interferon-v (IFN-γ) and tumor necrosis factor-α (TNF-α) expression. Oxymatrine (OM) has been shown to inhibit autoimmune responses, but there are no reports showing that it could prevent the development of EAE. OBJECTIVE: To observe the effect of OM on serum levels of IFN-γ and TNF-α in a rat model of EAE.DESIGN, TIME AND SETTING: A randomized, controlled, animal study was performed at the Experimental Animal Center of Henan Academy of Chinese Medicine and at the Key Disciplines Laboratory Clinical Medicine of Henan Province between July and December 2008. MATERIALS: OM was purchased from Chia-tai Tianqing Pharmaceutical, China; complete Freund's adjuvant was purchased from Sigma, USA. METHODS: Forty female Wistar rats were randomly assigned to four groups: EAE model (M), low-dose OM treatment (OM-L), high-dose OM treatment (OM-H), and normal control (N, no immunization), with 10 rats in each group. EAE was established in the M, OM-L, and OM-H groups following immunization with Guinea pig spinal cord homogenate and complete Freund's adjuvant. The M and N groups were intraperitoneally injected with normal saline (6.7 mL/kg per day), the OM-L group received an intraperitoneal injection of OM (100 mg/kg per day), and the OM-H group received OM (150 mg/kg per day). MAIN OUTCOME MEASURES: At 16 days after immunization, the degree of histopathological changes in the spinal cord was assessed by hematoxylin-eosin stanining. Enzyme-linked immunosorbent assay was used to detect serum levels of IFN-γ, and radioimmunoassay was utilized to determine serum TNF-α level. Neurological scores were measured on a daily basis according to a 0-5 scale. RESULTS: Daily injections of OM, both high and low doses, resulted in decreased neurological scores in EAE rats (P〈0.01), as well as reduced cellular infiltration in the spinal cord and decreased levels of serum IFN-γ and TNF-α (P〈 0.01). CONCLUSION: OM reduced the onset and severity of EAE, which correlated with decreased IFN-γ and TNF-α expression.
文摘AIM:To investigate the possibility of shortening the duration of peginterferon(Peg-IFN)plus ribavirin(RBV) combination therapy by incorporating interferon-β (IFN-β)induction therapy. METHODS:A one treatment arm,cohort prospective study was conducted on seventy one patients.The patients were Japanese adults with genotype 1b chronic hepatitis C,HCV-RNA levels of≥5.0 Log IU/mL or 100 KIU/mL,and platelet counts of≥90 000/μL.The treatment regimen consisted of a 2 wk course of twicedaily administration of IFN-βfollowed by 24 wk PegIFN plus RBV combination therapy.We prolonged the duration of the Peg-IFN plus RBV therapy to 48 wk if the patient requested it. RESULTS:The patients,including 44%males,were characterized by an median age of 63 years(range: 32-78 years),an median platelet count of 13.9(range: 9.1-30.6)×10 4 /μL,62%IFN-na?ve,and median HCV- RNA of 6.1(range:5.1-7.2)Log IU/mL.The sustained virologic response(SVR)rates were 34%(Peg-IFN:1-24 wk,n=61,95%confidence interval(CI): 24%-47%)and 55%(Peg-IFN:20-24 wk,n=31,95% CI:38%-71%,P<0.001;vs Peg-IFN:1-19 wk).TheSVR rate when the administration was discontinued early was 13%(Peg-IFN:1-19 wk,n=30,95%CI: 5%-30%),and that when the administration was prolonged was 50%(Peg-IFN:25-48 wk,n=10,95% CI:24%-76%,P<0.05;vs Peg-IFN:1-19 wk).In the patients who received 20-24 wk of Peg-IFN plus RBV,only the higher platelet count(≥130 000/μL) was significantly correlated with the SVR(odds ratio: 11.680,95%CI:2.3064-79.474,P=0.0024).In 45% (14/31)of the patients with a higher platelet count (≥130000/μL)before therapy,the HCV-RNA level decreased to below 3.3 Log IU/mL at the completion of IFN-β,and their SVR rate was 93%(13/14)after 20-24 wk administration of Peg-IFN plus RBV. CONCLUSION:These results suggest the possibilities of shortening the duration of Peg-IFN plus RBV combination therapy by actively reducing HCV-RNA levels using the IFN-βinduction regimen.
文摘Atherosclerosis is a chronic inflammatory disorder of the vasculature and is the primary cause of cardiovascular disease(CVD). CVD is currently the world's leading cause of death and the numbers are predicted to rise further because of a global increase in risk factors such as diabetes and obesity. Current therapies such as statins have had a major impact in reducing mortality from CVD. However, there is a marked residual CVD risk in patients on statin therapy. It is therefore important to understand the molecular basis of this disease in detail and to develop alternative novel therapeutics. Interferon-γ(IFN-γ) is a pro-inflammatory cytokine that is often regarded as a master regulator of atherosclerosis development. IFN-γ is able to influence several key steps during atherosclerosis development, including pro-inflammatory gene expression, the recruitment of monocytes from the blood to the activated arterial endothelium and plaque stability. This central role of IFN-γ makes it a promising therapeutic target. The purpose of this editorial is to describe the key role IFN-γ plays during atherosclerosis development, as well as discuss potential strategies to target it therapeutically.
基金Supported by National High Technology Research and Development Program of China,No.2007AA02Z151 to Lu J
文摘We report a case of severe thrombocytopenia following pegylated interferon-α 2a(Peg-IFN-α 2a)treatment of hepatitis C virus infection and summarize the clinical characteristics of 16 cases of IFN-α induced severe thrombocytopenia and its immune-mediated mechanism.Discontinuation of IFN-α and early administration of immunosuppressants are the effective therapy for IFN-αinduced severe thrombocytopenia.