OBJECTIVE To study the influence and mechanism of gamma-IFN on fibroblasts in hypertrophic scars(HTS). METHODS The cultured fibroblastic cells were isolated from the hypertrophic scars of 10 patients. The fibroblasts were divided into two groups, one group was treated with gamma-IFN (100 U/ml, 5 days) and the other without gamma-IFN as control. The proliferative activity in both groups was investigated and compared by blood cytometer, the proportion of myofibroblast (MFB) and the ratio of apoptosis were examined and analysed between two groups by flow cytometry using alpha-smooth muscle actin (alpha-SMA) as marker. RESULTS The proliferative activity was downregulated with gamma-IFN. In gamma-IFN treated group, the differentiation of MFB were reduced and the decreasing ratio was 3.2% at the 2nd day and up to 10.5% at the 8th day, then it reduced gradually. The apoptosic ratio is 17.7% in gamma-IFN treated group, and is 10.9% in control group. The difference was statistically significant. CONCLUSION gamma-IFN could downregulate the proliferation of fibroblasts, decrease the differentiation of MFB and induce the apoptosis. It has beneficial effect in the treatment of hypertrophic scars(HTS).
Objective To investigate the effects of gamma;-interferon (IFN-gamma; on the expression of costimulatory molecules B7-1 (CD80) and B7-2 (CD86) and Fas/FasL in human retina. Methods Nine human eyes were obtained from the eye-bank of Zhongshan Ophthalmic Center. Six eyes were used for making retinal wholemounts, and 12 retinal wholemounts from each eye were put into the 24-hole culture board which had 2ml DMEM/F12 culture medium in each hole. The wholemounts were divided into 3 groups whose concentration of IFN-gamma; was 0, 200, and 1000 U/ml respectively. After cultured in 37℃ culture box (95%O 2，5%CO 2) for 24 hours, the expressions of B7-1 (CD80), B7-2 (CD86), and Fas/FasL on these retinal wholemounts were detected by immunohistochemical method. The retinal wholemounts from 3 healthy people were detected by immunohistochemical method as the control. Results Expression of FasL but not B7-1, B7-2 or Fas was found in the control group, while the expression of B7-1, B7-2 and Fas and increased expression of FasL were found after cultured with IFN-gamma;. Conclusion IFN-gamma; may be involved in the occurrence of ocular immune response and induction of apoptosis via the stimulation of expression of costimulatory molecules and Fas/FasL, which plays an important role in the activation of T lymphocytes. (Chin J Ocul Fundus Dis, 2006, 22: 117-119)
Objective To assess the efficacy between Peginterferon α-2a and common Interferon in HBeAg positive chronic hepatitis B. Methods MEDLINE, EBSCO, PubMed, CNKI, WangFang were searched from the beginning to May 2009, and the references of eligible studies were manually screened. Randomized controlled trials comparing Peginterferon-alpha2a with common interferon in HBeAg positive chronic hepatitis B were eligible for inclusion. Jadad score method was adopted to evaluate the methodological quality of included studies. Meta analysis was conducted by RevMan 5.0 software supplied by the Cochrane Collaboration. Subgroup analyses were used in treatment and observation course. Results Six randomized controlled trials were included (n=688). The treatment duration of 48 weeks and 24 weeks were reported in four and two studies, respectively. We carried out subgroup analysis according to treatment. Meta-analysis showed that Peginterferon-alpha2a (180 ug/d, 48 W) could significantly clear HBeAg, clear HBVDNA, normalize ALT and HBeAg seroconversion compared with common Interferon (Plt;0.05). Peginterferon-alpha2a (180 ug/d, 24 W) could effectively clear HBV DNA [P=0.04, RR=1.44, 95%CI (1.01, 2.05)], but was not effective in loss of HBeAg, HBeAg seroconversion and ALT normalization (Pgt;0.05). Conclusion The efficacy of 48 weeks treatment with Peginterferon α-2a is better than common Interferon. The efficacy of 24 weeks treatment with Peginterferon α-2a is only better in HBV-DNA negative rate than common Interferon. However, because the methodological quality of included studies is not high, this conclusion should be carefully considered in clinical use.
Expression conditions of induction strategies for the cytoplasmic inclusion bodies (IBs) production of liver targeted interferon IFN-CSP by recombinant Escherichia coli (E.coli) BL21(DE3) were optimized in shake-flask cultures in this study. The factors of the optimized protocol included in the present study were pH, inducer IPTG (isopropyl β-D-thiogalactoside) concentration, culture growth temperature, incubation time and induction point. The effects of those factors were investigated by ‘single variable at a time’ method, aimed to analyze characterization of the recombinant strain. Orthogonal experimental design was further used to optimize the above critical factors for IFN-CSP production. According to the expression optimization result, it was confirmed that the main influence factors were cell density and induction temperature. The IFN-CSP gene expression optimized conditions were:pH value of the culture medium was 6.0, culture temperature 37℃, adding IPTG to final concentration 0.4 mmol/L when the recombinant strain growth density OD600 achieved 0.8 and induction time 4 h. At this point, the IBs represented 74.3% of the total cellular protein. Compared with the non-optimized condition, IFN-CSP production obtained in optimized induction strategies were increased by approx. 1.2-fold. The optimized induction strategy yielded 688.8 mg/L of IFN-CSP, providing experimental data to study the biology activity and productive technology of IFN-CSP.
PEGylating is an effective way for prolonging the half-time period and decreasing the immunogenicity of protein drugs. With experiments of single factor, it was proved that the optimal processes for PEGylating the fused protein of LL-37 and interferon (IFN)-α2a were:PEG molecular weight was 5 000, fused protein concentration was 0.6 mg/mL, the mole ratio of protein to mPEG5000-SS was 1:10, the reaction temperature was 4℃, and the pH was 9.0, respectively. With orthogonal experiments, we proved that the influential order of 3 main factors is:the fused protein concentration > the mole ratio of protein and mPEG5000-SS > pH and the optimal conditions were the fused protein concentration as 0.6 mg/mL, the mole ratio of protein and mPEG5000-SS as 1:10, pH as 8.8. Under these optimal conditions, the average rate of PEGylated protein with 3 times parallel experiments was 86.98%. After PEGylated, the interferon activity and antimicrobial activity of fused protein could be remained higher than 58% and 97%, respectively.
ObjectiveTo evaluate the clinical manifestation, radiological, pathological features and treatment of organizing pneumonia (OP) induced by aerosolized recombinant super compound interferon (rSIFN-co). MethodsClinical features and related laboratory examinations of a patient with OP developing after initiation of rSIFN-co for treatment of lung adenocarcinoma were analyzed, and the relevant literature was reviewed. ResultsA 48-year-old man developed cough, fevers, shortness of breath and weight loss, shortly half a month after initiation of therapy with rSIFN-co for lung adenocarcinoma. Chest high resolution computerized tomography (HRCT) showed multiple lung infection diseases. However, the anti-infection treatment was invalid. Lung tissue biopsy by bronchofibroscope was consistent with OP. After discontinuation of rSIFN-co and receiving pulse corticosteroid therapy followed by oral methylprednisolone, the pneumonic symptoms and chest manifestations markedly improved. After eight-month follow-up, the patient's condition was stable. The relative literature screening from Pubmed and Wanfangdata was implemented, but there was no report about OP caused by aerosolized rSIFN-co for lung adenocarcinoma. ConclusionThis report suggests that treatment with aerosolized rSIFN-co for lung adenocarcinoma may induce OP, a rare complication, and clinicians should have vigilance on it.
ObjectiveTo systematically review the efficacy of peginterferon alpha (PEG-IFNα) initially combined with lamivudine (LAM) or adefovir (ADV) in treatment of HBeAg-positive chronic hepatitis B (CHB) patients. MethodsWe electronically searched databases including The Cochrane Library (Issue 11, 2014), PubMed, CBM, CNKI, VIP, and WanFang Data from inception to December 2014, to collect randomized controlled trials (RCTs) about PEG-IFNα initially combined with LAM or ADV for HBeAg-positive CHB. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed by using RevMan 5.2 software. ResultsA total of 11 RCTs involving 2031 patients were included. The results of meta-analysis showed that: After 48 weeks of treatment, the HBsAg seroconversion rate of the PEG-IFNα plus ADV group was significantly higher than that of the PEG-IFNα monotherapy group (8.6% vs. 0%, OR=7.73, 95%CI 1.53 to 39.05, P=0.01) or the ADV monotherapy group (8.5% vs. 0%, OR=7.75, 95%CI 1.07 to 56.23, P=0.04); and the HBsAg seroclearance rate in the combination therapy group was significantly higher than that of the ADV monotherapy group (10.5% vs. 1.2%, OR=5.56, 95%CI to 2.14 to 14.47, P=0.0004). After 52 weeks of treatment, the HBsAg seroconversion rate of the PEG-IFNα plus LAM group was significantly higher than that of the PEG-IFNα monotherapy group (11.6% vs. 5.6%, OR=2.21, 95%CI 1.04 to 4.72, P=0.04). After 26 weeks of follow-up, no significant differences were found between the combination therapy group and the PEG-IFNα monotherapy group in HBsAg seroclearance rate and HBsAg seroconversion rate (all P values >0.05). ConclusionCurrent evidence shows that, compared with PEG-IFNα, LAM, or ADV monotherapy, PEG-IFNα plus LAM or ADV could improve the HBsAg seroclearance or seroconversion rate after 48-52 weeks of treatment for HBeAg-positive CHB, but this effect is still limited. Due to the limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.
ObjectiveTo observe effect of interferon-γ in preventing intestinal adhesion following abdominal surgery in rats.MethodsA total of 60 Wistar rats were selected, which were randomly divided into a sham operation (SO) group, model group, dexamethasone (DXMS) group, and interferon-γ group, then the interferon-γ group was randomly divided into a low, medium, and high concentrations subgroups. Except for the SO group, the laparotomies with file friction caecum were performed for all the other groups to establish the intestinal adhesion model. SO group and model group were intraperitoneally injected with saline for 4 mL/kg. The 10 mg/kg dexamethasone was injected into the abdominal cavity of rats in the DXMS group. The 7.5×104, 1.5×105, and 3.0×105 U/kg interferon-γ concentrations were injected into the abdominal cavity of rats in the low, medium, and high concentrations subgroups respectively. The Nair grading of cecum adhesion degree was assessed on the 8th day after the surgery, then the histopathological change was observed by the HE staining under the microscopy and the hydroxyproline content in the cecum tissue was detected.Results① The intestinal adhesion: Compared with the SO group, the intestinal adhesions occurred in all the other groups and the degrees of intestinal adhesions evaluated by the Nair grading were more significantly serious (P<0.05), which in the DXMS group and the medium and high concentrations of interferon-γ subgroups were significantly reduced (P<0.05) as compared with the model group, which in the high concentration of interferon-γ subgroup was significantly reduced (P<0.05) as compared with the DXMS group. ② The microscopic observation of histopathological results: Compared with the DXMS group, the high concentration of interferon-γ could effectively reduce the occurrence of fibrous tissue and inflammatory cell infiltration, the intestinal wall muscular layer structure was complete, a few inflammatory cells scattered in the infiltration. ③ The hydroxyproline content: The contents of hydroxyproline in the cecum tissue of the model group, DXMS group, and interferon-γ subgroups were significantly increased (P<0.05) as compared with the SO group, which of the DXMS group and medium and high concentrations of interferon-γ subgroups were significantly decreased (P<0.05) as compared with the model group, which of the high concentration of interferon-γ subgroup was significantly decreased (P<0.05) as compared with the DXMS group.ConclusionInterferon-γ has a preventive and therapeutic effect on postoperative intestinal adhesion and cecum injuries.
ObjectivesTo systematically review the efficacy and safety of pegylated interferon α-2a (Peg-IFNα-2a) combined with entecavir (ETV) versus Peg-IFNα-2a alone in treatment of HBeAg-positive chronic hepatitis B (CHB) patients.MethodsThe Cochrane Library, PubMed, Web of Science, EMbase, CNKI, VIP and WanFang Data databases were electronically searched to collect randomized controlled trials (RCTs) on Peg-IFNα-2a combined with ETV for HBeAg-positive CHB from inception to March, 2019. Two reviewers independently screened literature, extracted data and assessed risk of bias of included studies. Then, meta-analysis was performed by using RevMan 5.3 software.ResultsA total of 12 RCTs involving 1 130 patients were included. The results of meta-analysis showed that: compared with Peg-IFNα-2a monotherapy, Peg-IFNα-2a combined with ETV could improve the rate of serum HBV-DNA clearance (RR=2.55, 95%CI 1.83 to 3.55, P<0.000 01), ALT normalization (RR=2.37, 95%CI 1.76 to 3.20, P<0.000 01) and HBeAg seroconversion (RR=2.88, 95%CI 1.18 to 7.03, P=0.02) after 12 weeks of treatment. Additionally, it could improve the rate of serum HBV-DNA clearance (RR=2.10, 95%CI 1.74 to 2.53, P<0.000 01), AST normalization (RR=1.87, 95%CI 1.15 to 3.04, P=0.01), ALT normalization (RR=1.70, 95%CI 1.46 to 1.99, P<0.000 01), serum HBeAg clearance (RR=2.14, 95%CI 1.62 to 2.83, P<0.000 01), HBeAg seroconversion (RR=2.51, 95%CI 1.65 to 3.82, P<0.000 01) and serum HBsAg clearance (RR=2.78, 95%CI 1.06 to 7.31, P=0.04) after 24 weeks of treatment. It could also improve the rate of serum HBV-DNA clearance (RR=1.63, 95%CI 1.32 to 2.02, P<0.000 01), AST normalization (RR=2.75, 95%CI 1.82 to 4.16, P<0.000 01), ALT normalization (RR=1.47, 95%CI 1.33 to 1.63, P<0.000 01), serum HBeAg clearance (RR=1.65, 95%CI 1.42 to 1.91, P<0.000 01), HBeAg seroconversion (RR=1.91, 95%CI 1.51 to 2.41, P<0.000 01) and serum HBsAg clearance (RR=1.57, 95%CI 1.07 to 2.31, P=0.02) after 48 weeks of treatment. There was no statistically significance of adverse reactions in groups.ConclusionsCurrent evidence shows that Peg-IFNα-2a combined with ETV is superior to Peg-IFNα-2a monotherapy in the treatment of HBeAg-positive CHB, and does not increase the incidence of adverse reactions. Due to the limited quality and quantity of the included studies, more high quality studies are required to verify the above conclusion.
ObjectiveTo explore the functional heterogeneity of T lymphocytes in various organs after SARS-CoV-2 infection. Methods Using the public database GEO data (GSE171668, GSE159812, GSE159556, GSE167747) and the analysis method of single-cell technology, the functional differences of T lymphocytes in various organs of patients after infection with SARS-CoV-2 were analyzed. Results Through single-cell data extraction of 16 livers, 19 hearts,2 spleens, 6 brains, 58 lungs, 21 kidneys and 5 pancreases from SARS-CoV-2 infected patients, invasion genes were relatively highly expressed in T lymphocytes of the lung and pancreas. The lung had a special ability to express the interferon signaling pathway, while the expression of other organs was relatively low; at the same time, the T lymphocytes of the lung also highly expressed fatty acid binding sites. Conclusion After SARS-CoV-2 infection, compared with other organs, the lung has a special interferon-activated signaling pathway and fatty acid binding site.