The canonical signaling of interferon gamma(IFN-γ)through the Janus kinase 1 and 2–signal transducer and activator of transcription 1(STAT1)axis leads to the expression of several interferon-stimulated genes(ISGs),w...The canonical signaling of interferon gamma(IFN-γ)through the Janus kinase 1 and 2–signal transducer and activator of transcription 1(STAT1)axis leads to the expression of several interferon-stimulated genes(ISGs),which have diverse effects depending on the cellular context.In glioblastoma,a highly aggressive primary brain tumor in adults,elements of IFN-γcanonical signaling are deregulated,resulting in the overexpression of STAT1-target ISGs associated with tumor progression.This mini-review highlights key ISGs,including STAT1,interferon regulatory factor 1,programmed death-ligand 1,indoleamine 2,3-dioxygenase 1,and interferon-stimulated gene 15,involved in the pathology of glioblastoma.These genes may serve as valuable biomarkers and have therapeutic potential for targeting IFN-γsignaling in this malignancy.展开更多
AIM: To evaluate the antifibrotic effect of different doses of recombinant human Gamma-Interferon (IFN-gamma) in two rat models of hepatic fibrosis, and to observe its effect on moderate chronic hepatitis B virus fibr...AIM: To evaluate the antifibrotic effect of different doses of recombinant human Gamma-Interferon (IFN-gamma) in two rat models of hepatic fibrosis, and to observe its effect on moderate chronic hepatitis B virus fibrosis. METHODS: Hepatic fibrosis was successfully induced in 150 and 196 rats by subcutaneous injection of carbon tetrachloride (CCl4) and intraperitoneal injection of dimethylnitrosamine (DMN), respectively. Each of the two model groups was divided into: (1) fibrotic model group; (2) colchicine treatment group (0.1 mg/kg/day, gastrogavage for 8 weeks); (3) high-dose IFN-gamma group (15 MU/kg per day, i.m. for 8 weeks); (4) medium-dose IFN-gamma group (5 MU/kg daily, i.m. for 8 weeks); and (5) Y low-dose IFN-gamma group (1.67 MU/kg daily, i.m. for 8 weeks). Another group of 10 rats without any treatment was used as normal controls. At the end of the experiment, semi-quantitative histopathological scores of inflammation and fibrosis, liver alpha smooth muscle actin (alpha-SMA) expression level, liver hydroxyl proline content and serum hyaluronic acid levels were compared. And 47 medium chronic hepatitis B viral fibrosis patients were studied. They were given IFN-gamma treatment, 100 MU/day i.m. for the first three months and 100 MU qod i.m. for the next six months. Semi-quantitative pathological scores of inflammation and fibrosis and serum hepatic fibrosis indices were compared within the 9 months. RESULTS: In animal experiment, the pathological fibrosis scores and liver hydroxyl proline content were found to be significantly lower in rats treated with different doses of IFN-gamma as compared with rats in fibrotic model group induced by either CCl4 or DMN, in a dose-dependent manner. For CCl4-induced model, pathological fibrosis scores in high, medium and low doses IFN-gamma groups were 5.10 +/- 2.88, 7.70 +/- 3.53 and 8.00 +/- 3.30, respectively, but the score was 14.60 +/- 7.82 in fibrotic model group. Hydroxyl proline contents were 2.83 +/- 1.18, 3.59 +/- 1.22 and 4.80 +/- 1.62, in the three IFN-gamma groups, and 10.01 +/- 3.23 in fibrotic model group. The difference was statistically significant (P【0.01). Similar results were found in DMN-induced model. Pathological fibrosis scores were 6.30 +/- 0.48, 8.10 +/- 2.72 and 8.30 +/- 2.58, in high, medium and low doses IFN-gamma groups, and 12.60 +/- 3.57 in fibrotic model group. Hydroxyl proline contents were 2.72 +/- 0.58, 3.14 +/- 0.71 and 3.62 +/- 1.02, in the three IFN-gamma groups, and 12.79 +/- 1.54 in fibrotic model group. The difference was statistically significant (P【0.01).Serum hepatic fibrosis indices decreased significantly in the 47 patients after IFN-gamma treatment (HA: 433.38 +/- 373.00 vs 281.57 +/- 220.48; LN: 161.22 +/- 41.02 vs 146 +/- 35 +/- 44. 67; PC III: 192.59 +/- 89.95 vs 156.98 +/- 49.22; C-I: 156.30 +/- 44.01 vs 139.14 +/- 34.47) and the differences between the four indices were significant (P 【0.05). Thirty-three patients received two liver biopsies, one before and one after IFN-gamma treatment. In thirty of 33 patients IFN-gamma had better effects according to semi-quantitative pathological scores (8.40 +/- 5.83 vs 5.30 +/- 4.05, P【0.05). CONCLUSION: All the three doses of IFN-gamma are effective in treating rat liver fibrosis induced by either CCl4 or DMN, the higher the dose, the better the effect. And IFN-gamma is effective for patients with moderate chronic hepatitis B viral fibrosis.展开更多
AIM:To investigate the performance and diagnostic accuracy of interferon-gamma(IFN-γ) for tuberculous peritonitis(TBP) by meta-analysis.METHODS:A systematic search of English language studies was performed.We searche...AIM:To investigate the performance and diagnostic accuracy of interferon-gamma(IFN-γ) for tuberculous peritonitis(TBP) by meta-analysis.METHODS:A systematic search of English language studies was performed.We searched the following electronic databases:MEDLINE,EMBASE,Web of Science,BIOSIS,LILACS and the Cochrane Library.The Standards for Reporting Diagnostic Accuracy initiative and Quality Assessment for Studies of Diagnostic Accuracy tool were used to assess the methodological quality of the studies.Sensitivity,specificity,and other measures of the accuracy of IFN-γ concentration in the diagnosis of peritoneal effusion were pooled using random-effects models.Receiver operating characteristic(ROC) curves were applied to summarize overall test performance.Two reviewers independently judged study eligibility while screening the citations.RESULTS:Six studies met the inclusion criteria.The average inter-rater agreement between the two reviewers for items in the quality checklist was 0.92.Analysis of IFN-γ level for TBP diagnosis yielded a summary estimate:sensitivity,0.93(95%CI,0.87-0.97);specificity,0.99(95%CI,0.97-1.00);positive likelihood ratio(PLR),41.49(95%CI,18.80-91.55);negative likelihood ratio(NLR),0.11(95%CI,0.06-0.19);and diagnostic odds ratio(DOR),678.02(95%CI,209.91-2190.09).χ 2 values of the sensitivity,specificity,PLR,NLR and DOR were 5.66(P = 0.3407),6.37(P = 0.2715),1.38(P = 0.9265),5.46(P = 0.3621) and 1.42(P = 0.9220),respectively.The summary receiver ROC curve was positioned near the desirable upper left corner and the maximum joint sensitivity and specificity was 0.97.The area under the curve was 0.99.The evaluation of publication bias was not significant(P = 0.922).CONCLUSION:IFN-γ may be a sensitive and specific marker for the accurate diagnosis of TBP.The level of IFN-γ may contribute to the accurate differentiation of tuberculosis(TB) ascites from non-TB ascites.展开更多
AIM:To investigate the clinical usefulness of interferon-gamma release assays(IGRAs)in the differential diagnosis of intestinal tuberculosis(ITB)from Crohn’s disease(CD)by meta-analysis.METHODS:A systematic search of...AIM:To investigate the clinical usefulness of interferon-gamma release assays(IGRAs)in the differential diagnosis of intestinal tuberculosis(ITB)from Crohn’s disease(CD)by meta-analysis.METHODS:A systematic search of English language studies was performed.We searched the following databases:Medline,Embase,Web of Science and the Cochrane Library.The Standards for Reporting Diagnostic Accuracy initiative and Quality Assessment for Studies of Diagnostic Accuracy tool were used to assess the methodological quality of the studies.Sensitivity,specificity,and other measures of the accuracy of IGRAs in the differential diagnosis of ITB from CD were pooled and analyzed using random-effects models.Receiver operating characteristic curves were applied to summarize overall test performance.Two reviewers independently judged study eligibility while screening the citations.RESULTS:Five studies met the inclusion criteria.The average inter-rater agreement between the two reviewers for items in the quality checklist was 0.95.Analysis of IGRAs for the differential diagnosis of ITB from CD produced summary estimates as follows:sensitivity,0.74(95%CI:0.68-0.80);specificity,0.87(95%CI:0.82-0.90);positive likelihood ratio,5.98(95%CI:3.79-9.43);negative likelihood ratio,0.28(95%CI:0.18-0.43);and diagnostic odds ratio,26.21(95%CI:14.15-48.57).The area under the curve was 0.92.The evaluation of publication bias was not significant(P=0.235).CONCLUSION:Although IGRAs are not sensitive enough,they provide good specificity for the accurate diagnosis of ITB,which may be helpful in the differential diagnosis of ITB from CD.展开更多
Objective:To evaluate the performance of interferon gamma release assays and tuberculin skin test in HIV-infected children and adolescents with immune reconstitution.Methods:A cross-sectional study was conducted in HI...Objective:To evaluate the performance of interferon gamma release assays and tuberculin skin test in HIV-infected children and adolescents with immune reconstitution.Methods:A cross-sectional study was conducted in HIV-infected patients aged 5-18 years receiving antiretroviral treatment with CD4 T-lymphocytes>25%or>500 cells/mm3 for at least 6 months.QuantiF ERON-TB Gold,T-SPOT.TB,and tuberculin skin test were performed in each patient.Results:A total of 50 patients were enrolled with median age of 13.7 years,CD4 counts of 753(IQR:587-989)cells/mm3.Among 27 patients with tuberculosis(16)or tuberculosis exposure(11),8(29.6%)were positive to at least one test,2(7.4%)were positive QuantiFERON-TB Gold,3(11.1%)positive T-SPOT.TB,and 7(25.9%)had tuberculin skin test≥5 mm.Among 23 patients without history of tuberculosis or exposure,all had negative interferon gamma release assays,while 2(8.7%)had positive tuberculin skin test.Conclusions:All tests had low sensitivity despite immune reconstitution.展开更多
BACKGROUND:Fibrosis plays a key role in the development of liver cirrhosis.In this study,we investigated the effect of growth hormone and interferon gamma on hepatic collagen synthesis and the proliferation of hepatic...BACKGROUND:Fibrosis plays a key role in the development of liver cirrhosis.In this study,we investigated the effect of growth hormone and interferon gamma on hepatic collagen synthesis and the proliferation of hepatic stellate cells in a cirrhotic rat model.METHODS:Cirrhosis was induced in rats using carbon tetrachloride.Rats were simultaneously treated with daily subcutaneous injections of recombinant human growth hormone or interferon gamma combined with recombinant human growth hormone.The control group was given saline.The relative content of type I and type IV collagen was assessed by indirect immunofluorescence analysis.Activated hepatic stellate cells were prepared from cirrhotic rats.The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide(MTT)method was used to assess the effects of recombinant human growth hormone and interferon gamma on these cells in vitro.RESULTS:Both qualitative and quantitative analysis showed that type I and type IV collagen secretion increased with time after recombinant human growth hormone administration and was significantly higher than control and recombinant human growth hormone combined with interferon gamma administration.In vitro,recombinant human growth hormone significantly stimulated hepatic stellate cell proliferation in a concentration-dependent manner(10-3-10-1 mg/100μL),andinterferon gamma(10-2-10-1μg/100μL)significantly inhibited their growth compared to the control group.Interferon gamma combined with recombinant human growth hormone eliminated this growth-promoting effect to a certain degree in a concentration-dependent manner(10-1μg/100μL,P<0.05,10-2-10-3μg/100μL,P>0.05)and a time-dependent manner(P<0.05).CONCLUSIONS:Recombinant human growth hormone increased collagen secretion in cirrhotic rats in vivo and promoted the proliferation of hepatic stellate cells from cirrhotic rats in vitro.It is possible that concurrent interferon gamma therapy can offset these side-effects of recombinant human growth hormone.展开更多
AIM: To explore the effect of immunization with copolymer-1 (COP-1) and retinal stem cells (RSCs) transplantation on interferon-gamma (IFN-gamma) levels in a rat experimental glaucoma model. METHODS: An experimental g...AIM: To explore the effect of immunization with copolymer-1 (COP-1) and retinal stem cells (RSCs) transplantation on interferon-gamma (IFN-gamma) levels in a rat experimental glaucoma model. METHODS: An experimental glaucoma was induced by argon laser photocoagulation of the episcleral veins and limbal plexus in the right eye of rats. Immediately following glaucoma induction, rats were immunized with COP-1. RSCs were cultured and transplanted intravitreally into the eyes of glaucoma model animals 1 week post-laser treatment. Six experimental groups were used: COP-1/RSC, PBS/RSC, COP-1/PBS, PBS/PBS, glaucoma model group, and a normal control group. The concentration of IFN-gamma in aqueous humor (AH) and serum was measured by enzyme-linked immunosorbent assay (ELISA) in each of the six groups. Retinal ganglion cell (RGC) survival was assessed by quantifying apoptosis using Hoechst staining. RESULTS: Concentrations of IFN-gamma in AH and serum of rats that had undergone glaucoma induction were higher than those of non-induced control rats. The concentrations of IFN-gamma in AH and serum of the COP-1/RSCs treated group were determined to be 2371.9ng/L and 710.9ng/L, respectively, which were significantly lower than those in the other treated groups (P<0.05). In fact, IFN-gamma levels in the dual treated group were reduced to background levels. The COP-1/RSC group had lower number of apoptotic RGCs than the other three experimental groups (P<0.05). CONCLUSION: The reduced levels of IFN-gamma in AH and serum of the COP-1/RSC group may be related to synergistic effects between RSCs transplantation and COP-1 immune modulation. It is likely that the lower levels of IFN-gamma prevented RGCs glaucomatous apoptasis.展开更多
Capillary electrophoretic immunoassay with laser-induced fluorescence detection for recombinant human interferon-gamma (IFN-g) was established. The limits of detection for three forms of IFN-g are 6.9 ng/L, 5.7 ng/L ...Capillary electrophoretic immunoassay with laser-induced fluorescence detection for recombinant human interferon-gamma (IFN-g) was established. The limits of detection for three forms of IFN-g are 6.9 ng/L, 5.7 ng/L and 5.0 ng/L, respectively.展开更多
Objective:To determine the relationship of the capacity to produce interferon gamma(IFN-γ) in whole blood,bacteriological,hematological,radiographic and clinical presentations in new,HIV seronegative cases of pulmona...Objective:To determine the relationship of the capacity to produce interferon gamma(IFN-γ) in whole blood,bacteriological,hematological,radiographic and clinical presentations in new,HIV seronegative cases of pulmonary tuberculosis(TB).Methods:80 cases and 50 control subjects aged 15 years onwards,representative of Kasturba Hospital and Nursing schools of Wardha district of Maharashtra state in India were examined for their health condition with standard methodology.Results:Among these TB patients,73.8%were Quantiferon-TB gold (QFT) positive with IFN-γconcentration as 0.35 IU or more and there was none in healthy controls.The mean IFN-γconcentrations varied between 9.58 IU(50-59 yrs) and 2.58 IU(≥60 yrs),showing no trend.The differences in positivity and mean IFN-γconcentrations were statistically insignificant.Both the QFT positivity and IFN-γconcentrations were higher in normal lymphocyte percent as compared to below and above normal,but differences were not statistically significant.Conclusions:The IFN-γconcentrations are not correlated with any of the predictors of disease severity studied,the levels are significantly higher in observation group as compared to healthy group.展开更多
BACKGROUND： Neuropeptide Y （NPY） may influence differentiation of Th cells immunological pathology of experimental allergic encephalomyelitis （EAE） is differentiation of Th cells It is assumed that the related to...BACKGROUND： Neuropeptide Y （NPY） may influence differentiation of Th cells immunological pathology of experimental allergic encephalomyelitis （EAE） is differentiation of Th cells It is assumed that the related to abnormal OBJECTIVE： To investigate the effect of NPY on white matter demyelination, the serum levels interleukin-4 （IL-4） and gamma-interferon （IFN-γ ）, as well as EAE pathogenesis in an EAE guinea pig model following NPY injection into the lateral cerebral ventricle. DESIGN, TIME AND SETTING： A randomized controlled animal study, which was performed in the Infection Immunity Animal Laboratory, Affiliated Hospital of Luzhou Medical College, China, from October 2005 to April 2006. MATERIALS： Thirty healthy female guinea pigs of 8-12 weeks of age, and 10 healthy female rats of three months of age were used. NPY was provided by Sigma Company, USA. NPY kit was provided by Beijing Huaying Biotechnology Institute, China. METHODS： Thirty guinea pigs were randomly divided into three groups： normal control group, EAE model group, and NPY intervention group （n =10 per group）. Normal control group and EAE model group： Saline （10μ L, once） was injected into the lateral cerebral ventricle. After one week, the same volume of Freund＇s adjuvant complete was either injected subcutaneously into two post-palms or EAE was modeled. NPY intervention group： EAE was modeled after one week and NPY was injected （10 μ L of 6 nmol NPY, once） into the lateral cerebral ventricle. Myelin basic protein （MBP） antigen made from rat spinal cord homogenate and Freund＇s adjuvant complete were injected subcutaneously into both post-palms （0.2 mL per palm） to establish the EAE model. MAIN OUTCOME MEASURES： White matter demyelination of the cerebrum, cerebellum, brain stem, and spinal cord were observed by light microscopy after HE staining. Levels of serum IFN-γ and IL-4 were detected by the double antibody sandwich ABC-ELISA technique. NPY content was detected by radioimmunoassay. RESULTS： Pathological alterations in the NPY intervention groups were reduced compared to those in the EAE model group, suggesting a reduction and remission of white matter demyelination with NPY treatment. When compared to the model group, the serum IL-4 level was increased in the NPY intervention group during the high-frequent EAE stage （P 〈 0.01）, but the serum IFN-γ level was decreased （P 〈 0.01）. Furthermore, the EAE latency was prolonged （P 〈 0.01）, the neurological scores were decreased in the high-frequent EAE stage （P 〈 0.01）, and the death rate was decreased （P 〈 0.05）. NPY content and the serum IL-4 level at the peak stage were positively correlated with those in the latent phase （r =0.863-0.900, P 〈 0.01）, but negatively correlated with neurological scores at the peak stage （r=- -0.068 to -0.863, P 〈 0.05-0.01）. The IFN-γ level at the peak stage was negatively correlated to that in the latent phase （r = -0.683-0.650, P 〈 0.05）, but positively correlated to neurological scores at the peak stage （r =0.975, 0.845, P 〈 0.05）. CONCLUSION： NPY injection into the lateral cerebral ventricle can promote the secretion of IL-4, inhibit the production of IFN-γ, relieve white matter demyelination, and inhibit EAE attack in an experimental model of EAE.展开更多
Objective: To develop a gold nanoparticles complex conjugated with interferon-gamma(IFN-g) and methionine along with application of hyperthermia using near-infrared laser beams for the treatment of cancer cells.Method...Objective: To develop a gold nanoparticles complex conjugated with interferon-gamma(IFN-g) and methionine along with application of hyperthermia using near-infrared laser beams for the treatment of cancer cells.Methods: Gold nanorods(10 nm) were conjugated with IFN-g and methionine using carbodiimide family and characterized after purification by dialysis bags. Breast cancer cells were cultured and incubated with gold nanorods at different concentrations followed by irradiation with near-infrared laser beam. Samples were then evaluated for their viability in order to determine the effect of treatment and variables by MTT assy.Results: Zetasizer results confirmed the conjugation of gold nanorods with methionine and IFN-g. The median percentage of cell viability in 0.30 mg/m L concentration of gold nanorods was 82%. The cell viability reached to 85% at the same concentration of gold nanorods, which existed in the assayed complex. The results of MTT assay showed that the 0.60 mg/m L concentration of gold nanoparticles complex was toxic on tumor cells(P < 0.05). After exposure to hyperthermia, the viability of cells at 6 min decreased to77% in 0.30 mg/m L concentration of gold nanorods complex.Conclusions: The size and concentration of gold nanorods was not cytotoxic. However,their presence during irradiation near-infrared laser increased the number of dead cells during the treatment of cells.展开更多
Background: This study aimed to evaluate the diagnostic value of interferon-γ release assay (IGRA), a sensitive microbiological diagnostic method, in children and adolescents with suspected tuberculosis in a country ...Background: This study aimed to evaluate the diagnostic value of interferon-γ release assay (IGRA), a sensitive microbiological diagnostic method, in children and adolescents with suspected tuberculosis in a country with a high burden of tuberculosis. Method: This study included 581 children and adolescents aged 4 - 19 years who were suspected of having tuberculosis, were latently infected with Mycobacterium tuberculosis, and had received at least one dose of BCG vaccine between April 17, 2019, and February 24, 2021. The study evaluated the TST results of 106 patients who had a positive Quantiferon test and were suspected of having tuberculosis. Results: The study included 581 patients aged between 4 and 19 years. Of these, 106 patients tested positive for the Quantiferon test, while 19 were indeterminate and 456 were negative. The Quantiferon test positivity rate was 18.24%. Among the 106 QFT-Plus-positive cases, 23 patients also tested positive for TST. The difference in distribution was found to be statistically significant. Conclusion: The QFT-Plus test is considered an alternative to TST and other microbiological diagnostic methods for early tuberculosis diagnosis, particularly in children and adolescents.展开更多
Introduction: Tuberculosis (TB) remains a significant public health challenge, particularly in high-endemicity settings where latent TB infections (LTBI) contribute to ongoing transmission. Early identification and ma...Introduction: Tuberculosis (TB) remains a significant public health challenge, particularly in high-endemicity settings where latent TB infections (LTBI) contribute to ongoing transmission. Early identification and management of LTBI are crucial in limiting the spread of the disease. This study demonstrates the role of Interferon Gamma Release Assay (IGRA) as a screening tool for latent tuberculosis in high-burden region. Materials and Methods: This retrospective observational study assessed the detection of LTBI using the QuantiFERON-TB Gold Plus (QFT-Plus) test among 145 patients at the Department of Microbiology & Immunology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh, from August 2023 to August 2024. The study included patients suspected of TB, those screened before immunosuppressive therapy, organ transplantation, or kidney dialysis. Participants were tested IGRA using QFT-Plus, which detects interferon-gamma (IFN-γ) released in response to Mycobacterium tuberculosis antigens. Results and Discussion: Among 145 patients tested for the QFT-Gold Plus test, 55.17% (n = 80) were positive for LTBI, with a substantial agreement between TB1 and TB2 responses (p Conclusion: The results highlight that QFT-Plus may be utilized as a useful diagnostic screening tool for latent TB in regions with a high disease burden, though challenges related to cost and infrastructure persist. With growing global efforts to eliminate tuberculosis, focused screening and treatment of LTBI in high-risk groups could play a vital role in reducing the progression of TB. The study underscores the importance of targeted screening for LTBI to reduce the progression to active TB, particularly in resource-limited settings.展开更多
干扰素-γ诱导蛋白16(interferon gamma-inducible protein 16,IFI16)是含pyrin和造血表达、干扰素诱导特性和核定位(hematopoietic expression,interferon-inducible nature,and nuclear localization,HIN)结构域的蛋白质(pyrin and HI...干扰素-γ诱导蛋白16(interferon gamma-inducible protein 16,IFI16)是含pyrin和造血表达、干扰素诱导特性和核定位(hematopoietic expression,interferon-inducible nature,and nuclear localization,HIN)结构域的蛋白质(pyrin and HIN domain-containing protein,PYHIN)家族的重要成员,其独特的分子结构使其能够识别细胞内的多种核酸分子。作为一种关键的免疫调节因子,IFI16可通过多种途径参与天然免疫信号转导,在宿主抗病毒防御中发挥重要作用。本文综述了IFI16的分子特征及其在天然免疫和病毒感染中的调控机制,为抗病毒感染的治疗靶点及药物开发提供理论依据。展开更多
基金Supported by Colegio de Ciencia y Tecnología de la Universidad Autónoma de la Ciudad de México,No.CCYT-2025-CON-11.
文摘The canonical signaling of interferon gamma(IFN-γ)through the Janus kinase 1 and 2–signal transducer and activator of transcription 1(STAT1)axis leads to the expression of several interferon-stimulated genes(ISGs),which have diverse effects depending on the cellular context.In glioblastoma,a highly aggressive primary brain tumor in adults,elements of IFN-γcanonical signaling are deregulated,resulting in the overexpression of STAT1-target ISGs associated with tumor progression.This mini-review highlights key ISGs,including STAT1,interferon regulatory factor 1,programmed death-ligand 1,indoleamine 2,3-dioxygenase 1,and interferon-stimulated gene 15,involved in the pathology of glioblastoma.These genes may serve as valuable biomarkers and have therapeutic potential for targeting IFN-γsignaling in this malignancy.
文摘AIM: To evaluate the antifibrotic effect of different doses of recombinant human Gamma-Interferon (IFN-gamma) in two rat models of hepatic fibrosis, and to observe its effect on moderate chronic hepatitis B virus fibrosis. METHODS: Hepatic fibrosis was successfully induced in 150 and 196 rats by subcutaneous injection of carbon tetrachloride (CCl4) and intraperitoneal injection of dimethylnitrosamine (DMN), respectively. Each of the two model groups was divided into: (1) fibrotic model group; (2) colchicine treatment group (0.1 mg/kg/day, gastrogavage for 8 weeks); (3) high-dose IFN-gamma group (15 MU/kg per day, i.m. for 8 weeks); (4) medium-dose IFN-gamma group (5 MU/kg daily, i.m. for 8 weeks); and (5) Y low-dose IFN-gamma group (1.67 MU/kg daily, i.m. for 8 weeks). Another group of 10 rats without any treatment was used as normal controls. At the end of the experiment, semi-quantitative histopathological scores of inflammation and fibrosis, liver alpha smooth muscle actin (alpha-SMA) expression level, liver hydroxyl proline content and serum hyaluronic acid levels were compared. And 47 medium chronic hepatitis B viral fibrosis patients were studied. They were given IFN-gamma treatment, 100 MU/day i.m. for the first three months and 100 MU qod i.m. for the next six months. Semi-quantitative pathological scores of inflammation and fibrosis and serum hepatic fibrosis indices were compared within the 9 months. RESULTS: In animal experiment, the pathological fibrosis scores and liver hydroxyl proline content were found to be significantly lower in rats treated with different doses of IFN-gamma as compared with rats in fibrotic model group induced by either CCl4 or DMN, in a dose-dependent manner. For CCl4-induced model, pathological fibrosis scores in high, medium and low doses IFN-gamma groups were 5.10 +/- 2.88, 7.70 +/- 3.53 and 8.00 +/- 3.30, respectively, but the score was 14.60 +/- 7.82 in fibrotic model group. Hydroxyl proline contents were 2.83 +/- 1.18, 3.59 +/- 1.22 and 4.80 +/- 1.62, in the three IFN-gamma groups, and 10.01 +/- 3.23 in fibrotic model group. The difference was statistically significant (P【0.01). Similar results were found in DMN-induced model. Pathological fibrosis scores were 6.30 +/- 0.48, 8.10 +/- 2.72 and 8.30 +/- 2.58, in high, medium and low doses IFN-gamma groups, and 12.60 +/- 3.57 in fibrotic model group. Hydroxyl proline contents were 2.72 +/- 0.58, 3.14 +/- 0.71 and 3.62 +/- 1.02, in the three IFN-gamma groups, and 12.79 +/- 1.54 in fibrotic model group. The difference was statistically significant (P【0.01).Serum hepatic fibrosis indices decreased significantly in the 47 patients after IFN-gamma treatment (HA: 433.38 +/- 373.00 vs 281.57 +/- 220.48; LN: 161.22 +/- 41.02 vs 146 +/- 35 +/- 44. 67; PC III: 192.59 +/- 89.95 vs 156.98 +/- 49.22; C-I: 156.30 +/- 44.01 vs 139.14 +/- 34.47) and the differences between the four indices were significant (P 【0.05). Thirty-three patients received two liver biopsies, one before and one after IFN-gamma treatment. In thirty of 33 patients IFN-gamma had better effects according to semi-quantitative pathological scores (8.40 +/- 5.83 vs 5.30 +/- 4.05, P【0.05). CONCLUSION: All the three doses of IFN-gamma are effective in treating rat liver fibrosis induced by either CCl4 or DMN, the higher the dose, the better the effect. And IFN-gamma is effective for patients with moderate chronic hepatitis B viral fibrosis.
文摘AIM:To investigate the performance and diagnostic accuracy of interferon-gamma(IFN-γ) for tuberculous peritonitis(TBP) by meta-analysis.METHODS:A systematic search of English language studies was performed.We searched the following electronic databases:MEDLINE,EMBASE,Web of Science,BIOSIS,LILACS and the Cochrane Library.The Standards for Reporting Diagnostic Accuracy initiative and Quality Assessment for Studies of Diagnostic Accuracy tool were used to assess the methodological quality of the studies.Sensitivity,specificity,and other measures of the accuracy of IFN-γ concentration in the diagnosis of peritoneal effusion were pooled using random-effects models.Receiver operating characteristic(ROC) curves were applied to summarize overall test performance.Two reviewers independently judged study eligibility while screening the citations.RESULTS:Six studies met the inclusion criteria.The average inter-rater agreement between the two reviewers for items in the quality checklist was 0.92.Analysis of IFN-γ level for TBP diagnosis yielded a summary estimate:sensitivity,0.93(95%CI,0.87-0.97);specificity,0.99(95%CI,0.97-1.00);positive likelihood ratio(PLR),41.49(95%CI,18.80-91.55);negative likelihood ratio(NLR),0.11(95%CI,0.06-0.19);and diagnostic odds ratio(DOR),678.02(95%CI,209.91-2190.09).χ 2 values of the sensitivity,specificity,PLR,NLR and DOR were 5.66(P = 0.3407),6.37(P = 0.2715),1.38(P = 0.9265),5.46(P = 0.3621) and 1.42(P = 0.9220),respectively.The summary receiver ROC curve was positioned near the desirable upper left corner and the maximum joint sensitivity and specificity was 0.97.The area under the curve was 0.99.The evaluation of publication bias was not significant(P = 0.922).CONCLUSION:IFN-γ may be a sensitive and specific marker for the accurate diagnosis of TBP.The level of IFN-γ may contribute to the accurate differentiation of tuberculosis(TB) ascites from non-TB ascites.
文摘AIM:To investigate the clinical usefulness of interferon-gamma release assays(IGRAs)in the differential diagnosis of intestinal tuberculosis(ITB)from Crohn’s disease(CD)by meta-analysis.METHODS:A systematic search of English language studies was performed.We searched the following databases:Medline,Embase,Web of Science and the Cochrane Library.The Standards for Reporting Diagnostic Accuracy initiative and Quality Assessment for Studies of Diagnostic Accuracy tool were used to assess the methodological quality of the studies.Sensitivity,specificity,and other measures of the accuracy of IGRAs in the differential diagnosis of ITB from CD were pooled and analyzed using random-effects models.Receiver operating characteristic curves were applied to summarize overall test performance.Two reviewers independently judged study eligibility while screening the citations.RESULTS:Five studies met the inclusion criteria.The average inter-rater agreement between the two reviewers for items in the quality checklist was 0.95.Analysis of IGRAs for the differential diagnosis of ITB from CD produced summary estimates as follows:sensitivity,0.74(95%CI:0.68-0.80);specificity,0.87(95%CI:0.82-0.90);positive likelihood ratio,5.98(95%CI:3.79-9.43);negative likelihood ratio,0.28(95%CI:0.18-0.43);and diagnostic odds ratio,26.21(95%CI:14.15-48.57).The area under the curve was 0.92.The evaluation of publication bias was not significant(P=0.235).CONCLUSION:Although IGRAs are not sensitive enough,they provide good specificity for the accurate diagnosis of ITB,which may be helpful in the differential diagnosis of ITB from CD.
基金supported by the Faculty of Medicine Siriraj Hospital,Mahidol University,Bangkok,Thailand,[Grant Number(IO)R015832028].Oxford Immunotec and Biomed diagnostics(Thailand)provided the T-SPOT.TB test kit
文摘Objective:To evaluate the performance of interferon gamma release assays and tuberculin skin test in HIV-infected children and adolescents with immune reconstitution.Methods:A cross-sectional study was conducted in HIV-infected patients aged 5-18 years receiving antiretroviral treatment with CD4 T-lymphocytes>25%or>500 cells/mm3 for at least 6 months.QuantiF ERON-TB Gold,T-SPOT.TB,and tuberculin skin test were performed in each patient.Results:A total of 50 patients were enrolled with median age of 13.7 years,CD4 counts of 753(IQR:587-989)cells/mm3.Among 27 patients with tuberculosis(16)or tuberculosis exposure(11),8(29.6%)were positive to at least one test,2(7.4%)were positive QuantiFERON-TB Gold,3(11.1%)positive T-SPOT.TB,and 7(25.9%)had tuberculin skin test≥5 mm.Among 23 patients without history of tuberculosis or exposure,all had negative interferon gamma release assays,while 2(8.7%)had positive tuberculin skin test.Conclusions:All tests had low sensitivity despite immune reconstitution.
文摘BACKGROUND:Fibrosis plays a key role in the development of liver cirrhosis.In this study,we investigated the effect of growth hormone and interferon gamma on hepatic collagen synthesis and the proliferation of hepatic stellate cells in a cirrhotic rat model.METHODS:Cirrhosis was induced in rats using carbon tetrachloride.Rats were simultaneously treated with daily subcutaneous injections of recombinant human growth hormone or interferon gamma combined with recombinant human growth hormone.The control group was given saline.The relative content of type I and type IV collagen was assessed by indirect immunofluorescence analysis.Activated hepatic stellate cells were prepared from cirrhotic rats.The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide(MTT)method was used to assess the effects of recombinant human growth hormone and interferon gamma on these cells in vitro.RESULTS:Both qualitative and quantitative analysis showed that type I and type IV collagen secretion increased with time after recombinant human growth hormone administration and was significantly higher than control and recombinant human growth hormone combined with interferon gamma administration.In vitro,recombinant human growth hormone significantly stimulated hepatic stellate cell proliferation in a concentration-dependent manner(10-3-10-1 mg/100μL),andinterferon gamma(10-2-10-1μg/100μL)significantly inhibited their growth compared to the control group.Interferon gamma combined with recombinant human growth hormone eliminated this growth-promoting effect to a certain degree in a concentration-dependent manner(10-1μg/100μL,P<0.05,10-2-10-3μg/100μL,P>0.05)and a time-dependent manner(P<0.05).CONCLUSIONS:Recombinant human growth hormone increased collagen secretion in cirrhotic rats in vivo and promoted the proliferation of hepatic stellate cells from cirrhotic rats in vitro.It is possible that concurrent interferon gamma therapy can offset these side-effects of recombinant human growth hormone.
基金Supported by the Program for New Century Excellent Talents in University (No. NCET-05-0684)
文摘AIM: To explore the effect of immunization with copolymer-1 (COP-1) and retinal stem cells (RSCs) transplantation on interferon-gamma (IFN-gamma) levels in a rat experimental glaucoma model. METHODS: An experimental glaucoma was induced by argon laser photocoagulation of the episcleral veins and limbal plexus in the right eye of rats. Immediately following glaucoma induction, rats were immunized with COP-1. RSCs were cultured and transplanted intravitreally into the eyes of glaucoma model animals 1 week post-laser treatment. Six experimental groups were used: COP-1/RSC, PBS/RSC, COP-1/PBS, PBS/PBS, glaucoma model group, and a normal control group. The concentration of IFN-gamma in aqueous humor (AH) and serum was measured by enzyme-linked immunosorbent assay (ELISA) in each of the six groups. Retinal ganglion cell (RGC) survival was assessed by quantifying apoptosis using Hoechst staining. RESULTS: Concentrations of IFN-gamma in AH and serum of rats that had undergone glaucoma induction were higher than those of non-induced control rats. The concentrations of IFN-gamma in AH and serum of the COP-1/RSCs treated group were determined to be 2371.9ng/L and 710.9ng/L, respectively, which were significantly lower than those in the other treated groups (P<0.05). In fact, IFN-gamma levels in the dual treated group were reduced to background levels. The COP-1/RSC group had lower number of apoptotic RGCs than the other three experimental groups (P<0.05). CONCLUSION: The reduced levels of IFN-gamma in AH and serum of the COP-1/RSC group may be related to synergistic effects between RSCs transplantation and COP-1 immune modulation. It is likely that the lower levels of IFN-gamma prevented RGCs glaucomatous apoptasis.
文摘Capillary electrophoretic immunoassay with laser-induced fluorescence detection for recombinant human interferon-gamma (IFN-g) was established. The limits of detection for three forms of IFN-g are 6.9 ng/L, 5.7 ng/L and 5.0 ng/L, respectively.
文摘Objective:To determine the relationship of the capacity to produce interferon gamma(IFN-γ) in whole blood,bacteriological,hematological,radiographic and clinical presentations in new,HIV seronegative cases of pulmonary tuberculosis(TB).Methods:80 cases and 50 control subjects aged 15 years onwards,representative of Kasturba Hospital and Nursing schools of Wardha district of Maharashtra state in India were examined for their health condition with standard methodology.Results:Among these TB patients,73.8%were Quantiferon-TB gold (QFT) positive with IFN-γconcentration as 0.35 IU or more and there was none in healthy controls.The mean IFN-γconcentrations varied between 9.58 IU(50-59 yrs) and 2.58 IU(≥60 yrs),showing no trend.The differences in positivity and mean IFN-γconcentrations were statistically insignificant.Both the QFT positivity and IFN-γconcentrations were higher in normal lymphocyte percent as compared to below and above normal,but differences were not statistically significant.Conclusions:The IFN-γconcentrations are not correlated with any of the predictors of disease severity studied,the levels are significantly higher in observation group as compared to healthy group.
文摘BACKGROUND： Neuropeptide Y （NPY） may influence differentiation of Th cells immunological pathology of experimental allergic encephalomyelitis （EAE） is differentiation of Th cells It is assumed that the related to abnormal OBJECTIVE： To investigate the effect of NPY on white matter demyelination, the serum levels interleukin-4 （IL-4） and gamma-interferon （IFN-γ ）, as well as EAE pathogenesis in an EAE guinea pig model following NPY injection into the lateral cerebral ventricle. DESIGN, TIME AND SETTING： A randomized controlled animal study, which was performed in the Infection Immunity Animal Laboratory, Affiliated Hospital of Luzhou Medical College, China, from October 2005 to April 2006. MATERIALS： Thirty healthy female guinea pigs of 8-12 weeks of age, and 10 healthy female rats of three months of age were used. NPY was provided by Sigma Company, USA. NPY kit was provided by Beijing Huaying Biotechnology Institute, China. METHODS： Thirty guinea pigs were randomly divided into three groups： normal control group, EAE model group, and NPY intervention group （n =10 per group）. Normal control group and EAE model group： Saline （10μ L, once） was injected into the lateral cerebral ventricle. After one week, the same volume of Freund＇s adjuvant complete was either injected subcutaneously into two post-palms or EAE was modeled. NPY intervention group： EAE was modeled after one week and NPY was injected （10 μ L of 6 nmol NPY, once） into the lateral cerebral ventricle. Myelin basic protein （MBP） antigen made from rat spinal cord homogenate and Freund＇s adjuvant complete were injected subcutaneously into both post-palms （0.2 mL per palm） to establish the EAE model. MAIN OUTCOME MEASURES： White matter demyelination of the cerebrum, cerebellum, brain stem, and spinal cord were observed by light microscopy after HE staining. Levels of serum IFN-γ and IL-4 were detected by the double antibody sandwich ABC-ELISA technique. NPY content was detected by radioimmunoassay. RESULTS： Pathological alterations in the NPY intervention groups were reduced compared to those in the EAE model group, suggesting a reduction and remission of white matter demyelination with NPY treatment. When compared to the model group, the serum IL-4 level was increased in the NPY intervention group during the high-frequent EAE stage （P 〈 0.01）, but the serum IFN-γ level was decreased （P 〈 0.01）. Furthermore, the EAE latency was prolonged （P 〈 0.01）, the neurological scores were decreased in the high-frequent EAE stage （P 〈 0.01）, and the death rate was decreased （P 〈 0.05）. NPY content and the serum IL-4 level at the peak stage were positively correlated with those in the latent phase （r =0.863-0.900, P 〈 0.01）, but negatively correlated with neurological scores at the peak stage （r=- -0.068 to -0.863, P 〈 0.05-0.01）. The IFN-γ level at the peak stage was negatively correlated to that in the latent phase （r = -0.683-0.650, P 〈 0.05）, but positively correlated to neurological scores at the peak stage （r =0.975, 0.845, P 〈 0.05）. CONCLUSION： NPY injection into the lateral cerebral ventricle can promote the secretion of IL-4, inhibit the production of IFN-γ, relieve white matter demyelination, and inhibit EAE attack in an experimental model of EAE.
基金Supported by a grant from Iran National Science Foundation under the grant number 91002993
文摘Objective: To develop a gold nanoparticles complex conjugated with interferon-gamma(IFN-g) and methionine along with application of hyperthermia using near-infrared laser beams for the treatment of cancer cells.Methods: Gold nanorods(10 nm) were conjugated with IFN-g and methionine using carbodiimide family and characterized after purification by dialysis bags. Breast cancer cells were cultured and incubated with gold nanorods at different concentrations followed by irradiation with near-infrared laser beam. Samples were then evaluated for their viability in order to determine the effect of treatment and variables by MTT assy.Results: Zetasizer results confirmed the conjugation of gold nanorods with methionine and IFN-g. The median percentage of cell viability in 0.30 mg/m L concentration of gold nanorods was 82%. The cell viability reached to 85% at the same concentration of gold nanorods, which existed in the assayed complex. The results of MTT assay showed that the 0.60 mg/m L concentration of gold nanoparticles complex was toxic on tumor cells(P < 0.05). After exposure to hyperthermia, the viability of cells at 6 min decreased to77% in 0.30 mg/m L concentration of gold nanorods complex.Conclusions: The size and concentration of gold nanorods was not cytotoxic. However,their presence during irradiation near-infrared laser increased the number of dead cells during the treatment of cells.
文摘Background: This study aimed to evaluate the diagnostic value of interferon-γ release assay (IGRA), a sensitive microbiological diagnostic method, in children and adolescents with suspected tuberculosis in a country with a high burden of tuberculosis. Method: This study included 581 children and adolescents aged 4 - 19 years who were suspected of having tuberculosis, were latently infected with Mycobacterium tuberculosis, and had received at least one dose of BCG vaccine between April 17, 2019, and February 24, 2021. The study evaluated the TST results of 106 patients who had a positive Quantiferon test and were suspected of having tuberculosis. Results: The study included 581 patients aged between 4 and 19 years. Of these, 106 patients tested positive for the Quantiferon test, while 19 were indeterminate and 456 were negative. The Quantiferon test positivity rate was 18.24%. Among the 106 QFT-Plus-positive cases, 23 patients also tested positive for TST. The difference in distribution was found to be statistically significant. Conclusion: The QFT-Plus test is considered an alternative to TST and other microbiological diagnostic methods for early tuberculosis diagnosis, particularly in children and adolescents.
文摘Introduction: Tuberculosis (TB) remains a significant public health challenge, particularly in high-endemicity settings where latent TB infections (LTBI) contribute to ongoing transmission. Early identification and management of LTBI are crucial in limiting the spread of the disease. This study demonstrates the role of Interferon Gamma Release Assay (IGRA) as a screening tool for latent tuberculosis in high-burden region. Materials and Methods: This retrospective observational study assessed the detection of LTBI using the QuantiFERON-TB Gold Plus (QFT-Plus) test among 145 patients at the Department of Microbiology & Immunology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh, from August 2023 to August 2024. The study included patients suspected of TB, those screened before immunosuppressive therapy, organ transplantation, or kidney dialysis. Participants were tested IGRA using QFT-Plus, which detects interferon-gamma (IFN-γ) released in response to Mycobacterium tuberculosis antigens. Results and Discussion: Among 145 patients tested for the QFT-Gold Plus test, 55.17% (n = 80) were positive for LTBI, with a substantial agreement between TB1 and TB2 responses (p Conclusion: The results highlight that QFT-Plus may be utilized as a useful diagnostic screening tool for latent TB in regions with a high disease burden, though challenges related to cost and infrastructure persist. With growing global efforts to eliminate tuberculosis, focused screening and treatment of LTBI in high-risk groups could play a vital role in reducing the progression of TB. The study underscores the importance of targeted screening for LTBI to reduce the progression to active TB, particularly in resource-limited settings.
文摘干扰素-γ诱导蛋白16(interferon gamma-inducible protein 16,IFI16)是含pyrin和造血表达、干扰素诱导特性和核定位(hematopoietic expression,interferon-inducible nature,and nuclear localization,HIN)结构域的蛋白质(pyrin and HIN domain-containing protein,PYHIN)家族的重要成员,其独特的分子结构使其能够识别细胞内的多种核酸分子。作为一种关键的免疫调节因子,IFI16可通过多种途径参与天然免疫信号转导,在宿主抗病毒防御中发挥重要作用。本文综述了IFI16的分子特征及其在天然免疫和病毒感染中的调控机制,为抗病毒感染的治疗靶点及药物开发提供理论依据。
