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
Mesenchymal stem cells(MSC) are cells of stromal origin which exhibit unlimited self-renewal capacity and pluripotency in vitro.It has recently been observed that MSC may also exert a profound immunosuppressive and an...Mesenchymal stem cells(MSC) are cells of stromal origin which exhibit unlimited self-renewal capacity and pluripotency in vitro.It has recently been observed that MSC may also exert a profound immunosuppressive and anti-inflammatory effect both in vitro and in vivo with consequent potential use in autoimmune disorders.We present the case of a patient suffering from childhood-onset, multidrug resistant and steroiddependent Crohn's disease who underwent systemic infusions of MSC, which led to a temporary reduction in CCR4, CCR7 and CXCR4 expression by T-cells, and a temporary decrease in switched memory B-cells, In addition, following MSC infusion, lower doses of steroids were needed to inhibit proliferation of the patient's peripheral blood mononuclear cells.Despite these changes, no significant clinical benefit was observed, and the patient required rescue therapy with infliximab and subsequent autologous hematopoietic stem cell transplantation.The results of biological and in vitro observations after MSC use and the clinical effects of infusion are discussed, and a brief description is provided of previous data on MSC-based therapy in autoimmune disorders.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
Background: Interferon-γ(IFN-γ) is critical for innate and adaptive immunity against viral and bacterial infections. IFN-γ reportedly affects the phagocytic ability of monocytes and macrophages as well as regulates...Background: Interferon-γ(IFN-γ) is critical for innate and adaptive immunity against viral and bacterial infections. IFN-γ reportedly affects the phagocytic ability of monocytes and macrophages as well as regulates pituitary function in humans and mice. The present study analyzed the impact of IFN-γ on monocyte and macrophage phagocytosis, production performance, and pituitary function in vivo and in vitro(in dwarf chickens). IFN-γ was injected into dwarf chickens through a vein, and then, the laying rate, average egg weight, and levels of follicle-stimulating hormone(FSH) and IFN-γ were measured in treatment and control groups. For the in vitro experiment, the pituitary tissues were supplemented with IFN-γ, and the m RNA expression levels of follicle-stimulating hormone beta subunit(FSH-β), interferon gamma receptor 1(IFNGR1),and interferon gamma receptor 2(IFNGR2) in the pituitary were assessed.Results: Monocyte and macrophage phagocytosis product(PP) was decreased by IFN-γ treatment in a dose-dependent manner in vitro. In the in vivo experiment, the level of IFN-γ in the treatment group was higher than that in the control group at 7 d(P < 0.05), 14 d(P < 0.01), and 21 d(P < 0.01) post-injection.Compared with the control group, monocyte and macrophage PP was lower in the treatment group after injection(P < 0.01). The laying rate was higher in the treatment group than in the control group at 2 and3 wk post-injection(P < 0.05). There was a significant difference between the treatment and control groups in the levels of FSH at 1, 3, 7, and 14 d post-injection(P < 0.01). In the in vitro experiment, increased m RNA expression levels of FSH-β, IFNGR1, and IFNGR2 were observed in the treatment group after stimulation with100 U/m L IFN-γ for 24 h compared to those in the control group(P < 0.05).Conclusions: IFN-γ inhibited the phagocytosis of monocytes and macrophages; up-regulated the m RNA expression levels of the FSH-β, IFNGR1, and IFNGR2; enhanced the secretion of FSH; and improved the laying rate. IFN-γ might be an important regulator in the trade-off between the immune effect and production performance in dwarf chickens.展开更多
The aqueous two-phase system of PEG-4000/K<sub>3</sub>PO<sub>4</sub> is selected to extract interferon-γ（γ-IFN）from the broth of homogenized E.coil cells,which were recombined genetically a...The aqueous two-phase system of PEG-4000/K<sub>3</sub>PO<sub>4</sub> is selected to extract interferon-γ（γ-IFN）from the broth of homogenized E.coil cells,which were recombined genetically and werefermented in high expressivity.The effects of pH value and the concentrations of PEG and phos-phate on the partition behavious of γ-IFN and contaminating proteins have been investigated.Theresults show that the pH value is the most influential factor effecting the extraction yield of γ-IFN.Under a suitable condition,an effective separation with high yield of γ-IFN can be achieved.展开更多
OBJECTIVE Programmed death ligand-1(PD-L1)and indoleamine 2,3-dioxygenase 1(IDO1)are immune checkpoints which can be induced by interferon-γ(IFN-γ)in the tumor microenvironment,leading to immune escape of tumors.Myr...OBJECTIVE Programmed death ligand-1(PD-L1)and indoleamine 2,3-dioxygenase 1(IDO1)are immune checkpoints which can be induced by interferon-γ(IFN-γ)in the tumor microenvironment,leading to immune escape of tumors.Myricetin(MY)is a flavonoid distributed in many edible and medicinal plants.The aim of this study is to clarify the effect and the mechanism of MY on inhibiting IFN-γ-induced PD-L1 and IDO1 in lung cancer cells.METHODS Expressions of PD-L1 and major histocompatibility complex-I(MHC-I)were evaluated by flow cytometry and Western blotting,and the expression of IDO1 was measured by Western blotting.qRT-PCR was used to detect their mRNA levels.The function of T cells was evaluated using a co-culture system consist of lung cancer cells and the Jurkat-PD-1 T cell line that overexpressing PD-1.Molecular docking analysis,Western blotting and immunofluorescence were used for mechanism study.RESULTS MY potently inhibited IFN-γ-induced PD-L1 and IDO1 expression in human lung cancer cells,while didn't show obvious effect on the expression of MHC-I.In addition,MY restored the survival,proliferation,CD69 expression and interleukin-2(IL-2)secretion of Jurkat-PD-1 T cells suppressed by IFN-γ-treated lung cancer cells in the co-culture system.Mechanistically,IFN-γup-regulated PD-L1 and IDO1 at the transcriptional level through the JAK-STAT-IRF1 axis,which was targeted and inhibited by MY.CONCLUSION Our research revealed a new insight into the anti-tumor effects of MY which inhibited IFN-γ-induced PD-L1 and IDO1 expression,supporting the potential of MY in anti-tumor immunotherapy.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
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 malignan...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(AUCROC) 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 AUCROC 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 AUCROC 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 if and how the proinflammatory cytokine interferon γ(IFNγ) affects ghrelin expression in mice.METHODS:The plasma concentration of ghrelin,andgastric ghrelin and somatostatin expression,were examin...AIM:To investigate if and how the proinflammatory cytokine interferon γ(IFNγ) affects ghrelin expression in mice.METHODS:The plasma concentration of ghrelin,andgastric ghrelin and somatostatin expression,were examined in wild-type mice and mice infected with Helicobacter pylori(H.pylori).Furthermore,ghrelin expression was examined in two achlorhydric mouse models with varying degrees of gastritis due to bacterial overgrowth.To study the effect of IFNγ alone,mice were given a subcutaneous infusion of IFNγ for 7 d.Finally,the influence of IFNγ and somatostatin on the ghrelin promoter was characterized.RESULTS:H.pylori infection was associated with a 50% reduction in ghrelin expression and plasma concentration.Suppression of ghrelin expression was inversely correlated with gastric inflammation in achlorhdyric mouse models.Subcutaneous infusion of IFNγ suppressed fundic ghrelin mRNA expression and plasma ghrelin concentrations.Finally,we showed that the ghrelin promoter operates under the control of somatostatin but not under that of IFNγ.CONCLUSION:Gastric infection and inflammation is associated with increased IFNγ expression and reduced ghrelin expression.IFNγ does not directly control ghrelin expression but inhibits it indirectly via somatostatin.展开更多
Objective:To observe the effects of immunosuppressants triptolide(TL)and cyclosporineA(CSA)on HLA antigens expression induced by interferon-γ（INF-γ）in vitro.Method:By using an indirect immunofluorescent method and...Objective:To observe the effects of immunosuppressants triptolide(TL)and cyclosporineA(CSA)on HLA antigens expression induced by interferon-γ（INF-γ）in vitro.Method:By using an indirect immunofluorescent method and analysing with ACAS-570,the abnormal HLA antigen expression of cultured corneal epithelial cells was induced by INF-γ，After incubation with one of the immunosuppressants(CSA,TL) for72hrs.the amount of HLA-ABCand HLA-DRantigens was measured.Result:There was no significant difference(P>0.05)between the group with CAS and the positive control group without CAS.In contrast to CSA,TL dramatically inhibited INF-γinduced expression of HLA antigens of corneal epithelial cells(P<0.001),compared with the control group withoutTL.Conclusion:TL had direct inhibition on the expression of HLA-ABCand HLA-DRantige ns induced by INF-γin vitro,while CSAhad no obvious inhibition,Eye Science2000;16:34-37.展开更多
AIM:To evaluate anti-hepatitis B virus (HBV) activity and cytotoxicity of interferon (IFN-γ) and tumor necrosis factor (TNF-α) following lamivudine treatment of HepG2.2.15 cells.METHODS:HepG2.2.15 cells were treated...AIM:To evaluate anti-hepatitis B virus (HBV) activity and cytotoxicity of interferon (IFN-γ) and tumor necrosis factor (TNF-α) following lamivudine treatment of HepG2.2.15 cells.METHODS:HepG2.2.15 cells were treated with 2 mol/L lamivudine for 16 d (lamivudine group),cultured for 10 d,followed by 5 ng/mL TNF-α and 1000 U/mL IFN-γ for 6 d (cytokine group),or treated with 2 mol/L lamivudine for 10 d followed by 5 ng/mL TNF-α and 1000 U/mL IFN-γ for 6 d (sequential group),or cultured without additions for 16 d (control group).Intracellular DNA was extracted from 3 × 105 HepG2.2.15 cells from each group.The extracted DNA was further purified with mung bean nuclease to remove HBV relaxed circular DNA that may have remained.Both HBV covalently closed circular DNA (cccDNA) and HBV DNA were examined with real-time polymerase chain reaction.The titers of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were quantified with enzyme-linked immunosorbent assay.Cell viability was measured with the cell counting kit-8 assay.RESULTS:Compared to lamivudine alone (22.63% ± 0.12%),both sequential (51.50% ± 0.17%,P = 0.034) and cytokine treatment (49.66% ± 0.06%,P = 0.041) showed a stronger inhibition of HBV cccDNA;the difference between the sequential and cytokine groups was not statistically significant (51.50% ± 0.17% vs 49.66% ± 0.06%,P = 0.88).The sequential group showed less inhibition of HBV DNA replication than the lamivudine group (67.47% ± 0.02% vs 82.48% ± 0.05%,P = 0.014);the difference between the sequential and cytokine groups was not statistically significant (67.47% ± 0.02% vs 57.45% ± 0.07%,P = 0.071).The levels of HBsAg and HBeAg were significantly decreased in the sequential treatment group compared to the other groups [HBsAg:3.48 ± 0.04 (control),3.09 ± 0.08 (lamivudine),2.55 ± 0.13 (cytokine),2.32 ± 0.08 (sequential),P = 0.042 for each between-group comparison;HBeAg:3.48 ± 0.01 (control),3.08 ± 0.08 (lamivudine),2.57 ± 0.15 (cytokine),2.34 ± 0.12 (sequential),P = 0.048 for each between-group comparison].Cell viability in the cytokine group was reduced to 58.03% ± 8.03% compared with control cells (58.03% ± 8.03% vs 100%,P = 0.000).Lamivudine pretreatment significantly reduced IFN-γ + TNF-α-mediated toxicity of HepG2.2.15 cells [85.82% ± 5.43% (sequential) vs 58.03% ± 8.03% (cytokine),P = 0.002].CONCLUSION:Sequential treatment overcame the lower ability of lamivudine alone to inhibit cccDNA and precluded the aggressive cytotoxicity involving IFN-γ and TNF-α by decreasing the viral load.展开更多
Interferon-γis a kind of protein with a wide range of biological activities,which can regulate the immune function of the body,and can be used as an important marker to detect and treat bovine tuberculosis diseases.H...Interferon-γis a kind of protein with a wide range of biological activities,which can regulate the immune function of the body,and can be used as an important marker to detect and treat bovine tuberculosis diseases.Here,a picogram-level bovine interferon-γ(BoIFN-γ)electrochemical impedance immunosensor was constructed for the first time using mesoporous silica nanospheres(MS Ns)to immobilize specific monoclonal BoIFN-y antibodies.The MS Ns and BoIFN-γimmuno sensors were characterized using scanning electron microscopy,transmission electron microscope,nitrogen adsorption experiment,X-ray photoelectron spectra,and contact angle measurements.MSNs possess a substantial specific surface area and significant hydrophilicity,and can immobilize many antibody molecules,thereby improving detection sensitivity.The immunosensor has a linear detection range from 0.001 to 10.0 ng/mL with an exceptionally low detection limit of 0.62 pg/mL.Compared to the traditional BoIFN-γanalysis method,BoIFN-γimmunosensor presents superiorities in sensitivity,wide linear range as well as short processing time.More importantly,the BoIFN-γsensor exhibits high selectivity,reliable repeatability as well as stability,providing a promising application prospect for the early diagnosis of Mycobacterium bovis infection.展开更多
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
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.
文摘Mesenchymal stem cells(MSC) are cells of stromal origin which exhibit unlimited self-renewal capacity and pluripotency in vitro.It has recently been observed that MSC may also exert a profound immunosuppressive and anti-inflammatory effect both in vitro and in vivo with consequent potential use in autoimmune disorders.We present the case of a patient suffering from childhood-onset, multidrug resistant and steroiddependent Crohn's disease who underwent systemic infusions of MSC, which led to a temporary reduction in CCR4, CCR7 and CXCR4 expression by T-cells, and a temporary decrease in switched memory B-cells, In addition, following MSC infusion, lower doses of steroids were needed to inhibit proliferation of the patient's peripheral blood mononuclear cells.Despite these changes, no significant clinical benefit was observed, and the patient required rescue therapy with infliximab and subsequent autologous hematopoietic stem cell transplantation.The results of biological and in vitro observations after MSC use and the clinical effects of infusion are discussed, and a brief description is provided of previous data on MSC-based therapy in autoimmune disorders.
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 grants from National Natural Science Foundation of China(3157130570)Young Scientist Supporting Project,Program for Changjiang Scholars and Innovative Research Team in University(IRT_15R62)+1 种基金Farm Animals Germplasm Resource Platform,National Transgenic Creature Breeding Grand Project(2016ZX08008-003)Innovation Base Cultivation and Development Project-research on precise genetic modify in sheep(Z171100002217072)
文摘Background: Interferon-γ(IFN-γ) is critical for innate and adaptive immunity against viral and bacterial infections. IFN-γ reportedly affects the phagocytic ability of monocytes and macrophages as well as regulates pituitary function in humans and mice. The present study analyzed the impact of IFN-γ on monocyte and macrophage phagocytosis, production performance, and pituitary function in vivo and in vitro(in dwarf chickens). IFN-γ was injected into dwarf chickens through a vein, and then, the laying rate, average egg weight, and levels of follicle-stimulating hormone(FSH) and IFN-γ were measured in treatment and control groups. For the in vitro experiment, the pituitary tissues were supplemented with IFN-γ, and the m RNA expression levels of follicle-stimulating hormone beta subunit(FSH-β), interferon gamma receptor 1(IFNGR1),and interferon gamma receptor 2(IFNGR2) in the pituitary were assessed.Results: Monocyte and macrophage phagocytosis product(PP) was decreased by IFN-γ treatment in a dose-dependent manner in vitro. In the in vivo experiment, the level of IFN-γ in the treatment group was higher than that in the control group at 7 d(P < 0.05), 14 d(P < 0.01), and 21 d(P < 0.01) post-injection.Compared with the control group, monocyte and macrophage PP was lower in the treatment group after injection(P < 0.01). The laying rate was higher in the treatment group than in the control group at 2 and3 wk post-injection(P < 0.05). There was a significant difference between the treatment and control groups in the levels of FSH at 1, 3, 7, and 14 d post-injection(P < 0.01). In the in vitro experiment, increased m RNA expression levels of FSH-β, IFNGR1, and IFNGR2 were observed in the treatment group after stimulation with100 U/m L IFN-γ for 24 h compared to those in the control group(P < 0.05).Conclusions: IFN-γ inhibited the phagocytosis of monocytes and macrophages; up-regulated the m RNA expression levels of the FSH-β, IFNGR1, and IFNGR2; enhanced the secretion of FSH; and improved the laying rate. IFN-γ might be an important regulator in the trade-off between the immune effect and production performance in dwarf chickens.
文摘The aqueous two-phase system of PEG-4000/K<sub>3</sub>PO<sub>4</sub> is selected to extract interferon-γ（γ-IFN）from the broth of homogenized E.coil cells,which were recombined genetically and werefermented in high expressivity.The effects of pH value and the concentrations of PEG and phos-phate on the partition behavious of γ-IFN and contaminating proteins have been investigated.Theresults show that the pH value is the most influential factor effecting the extraction yield of γ-IFN.Under a suitable condition,an effective separation with high yield of γ-IFN can be achieved.
基金Science and Technology Development Fund,Macao SAR(0129/2019/A3176/2017/A3)and University of Macao(MYRG2018-00165-ICMS)。
文摘OBJECTIVE Programmed death ligand-1(PD-L1)and indoleamine 2,3-dioxygenase 1(IDO1)are immune checkpoints which can be induced by interferon-γ(IFN-γ)in the tumor microenvironment,leading to immune escape of tumors.Myricetin(MY)is a flavonoid distributed in many edible and medicinal plants.The aim of this study is to clarify the effect and the mechanism of MY on inhibiting IFN-γ-induced PD-L1 and IDO1 in lung cancer cells.METHODS Expressions of PD-L1 and major histocompatibility complex-I(MHC-I)were evaluated by flow cytometry and Western blotting,and the expression of IDO1 was measured by Western blotting.qRT-PCR was used to detect their mRNA levels.The function of T cells was evaluated using a co-culture system consist of lung cancer cells and the Jurkat-PD-1 T cell line that overexpressing PD-1.Molecular docking analysis,Western blotting and immunofluorescence were used for mechanism study.RESULTS MY potently inhibited IFN-γ-induced PD-L1 and IDO1 expression in human lung cancer cells,while didn't show obvious effect on the expression of MHC-I.In addition,MY restored the survival,proliferation,CD69 expression and interleukin-2(IL-2)secretion of Jurkat-PD-1 T cells suppressed by IFN-γ-treated lung cancer cells in the co-culture system.Mechanistically,IFN-γup-regulated PD-L1 and IDO1 at the transcriptional level through the JAK-STAT-IRF1 axis,which was targeted and inhibited by MY.CONCLUSION Our research revealed a new insight into the anti-tumor effects of MY which inhibited IFN-γ-induced PD-L1 and IDO1 expression,supporting the potential of MY in anti-tumor immunotherapy.
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 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(AUCROC) 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 AUCROC 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 AUCROC 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.
基金Supported by The Danish MRC Grant271-08-0378(LFH)the ALF grant(TW)The Lundbeck foundation(KBVD)
文摘AIM:To investigate if and how the proinflammatory cytokine interferon γ(IFNγ) affects ghrelin expression in mice.METHODS:The plasma concentration of ghrelin,andgastric ghrelin and somatostatin expression,were examined in wild-type mice and mice infected with Helicobacter pylori(H.pylori).Furthermore,ghrelin expression was examined in two achlorhydric mouse models with varying degrees of gastritis due to bacterial overgrowth.To study the effect of IFNγ alone,mice were given a subcutaneous infusion of IFNγ for 7 d.Finally,the influence of IFNγ and somatostatin on the ghrelin promoter was characterized.RESULTS:H.pylori infection was associated with a 50% reduction in ghrelin expression and plasma concentration.Suppression of ghrelin expression was inversely correlated with gastric inflammation in achlorhdyric mouse models.Subcutaneous infusion of IFNγ suppressed fundic ghrelin mRNA expression and plasma ghrelin concentrations.Finally,we showed that the ghrelin promoter operates under the control of somatostatin but not under that of IFNγ.CONCLUSION:Gastric infection and inflammation is associated with increased IFNγ expression and reduced ghrelin expression.IFNγ does not directly control ghrelin expression but inhibits it indirectly via somatostatin.
文摘Objective:To observe the effects of immunosuppressants triptolide(TL)and cyclosporineA(CSA)on HLA antigens expression induced by interferon-γ（INF-γ）in vitro.Method:By using an indirect immunofluorescent method and analysing with ACAS-570,the abnormal HLA antigen expression of cultured corneal epithelial cells was induced by INF-γ，After incubation with one of the immunosuppressants(CSA,TL) for72hrs.the amount of HLA-ABCand HLA-DRantigens was measured.Result:There was no significant difference(P>0.05)between the group with CAS and the positive control group without CAS.In contrast to CSA,TL dramatically inhibited INF-γinduced expression of HLA antigens of corneal epithelial cells(P<0.001),compared with the control group withoutTL.Conclusion:TL had direct inhibition on the expression of HLA-ABCand HLA-DRantige ns induced by INF-γin vitro,while CSAhad no obvious inhibition,Eye Science2000;16:34-37.
基金Supported by Zhongshan Youth Foundation of Fudan University,China,No.257
文摘AIM:To evaluate anti-hepatitis B virus (HBV) activity and cytotoxicity of interferon (IFN-γ) and tumor necrosis factor (TNF-α) following lamivudine treatment of HepG2.2.15 cells.METHODS:HepG2.2.15 cells were treated with 2 mol/L lamivudine for 16 d (lamivudine group),cultured for 10 d,followed by 5 ng/mL TNF-α and 1000 U/mL IFN-γ for 6 d (cytokine group),or treated with 2 mol/L lamivudine for 10 d followed by 5 ng/mL TNF-α and 1000 U/mL IFN-γ for 6 d (sequential group),or cultured without additions for 16 d (control group).Intracellular DNA was extracted from 3 × 105 HepG2.2.15 cells from each group.The extracted DNA was further purified with mung bean nuclease to remove HBV relaxed circular DNA that may have remained.Both HBV covalently closed circular DNA (cccDNA) and HBV DNA were examined with real-time polymerase chain reaction.The titers of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were quantified with enzyme-linked immunosorbent assay.Cell viability was measured with the cell counting kit-8 assay.RESULTS:Compared to lamivudine alone (22.63% ± 0.12%),both sequential (51.50% ± 0.17%,P = 0.034) and cytokine treatment (49.66% ± 0.06%,P = 0.041) showed a stronger inhibition of HBV cccDNA;the difference between the sequential and cytokine groups was not statistically significant (51.50% ± 0.17% vs 49.66% ± 0.06%,P = 0.88).The sequential group showed less inhibition of HBV DNA replication than the lamivudine group (67.47% ± 0.02% vs 82.48% ± 0.05%,P = 0.014);the difference between the sequential and cytokine groups was not statistically significant (67.47% ± 0.02% vs 57.45% ± 0.07%,P = 0.071).The levels of HBsAg and HBeAg were significantly decreased in the sequential treatment group compared to the other groups [HBsAg:3.48 ± 0.04 (control),3.09 ± 0.08 (lamivudine),2.55 ± 0.13 (cytokine),2.32 ± 0.08 (sequential),P = 0.042 for each between-group comparison;HBeAg:3.48 ± 0.01 (control),3.08 ± 0.08 (lamivudine),2.57 ± 0.15 (cytokine),2.34 ± 0.12 (sequential),P = 0.048 for each between-group comparison].Cell viability in the cytokine group was reduced to 58.03% ± 8.03% compared with control cells (58.03% ± 8.03% vs 100%,P = 0.000).Lamivudine pretreatment significantly reduced IFN-γ + TNF-α-mediated toxicity of HepG2.2.15 cells [85.82% ± 5.43% (sequential) vs 58.03% ± 8.03% (cytokine),P = 0.002].CONCLUSION:Sequential treatment overcame the lower ability of lamivudine alone to inhibit cccDNA and precluded the aggressive cytotoxicity involving IFN-γ and TNF-α by decreasing the viral load.
基金Acknowledgements Research in the author＇s laboratory was supported by grants from the Israel Science Foundation （537/03） and the Deutsche Forschungsgemeinschaft （H0- 1116）,
基金funded by by National Key Research and Development Program of China(2021YFD1800403)National Natural Science Foundation of China(21475116,21575125 and 81302016)+4 种基金Natural Science Foundation of Jiangsu Province(BK20221370,BK20221281)Key University Natural Science Foundation of Jiangsu Province(20KJA150004)the Project for Science and Technology of Yangzhou(YZ2022074,YZ2020076)Crosscooperation project of Subei Peoples’Hospital of Jiangsu Province(SBJC220009)the Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX21_3203)
文摘Interferon-γis a kind of protein with a wide range of biological activities,which can regulate the immune function of the body,and can be used as an important marker to detect and treat bovine tuberculosis diseases.Here,a picogram-level bovine interferon-γ(BoIFN-γ)electrochemical impedance immunosensor was constructed for the first time using mesoporous silica nanospheres(MS Ns)to immobilize specific monoclonal BoIFN-y antibodies.The MS Ns and BoIFN-γimmuno sensors were characterized using scanning electron microscopy,transmission electron microscope,nitrogen adsorption experiment,X-ray photoelectron spectra,and contact angle measurements.MSNs possess a substantial specific surface area and significant hydrophilicity,and can immobilize many antibody molecules,thereby improving detection sensitivity.The immunosensor has a linear detection range from 0.001 to 10.0 ng/mL with an exceptionally low detection limit of 0.62 pg/mL.Compared to the traditional BoIFN-γanalysis method,BoIFN-γimmunosensor presents superiorities in sensitivity,wide linear range as well as short processing time.More importantly,the BoIFN-γsensor exhibits high selectivity,reliable repeatability as well as stability,providing a promising application prospect for the early diagnosis of Mycobacterium bovis infection.
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.
