Diabetic retinopathy(DR)is one of the major causes of visual impairment and irreversible blindness in developed regions.Aside from abnormal angiogenesis,inflammation is the most specific and might be the initiating fa...Diabetic retinopathy(DR)is one of the major causes of visual impairment and irreversible blindness in developed regions.Aside from abnormal angiogenesis,inflammation is the most specific and might be the initiating factor of DR.As a key participant in inflammation,interferon-gamma(IFN-γ)can be detected in different parts of the eye and is responsible for the breakdown of the blood-retina barrier and activation of inflammatory cells and other cytokines,which accelerate neovascularization and neuroglial degeneration.In addition,IFN-γis involved in other vascular complications of diabetes mellitus and angiogenesis-dependent diseases,such as diabetic nephropathy,cerebral microbleeds,and age-related macular degeneration.Traditional treatments,such as anti-vascular endothelial growth factor agents,vitrectomy,and laser photocoagulation therapy,are more effective for angiogenesis and not tolerable for every patient.Many ongoing clinical trials are exploring effective drugs that target inflammation.For instance,IFN-αacts against viruses and angiogenesis and is commonly used to treat malignant tumors.Moreover,IFN-αhas been shown to contribute to alleviating the progression of DR and other ocular diseases.In this review,we emphasize the roles that IFNs play in the pathogenesis of DR and discuss potential clinical applications of IFNs in DR,such as diagnosis,prognosis,and therapeutic treatment.展开更多
Hepatitis B virus(HBV) infection is one of the major causes of liver diseases, affecting more than 350 million people worldwide. The interferon(IFN)-mediated innate immune responses could restrict HBV replication at t...Hepatitis B virus(HBV) infection is one of the major causes of liver diseases, affecting more than 350 million people worldwide. The interferon(IFN)-mediated innate immune responses could restrict HBV replication at the different steps of viral life cycle. Indeed, IFN-α has been successfully used for treatment of patients with chronic hepatitis B. However, the role of the innate immune response in HBV replication and the mechanism of the anti-HBV effect of IFN-α are not completely explored. In this review, we summarized the currently available knowledge about the IFN-mediated anti-HBV effect in the HBV life cycle and the possible effectors downstream the IFN signaling pathway. The antiviral effect of Toll-like receptors(TLRs) in HBV replication is briefly discussed. The strategies exploited by HBV to evade the IFN- and TLR-mediated antiviral actions are summarized.展开更多
Grass carp hemorrhagic disease caused by grass carp reovirus(GCRV)results in significant economic losses to the global grass carp aquaculture industry.Oral vaccination is an ideal choice for disease precaution in aqua...Grass carp hemorrhagic disease caused by grass carp reovirus(GCRV)results in significant economic losses to the global grass carp aquaculture industry.Oral vaccination is an ideal choice for disease precaution in aquaculture.However,oral vaccine can be degraded in the gut.Therefore,the selection of loading materials is essential.In this study,the S6 and S7 fragments(encoding the outer capsid protein VP4 and fibronectin VP56 of GCRV)and grass carp interferons(IFNs),including IFN1,IFN3,and IFNγ2 were used to create DNA vaccines and adjuvants based on pcDNA3.1,respectively.The oral DNA vaccine was encapsulated in poly(lactic-co-glycolic acid)(PLGA)and polyvinyl alcohol(PVA)with IFNs.The PLGA-PVA(PP)nano-microspheres were prepared by double emulsionsolvent evaporation technique.Using transmission electron microscopy and dynamic light scattering assays,it was determined the vaccines had a spherical structure with uniform particle size(643.5±35.3 nm).The nanomicrospheres possessed excellent encapsulation efficiency(81.6±2.6%)and loading rate(0.54±0.02%),and simultaneously exhibited negligible hemolytic activity and cell toxicity.The protection rate and tissue viral loads post-GCRV challenge in grass carp were assessed.The oral PP nano-microsphere with pVP4 t pIFN1(PP41)vaccine increased protection rate by 44%compared with the control group and was correlated with relatively low viral loads in the spleen,head kidney,and hindgut.Further,three crucial serum biochemical indexes,total superoxide dismutase(TSOD),complement C3(C3),and lysozyme(LZM),were also dramatically increased.Furthermore,mRNA expressions of representative immune-related genes(IgM,IFN1,IFNγ2,MHC-I,and CD8α)in the head kidney and spleen were significantly enhanced.In addition,mRNA expression of IgT was significantly boosted in the hindgut.The results indicate that DNA vaccine capsulated with PP is effective against GCRV infection.The present study provides insights into a prospective strategy for oral vaccine development in aquaculture.展开更多
A hallmark of systemic lupus erythematosus(SLE)is the breaking of B-cell tolerance with the generation of high-affinity autoantibodies;however,the antibody-independent features of the B-cell compartment in SLE are les...A hallmark of systemic lupus erythematosus(SLE)is the breaking of B-cell tolerance with the generation of high-affinity autoantibodies;however,the antibody-independent features of the B-cell compartment in SLE are less understood.In this study,we performed an extensive examination of B-cell subsets and their proinflammatory properties in a Chinese cohort of new-onset SLE patients.We observed that SLE patients exhibited an increased frequency of transitional B cells compared with healthy donors and rheumatoid arthritis patients.Plasma from SLE patients potently promoted the survival of transitional B cells in a type I IFN-dependent manner,which can be recapitulated by direct IFN-αtreatment.Furthermore,the effect of IFN-αon enhanced survival of transitional B cells was associated with NF-κB pathway activation and reduced expression of the pro-apoptotic molecule Bax.Transitional B cells from SLE patients harbored a higher capacity to produce proinflammatory cytokine IL-6,which was also linked to the overactivated type I IFN pathway.In addition,the frequency of IL-6-producing transitional B cells was positively correlated with disease activity in SLE patients,and these cells were significantly reduced after short-term standard therapies.Thus,the current study provides a direct link between type I IFN pathway overactivation and the abnormally high frequency and proinflammatory properties of transitional B cells in active SLE patients,which contributes to the understanding of the roles of type I IFNs and B cells in the pathogenesis of SLE.展开更多
Uncovering the risk factors of pulmonary hypertension and its mechanisms is crucial for the prevention and treatment of the disease.In the current study,we showed that experimental periodontitis,which was established ...Uncovering the risk factors of pulmonary hypertension and its mechanisms is crucial for the prevention and treatment of the disease.In the current study,we showed that experimental periodontitis,which was established by ligation of molars followed by orally smearing subgingival plaques from patients with periodontitis,exacerbated hypoxia-induced pulmonary hypertension in mice.Mechanistically,periodontitis dysregulated the pulmonary microbiota by promoting ectopic colonization and enrichment of oral bacteria in the lungs,contributing to pulmonary infiltration of interferon gamma positive(IFNγ^(+))T cells and aggravating the progression of pulmonary hypertension.In addition,we identified Prevotella zoogleoformans as the critical periodontitis-associated bacterium driving the exacerbation of pulmonary hypertension by periodontitis,and the exacerbation was potently ameliorated by both cervical lymph node excision and IFNγneutralizing antibodies.Our study suggests a proof of concept that the combined prevention and treatment of periodontitis and pulmonary hypertension are necessary.展开更多
The intricate interplay between the human immune system and cancer development underscores the central role of immunotherapy in cancer treatment.Within this landscape,the innate immune system,a critical sentinel prote...The intricate interplay between the human immune system and cancer development underscores the central role of immunotherapy in cancer treatment.Within this landscape,the innate immune system,a critical sentinel protecting against tumor incursion,is a key player.The cyclic GMP-AMP synthase(c GAS)and stimulator of interferon genes(STING)pathway has been found to be a linchpin of innate immunity:activation of this signaling pathway orchestrates the production of type I interferon(IFN-α/β),thus fostering the maturation,differentiation,and mobilization of immune effectors in the tumor microenvironment.Furthermore,STING activation facilitates the release and presentation of tumor antigens,and therefore is an attractive target for cancer immunotherapy.Current strategies to activate the STING pathway,including use of pharmacological agonists,have made substantial advancements,particularly when combined with immune checkpoint inhibitors.These approaches have shown promise in preclinical and clinical settings,by enhancing patient survival rates.This review describes the evolving understanding of the c GAS-STING pathway's involvement in tumor biology and therapy.Moreover,this review explores classical and non-classical STING agonists,providing insights into their mechanisms of action and potential for optimizing immunotherapy strategies.Despite challenges and complexities,the c GAS-STING pathway,a promising avenue for enhancing cancer treatment efficacy,has the potential to revolutionize patient outcomes.展开更多
Sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has...Sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has been involved in the modulation of key inflammatory signaling pathways and transcription factors by deacetylating specific targets, such as nuclear factor κB and nucleotide-binding oligomerization domain-leucine-rich-repeat and pyrin domain-containing protein 3(NLRP3). However, whether sirtuin 2-mediated pathways induce a pro-or an anti-inflammatory response remains controversial. Sirtuin 2 has been implicated in promoting inflammation in conditions such as asthma and neurodegenerative diseases, suggesting that its inhibition in these conditions could be a potential therapeutic strategy. Conversely, arthritis and type 2 diabetes mellitus studies suggest that sirtuin 2 is essential at the peripheral level and, thus, its inhibition in these pathologies would not be recommended. Overall, the precise role of sirtuin 2 in inflammation appears to be context-dependent, and further investigation is needed to determine the specific molecular mechanisms and downstream targets through which sirtuin 2 influences inflammatory processes in various tissues and pathological conditions. The present review explores the involvement of sirtuin 2 in the inflammation associated with different pathologies to elucidate whether its pharmacological modulation could serve as an effective strategy for treating this prevalent symptom across various diseases.展开更多
Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to...Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and CD86.Method This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow cytometer.Results In total,143 patients were enrolled(NH group,n=49;NA group,n=47;P group,n=47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P all<0.001.Conclusion Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.展开更多
Rheumatoid arthritis(RA)is an autoimmune disease.Early studies hold an opinion that gut microbiota is environmentally acquired and associated with RA susceptibility.However,accumulating evidence demonstrates that gene...Rheumatoid arthritis(RA)is an autoimmune disease.Early studies hold an opinion that gut microbiota is environmentally acquired and associated with RA susceptibility.However,accumulating evidence demonstrates that genetics also shape the gut microbiota.It is known that some strains of inbred laboratory mice are highly susceptible to collagen-induced arthritis(CIA),while the others are resistant to CIA.Here,we show that transplantation of fecal microbiota of CIA-resistant C57BL/6J mice to CIA-susceptible DBA/1J mice confer CIA resistance in DBA/1J mice.C57BL/6J mice and healthy human individuals have enriched B.fragilis than DBA/1J mice and RA patients.Transplantation of B.fragilis prevents CIA in DBA/1J mice.We identify that B.fragilis mainly produces propionate and C57BL/6J mice and healthy human individuals have higher level of propionate.Fibroblast-like synoviocytes(FLSs)in RA are activated to undergo tumor-like transformation.Propionate disrupts HDAC3-FOXK1 interaction to increase acetylation of FOXK1,resulting in reduced FOXK1 stability,blocked interferon signaling and deactivation of RA-FLSs.We treat CIA mice with propionate and show that propionate attenuates CIA.Moreover,a combination of propionate with anti-TNF etanercept synergistically relieves CIA.These results suggest that B.fragilis or propionate could be an alternative or complementary approach to the current therapies.展开更多
Cytokines including tumor necrosis factor, interleukins, interferons, and chemokines are abundantly produced in various diseases. As pleiotropic factors, cytokines are involved in nearly every aspect of cellular funct...Cytokines including tumor necrosis factor, interleukins, interferons, and chemokines are abundantly produced in various diseases. As pleiotropic factors, cytokines are involved in nearly every aspect of cellular functions such as migration, survival, proliferation, and differentiation. Oligodendrocytes are the myelin-forming cells in the central nervous system and play critical roles in the conduction of action potentials, supply of metabolic components for axons, and other functions. Emerging evidence suggests that both oligodendrocytes and oligodendrocyte precursor cells are vulnerable to cytokines released under pathological conditions. This review mainly summarizes the effects of cytokines on oligodendrocyte lineage cells in central nervous system diseases. A comprehensive understanding of the effects of cytokines on oligodendrocyte lineage cells contributes to our understanding of central nervous system diseases and offers insights into treatment strategies.展开更多
Chronic viral hepatitis causes an increased risk of progressive liver disease and hepatocellular carcinoma.On the wave of the World Health Organization’s goal to reduce new cases and deaths from hepatitis B and C by ...Chronic viral hepatitis causes an increased risk of progressive liver disease and hepatocellular carcinoma.On the wave of the World Health Organization’s goal to reduce new cases and deaths from hepatitis B and C by 2030,there is an increasing call to expand the indications for treatment of chronic hepatitis B.Currently,the main goal of treatment is to achieve a functional cure due to the inability of current drugs to completely eradicate the virus.There are still many discrepancies between available guidelines in terms of eligibility for treatment as well as an uncertainty about the appropriate treatment duration.This editorial addresses key questions about the topic and whether indications for treatment should be expanded.展开更多
Objective:To explore expression level of interferon-stimulated genes PKR,OAS1,MX1,and ISG15 in peripheral blood mononuclear cells of COVID-19 patients.Methods:In this study,changes in the expression of four interferon...Objective:To explore expression level of interferon-stimulated genes PKR,OAS1,MX1,and ISG15 in peripheral blood mononuclear cells of COVID-19 patients.Methods:In this study,changes in the expression of four interferon-stimulated genes(ISGs),including PKR,OAS1,MX1,and ISG15,in peripheral blood mononuclear cells of 45 COVID-19 patients with different severities were evaluated by real-time PCR method.Results:OAS1,MX1,PKR,and ISG15 were differently expressed in COVID-19 patients with different severity.The results showed that the expression of OAS1,MX1,PKR,and ISG15 genes was significantly(P=0.001)lower in severe patients.Conclusions:Weak and defective IFN response and subsequent disruption of ISGs may be associated with COVID-19 severity.展开更多
BACKGROUND Secondary hemophagocytic lymphohistiocytosis(sHLH)triggered by Salmonella enterica serovar Typhimurium is rare in pediatric patients.There is no consensus on how to treat S.typhimurium-triggered sHLH.CASE S...BACKGROUND Secondary hemophagocytic lymphohistiocytosis(sHLH)triggered by Salmonella enterica serovar Typhimurium is rare in pediatric patients.There is no consensus on how to treat S.typhimurium-triggered sHLH.CASE SUMMARY A 9-year-old boy with intermittent fever for 3 d presented to our hospital with positive results for S.typhimurium,human rhinovirus,and Mycoplasma pneumoniae infections.At the time of admission to our institution,the patient’s T helper 1/T helper 2 cytokine levels were 326 pg/mL for interleukin 6(IL-6),9.1 pg/mL for IL-10,and 246.7 pg/mL for interferon-gamma(IFN-γ),for which the ratio of IL-10 to IFN-γwas 0.04.In this study,the patient received meropenem,linezolid,and cefoperazone/sulbactam in combination with high-dose methylprednisolone therapy(10 mg/kg/d for 3 d)and antishock supportive treatment twice.After careful evaluation,this patient did not receive HLH chemotherapy and recovered well.CONCLUSION S.Typhimurium infection-triggered sHLH patient had a ratio of IL-10 to IFN-γ≤1.33,an IL-10 concentration≤10.0 pg/mL,and/or an IFN-γconcentration≤225 pg/mL at admission.Early antimicrobial and supportive treatment was sufficient,and the HLH-94/2004 protocol was not necessary under these conditions.展开更多
Achievement of a‘clinical cure’in chronic hepatitis B(CHB)implies sustained virological suppression and immunological control over the infection,which is the ideal treatment goal according to domestic and internatio...Achievement of a‘clinical cure’in chronic hepatitis B(CHB)implies sustained virological suppression and immunological control over the infection,which is the ideal treatment goal according to domestic and international CHB management guidelines.Clinical practice has shown encouraging results for specific patient cohorts using tailored treatment regimens.These regimens incorporate either nucleos(t)ide analogs,immunomodulatory agents such as pegylated interferonα,or a strategic combination of both,sequentially or concurrently administered.Despite these advancements in the clinical handling of hepatitis B,achieving a clinical cure remains elusive for a considerable subset of patients due to the number of challenges that preclude the realization of optimal treatment outcomes.These include,but are not limited to,the emergence of antiviral resistance,incomplete immune recovery,and the persistence of covalently closed circular DNA.Moreover,the variance in response to interferon therapy and the lack of definitive biomarkers for treatment cessation also contribute to the complexity of achieving a clinical cure.This article briefly overviews the current research progress and existing issues in pursuing a clinical cure for hepatitis B.展开更多
The treatment of hepatitis C has undergone a significant boom since the advent of direct acting antivirals (DAA). Indeed, the interferon-ribavirin combination that has been used to treat hepatitis C has a virological ...The treatment of hepatitis C has undergone a significant boom since the advent of direct acting antivirals (DAA). Indeed, the interferon-ribavirin combination that has been used to treat hepatitis C has a virological response in only 45% of cases with significant side effects. The advent of direct-acting antivirals has changed the prognosis of cirrhotic patients with hepatitis C. DAAs have ensured a sustained viral response in the majority of patients. Our work aims to see the evolution of hepatitis C patients at the cirrhosis stage under DAA. We conducted a retrospective study over 15 years (January 2009, January 2024) including all patients with post-viral cirrhosis C, whom we divided into two groups: group A, cirrhotic patients who received ribavirin and interferon, and group B, patients on DAA. From January 2009 to January 2024, we conducted a study of 182 patients with viral hepatitis C, including 102 cirrhotic patients. The mean age was 55 years. 66% of patients were initially treated with the ribavirin interferon combination, while 34% received direct-acting antivirals (DAAs). Since the introduction of DAAs, the most commonly used regimens have been sofosbuvir/daclatasvir with or without ribavirin and sofosbuvir/ledipasvir with or without ribavirin. Group A achieved sustained virological response (SVR) in 60% of cases, with notable side effects. In Group B, SVR was 98.18%, with improved tolerability and fewer side effects than previous treatments. Fifteen patients developed hepatocellular carcinoma (HCC), with a significantly lower mortality rate in those treated with DAAs compared with pegylated dual therapy (p: 0.001).展开更多
Introduction: Kaposi sarcoma disease is a proliferative and multifocal disorder with dual components, vascular and fibroblastic cellular, cutaneous and visceral expression. Kaposi Sarcoma can affect the ocular surface...Introduction: Kaposi sarcoma disease is a proliferative and multifocal disorder with dual components, vascular and fibroblastic cellular, cutaneous and visceral expression. Kaposi Sarcoma can affect the ocular surface and adnexa and can masquerade as other entities, delaying prompt diagnosis can lead to diagnostic wandering delaying treatment. Our aim is to describe a case of KS of the eyelid in an HIV seronegative patient. Case Presentation: A seventy-year-old man developed a bilateral growing tumoral reddish purple vascular mass on both the lower and upper eyelid involving rapidly for 6 months. Both feet and the two shanks show the presence of a brown-violet tumor-shaped formation. The patient was negative for HIV. Histology examination showed a nodular tumor-like mass with a fibro hemangioma-epitheliomatous. Polymerase chain reaction was positive for human herpes virus 8. Initial chemotherapy followed by surgery was proposed to the patient. Unfortunately, the patient rejected treatment and was lost to follow-up. Conclusion: This case reports the difficulty of managing KS in developing countries.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
Purpose To review the efficacy and safety of pegylated interferons (peginterferons) in the treatment of chronic hepatitis C Data sources An English language literature search (MEDLINE 1988-2001) was performed and a...Purpose To review the efficacy and safety of pegylated interferons (peginterferons) in the treatment of chronic hepatitis C Data sources An English language literature search (MEDLINE 1988-2001) was performed and a total of 19 original articles related to the issue were selected Data extraction After careful review of the selected papers, the meaningful results and conclusions were extracted using scientific criteria The papers reviewed pertained mainly to the efficacy and safety profiles of peginterferons in the treatment of chronic hepatitis C Results Peginterferon can effectively prolong the half-life of interferon and can be effectively administered conveniently as a once-a-week dose The antiviral effect using peginterferon was enhanced compared with that of standard interferon, but the frequency and severity of adverse events were typical of those associated with interferon-α Conclusions Based on its efficacy, safety and convenient dosing, peginterferon is more favorable than standard interferon in the treatment of chronic hepatitis C展开更多
The mammalian innate immune system provides the first line of defensive mechanisms to protect the host against invading pathogens.These defensive responses are initiated by recognition of microbial pathogen-associated...The mammalian innate immune system provides the first line of defensive mechanisms to protect the host against invading pathogens.These defensive responses are initiated by recognition of microbial pathogen-associated molecular patterns(PAMPs).展开更多
It is well known that interferons are potential antivirus proteins and possess anticancer capability. In the Thirty-fifth Symposium of the Society for General Microbiology on Interferons held in 1983, Hans Strander re...It is well known that interferons are potential antivirus proteins and possess anticancer capability. In the Thirty-fifth Symposium of the Society for General Microbiology on Interferons held in 1983, Hans Strander reported that interferons had been successfully applied in the treatment of juvenile laryngeal papilloma, papilloma accuminatum, malignant mydomatosis, osteosarcoma, breast cancer, cancer of the colon, non-Hodgkin lymphoma,展开更多
基金Supported by National Natural Science Foundation of China,No.81800855 and No.82070967Natural Science Foundation of Hunan Province,No.2018JJ3765.
文摘Diabetic retinopathy(DR)is one of the major causes of visual impairment and irreversible blindness in developed regions.Aside from abnormal angiogenesis,inflammation is the most specific and might be the initiating factor of DR.As a key participant in inflammation,interferon-gamma(IFN-γ)can be detected in different parts of the eye and is responsible for the breakdown of the blood-retina barrier and activation of inflammatory cells and other cytokines,which accelerate neovascularization and neuroglial degeneration.In addition,IFN-γis involved in other vascular complications of diabetes mellitus and angiogenesis-dependent diseases,such as diabetic nephropathy,cerebral microbleeds,and age-related macular degeneration.Traditional treatments,such as anti-vascular endothelial growth factor agents,vitrectomy,and laser photocoagulation therapy,are more effective for angiogenesis and not tolerable for every patient.Many ongoing clinical trials are exploring effective drugs that target inflammation.For instance,IFN-αacts against viruses and angiogenesis and is commonly used to treat malignant tumors.Moreover,IFN-αhas been shown to contribute to alleviating the progression of DR and other ocular diseases.In this review,we emphasize the roles that IFNs play in the pathogenesis of DR and discuss potential clinical applications of IFNs in DR,such as diagnosis,prognosis,and therapeutic treatment.
基金Supported by National Natural Science Foundation of China to Pei RJ and Chen XC,Nos.31200135 and 31200699German Research Foundation to Lu MG,Nos.TRR60,GK1045/2 and GK1949
文摘Hepatitis B virus(HBV) infection is one of the major causes of liver diseases, affecting more than 350 million people worldwide. The interferon(IFN)-mediated innate immune responses could restrict HBV replication at the different steps of viral life cycle. Indeed, IFN-α has been successfully used for treatment of patients with chronic hepatitis B. However, the role of the innate immune response in HBV replication and the mechanism of the anti-HBV effect of IFN-α are not completely explored. In this review, we summarized the currently available knowledge about the IFN-mediated anti-HBV effect in the HBV life cycle and the possible effectors downstream the IFN signaling pathway. The antiviral effect of Toll-like receptors(TLRs) in HBV replication is briefly discussed. The strategies exploited by HBV to evade the IFN- and TLR-mediated antiviral actions are summarized.
基金supported by the National Key R&D Program of China(2022YFF1000302)Major Project of Hubei Hongshan Laboratory(2022hszd011).
文摘Grass carp hemorrhagic disease caused by grass carp reovirus(GCRV)results in significant economic losses to the global grass carp aquaculture industry.Oral vaccination is an ideal choice for disease precaution in aquaculture.However,oral vaccine can be degraded in the gut.Therefore,the selection of loading materials is essential.In this study,the S6 and S7 fragments(encoding the outer capsid protein VP4 and fibronectin VP56 of GCRV)and grass carp interferons(IFNs),including IFN1,IFN3,and IFNγ2 were used to create DNA vaccines and adjuvants based on pcDNA3.1,respectively.The oral DNA vaccine was encapsulated in poly(lactic-co-glycolic acid)(PLGA)and polyvinyl alcohol(PVA)with IFNs.The PLGA-PVA(PP)nano-microspheres were prepared by double emulsionsolvent evaporation technique.Using transmission electron microscopy and dynamic light scattering assays,it was determined the vaccines had a spherical structure with uniform particle size(643.5±35.3 nm).The nanomicrospheres possessed excellent encapsulation efficiency(81.6±2.6%)and loading rate(0.54±0.02%),and simultaneously exhibited negligible hemolytic activity and cell toxicity.The protection rate and tissue viral loads post-GCRV challenge in grass carp were assessed.The oral PP nano-microsphere with pVP4 t pIFN1(PP41)vaccine increased protection rate by 44%compared with the control group and was correlated with relatively low viral loads in the spleen,head kidney,and hindgut.Further,three crucial serum biochemical indexes,total superoxide dismutase(TSOD),complement C3(C3),and lysozyme(LZM),were also dramatically increased.Furthermore,mRNA expressions of representative immune-related genes(IgM,IFN1,IFNγ2,MHC-I,and CD8α)in the head kidney and spleen were significantly enhanced.In addition,mRNA expression of IgT was significantly boosted in the hindgut.The results indicate that DNA vaccine capsulated with PP is effective against GCRV infection.The present study provides insights into a prospective strategy for oral vaccine development in aquaculture.
基金This work was supported by the National Basic Research Program of China(No.2014CB541904)the National Natural Science Foundation of China(Nos.31470879 81571575 8171101311 and 31770960)+2 种基金the Interdisciplinary Innovation Team,External Cooperation Program(No.GJHZ201312)Key Project QYZDB-SSW-SMC036the Strategic Priority Research Program(No.XDPB0303),Chinese Academy of Sciences.
文摘A hallmark of systemic lupus erythematosus(SLE)is the breaking of B-cell tolerance with the generation of high-affinity autoantibodies;however,the antibody-independent features of the B-cell compartment in SLE are less understood.In this study,we performed an extensive examination of B-cell subsets and their proinflammatory properties in a Chinese cohort of new-onset SLE patients.We observed that SLE patients exhibited an increased frequency of transitional B cells compared with healthy donors and rheumatoid arthritis patients.Plasma from SLE patients potently promoted the survival of transitional B cells in a type I IFN-dependent manner,which can be recapitulated by direct IFN-αtreatment.Furthermore,the effect of IFN-αon enhanced survival of transitional B cells was associated with NF-κB pathway activation and reduced expression of the pro-apoptotic molecule Bax.Transitional B cells from SLE patients harbored a higher capacity to produce proinflammatory cytokine IL-6,which was also linked to the overactivated type I IFN pathway.In addition,the frequency of IL-6-producing transitional B cells was positively correlated with disease activity in SLE patients,and these cells were significantly reduced after short-term standard therapies.Thus,the current study provides a direct link between type I IFN pathway overactivation and the abnormally high frequency and proinflammatory properties of transitional B cells in active SLE patients,which contributes to the understanding of the roles of type I IFNs and B cells in the pathogenesis of SLE.
基金fundings from the National Natural Science Foundation of China(82330015,81991503,81921002,and 82303275)Science and Technology Commission of Shanghai Municipality(23ZR1438300).
文摘Uncovering the risk factors of pulmonary hypertension and its mechanisms is crucial for the prevention and treatment of the disease.In the current study,we showed that experimental periodontitis,which was established by ligation of molars followed by orally smearing subgingival plaques from patients with periodontitis,exacerbated hypoxia-induced pulmonary hypertension in mice.Mechanistically,periodontitis dysregulated the pulmonary microbiota by promoting ectopic colonization and enrichment of oral bacteria in the lungs,contributing to pulmonary infiltration of interferon gamma positive(IFNγ^(+))T cells and aggravating the progression of pulmonary hypertension.In addition,we identified Prevotella zoogleoformans as the critical periodontitis-associated bacterium driving the exacerbation of pulmonary hypertension by periodontitis,and the exacerbation was potently ameliorated by both cervical lymph node excision and IFNγneutralizing antibodies.Our study suggests a proof of concept that the combined prevention and treatment of periodontitis and pulmonary hypertension are necessary.
基金the National Key Research and Development Program of China(Grant Nos.2022YFC3401500 and 2020YFA0803201 to P.W.,and 2021YFA1302200 to L.F.)the National Natural Science Foundation of China(Grant Nos.31830053,31920103007,and 82341028 to P.W.+1 种基金82122056,82073153,and 31871398 to L.F.and 31900568 to P.W.)the Natural Science Foundation of Shanghai(Grant No.22ZR1450700 to Z.J.W.)。
文摘The intricate interplay between the human immune system and cancer development underscores the central role of immunotherapy in cancer treatment.Within this landscape,the innate immune system,a critical sentinel protecting against tumor incursion,is a key player.The cyclic GMP-AMP synthase(c GAS)and stimulator of interferon genes(STING)pathway has been found to be a linchpin of innate immunity:activation of this signaling pathway orchestrates the production of type I interferon(IFN-α/β),thus fostering the maturation,differentiation,and mobilization of immune effectors in the tumor microenvironment.Furthermore,STING activation facilitates the release and presentation of tumor antigens,and therefore is an attractive target for cancer immunotherapy.Current strategies to activate the STING pathway,including use of pharmacological agonists,have made substantial advancements,particularly when combined with immune checkpoint inhibitors.These approaches have shown promise in preclinical and clinical settings,by enhancing patient survival rates.This review describes the evolving understanding of the c GAS-STING pathway's involvement in tumor biology and therapy.Moreover,this review explores classical and non-classical STING agonists,providing insights into their mechanisms of action and potential for optimizing immunotherapy strategies.Despite challenges and complexities,the c GAS-STING pathway,a promising avenue for enhancing cancer treatment efficacy,has the potential to revolutionize patient outcomes.
基金funded by FEDER/Ministerio de Ciencia,Innovación y Universidades Agencia Estatal de Investigación/Project(PID2020-119729GB-100,REF/AEI/10.13039/501100011033)(to EP)a predoctoral fellowship from the Spanish Ministry of Universities(FPU)and Amigos de la Universidad de Navarra(to NSS)“Programa MRR Investigo 2023”(to MGB and MMD)。
文摘Sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has been involved in the modulation of key inflammatory signaling pathways and transcription factors by deacetylating specific targets, such as nuclear factor κB and nucleotide-binding oligomerization domain-leucine-rich-repeat and pyrin domain-containing protein 3(NLRP3). However, whether sirtuin 2-mediated pathways induce a pro-or an anti-inflammatory response remains controversial. Sirtuin 2 has been implicated in promoting inflammation in conditions such as asthma and neurodegenerative diseases, suggesting that its inhibition in these conditions could be a potential therapeutic strategy. Conversely, arthritis and type 2 diabetes mellitus studies suggest that sirtuin 2 is essential at the peripheral level and, thus, its inhibition in these pathologies would not be recommended. Overall, the precise role of sirtuin 2 in inflammation appears to be context-dependent, and further investigation is needed to determine the specific molecular mechanisms and downstream targets through which sirtuin 2 influences inflammatory processes in various tissues and pathological conditions. The present review explores the involvement of sirtuin 2 in the inflammation associated with different pathologies to elucidate whether its pharmacological modulation could serve as an effective strategy for treating this prevalent symptom across various diseases.
基金supported by the National Key Research and Development Program[2022YFC2603500,2022YFC2603505]Capital Clinical Diagnostic Techniques and Translational Application Projects(Z211100002921059)+2 种基金Capital’s Funds for Health Improvement and Research[2022-1-2172]Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support[XMLX 202127]National Science and Technology Major Project of China[2017ZX10203202-003]。
文摘Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and CD86.Method This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow cytometer.Results In total,143 patients were enrolled(NH group,n=49;NA group,n=47;P group,n=47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P all<0.001.Conclusion Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.
基金supported by the National Natural Science Foundation Council of China(82172386 and 81922081 to C.L.,82100943 to X.F.,82104216 to J.L.,and 82230081,82250710175 and 8226116039 to G.X.)the Department of Education of Guangdong Province(2021KTSCX104 to C.L.)+5 种基金the 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund(Guangdong-Hong Kong-Macao Joint Lab)(2020B1212030006 to A.L.)the Guangdong Provincial Science and Technology Innovation Council Grant(2017B030301018 to G.X.)the Guangdong Basic and Applied Basic Research Foundation(2022A1515012164 to C.L.,and 2023A1515012000 to X.F.)the Science,Technology and Innovation Commission of Shenzhen(JCYJ20210324104201005 to C.L.,JCYJ20220530115006014 to X.F.,JCYJ20230807095118035 to J.L.,and JCYJ20220818100617036 to G.X.)the Hong Kong General Research Fund(12102722 to A.L.)the Hong Kong RGC Themebased Research Scheme(T12-201/20-R to A.L.).
文摘Rheumatoid arthritis(RA)is an autoimmune disease.Early studies hold an opinion that gut microbiota is environmentally acquired and associated with RA susceptibility.However,accumulating evidence demonstrates that genetics also shape the gut microbiota.It is known that some strains of inbred laboratory mice are highly susceptible to collagen-induced arthritis(CIA),while the others are resistant to CIA.Here,we show that transplantation of fecal microbiota of CIA-resistant C57BL/6J mice to CIA-susceptible DBA/1J mice confer CIA resistance in DBA/1J mice.C57BL/6J mice and healthy human individuals have enriched B.fragilis than DBA/1J mice and RA patients.Transplantation of B.fragilis prevents CIA in DBA/1J mice.We identify that B.fragilis mainly produces propionate and C57BL/6J mice and healthy human individuals have higher level of propionate.Fibroblast-like synoviocytes(FLSs)in RA are activated to undergo tumor-like transformation.Propionate disrupts HDAC3-FOXK1 interaction to increase acetylation of FOXK1,resulting in reduced FOXK1 stability,blocked interferon signaling and deactivation of RA-FLSs.We treat CIA mice with propionate and show that propionate attenuates CIA.Moreover,a combination of propionate with anti-TNF etanercept synergistically relieves CIA.These results suggest that B.fragilis or propionate could be an alternative or complementary approach to the current therapies.
基金supported by the Natural Science Foundation of Zhejiang Province,No.LQ23C090003 (to CZ)the Major Project on Brain Science and Analog Brain Research of Ministry of Science and Technology of China,No.2022ZD0204701 (to MQ)the National Natural Science Foundation of China,No.32170969 (to MQ)。
文摘Cytokines including tumor necrosis factor, interleukins, interferons, and chemokines are abundantly produced in various diseases. As pleiotropic factors, cytokines are involved in nearly every aspect of cellular functions such as migration, survival, proliferation, and differentiation. Oligodendrocytes are the myelin-forming cells in the central nervous system and play critical roles in the conduction of action potentials, supply of metabolic components for axons, and other functions. Emerging evidence suggests that both oligodendrocytes and oligodendrocyte precursor cells are vulnerable to cytokines released under pathological conditions. This review mainly summarizes the effects of cytokines on oligodendrocyte lineage cells in central nervous system diseases. A comprehensive understanding of the effects of cytokines on oligodendrocyte lineage cells contributes to our understanding of central nervous system diseases and offers insights into treatment strategies.
文摘Chronic viral hepatitis causes an increased risk of progressive liver disease and hepatocellular carcinoma.On the wave of the World Health Organization’s goal to reduce new cases and deaths from hepatitis B and C by 2030,there is an increasing call to expand the indications for treatment of chronic hepatitis B.Currently,the main goal of treatment is to achieve a functional cure due to the inability of current drugs to completely eradicate the virus.There are still many discrepancies between available guidelines in terms of eligibility for treatment as well as an uncertainty about the appropriate treatment duration.This editorial addresses key questions about the topic and whether indications for treatment should be expanded.
基金the research council of Kerman University of Medical Sciences,Kerman,Iran(Grant Number:400000232).
文摘Objective:To explore expression level of interferon-stimulated genes PKR,OAS1,MX1,and ISG15 in peripheral blood mononuclear cells of COVID-19 patients.Methods:In this study,changes in the expression of four interferon-stimulated genes(ISGs),including PKR,OAS1,MX1,and ISG15,in peripheral blood mononuclear cells of 45 COVID-19 patients with different severities were evaluated by real-time PCR method.Results:OAS1,MX1,PKR,and ISG15 were differently expressed in COVID-19 patients with different severity.The results showed that the expression of OAS1,MX1,PKR,and ISG15 genes was significantly(P=0.001)lower in severe patients.Conclusions:Weak and defective IFN response and subsequent disruption of ISGs may be associated with COVID-19 severity.
基金Supported by Zhejiang Province Health and Wellness Science and Technology Program in 2022,China,No.2022RC202.
文摘BACKGROUND Secondary hemophagocytic lymphohistiocytosis(sHLH)triggered by Salmonella enterica serovar Typhimurium is rare in pediatric patients.There is no consensus on how to treat S.typhimurium-triggered sHLH.CASE SUMMARY A 9-year-old boy with intermittent fever for 3 d presented to our hospital with positive results for S.typhimurium,human rhinovirus,and Mycoplasma pneumoniae infections.At the time of admission to our institution,the patient’s T helper 1/T helper 2 cytokine levels were 326 pg/mL for interleukin 6(IL-6),9.1 pg/mL for IL-10,and 246.7 pg/mL for interferon-gamma(IFN-γ),for which the ratio of IL-10 to IFN-γwas 0.04.In this study,the patient received meropenem,linezolid,and cefoperazone/sulbactam in combination with high-dose methylprednisolone therapy(10 mg/kg/d for 3 d)and antishock supportive treatment twice.After careful evaluation,this patient did not receive HLH chemotherapy and recovered well.CONCLUSION S.Typhimurium infection-triggered sHLH patient had a ratio of IL-10 to IFN-γ≤1.33,an IL-10 concentration≤10.0 pg/mL,and/or an IFN-γconcentration≤225 pg/mL at admission.Early antimicrobial and supportive treatment was sufficient,and the HLH-94/2004 protocol was not necessary under these conditions.
基金Supported by National Key Research and Development Program of China 2023,No:2023YFC2308100.
文摘Achievement of a‘clinical cure’in chronic hepatitis B(CHB)implies sustained virological suppression and immunological control over the infection,which is the ideal treatment goal according to domestic and international CHB management guidelines.Clinical practice has shown encouraging results for specific patient cohorts using tailored treatment regimens.These regimens incorporate either nucleos(t)ide analogs,immunomodulatory agents such as pegylated interferonα,or a strategic combination of both,sequentially or concurrently administered.Despite these advancements in the clinical handling of hepatitis B,achieving a clinical cure remains elusive for a considerable subset of patients due to the number of challenges that preclude the realization of optimal treatment outcomes.These include,but are not limited to,the emergence of antiviral resistance,incomplete immune recovery,and the persistence of covalently closed circular DNA.Moreover,the variance in response to interferon therapy and the lack of definitive biomarkers for treatment cessation also contribute to the complexity of achieving a clinical cure.This article briefly overviews the current research progress and existing issues in pursuing a clinical cure for hepatitis B.
文摘The treatment of hepatitis C has undergone a significant boom since the advent of direct acting antivirals (DAA). Indeed, the interferon-ribavirin combination that has been used to treat hepatitis C has a virological response in only 45% of cases with significant side effects. The advent of direct-acting antivirals has changed the prognosis of cirrhotic patients with hepatitis C. DAAs have ensured a sustained viral response in the majority of patients. Our work aims to see the evolution of hepatitis C patients at the cirrhosis stage under DAA. We conducted a retrospective study over 15 years (January 2009, January 2024) including all patients with post-viral cirrhosis C, whom we divided into two groups: group A, cirrhotic patients who received ribavirin and interferon, and group B, patients on DAA. From January 2009 to January 2024, we conducted a study of 182 patients with viral hepatitis C, including 102 cirrhotic patients. The mean age was 55 years. 66% of patients were initially treated with the ribavirin interferon combination, while 34% received direct-acting antivirals (DAAs). Since the introduction of DAAs, the most commonly used regimens have been sofosbuvir/daclatasvir with or without ribavirin and sofosbuvir/ledipasvir with or without ribavirin. Group A achieved sustained virological response (SVR) in 60% of cases, with notable side effects. In Group B, SVR was 98.18%, with improved tolerability and fewer side effects than previous treatments. Fifteen patients developed hepatocellular carcinoma (HCC), with a significantly lower mortality rate in those treated with DAAs compared with pegylated dual therapy (p: 0.001).
文摘Introduction: Kaposi sarcoma disease is a proliferative and multifocal disorder with dual components, vascular and fibroblastic cellular, cutaneous and visceral expression. Kaposi Sarcoma can affect the ocular surface and adnexa and can masquerade as other entities, delaying prompt diagnosis can lead to diagnostic wandering delaying treatment. Our aim is to describe a case of KS of the eyelid in an HIV seronegative patient. Case Presentation: A seventy-year-old man developed a bilateral growing tumoral reddish purple vascular mass on both the lower and upper eyelid involving rapidly for 6 months. Both feet and the two shanks show the presence of a brown-violet tumor-shaped formation. The patient was negative for HIV. Histology examination showed a nodular tumor-like mass with a fibro hemangioma-epitheliomatous. Polymerase chain reaction was positive for human herpes virus 8. Initial chemotherapy followed by surgery was proposed to the patient. Unfortunately, the patient rejected treatment and was lost to follow-up. Conclusion: This case reports the difficulty of managing KS in developing countries.
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Purpose To review the efficacy and safety of pegylated interferons (peginterferons) in the treatment of chronic hepatitis C Data sources An English language literature search (MEDLINE 1988-2001) was performed and a total of 19 original articles related to the issue were selected Data extraction After careful review of the selected papers, the meaningful results and conclusions were extracted using scientific criteria The papers reviewed pertained mainly to the efficacy and safety profiles of peginterferons in the treatment of chronic hepatitis C Results Peginterferon can effectively prolong the half-life of interferon and can be effectively administered conveniently as a once-a-week dose The antiviral effect using peginterferon was enhanced compared with that of standard interferon, but the frequency and severity of adverse events were typical of those associated with interferon-α Conclusions Based on its efficacy, safety and convenient dosing, peginterferon is more favorable than standard interferon in the treatment of chronic hepatitis C
文摘The mammalian innate immune system provides the first line of defensive mechanisms to protect the host against invading pathogens.These defensive responses are initiated by recognition of microbial pathogen-associated molecular patterns(PAMPs).
文摘It is well known that interferons are potential antivirus proteins and possess anticancer capability. In the Thirty-fifth Symposium of the Society for General Microbiology on Interferons held in 1983, Hans Strander reported that interferons had been successfully applied in the treatment of juvenile laryngeal papilloma, papilloma accuminatum, malignant mydomatosis, osteosarcoma, breast cancer, cancer of the colon, non-Hodgkin lymphoma,