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Introducción: El lupus eritematoso sistémico (LES) es una enfermedad autoinmune que causa inflamación sistémica y alteraciones en la tolerancia inmunológica. La activación de los genes inducibles por interferón (IFN), contribuye en más del 50% de su patogenia. Objetivo: relacionar el papel del IFN-λ en la patogenia del LES. Materiales y Métodos: Búsqueda sistémica en base de datos; a través de las palabras claves del MeSH and DeCS. Fue incluido adicionalmente la palabra "Interferón Lambda". Resultados: Se encontró que la producción aberrante de interferón tipo I contribuye a la desregulación de IFN-λ, producido principalmente por células dendríticas plasmocitoides. Este proceso conduce a la estimulación inmunológica por autoanticuerpos y a un aumento de IFNλR-1 en células B, potenciando la generación de anticuerpos. IFN-λ3 se asocia particularmente con nefritis lúpica, y el IFN-λ en general aumenta la expresión de MHC-I, intensificando la respuesta de células T CD8+ y posiblemente afectando la tolerancia central y la regulación en el timo. Conclusión: Se destaca que el IFN-λ favorece la activación inmune, formación de inmunocomplejos, inflamación crónica y producción de autoanticuerpos, vinculándose niveles altos de IFN-λ3 con mayor actividad de la enfermedad.
Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease that causes systemic inflammation and alterations in immunological tolerance. The activation of interferon (IFN)-inducible genes contributes to more than 50% of its pathogenesis. Objective: to review the role of IFN-λ in the pathogenesis of SLE. Materials and Methods: Systemic search in database; through the MeSH and DeCS keywords. The word "Lambda Interferon" was additionally included. Results: Aberrant production of type I interferon was found to contribute to the deregulation of IFN-λ, produced mainly by plasmacytoid dendritic cells. This process leads to immunological stimulation by autoantibodies and an increase in IFNλR-1 in B cells, enhancing the generation of antibodies. IFN-λ3 is particularly associated with lupus nephritis, and IFN-λ generally increases MHC-I expression, enhancing the CD8+ T cell response and possibly affecting central tolerance and regulation in the thymus. Conclusion: It is highlighted that IFN-λ favors immune activation, formation of immune complexes, chronic inflammation and production of autoantibodies, linking high levels of IFN-λ3 with greater disease activity.
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This guideline aims to provide comprehensive and practical guidance for clinical management of tuberculosis in kidney transplant recipients. First, it summarizes the particularity of tuberculosis in kidney transplant recipients, and highlights the high incidence and diverse clinical manifestations. To better understand the patients' conditions, relevant assessment of tuberculosis is recommended before kidney transplantation. Extensive attention should be paid to the monitoring of tuberculosis after kidney transplantation. Regarding the diagnosis, the guideline explicitly introduces common diagnostic approaches for tuberculosis, and evaluates the applicability in kidney transplant recipients. After the diagnosis is confirmed, it discusses how to balance the treatment and rejection of tuberculosis under the background of immunosuppressants, and focuses upon the potential drug interaction. In terms of prevention, it emphasizes the screening of tuberculosis prior to kidney transplantation. This guideline is designed to deepen the understanding of medical staff for tuberculosis management in kidney transplant recipients, promote more effective clinical practice and improve the quality of life of the recipients.
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Objective:To investigate the level change of cytokines in patients with Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (EBV-HLH).Methods:A retrospective case control study was conducted. The clinical data of 65 patients with EBV-HLH, 30 patients with infectious mononucleosis (IM) (IM group) and 40 patients with non-EBV infection-associated hemophagocytic lymphohistiocytosis (non-EBV-HLH group) who admitted to Tongji Hospital,Tongji Medical College of Huazhong University of Science and Technology from February 2022 to February 2023 were retrospectively analyzed. The enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of the interleukin (IL)-6, IL-2, IL-10, IL-8, IL-1β, tumor necrosis factor-α (TNF-α) and interferon γ (IFN-γ) in serum samples of patients in the above 3 groups. The cytokines levels in EBV-HLH group were compared with those in IM group and non-EBV-HLH group, respectively.Results:The cytokines levels of IL-6, IL-2, IL-10, IL-8, IL-1β, TNF-α and IFN-γ in EBV-HLH group were higher than those in the non-EBV-HLH group, and the differences were statistically significant (all P < 0.05). The cytokines levels of IL-2, IL-10 and IFN-γ in EBV-HLH group were higher than those in IM group, and the differences were statistically significant (all P < 0.05). Conclusions:The cytokines levels of IL-6, IL-2, IL-10, IL-8, IL-1β, TNF-α, IFN-γ are increased in EBV-HLH patients, which may play an important role in the development and progression of EBV-HLH.
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Objective To explore the effect of scutellarin on lipopolysaccharide(LPS)induced neuroinflammation in BV-2 microglia cells.Methods BV-2 microglia were cultured and randomly divided into 6 groups:control group(Ctrl),cyclic GMP-AMP synthetase(cGAS)inhibitor RU320521 group(RU.521 group),LPS group,LPS+RU.521 group,LPS+scutellarin pretreatment group(LPS+S)and LPS+S+RU.521 group.The expressions of cGAS,stimulator of interferon gene(STING),nuclear factor kappa B(NF-κB),phosphorylated NF-κB(p-NF-κB),neuroinflammatory factors PYD domains-containing protein 3(NLRP3)and tumor necrosis factor α(TNF-α)in BV-2 microglia were detected by Western blotting and immunofluorescent double staining(n= 3).Results Western blotting and immunofluorescent double staining showed that compared with the control group,the expression of cGAS,STING,p-NF-κB,NLRP3 and TNF-α in BV-2 microglia increased significantly after LPS induction(P<0.05),while the expression of cGAS,STING,p-NF-κB,NLRP3 and TNF-α in LPS+S group were significantly lower than those in LPS group(P<0.05).Treatment with cGAS pathway inhibitor RU.521 showed similar effects as the pre-treatment group with scutellarin.In addition,the change of NF-κB in each group was not statistically significant(P>0.05).Conclusion Scutellarin inhibits the neuroinflammation mediated by BV-2 microglia cells,which may be related to cGAS-STING signaling pathway.
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Objective To investigate the expression of activating transcription factor 6(ATF6)and interferon α(IFN-α)and their significance in laryngeal squamous cell carcinoma(LSCC)tissue.Methods A total of 100 LSCC patients admitted to Clinical Medical College of Henan University of Science and Technology/the First Affiliated Hospital of Henan University of Science and Technology from March 2015 to March 2020 were selected,and their clinicopathological features such as tumor location,degree of differentiation,and lymph node metastasis were collected and organized.Immunohistochemical method was applied to detect the expression of ATF6 and IFN-α in tissues.Spearman method was used to analyze the correlation between ATF6 and IFN-α expression in LSCC tissue.Kaplan-Meier method was applied to analyze the relationship between ATF6 and IFN-α expression in LSCC tissue and 3-year survival rate of patients.Cox regression was used to analyze the influencing factors of 3-year mortality in LSCC patients.Results The positive rate of ATF6 in LSCC tissue(76.00%)was higher than that in normal tissues adjacent to cancer(13.00%),the positive rate of IFN-α in LSCC tissue(29.00%)was lower than that in normal tissues adjacent to cancer(74.00%),and the difference was statistically significant(χ2=80.352,40.536,all P<0.05).The proportions of ATF6 positive expression in LSCC patients with TNM stage Ⅲ+Ⅳ,deep infiltration depth,and lymph node metastasis were significantly higher than those in LSCC patients with TNM stage Ⅰ+Ⅱ,shallow infiltration depth,and no lymph node metastasis(χ2=7.310,9.223,5.123,all P＜0.05).The proportions of IFN-α negative expression in LSCC patients with TNM stage Ⅲ+Ⅳ,deep infiltration depth,and lymph node metastasis were significantly higher than those in LSCC patients with TNM stage Ⅰ+Ⅱ,shallow infiltration depth,and no lymph node metastasis(χ2=8.564,5.021,5.203,all P＜0.05).There was a negative correlation between ATF6 and IFN-α expression in LSCC tissues(r=-0.415,P<0.05).The 3-year survival rate of LSCC patients in the ATF6 positive expression group(50.00%)was significantly lower than that in the ATF6 negative expression group(83.33%),while the 3-year survival rate of LSCC patients in the IFN-α positive expression group(82.76%)was significantly higher than that in the IFN-α negative expression group(47.89%)(Log rank χ2=8.002,10.854,all P<0.05).ATF6(HR=1.735,95%CI:1.159～2.598)and IFN-α(HR=0.624,95%CI:0.439～0.886)were influencing factors for the mortality of LSCC patients.Conclusion The positive expression rate of ATF6 increased and the positive expression rate of IFN-α decreased in LSCC tissues.They were closely related to the clinical pathological characteristics and prognosis of patients.
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Objective:To investigate the mechanism of interferon γ(IFN-γ)combined with ferroptosis inducer Erastin in the inhibi-tion of the growth of oral tongue squamous cell carcinoma(OTSCC).Methods:The expression of SLC7A11 in OTSCC was studied by bioinformatics analysis and immunohistochemical staining.SLC7A11 gene in OTSCC CAL-27 cells was knocked out by CRISPR-CAS9,and the survival rate of WT and SLC7A11 KO cells treated with Erastin was measured by MTT assay.Glutathione kit,lipid oxidation kit and flow cytometry were used to detect the changes of lipid peroxides in the cells treated with Erastin.After 24 h pretreatment with IFN-γ,MTT assay was used to detect the changes of cell sensitivity to Erastin,and the changes in lipid peroxides were detected by glu-tathione kits,lipid oxidation kits and flow cytometry.Results:Bioinformatics analysis and immunohistochemical staining showed that SLC7A11 was highly expressed in OTSCC.SLC7A11 KO CAL-27 cells were more sensitive to Erastin than WT cells.The GSH content of SLC7A11 KO cells was lower than that of WT cells,and the lipid peroxide content was higher than that of WT cells after treatment with Erastin.IFN-γ increased cell sensitivity to Erastin,decreased GSH content and increased lipid peroxides content in the cells.Conclusion:IFN-γ can reduce GSH and increase MDA and Lipid ROS levels by degrading SLC7A11,this increases the sensitivity of OTSCC to Erastin.
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BACKGROUND:Diabetic ulcers are a common complication of diabetes mellitus,which is manifested as foot ulcers complicated with infection,long treatment cycle,high disability rate and mortality rate,and brings a heavy burden to patients and social care. OBJECTIVE:To review the mechanism of action and the latest treatment progress of traditional Chinese medicine(TCM)in the treatment of diabetic ulcers,and to provide a basis for further theoretical research and clinical application. METHODS:CNKI,WanFang Database and PubMed database were searched for relevant literature using the keywords of"diabetic ulcer,medicinal herb,inflammation,interleukin-1β,interleukin-6,tumor necrosis factor,hypersensitive C-reactive protein,γ-interferon,interleukin-4,interleukin-10"in Chinese and English,respectively.The relevant literature in recent years was searched,and finally 75 articles were included for review. RESULTS AND CONCLUSION:The high glucose environment of the body will increase the level of pro-inflammatory cytokines,so that diabetic ulcer wounds are in a state of chronic inflammatory response for a long time,and difficult to heal or even not heal.TCM has summed up a lot of experience in the long-term struggle with diabetic ulcer.At present,TCM divides diabetic ulcers into four syndrome types:dampness and heat poison syndrome,blood and blood stasis obstruction pattern,heat poison injury Yin pattern,and Qi and blood deficiency syndrome,as well as representative prescriptions for treatment.According to their clinical characteristics,diabetic ulcers can be also divided into three stages:primary,middle and late stages.Different treatment methods are proposed:"clear method,""warm and clear combined use"and"maintenance method."Under the guidance of dialectical typing and staging of TCM,TCM monomers,extracts and compounds inhibit the inflammatory response and promote the healing of diabetic ulcers by down-regulating the expression of pro-inflammatory factors and/or up-regulating the expression of anti-inflammatory factors.Compared with modern medicine,TCM has significant advantages in the treatment of diabetic ulcers.There are many TCM monomers,extracts and compounds for the treatment of diabetic ulcers,such as angelica,curcumin,improved Chonghe ointment,Sanhuang blood exhaustion prescription and sore-ulcer I.formula,etc.It has been found that TCM for the treatment of diabetic ulcers is mainly heat-clearing and detoxifying,invigorating blood circulation and removing blood stasis,and amassing sores and muscle-building drugs,and the frequency of use,treatment scope and therapeutic effect of TCM compounds are obviously better than those of TCM monomers and extracts.Among them,the most commonly used are the Sanhuang blood exhaustion prescription and the sore-ulcer I as well as prescription for the treatment of damp heat toxicity syndrome and Zizhu ointment for the treatment of non-ischemic diabetic ulcers.However,there are also some shortcomings in the treatment of diabetic ulcers with TCM.First,there are few clinical syndrome studies on diabetic ulcers.Secondly,there are a wide variety of TCM monomers,extracts and compounds for the treatment of diabetic ulcers,and the relevant research is insufficiently in-depth.Finally,the research on the mechanism underlying TCM treatment of diabetic ulcers is still in the preliminary exploration stage,and the mechanism of action still needs to be further explored.In the future,it is necessary to strengthen the research on the pharmacology of TCM and the clinical syndrome of diabetic ulcers,analyze the potential targets and related signaling pathways of TCM in the treatment of diabetic ulcers,give full play to the therapeutic advantages of TCM with multiple targets,multiple pathways,multiple levels and multiple systems,and develop TCM with significant efficacy,active ingredients and clear targets.
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Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly worldwide and is characterized by degeneration of the photoreceptor, retinal pigment epithelium, Bruch membrane and choriocapillaris complex.Impairment of RPE cell function is an early and critical event in the molecular pathways leading to clinically relevant AMD changes.Programmed cell death (PCD) plays an important role in response to stress and regulation of homeostasis and disease.In recent years, multiple studies have shown that apoptosis, pyroptosis, necroptosis and ferroptosis are likely involved in RPE cell PCD and correlate with the onset and development of AMD.There may be interaction or synergy between the various death pathways.This article reviewed the pathogenic mechanism of apoptosis, pyroptosis, necroptosis and ferroptosis in retinal pigment epithelial cell and their research progress in AMD, which might provide new approaches for the prevention and treatment of AMD.
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Objective To explore the efficacy of T-cell spot test of tuberculosis infection(T-SPOT.TB)in the differential diagnosis of spinal tuberculosis(STB),and optimize diagnostic efficacy through the optimal cut-off value of receiver operating characteristic(ROC)curve.Methods Clinical data of patients with spinal infection in a hospi-tal from January 2010 to May 2019 were collected,including preoperative T-SPOT.TB test results,white blood cell count,C-reactive protein,erythrocyte sedimentation rate,procalcitonin,and tuberculosis antibodies,etal.Clinical diagnosis was conducted based on diagnostic criteria.The sensitivity and specificity of T-SPOT.TB in preoperative diagnosis of STB and other spinal infection was analyzed,and the diagnostic efficacy of the optimized T-SPOT.TB indicators was evaluated.Results A total of 132 patients were included in this study,out of whom 78 patients(59.09％)were diagnosed with STB,and 54(40.91％)were diagnosed with non-tuberculosis(non-TB)spinal in-fection.The sensitivity and specificity of T-SPOT.TB in differential diagnosis of STB were 67.68％and 66.67％,respectively.Univariate logistic regression analysis showed that compared with non-TB spinal infection,the OR va-lue of T-SPOT.TB test in diagnosing STB was 4.188(95％CI:1.847-9.974,P＜0.001).The optimized T-SPOT.TB evaluation index through ROC curve to determine the optimal cut-off values of ESAT-6,CFP-10,and CFP-10+ESAT-6 for differential diagnosis of STB and non-TB spinal infection were 12.5,19.5,and 36,respec-tively,and area under curve(AUC)values were 0.765 6,0.741 5,and 0.778 6,respectively,all with good diag-nostic efficacy.CFP-10+ESAT-6 had the highest AUC.CFP-10+ESAT-6 specific spot count had higher efficacy in the diagnosis of STB,with a diagnostic accuracy of 75.56％,higher than 67.42％of pre-optimized T-SPOT.TB.Conclusion T-SPOT.TB test has high diagnostic efficacy in differentiating STB from non-TB spinal infection.Posi-tivity in T-SPOT.TB test,especially with spot count of CFP-10+ESAT-6 over 36,indicates a higher likelihood of STB.
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Objective:To investigate effects of short-term cigarette smoke exposure combined with poly(I:C)stimulation on lung immune response and interferon expression in mice.Methods:BALB/c mice were randomly divided into 4 groups:control group,smoke group,poly(I:C)group and smoke combined poly(I:C)group.Total cell number and cell classification count of bronchoalveo-lar lavage fluid(BALF)were detected,and cell morphology was observed under ordinary light.Cytokines,chemokines,interferon and interferon stimulating genes expressions in lung tissues were detected by fluorescence quantitative PCR.Results:Compared with control group,total cell count,macrophage count and neutrophil count in smoke combined poly(I:C)group were significantly increased(P<0.05),and macrophage count was higher than that in poly(I:C)group.Macrophages of airway lavage fluid of mice in smoke combined with poly(I:C)group were larger in size,round or irregular in shape,and had more vacuoles in cytoplasm.Com-pared with control group,mRNA expressions of neutrophil chemokine CXCL1(P<0.05),CXCL2(P<0.01)and lymphocyte chemo-kine CCL2(P<0.01)in lung tissues of mice in smoke combined with poly(I:C)group were increased.IL-1β,IL-6,TNF-α mRNA expressions were significantly increased(P<0.01),IFN-β(P<0.01),IFN-γ(P<0.05),MX2(P<0.01)and IP-10(P<0.01)expre-ssions in lung tissues were significantly increased,and compared with poly(I:C)group,mRNA expressions of CXCL2(P<0.05),TNF-α(P<0.01)and IFN-β(P<0.05)in lung tissues of mice in smoke combined with poly(I:C)group were significantly increased.Conclusion:Cigarette smoke combined with poly(I:C)induces lung inflammation and expressions of interferon and interferon stimu-lating genes in mice.Cigarette exposure also increases poly(I:C)-induced acute lung inflammation and type Ⅰ interferon expression in mice.
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Type 2 diabetes mellitus(T2DM)is a chronic metabolic disease that can lead to the damage of multiple tissues and organs throughout the body.Stimulator of interferon genes(STING)is an endoplasmic reticulum membrane protein that acts as an indirect cytoplasmic DNA sensor.The activation of the STING signaling pathway may be involved in T2DM and its microvascular complications through various mechanisms.This article reviews the research progress in the mechanism of STING in T2DM and its microvascular complications.
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Objectives:To explore the effect and possible mechanisms of mild hypothermia on interferon(IFN)-α2b-induced AC16 cardiomyocytes apoptosis. Methods:Cardiomyocytes were stimulated in ordinary temperature and mild hypothermia by IFN-α2b under different concentrations for different times.Proliferation activity of cardiomyocytes was detected by CCK-8 assay.Apoptosis was detected by flow cytometry technique.The effects of different interventions on mitochondrial morphology were examined using Mito-Tracker Green and laser scanning confocal microscope,respectively.The mitochondrial membrane potentials under different intervention conditions were detected by flow cytometry.The fusion of dynamin-related protein 1(Drp1)and mitochondria,and the effects of different interventions on the mitochondria was examined by Drp1 or mitochondrial fluorescent probes and laser scanning confocal microscope.The effects of different intervention conditions on the protein expression level of Phospho-Drp1(p-Drp1)Ser616,Drp1,cleaved poly ADP-ribose polymerase1(cleaved-PARP1),poly ADP-ribose polymerase1(PARP1)were detected by Western blot. Results:CCK-8 assay and flow cytometry results showed that IFN-α2b inhibited the proliferation and enhanced the apoptosis of AC16 cardiomyocytes in a time and dose-dependent manner,these effects could be attenuated by mild hypothermia.Mito-Tracker Green,laser scanning confocal microscope and flow cytometry results showed that the extent of damage of mitochondria with different interventions were attenuated in the setting of mild hypothermia as compared with ordinary temperature.The morphology of mitochondria remained intact and the mitochondrial membrane potentials were the highest in mild hypothermia group.Injured AC16 cardiomyocytes released Drp1 from cytoplasm to mitochondria and increased mitochondrial fission,these effects were abolished after mild hypothermia.p-Drp1 Ser616/Drp1 ratio and cleaved-PARP1/PARP1 ratio were decreased after mild hypothermia,and above effects could be reversed by mitochondrial division inhibitor-1(Mdivi-1)pretreatment. Conclusions:Mild hypothermia inhibits IFN-α2b-induced AC16 cardiomyocytes apoptosis via improving mitochondrial function.
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Interferon γ-inducible protein 16(IFI16)is one member of human pyrin and HIN domain-containing protein(PYHIN)family(also known as interferon-inducible p200 pro-tein family),which is widely present in human organs and tis-sues,and is involved in cell cycle regulation,senescence and ap-optosis,even in immune reaction.The content and localization of IFI16 may change under different physiological and pathological conditions,and recent studies have revealed that it may play an important role in the development of antiviral,tumor,inflammato-ry diseases and other diseases.In this paper,we review its mechanism and the current status of its research in diseases,with the aim of providing a reference for the in-depth study of IFI16.
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Objective:To explore the correlation between serum levels of interleukin-9 (IL-9), platelet activating factor (PAF), total immunoglobulin E (IgE), interferon γ (IFN-γ), and interleukin-4 (IL-4) in patients with chronic spontaneous urticaria (CSU).Methods:Sixty CSU active phase patients admitted to the First Affiliated Hospital of Hebei North University from March 2018 to March 2019 were selected and included in the CSU active phase group. Based on the 7-day Urticaria Activity Score (UAS7), they were divided into three groups: 15 mild group, 25 moderate group, and 20 severe group; And 19 patients who entered the quiescent phase of the disease after 28 days of standardized antihistamine treatment were included in the CSU quiescent phase group. Another 30 healthy subjects who participated in the physical examination at the same time at our hospital′s physical examination center were selected to be included in the healthy control group. 5 ml of fasting elbow vein blood was collected from CSU active and stationary patients, as well as healthy subjects. The serum levels of IL-9, PAF, total IgE, IFN-γ, and IL-4 were detected using enzyme-linked immunosorbent assay. Pearson correlation test was used to analyze the correlation between serum IL-9, PAF levels and total IgE, IFN-γ, and IL-4 levels in CSU active patients.Results:The serum levels of IL-9, PAF, total IgE, and IL-4 in the CSU active phase group were higher than those in the CSU stationary phase group and healthy control group (all P<0.05), and the serum IFN-γ levels were lower than those in the CSU stationary phase group and healthy control group (all P<0.05). There was no statistically significant difference in the levels of the above indicators between the healthy control group and the CSU stationary group (all P>0.05). The serum levels of IL-9, PAF, total IgE, and IL-4 in the severe group were significantly higher than those in the mild and moderate groups (all P<0.05), and the serum IFN-γ levels were significantly lower than those in the mild and moderate groups (all P<0.05); The serum levels of IL-9, PAF, total IgE, and IL-4 in the moderate group were significantly higher than those in the mild group (all P<0.05), and the serum IFN-γ levels were significantly lower than those in the mild group ( P<0.05). Pearson correlation analysis showed that serum IL-9 and PAF levels were positively correlated with serum total IgE and IL-4 levels in CSU active phase patients (IL-9: r=0.726, 0.870, PAF: r=0.788, 0.795, all P<0.01), and negatively correlated with serum IFN-γ levels (IL-9: r=-0.831, PAF: r=-0.816, all P<0.01). Conclusions:The serum levels of IL-9 and PAF in patients with active CSU are elevated and correlated with total IgE, IFN-γ, and IL-4 levels, suggesting that IL-9 and PAF may be related to the occurrence and development of CSU.
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Objective:To investigate the factors influencing phytohemagglutinin (PHA) response in the detection of Mycobacterium tuberculosis infection by gamma interferon release assay (IGRA). Methods:A retrospective case-control study was conducted on 360 hospitalized patients who received IGRA in West China Hospital of Sichuan University from January 2019 to December 2021. According to PHA response (IFN-γ level), they were divided into three groups: negative mitogen response group (IFN-γ<2 pg/ml), weak positive mitogen response group (IFN-γ: 2-100 pg/ml), and normal mitogen response group (IFN-γ>400 pg/ml).Results:Immune diseases were independently associated with negative (OR=0.34, 95%CI: 0.17-0.72, P=0.004) and weak positive mitogen responses (OR=0.29, 95%CI: 0.16-0.55, P<0.001). Infections caused by pathogens other than Mycobacterium tuberculosis was independently associated with negative mitogen response (OR=0.266, 95%CI: 0.09-0.83, P=0.023), while immunodeficiency was independently associated with weak positive mitogen response (OR=0.280, 95%CI: 0.12-0.63, P=0.002). Mitogen response was significantly correlated with the levels of albumin and hemoglobin in serum and the counts of neutrophils and lymphocytes ( P<0.001). Conclusions:Immune diseases and immunodeficiency can affect mitogen response. Therefore, clinicians should give attention to mitogen response in the interpretation of IGRA test results to prevent misdiagnosis and underdiagnosis. Besides, to a certain extent, mitogen response can reflect the infection status of hospitalized patients.
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Decline of immunity is an epidemiological feature of opioid addicts. Recent work reveals a landscape of peripheral immune microenvironment in opioid addicts. Opioid addicts exhibit a significant expansion of fragile-like regulatory T cells (Tregs) and enhanced Treg-derived interferon-γ (IFN-γ) expression. IFN-γ signaling reshapes synaptic morphology in nucleus accumbens (NAc) neurons, modulating subsequent withdrawal symptoms. Treg fragility transformation from WT Tregs is primarily due to opioid-induced global hypoxia during acute withdrawal period. Opioids increase the expression of neuron-derived C-C motif chemokine ligand 2 (Ccl2) and disrupt blood-brain barrier (BBB) integrity through the downregulation of astrocyte-derived fatty-acid-binding protein 7 (Fabp7), both of which trigger peripheral Treg infiltration into NAc. Recent studies suggest that subtle homeostatic changes in the peripheralimmune milieu may also contribute to modulating synapses that are responsible for addictive behaviors, which may lead to the development of new therapeutic strategies.
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@#Objective To construct a new human-derived consensus interferon α(cIFNα)sequence and verify its antiviral effect.Methods Total 57 human-derived IFNα sequences were synthesized,and the conservative amino acid preference at each site was selected by software comparison analysis.A new cIFN sequence,hIC,was synthesized into pUC-57 vector and connected with pCK to construct eukaryotic expression vector pCK-hIC,which was transfected into 293T cells to express the target protein hIC.A549 cells were incubated with the target protein before and after infection with enhanced green fluorescent protein vesicular stomatitis virus(VSV-EGFP).The effect of hIC on VSV-EGFP replication was analyzed by fluorescence observation,crystal violet staining and flow cytometry in vitro,and the downstream gene expression of IFN was verified by qPCR.Results The plasmid pCK-hIC was constructed correctly as verified by double enzyme digestion and sequen-cing.The expressed hIC protein,with a relative molecular mass of about 27 000,significantly reduced the fluorescence expression of VSV-EGFP,significantly inhibited virus proliferation and activated the expression of interferon-stimulated gene 15(ISG15),2′-5′-oligoadenylate synthetase 1(OAS1)and interferon-inducible transmembrane protein(IFITM).Conclusion The hIC has good antiviral effect,which lays a foundation for the follow-up research and development.
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According to the latest global cancer statistics， the incidence and mortality of lung cancer rank first in China. Classical therapies remain the most common cancer treatment options， such as surgical resection， radiotherapy， and chemotherapy， but not all cancer patients respond to classical therapies， which require new lung cancer treatment strategies. After decades of research and development， cancer immunotherapy has achieved certain curative effect， which provides new possibilities for cancer treatment. Cyclic guanosine monophosphate-adenosine monophosphate synthase （cGAS） is a cytosolic DNA sensor. It can induce protective immune defense responses against various DNA-containing pathogens and provide anti-tumor immunity by activating the interferon （IFN） gene stimulator （STING） protein. At present， relevant researchers in China and abroad have done a lot of research on the occurrence and development of lung cancer and the pathophysiological mechanism of drug intervention in the treatment of lung cancer. The results show that cGAS/STING signaling pathway plays an important role in the development of the disease， and traditional Chinese medicine monomers or compounds can intervene in lung cancer cells by regulating the cGAS/STING signaling pathway， induce their autophagy and death， regulate their cycle operation， promote senescence， inhibit their proliferation and tumor angiogenesis， promote their invasion and metastasis， and promote the immune activation of anti-lung cancer cells， so as to inhibit or delay the occurrence and development of lung cancer. In recent years， the related research results have been updated rapidly， and the previous literature has not included the latest research results in time， which causes a lot of inconvenience for many scholars to search the literature. Based on this， this paper mainly summarized the mechanism of cGAS/STING signaling pathway intervention in lung cancer in China and abroad in recent years， as well as the research progress of related traditional Chinese medicine intervention， so as to provide new ideas for the development of lung cancer in molecular biology， drug treatment research， and clinical new drug research and provide a reference for further mechanism research.
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ObjectiveTo investigate the antiviral effect of Menispermi Rhizoma total alkaloids and its relationship with the type Ⅰ interferon （IFN-Ⅰ） signaling pathway. MethodThe effects of Menispermi Rhizoma total alkaloids on the intracellular replication of influenza A virus （H1N1）， vesicular stomatitis virus （VSV）， and cerebral myocarditis virus （EMCV） were detected by fluorescent inverted microscope， flow cytometry， Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and Western blot. A mouse model infected with H1N1 was constructed， and the mice were divided into a control group， H1N1 model group， Menispermi Rhizoma total alkaloids groups （10， 20， 30 mg·kg-1）， and oseltamivir group （40 mg·kg-1）， so as to study the effects on the weight and survival rate of infected mice. Real-time PCR was used to detect the activation effect of Menispermi Rhizoma total alkaloids on the IFN-Ⅰ pathway in cells， and the relationship between the antiviral effect of Menispermi Rhizoma total alkaloids in IFNAR1 knockout A549 cells （IFNAR1-/--A549） and IFN-Ⅰ pathway was detected. ResultCompared with the control group， the virus proliferated significantly in the model group （P<0.01）. Compared with the model group， Menispermi Rhizoma total alkaloids could significantly inhibit the replication of H1N1， VSV， and EMCV in vitro （P<0.01）， inhibit the weight loss of the mice infected with the H1N1 in vivo， and improve the survival rate of mice （P<0.05）. In addition， Menispermi Rhizoma total alkaloids activated the IFN-I pathway and relied on this pathway to exert the function of antiviral infection. ConclusionMenispermi Rhizoma total alkaloids exert antiviral effects in vivo and in vitro by activating the IFN-Ⅰ pathway.
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@#Abstract: Type I interferons play an important role in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). Monoclonal antibody shows therapeutic potential by blocking the signaling pathway. This study used recombinant human subunit 1 of the type I interferon receptor (IFNAR1) protein to immunize New Zealand white rabbits, and applied B cell cloning technology to screen and obtain rabbit parental antibodies. After humanization modification, QX006N was obtained. In vitro biological studies showed that QX006N could specifically bind to human IFNAR1 with an affinity of 108 pmol/L, and neutralize the type I interferon signaling pathway and this pathway mediated biological effects. This study provides a solid foundation for the development of antibody drugs targeting the type I interferon signaling pathway for the treatment of SLE.