RESUMEN
ABSTRACT A patient presented with corneoscleral thinning five months after the treatment of suspected ocular squamous surface neoplasia with mitomycin-C and interferon. For tectonic and aesthetic purposes, we decided to perform lamellar corneoscleral transplantation. The approach used established new tectonic support and corneal homeostasis. This technique might be an option in similar cases.
RESUMEN
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.
RESUMEN
ObjectiveTo investigate the change and potential role of Mindin protein in the treatment of chronic hepatitis B （CHB） with PEG-IFNα-2b. MethodsA total of 29 CHB patients who received the treatment with PEG-IFNα-2b in The Second Affiliated Hospital of Xi’an Jiaotong University from January 2018 to December 2019 were enrolled， and according to their clinical outcome， they were divided into cured group with 17 patients and uncured group with 12 patients. Peripheral blood samples were collected from both groups at baseline， 12 weeks， and 24 weeks to measure blood routine indices， liver function parameters， hepatitis B markers， and Mindin protein. HBsAg， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and Mindin protein at different time points were compared between the two groups. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； a Spearman correlation analysis was used to investigate correlation； a multiple linear regression analysis was used to investigate the influence of HBsAg and ALT on the content of Mindin protein. ResultsThe analysis of baseline data showed that there were significant differences in the levels of HBsAg， HBeAb， albumin， and albumin/globulin ratio between the cured group and the uncured group （all P<0.05）. The cured group tended to have a gradual increase in the level of Mindin， and the level of Mindin at 24 weeks was significantly higher than that at baseline （P<0.05）. The cured group had a significantly higher level of Mindin protein than the uncured group at 24 weeks （P=0.019）. The cured group had a significantly lower level of HBsAg than the uncured group （P<0.05）， with a significant change from baseline to each time point within the cured group （P<0.05）. In addition， the levels of ALT and AST in the cured group tended to first increase and then decrease， and the expression levels at 12 weeks were significantly higher than those at baseline （P<0.05）. At 12 weeks， there was a strong linear correlation between Mindin protein levels and ALT in the untreated group （r=0.760 8， P<0.05）， and further multiple linear regression analysis also demonstrated a linear relationship between the two （b=1.571， P=0.019）. ConclusionThere is a significant difference in the level of Mindin protein between the cured group and the non-cured group after 24 weeks of PEG-IFNα-2b antiviral treatment， and therefore， detecting the dynamic changes of Mindin protein can better predict the treatment outcome of CHB， which provides a reference for clinical practice.
RESUMEN
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.
RESUMEN
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.
RESUMEN
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.
RESUMEN
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.
RESUMEN
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.
RESUMEN
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.
RESUMEN
Objective:To elucidate the pathophysiological mechanisms of idiopathic inflammatory myopathy subtypes by analyzing the gene expression profiles of peripheral blood mononuclear cells (PBMCs) from anti-MDA5 antibody-positive and anti-Jo-1 antibody-positive myositis patients.Methods:Gene expression profiling screening and analysis of PBMCs from 12 anti-MDA5 positive, 16 anti-Jo-1 positive myositis patients and 43 healthy controls were performed using Illumina HT-12 v4 expression profiling microarrays. Applying the unpaired t test with Benjamini-Hochberg correction, the genes with the absolute value of fold change (FC) in gene expression signal ≥2 and adjusted P<0.05 were selected as differentially expressed genes. Differential gene sets were subjected to Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, with P<0.05 as the threshold for being significantly enriched. Validation of differentially expressed genes by real time-PCR. The Kolmogorov-Smirnov test was used to test the normality of continuous variables. If the distribution was normal and the variance was homogeneous, analysis of variance (one-way ANOVA) was used.If the distribution was not normal, Kruskal-Wallis test was used, and P<0.05 was regarded as statistically significant difference. Results:Analysis of gene expression profiles of PBMCs from patients with positive anti-MDA5 and anti-Jo-1 antibody revealed significant differences in gene expression of PBMCs from patients with the two myositis subtypes. The number of differentially expressed genes that specifically up-regulated in anti-MDA5 antibody positive patients was 407, and the GO functional enrichment analysis was mainly enriched in biological processes such as innate immune response ( P<0.001), response to virus ( P<0.001) and type Ⅰ interferon signaling pathway ( P<0.001), and the KEGG pathway enrichment analysis was mainly enriched in the viral infection-associated pathway ( P<0.001), RIG-Ⅰ like receptor signaling pathway ( P<0.001) and Toll-like receptor signaling pathway ( P=0.002), etc. The 259 differential genes specifically down-regulated in the anti-MDA5 antibody positive group were mainly enriched in biological processes such as immune response ( P=0.006), TGF-β receptor signaling pathway ( P=0.010) and natural killer cell mediated immunity ( P=0.015) in GO functional enrichment analysis. There were 162 differentially expressed genes up-regulated specifically in anti-Jo-1 antibody positive patients, and GO functional enrichment analysis was mainly enriched in biological processes such as nucleosome assembly ( P<0.001), negative regulation of cell growth ( P=0.001), negative regulation of apoptotic process P=0.004), and innate immune response in mucosa ( P=0.012), and the KEGG pathway enrichment analysis mainly enriched in metabolic-related signaling pathways ( P<0.001) and immune-related pathways ( P<0.001), etc. Real-time PCR confirmed that IFIH1 ( P=0.037), ISG15 ( P=0.003), and DDX58 ( P=0.032) in the RIG-Ⅰ-like receptor pathway as well as chemokines MCP-1 ( P=0.003), MCP-2 ( P<0.001), and transcription factor BATF2 ( P=0.002), and inflammatory signaling pathway-associated MYD88 ( P<0.001) were highly expressed in PBMCs from anti-MDA5 antibody-positive myositis patients. Conclusion:The gene expression profile of PBMCs in anti-MDA5 antibody-positive patients suggests that the pathogenesis of patients with anti-MDA 5 antibody positive is closely related to biological processes such as innate immune response, viral infection, and interferon response.
RESUMEN
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.
RESUMEN
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.
RESUMEN
@#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.
RESUMEN
Objective@#To evaluate the effectiveness of recombinant Mycobacterium tuberculosis fusion protein skin test (EC-ST) in screening for latent tuberculosis infection (LTBI) among HIV/AIDS patients, so as to provide insights into the applicability of EC-ST in LTBI screening among HIV/AIDS patients.@*Methods@#From April to June 2023, HIV/AIDS patients under management and treatment in Yangzhou City, Jiangsu Province, were selected as study subjects. Basic information was collected through questionnaire surveys. LTBI was screened by EC-ST and interferon-gamma release assay (IGRA). Taking IGRA results as the diagnostic standard, the positive rate, sensitivity, specificity and consistency rate of EC-ST, and the impact of CD4+T lymphocyte (CD4) counts on the screening effect of EC-ST were analyzed.@*Results@#A total of 523 HIV/AIDS patients were screened, including 458 males (87.57%) and 65 females (12.43%). The median age was 48.00 (interquartile range, 21.00) years. The positive rate of EC-ST was 7.27% and the positive rate of IGRA was 7.46%, with no statistically significant difference (P>0.05). The consistency rate of the two methods was 94.84%, and the Kappa value of 0.621 (95%CI: 0.489-0.752, P<0.05). The sensitivity of EC-ST was 64.10% and the specificity was 97.31%. Comparing the groups with CD4 counts <500 and ≥500 cells/μL, the consistency rates of the two methods were 95.32% and 94.44%, and the Kappa values were 0.568 and 0.650, respectively (both P<0.05). There were no statistically significant differences in the positive rates, sensitivity, and specificity of EC-ST (all P>0.05). Comparing the groups with CD4 counts <200 and ≥200 cells/μL, the consistency rates of the two methods were 96.55% and 94.62%, and the Kappa values were 0.648 and 0.619, respectively (both P<0.05). There were no statistically significant differences in the positive rates, sensitivity, and specificity of EC-ST (all P>0.05).@*Conclusion@#The effectiveness of EC-ST in screening for LTBI among HIV/AIDS patients is consistent with that of IGRA and is not affected by CD4 counts.
RESUMEN
Ischemic stroke is a common clinical cerebrovascular disease，and its incidence is increasing year by year. Current clinical treatments for stroke mainly include thrombolysis and intravenous thrombectomy，both of which are subject to significant time constraints and often result in residual symptoms，reducing the quality of life for patients. Research has found that there are multiple pathways and mechanisms in the pathological process of stroke，such as the cyclic GMP-AMP synthase （cGAS）/stimulator of interferon gene （STING） pathway. Currently，researchers in China and abroad have conducted extensive studies on the occurrence and development of ischemic stroke， as well as the mechanism of traditional Chinese medicine （TCM） intervention for stroke. The results indicate that traditional Chinese medicine（TCM） can regulate the cGAS/STING pathway to reduce inflammation and oxidative stress，decrease neuronal cell death，and effectively alleviate brain damage from stroke，and it has unique advantages in improving symptoms and prognosis. This article summarized the recent research progress of the mechanism of cGAS/STING pathway regulation in stroke and related TCM intervention，so as to provide new ideas for the treatment of ischemic stroke with TCM characteristics.
RESUMEN
@#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.
RESUMEN
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.
RESUMEN
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.
RESUMEN
ObjectiveTo clone the gene of Marmota himalayana type Ⅰ interferon receptor β subunit （mhIFNAR2）， and to perform antibody preparation and functional identification. MethodsRT-PCR was used for amplification in the spleen tissue of Marmota himalayana to obtain the sequence， which was cloned to the prokaryotic expression vector pRSET-B to express the recombinant protein. Electrophoresis and Western blot were used for identification. BALB/c mice were immunized with the recombinant protein to prepare the polyclonal antibody of its extracellular domain； immunohistochemistry， immunofluorescence assay， and Western Blot were used for identification， and the method of siRNA blockade was used to investigate its function. An analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for comparison between two groups. ResultsA fragment of mhIFNAR2 （149 — 1 300 bp） was obtained from spleen tissue， which showed the highest homology of 98.05% in marmot. A prokaryotic expression plasmid was successfully constructed for expression of the extracellular domain of the mhIFNAR2（50-181aa） and was named pRSET-B.mhIFNAR2， and the recombinant protein expressed by this plasmid had a molecular weight of 27 kD， a purity of about 95% after purification， and a concentration of 160 μg/mL. After BALB/c mice were immunized with the purified recombinant protein， 1∶1 000 specific polyclonal antibodies were obtained， and immunohistochemistry and immunofluorescence assay showed the expression in cell membrane and cytoplasm. Among the three siRNAs synthesized， the siRNA starting from the 277 locus （siRNA277） could silence the expression of target genes and weaken the interferon signaling pathway compared with the blank control group and the negative control group （both P<0.05）. ConclusionThe fragment of mhIFNAR2 is obtained， and the polyclonal antibody for the extracellular domain of mhIFNAR2 is successfully prepared， with relatively high titer and specificity， and can be used for immunohistochemistry， immunofluorescence assay， and Western blot.
RESUMEN
Targeting cGAS-STING pathway is a promising strategy in tumor treatment. The pattern recognition receptor cGAS identifies dsDNA and catalyzes the formation of the second messenger 2'3'-cGAMP, activating the downstream interferons and pro-inflammatory cytokines through the adaptor protein STING. Notably, in tumor immune microenvironment, key components of cGAS-STING pathway are transferred among neighboring cells. The intercellular transmission under these contexts serves to sustain and amplify innate immune responses while facilitating the emergence of adaptive immunity. The membrane-based system, including extracellular vesicles transport, phagocytosis and membrane fusion transmit dsDNA, cGAMP and activated STING, enhancing the immune surveillance and inflammatory. The membrane proteins, including specific protein channel and intercellular gap junctions, transfer cGAMP and dsDNA, which are crucial to regulate immune responses. And the ligand-receptor interactions for interferons transmission amplifies the anti-tumor response. This review elaborates on the regulatory mechanisms of cell-to-cell communications of cGAS-STING pathway in tumor immune microenvironment. We further explore how these mechanisms modulate immunological processes and discuss potential interventions and immunotherapeutic strategies targeting these signaling cascades.