Objective Sepsis patients exhibit diverse immune states,making it crucial to identify subtypes with distinct inflammatory profiles through Th1/Th2 cytokine data for personalized treatment and improved prognosis.Method...Objective Sepsis patients exhibit diverse immune states,making it crucial to identify subtypes with distinct inflammatory profiles through Th1/Th2 cytokine data for personalized treatment and improved prognosis.Methods We retrieved data from sepsis patients who underwent Th1/Th2 cytokine testing in Nanfang Hospital,Southern Medical University from June 1,2020,to February 1,2022.An unsupervised K-means clustering method classified participants based on Th1/Th2 cytokine levels,with the primary outcome being the 7-day mortality rate post-ICU admission.Cox proportional hazards and Restricted Mean Survival Time(RMST)analyses were utilized to explore survival outcomes.Results A total of 321 sepsis patients were included.IL-6(HR 1.69,95%CI:1.22,2.34)and IL-10(HR 1.81,95%CI:1.37,2.40)emerged as independent predictors of 7-day mortality.Unsupervised K-means clustering revealed 3 inflammatory/immune subgroups:Cluster 1(n=166,low inflammatory response),Cluster 2(n=99,moderate inflammatory response with immune suppression),and Cluster 3(n=56,strong inflammatory and immune suppression).Compared to Cluster 1,Clusters 2 and 3 had higher 7-day mortality risks(14.4%vs 23.2%,HR=4.30,95%CI:1.51-12.26;14.4%vs 35.7%,HR=7.32,95%CI:2.57-20.79).Conclusion Septic patients in a protective immune response state(Cluster 1)exhibit better short-term prognoses,suggesting the importance of understanding inflammatory/immune states for precise treatment and improved outcomes.展开更多
SalicS1 is a genetically encoded,ratiometric FRET biosensor that brings salicylic acid(SA)research to the same real-time imaging standard long available for ABA and GA.Built through a modular Golden Gate platform and ...SalicS1 is a genetically encoded,ratiometric FRET biosensor that brings salicylic acid(SA)research to the same real-time imaging standard long available for ABA and GA.Built through a modular Golden Gate platform and informed by NPR-NIMIN structural biology,SalicS1 achieves SA specificity,tunable affinity,reversibility,and non-perturbing expression in Arabidopsis.Using this sensor,pathogen infection,non-adapted fungal challenge,and aphid feeding are shown to elicit spatially propagating SA surges rather than purely local accumulation,revealing a tissue-level organization of immune signaling that bulk assays could not resolve.SalicS1 therefore provides a broadly deployable tool for dissecting the geometry,timing,and genotype dependence of SA-mediated plant defense.展开更多
Anti-programmed cell death protein 1(PD-1)or its ligand(PD-L1)are immune checkpoint inhibitors(ICIs)that have revolutionized cancer therapy.However,the efficacy of anti-PD-1 and anti-PD-L1 is limited by resistance and...Anti-programmed cell death protein 1(PD-1)or its ligand(PD-L1)are immune checkpoint inhibitors(ICIs)that have revolutionized cancer therapy.However,the efficacy of anti-PD-1 and anti-PD-L1 is limited by resistance and inter-individual variability.In recent years increasing evidence has highlighted the pivotal role of the gut microbiota in modulating the response to PD-1/PD-L1 immunotherapy.Extensive preclinical studies have demonstrated that commensal microbes can increase the efficacy of PD-1/PD-L1 blockade through multiple mechanisms,including the production of metabolites,such as short-chain fatty acids(SCFAs),tryptophan derivatives,and extracellular polysaccharides that remodel the tumor microenvironment,as well as the activation of immune pathways involving dendritic cells,CD8+T cells,and M1 macrophages to increase antitumor immunity.Moreover,clinical studies have shown that fecal microbiota transplantation(FMT)and targeted probiotic interventions show promise for improving the response to PD-1/PD-L1 therapy,while reducing the risk of immune-related adverse events(irAEs).This review systematically explores the multifaceted regulatory roles of the commensal microbiota in PD-1/PD-L1 therapy and examines the preclinical prospects of microbiota-based personalized immunotherapeutic strategies.The integration of multiomics technologies,synthetic biology,and precise microbiota interventions may further optimize PD-1/PD-L1 immunotherapy and offer novel insights into antitumor immune modulation.展开更多
Objectives:Gastric cancer(GC)remains a major global health concern,and Phosphoinositide-3-Kinase Regulatory Subunit 1(PIK3R1),a regulatory subunit of the PI3K signaling pathway,may play a critical yet underexplored ro...Objectives:Gastric cancer(GC)remains a major global health concern,and Phosphoinositide-3-Kinase Regulatory Subunit 1(PIK3R1),a regulatory subunit of the PI3K signaling pathway,may play a critical yet underexplored role in GC progression.This study aimed to investigate the prognostic significance of PIK3R1 in GC and its association with the tumor immune microenvironment.Methods:PIK3R1 expression and its clinical relevance were analyzed using datasets from GC patients who underwent gastrectomy,including cohorts from The Cancer Genome Atlas(TCGA)and the Sun Yat-sen University Cancer Center(SYSUCC).Prognostic models integrating PIK3R1 expression with clinical parameters were constructed for both cohorts.The immune microenvironment associated with PIK3R1 expression was assessed through immunohistochemistry and single-cell RNA sequencing.In vitro assays were conducted to evaluate the effects of PIK3R1 on GC cell proliferation and migration.Results:PIK3R1 was significantly overexpressed in GC tissues and was closely associated with aggressive tumor characteristics and poor clinical outcomes.A nomogram combining PIK3R1 expression with clinicopathological features effectively predicted patient prognosis.Knockdown of PIK3R1 in GC cells reduced proliferation and migration in vitro.Immunological profiling revealed that high PIK3R1 expression correlated with increased infiltration of forkhead box protein P3(Foxp3^(+))and cluster of differentiation 73(CD73^(+))T cells.Patients with low PIK3R1 expression and low CD73^(+)T cell infiltration had significantly better survival.Conclusions:PIK3R1 overexpression is linked to poor prognosis in GC and influences the extent of immune cell infiltration within the tumor microenvironment.A novel prognostic model integrating PIK3R1 and CD73 expression with clinical parameters was established to stratify GC patients into distinct risk groups,offering potential value for personalized therapeutic strategies.展开更多
Cerebrovascular diseases are considered to be amongst the most serious public health issues,since they are the third leading cause of death（WHO,2014）and the most common cause of disability worldwide.Its monetary sig...Cerebrovascular diseases are considered to be amongst the most serious public health issues,since they are the third leading cause of death（WHO,2014）and the most common cause of disability worldwide.Its monetary significance is evidenced by the economic burden imposed on health care systems,given that the cost of medical care for a patient that has suffered a stroke is around$25,741US dollars every 5 years（Luengo-Fernandez et al.,2012）.A stroke occurs as a result of a disturbance or interruption of cerebral blood flow that significantly reduces the supply of oxygen and glucose to the neural tissue. Consequently, several cell death mechanisms （secondary lesion mechanisms） such as necrosis, excitotoxicity, free radical production and inflammation are triggered （Castillo, 2000）.展开更多
AIM: To explore the effect of immunization with copolymer-1 (COP-1) and retinal stem cells (RSCs) transplantation on interferon-gamma (IFN-gamma) levels in a rat experimental glaucoma model. METHODS: An experimental g...AIM: To explore the effect of immunization with copolymer-1 (COP-1) and retinal stem cells (RSCs) transplantation on interferon-gamma (IFN-gamma) levels in a rat experimental glaucoma model. METHODS: An experimental glaucoma was induced by argon laser photocoagulation of the episcleral veins and limbal plexus in the right eye of rats. Immediately following glaucoma induction, rats were immunized with COP-1. RSCs were cultured and transplanted intravitreally into the eyes of glaucoma model animals 1 week post-laser treatment. Six experimental groups were used: COP-1/RSC, PBS/RSC, COP-1/PBS, PBS/PBS, glaucoma model group, and a normal control group. The concentration of IFN-gamma in aqueous humor (AH) and serum was measured by enzyme-linked immunosorbent assay (ELISA) in each of the six groups. Retinal ganglion cell (RGC) survival was assessed by quantifying apoptosis using Hoechst staining. RESULTS: Concentrations of IFN-gamma in AH and serum of rats that had undergone glaucoma induction were higher than those of non-induced control rats. The concentrations of IFN-gamma in AH and serum of the COP-1/RSCs treated group were determined to be 2371.9ng/L and 710.9ng/L, respectively, which were significantly lower than those in the other treated groups (P<0.05). In fact, IFN-gamma levels in the dual treated group were reduced to background levels. The COP-1/RSC group had lower number of apoptotic RGCs than the other three experimental groups (P<0.05). CONCLUSION: The reduced levels of IFN-gamma in AH and serum of the COP-1/RSC group may be related to synergistic effects between RSCs transplantation and COP-1 immune modulation. It is likely that the lower levels of IFN-gamma prevented RGCs glaucomatous apoptasis.展开更多
[Objective] This study aimed to construct DNA vaccine of foot-and-mouth disease （FMD）.[Method] Plasmid carriers plESZP1 and pUTK3CP1 with PRV were constructed for FMDV P1 gene expression.Mice were immunized,and thei...[Objective] This study aimed to construct DNA vaccine of foot-and-mouth disease （FMD）.[Method] Plasmid carriers plESZP1 and pUTK3CP1 with PRV were constructed for FMDV P1 gene expression.Mice were immunized,and their antibody level was detected.The two eukaryotic expression plasmids constructed were transfected into Vero cells.PCR,IFA and Westem-blot were carried out to detect the transcription and expression of the objective gene.Balb/C mice were intramuscularly inoculated with the DNA plasmid which expressed the target gene correctly,and the antibody level in mice was detected by the means of ELISA and serum neutralization （SN）.[Result] DNA plasmid carrying P1 gene which encodes FMDV capsid protein caused specific body fluid immunoreaction in mice,and the antibody level of anti-FMDV had no difference in the mice induced by the two recombinant plasmids.[Conclusion] This study lays a foundation for evaluating the genetically modified vaccine by immunizing animals with recombinant PRV containing the FMDV P1 gene and recombinant virus.展开更多
Copolymer-1（Cop-1） is a peptide with immunomodulatory properties, approved by the Food and Drug Administration of United States in the treatment of multiple sclerosis. Cop-1 has been shown to exert neuroprotective e...Copolymer-1（Cop-1） is a peptide with immunomodulatory properties, approved by the Food and Drug Administration of United States in the treatment of multiple sclerosis. Cop-1 has been shown to exert neuroprotective effects and induce neurogenesis in cerebral ischemia models. Nevertheless, the mechanism involved in the neurogenic action of this compound remains unknown. The choroid plexus（CP） is a network of cells that constitute the interphase between the immune and central nervous systems, with the ability to mediate neurogenesis through the release of cytokines and growth factors. Therefore, the CP could play a role in Cop-1-induced neurogenesis. In order to determine the participation of the CP in the induction of neurogenesis after Cop-1 immunization, we evaluated the gene expression of various growth factors（brain-derived neurotrophic factor, insulin-like growth factor 1, neurotrophin-3） and cytokines（tumor necrosis factor alpha, interferon-gamma, interleukin-4（IL-4）, IL-10 and IL-17）, in the CP at 14 days after ischemia. Furthermore, we analyzed the correlation between the expression of these genes and neurogenesis. Our results showed that Cop-1 was capable of stimulating an upregulation in the expression of the genes encoding for brain-derived neurotrophic factor, insulin-like growth factor 1, neurotrophin-3 and IL-10 in the CP, which correlated with an increase in neurogenesis in the subventricular and subgranular zone. As well, we observed a downregulation of IL-17 gene expression. This study demonstrates the effect of Cop-1 on the expression of growth factors and IL-10 in the CP, in the same way, presents a possible mechanism involved in the neurogenic effect of Cop-1.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact mo...BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact molecular mechanisms leading to the progression of HCC are still unclear.Research has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor tissues.In this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between them.AIM To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC patients.METHODS In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC patients.Furthermore,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,etc.The statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank test.RESULTS In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival rate.ASH1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated region.Furthermore,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via ASH1L.For the exploration mechanism,we found ASH1L may promote an immunosuppressive microenvironment in HCC and ASH1L affects the expression of the cell junction protein zonula occludens-1,which is potentially relevant to the immune system.CONCLUSION Loss function of microRNA-142-3p induces cancer progression and immune evasion through upregulation of ASH1L in HCC.Both microRNA-142-3p and ASH1L can feature as new biomarker for HCC in the future.展开更多
Objective:Small cell lung cancer(SCLC)is commonly recognized as the most fatal lung cancer type.Despite substantial advances in immune checkpoint blockade therapies for treating solid cancers,their benefits are limite...Objective:Small cell lung cancer(SCLC)is commonly recognized as the most fatal lung cancer type.Despite substantial advances in immune checkpoint blockade therapies for treating solid cancers,their benefits are limited to a minority of patients with SCLC.In the present study,novel indicators for predicting the outcomes and molecular targets for SCLC treatment were elucidated.Methods:We conducted bioinformatics analysis to identify the key genes associated with tumor-infiltrating lymphocytes in SCLC.The functional role of the key gene identified in SCLC was determined both in vitro and in vivo.Results:A significant correlation was observed between patient survival and CD56dim natural killer(NK)cell proportion.Furthermore,we noted that the hub gene ubiquitin-specific protease 1(USP1)is closely correlated with both CD56dim NK cells and overall survival in SCLC.Bioinformatics analysis revealed that USP1 is upregulated in SCLC.In addition,gene set enrichment analysis revealed that USP1 overexpression hinders NK cell-mediated immune responses.By co-cultivating NK-92 cells with SCLC cells,we demonstrated that NK cell cytotoxicity against SCLC could be improved either via USP1 knock-down or pharmacological inhibition.Furthermore,using a nude-mice xenograft tumor model,we noted that USP1 inhibition effectively suppressed tumor proliferation and increased the expression of NK cell-associated markers.Conclusions:Our study findings highlight the importance of NK cells in regulating SCLC.USP1 overexpression can inhibit NK cell-mediated immunity;therefore,USP1 may serve not only as a prognostic biomarker but also as a potential molecular target of SCLC therapy.展开更多
Objective:Actin filament-associated protein 1 like 1(AFAP1L1)is an adaptor protein lacking enzymatic and transcriptional activity,but the AFAP1L1 gene functions as an oncogene in colorectal cancer and gastric cancers....Objective:Actin filament-associated protein 1 like 1(AFAP1L1)is an adaptor protein lacking enzymatic and transcriptional activity,but the AFAP1L1 gene functions as an oncogene in colorectal cancer and gastric cancers.This study aims to investigate the role of AFAP1L1 in glioma and to explore changes in AFAP1L1 expression during glioma progression.Methods:Clinical and transcriptomic data of glioma patients were downloaded from The Cancer Genome Atlas(TCGA),the Chinese Glioma Genome Atlas(CGGA),and the Gene Expression Omnibus(GEO)databases to analyze the associations between AFAP1L1 expression and glioma prognosis,somatic mutations,immune cell infiltration,and enriched signaling pathways.Western blotting and real-time polymerase chain reaction(PCR)were used to detect AFAP1L1 messenger RNA(mRNA)and protein expression in glioma patients.Results:Patients with high AFAP1L1 expression had poorer prognosis,and AFAP1L1 was identified as an independent risk factor for glioma.In addition,glioma patients with high AFAP1L1 expression exhibited lower levels of somatic mutations,including amplification of oncogenes such as epidermal growth factor receptor and deletion of tumor suppressor genes such as cyclin-dependent kinase inhibitor 2A(CDKN2A).Estimation of STromal and Immune cells in Malignant Tumours using Expression(ESTIMATE)algorithm analysis showed that AFAP1L1 expression was positively correlated with the immune microenvironment.Tumor immune dysfunction and exclusion(TIDE)analysis indicated that glioma patients with high AFAP1L1 expression responded poorly to immunotherapy.Single cell analysis showed that AFAP1L1 expression was mainly concentrated in glioma cells.Enrichment analysis suggested that AFAP1L1 was potentially associated with small guanosine triphosphatases(GTPases),hypoxia-inducible factor-1(HIF-1),focal adhesion,and mitogen-activated protein kinase(MAPK)signaling pathways.Conclusion:AFAP1L1 is a novel biomarker indicating glioma progression and a potential therapeutic target for glioma.展开更多
AIM:Regulatory T cells(Tregs)are a specialized subset of CD4^(+)T cells primarily involved in im⁃munosuppressive functions.AMP-activated protein kinase(AMPK)serves as a metabolic sensor that governs the differen⁃tiati...AIM:Regulatory T cells(Tregs)are a specialized subset of CD4^(+)T cells primarily involved in im⁃munosuppressive functions.AMP-activated protein kinase(AMPK)serves as a metabolic sensor that governs the differen⁃tiation,maturation,and immune functions of Tregs through metabolic reprogramming.However,the impact of AMPKα1(the catalytic subunit of AMPK)knockout specifically in Tregs on the host's immune microenvironment remains largely un⁃explored.METHODS:Histological changes in immune organs were assessed using HE staining.The types of immune cells and their relative population percentages in immune organs and blood were quantified through flow cytometry in both AMPKα1flox/flox(AMPKα1^(fl/fl))mice and Treg-specific AMPKα1 knockout mice(AMPKα1^(fl/fl)Foxp3^(cre)mice).RESULTS:Compared to AMPKα1^(fl/fl)mice,the percentage of eosinophils in the bone marrow of AMPKα1^(fl/fl)Foxp3^(cre)mice was significant⁃ly reduced.Additionally,while the thymus of AMPKα1^(fl/fl)Foxp3^(cre)mice exhibited normal structure,both its size and the ratio of thymus weight to body weight were significantly decreased.The knockout of AMPKα1 in Tregs led to a notable reduction in the total percentage of immature double-negative(DN)cells.Consequently,the percentage of CD4^(+)T cells derived from these DN cells also decreased,even though the percentages of DN1 and DN4 cells were higher in the thymus of AMPKα1^(fl/fl)Foxp3^(cre)mice compared to AMPKα1^(fl/fl)mice.Importantly,the proportion of Siglec-F+CD11b^(+)eosinophils in the thymus was significantly lower in AMPKα1^(fl/fl)Foxp3^(cre)mice.Knockout of AMPKα1 in Tregs resulted in a marked increase in the percentage of CD4^(+)T cells in peripheral blood,alongside a decrease in the proportion of mature CD8^(+)T cells.Similarly,the proportion of CD4^(+)T cells in the spleen of AMPKα1^(fl/fl)Foxp3^(cre)mice was elevated compared to AMPKα1^(fl/fl)mice.In contrast,the proportion of neutrophils significantly decreased,while mononuclear cell proportions increased in the spleen of AMPKα1^(fl/fl)Foxp3^(cre)mice.In lymph nodes,the medullary boundaries in AMPKα1^(fl/fl)Foxp3^(cre)mice were blurred,and the lymphoid follicles were missing,a feature not observed in AMPKα1^(fl/fl)mice.Furthermore,the knockout of AMPKα1 in Tregs reduced the CD3^(+)T cell population,particularly the CD8^(+)T cell population,in lymph nodes.Although the mature Treg cell population was significantly lower in AMPKα1^(fl/fl)Foxp3^(cre)mice,the percentage of CD4^(+)T cells was markedly in⁃creased.In contrast,there was no statistically significant difference in granulocyte populations between AMPKα1^(fl/fl)Foxp3^(cre)and AMPKα1^(fl/fl)mice.CONCLUSION:The populations of mature Tregs,CD8^(+)T cells and eosinophils in various im⁃mune organs were significantly altered in mice with Treg-specific AMPKα1 knockout,suggesting a potential remodeling of the host immune microenvironment in response to inflammatory stimuli.展开更多
High expression of pescadillo ribosomal biogenesis factor 1(PES1)has been re-ported across multiple cancer types and is significantly associated with poor prog-nosis.Hu et al in their recent paper described their inve...High expression of pescadillo ribosomal biogenesis factor 1(PES1)has been re-ported across multiple cancer types and is significantly associated with poor prog-nosis.Hu et al in their recent paper described their investigation of PES1 in gastric cancer and head and neck squamous cell carcinoma,demonstrating positive cor-relations between PES1 and programmed death-ligand 1(PD-L1)expression(51.72%for PES1 and 58.62%for PD-L1),as well as associations with lymph node metastasis and tumor invasion depth.However,the relationship between PES1 and PD-L1 remains incompletely defined.To further address this gap,we ana-lyzed The Cancer Genome Atlas gastric adenocarcinoma dataset and found a negative correlation between PES1 expression and CD8+T cell infiltration,along-side a positive correlation with PD-L1 expression.Based on prior findings,we hypothesize that PES1 may regulate PD-L1 through the phosphatidylinositol 3-kinase/protein kinase B pathway or cellular Myc-mediated mechanisms.While these pathways require experimental validation,our observations highlight PES1 as a potential regulator of immune evasion and a promising target for cancer immunotherapy.展开更多
Posttranslational modifications(PTMs)are essential regulatory mechanisms that play a critical role in plant immunity.Previously,we demonstrated that OsBBI1,a RING finger type E3 ligase,contributes to rice resistance a...Posttranslational modifications(PTMs)are essential regulatory mechanisms that play a critical role in plant immunity.Previously,we demonstrated that OsBBI1,a RING finger type E3 ligase,contributes to rice resistance against blast disease.In this study,we identified two Eps15 homology domain(EHD)-containing proteins,OsEHD1 and OsEHD2,as substrates of OsBBI1 and investigated their roles in rice immunity against Magnaporthe oryzae and Xanthomonas oryzae pv.oryzae(Xoo).We found that OsBBI1 ubiquitinated and promoted the degradation of OsEHD1 and OsEHD2 via ubiquitin/26S proteasome system(UPS)pathway.CRISPR/Cas9-mediated knockout of OsEHD1 and OsEHD2 led to enhanced immunity against M.oryzae and Xoo,improved expression of pathogen-induced immunity-associated genes,and strengthened pattern-triggered immunity(PTI),while overexpression of OsEHD1 resulted in opposite phenotypes.Additionally,OsEHD1 and OsEHD2 interacted with three SUMO proteins,OsSUMO3,OsSUMO5,or OsSUMO6,with SUMOylation sites in OsEHD1 and OsEHD2 being critical for these interactions.OsSUMO6 enhanced the stability of OsEHD1 and OsEHD2 to promote their negative immune regulation,whereas OsBBI1 reversed these negative immune functions.This study delineates a regulatory network of OsEHD1 and OsEHD2 proteins in rice immunity,highlighting the balance between OssBBI1-mediated ubiquitination and SUMOylation.展开更多
An article recently published in the World Journal of Diabetes,provides valuable insights into using immune biomarkers to identify renal damage in pediatric patients with newly diagnosed type 1 diabetes(T1D).Although ...An article recently published in the World Journal of Diabetes,provides valuable insights into using immune biomarkers to identify renal damage in pediatric patients with newly diagnosed type 1 diabetes(T1D).Although these findings are promising,clinical translation of these immune markers into routine diagnostics and preventive care remains challenging.In this letter,we propose building on the authors’work by exploring the integration of immune biomarkers into a more comprehensive dynamic risk stratification model for early renal injury.Com-bining immune system indicators with metabolic and genetic factors could enhance the predictive accuracy and support more personalized interventions.Longitudinal studies are needed to evaluate temporal changes in immune biomarkers and their association with long-term renal outcomes in children with T1Ds.Immunomodulatory therapies targeting early immune dysfunction can prevent or slow the progression of diabetic nephropathy.By incorporating these aspects,we hope to translate immune biomarkers from research into practical clinical tools,ultimately improving patient outcomes and reducing the burden of kidney-related complications in pediatric diabetes.展开更多
This editorial delves into the potential of systemic immune indicators(SIIs)as early predictors of renal damage in children with newly diagnosed type 1 diabetes mellitus.By exploring the recent study published by Cao ...This editorial delves into the potential of systemic immune indicators(SIIs)as early predictors of renal damage in children with newly diagnosed type 1 diabetes mellitus.By exploring the recent study published by Cao et al,this article aims to highlight the importance of early detection and intervention.This study compre-hensively analyzes various SIIs,examining their correlation with renal compli-cations in newly diagnosed type 1 diabetic children.The findings reveal a sig-nificant association between immune system dysregulation and the onset of renal damage,suggesting that certain immune indicators can be early markers for predicting renal complications.This editorial emphasizes the clinical implications and applications of utilizing SIIs for early detection in pediatric diabetes care.It underscores the importance of innovative diagnostic approaches and illustrates real-world applications and outcomes.Additionally,it addresses the challenges and considerations in adopting these indicators and outlines future research directions to enhance diabetes management in children.展开更多
文摘Objective Sepsis patients exhibit diverse immune states,making it crucial to identify subtypes with distinct inflammatory profiles through Th1/Th2 cytokine data for personalized treatment and improved prognosis.Methods We retrieved data from sepsis patients who underwent Th1/Th2 cytokine testing in Nanfang Hospital,Southern Medical University from June 1,2020,to February 1,2022.An unsupervised K-means clustering method classified participants based on Th1/Th2 cytokine levels,with the primary outcome being the 7-day mortality rate post-ICU admission.Cox proportional hazards and Restricted Mean Survival Time(RMST)analyses were utilized to explore survival outcomes.Results A total of 321 sepsis patients were included.IL-6(HR 1.69,95%CI:1.22,2.34)and IL-10(HR 1.81,95%CI:1.37,2.40)emerged as independent predictors of 7-day mortality.Unsupervised K-means clustering revealed 3 inflammatory/immune subgroups:Cluster 1(n=166,low inflammatory response),Cluster 2(n=99,moderate inflammatory response with immune suppression),and Cluster 3(n=56,strong inflammatory and immune suppression).Compared to Cluster 1,Clusters 2 and 3 had higher 7-day mortality risks(14.4%vs 23.2%,HR=4.30,95%CI:1.51-12.26;14.4%vs 35.7%,HR=7.32,95%CI:2.57-20.79).Conclusion Septic patients in a protective immune response state(Cluster 1)exhibit better short-term prognoses,suggesting the importance of understanding inflammatory/immune states for precise treatment and improved outcomes.
基金supported by the Anhui Province Tongxin Science and Technology Innovation Project(202523b11020014)the Anhui Province Higher Education Quality Engineering Program(2024fwxx003).
文摘SalicS1 is a genetically encoded,ratiometric FRET biosensor that brings salicylic acid(SA)research to the same real-time imaging standard long available for ABA and GA.Built through a modular Golden Gate platform and informed by NPR-NIMIN structural biology,SalicS1 achieves SA specificity,tunable affinity,reversibility,and non-perturbing expression in Arabidopsis.Using this sensor,pathogen infection,non-adapted fungal challenge,and aphid feeding are shown to elicit spatially propagating SA surges rather than purely local accumulation,revealing a tissue-level organization of immune signaling that bulk assays could not resolve.SalicS1 therefore provides a broadly deployable tool for dissecting the geometry,timing,and genotype dependence of SA-mediated plant defense.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.82222058,82425046,and 82273142).
文摘Anti-programmed cell death protein 1(PD-1)or its ligand(PD-L1)are immune checkpoint inhibitors(ICIs)that have revolutionized cancer therapy.However,the efficacy of anti-PD-1 and anti-PD-L1 is limited by resistance and inter-individual variability.In recent years increasing evidence has highlighted the pivotal role of the gut microbiota in modulating the response to PD-1/PD-L1 immunotherapy.Extensive preclinical studies have demonstrated that commensal microbes can increase the efficacy of PD-1/PD-L1 blockade through multiple mechanisms,including the production of metabolites,such as short-chain fatty acids(SCFAs),tryptophan derivatives,and extracellular polysaccharides that remodel the tumor microenvironment,as well as the activation of immune pathways involving dendritic cells,CD8+T cells,and M1 macrophages to increase antitumor immunity.Moreover,clinical studies have shown that fecal microbiota transplantation(FMT)and targeted probiotic interventions show promise for improving the response to PD-1/PD-L1 therapy,while reducing the risk of immune-related adverse events(irAEs).This review systematically explores the multifaceted regulatory roles of the commensal microbiota in PD-1/PD-L1 therapy and examines the preclinical prospects of microbiota-based personalized immunotherapeutic strategies.The integration of multiomics technologies,synthetic biology,and precise microbiota interventions may further optimize PD-1/PD-L1 immunotherapy and offer novel insights into antitumor immune modulation.
基金supported by the National Natural Science Foundation of China(grant no.81602426).
文摘Objectives:Gastric cancer(GC)remains a major global health concern,and Phosphoinositide-3-Kinase Regulatory Subunit 1(PIK3R1),a regulatory subunit of the PI3K signaling pathway,may play a critical yet underexplored role in GC progression.This study aimed to investigate the prognostic significance of PIK3R1 in GC and its association with the tumor immune microenvironment.Methods:PIK3R1 expression and its clinical relevance were analyzed using datasets from GC patients who underwent gastrectomy,including cohorts from The Cancer Genome Atlas(TCGA)and the Sun Yat-sen University Cancer Center(SYSUCC).Prognostic models integrating PIK3R1 expression with clinical parameters were constructed for both cohorts.The immune microenvironment associated with PIK3R1 expression was assessed through immunohistochemistry and single-cell RNA sequencing.In vitro assays were conducted to evaluate the effects of PIK3R1 on GC cell proliferation and migration.Results:PIK3R1 was significantly overexpressed in GC tissues and was closely associated with aggressive tumor characteristics and poor clinical outcomes.A nomogram combining PIK3R1 expression with clinicopathological features effectively predicted patient prognosis.Knockdown of PIK3R1 in GC cells reduced proliferation and migration in vitro.Immunological profiling revealed that high PIK3R1 expression correlated with increased infiltration of forkhead box protein P3(Foxp3^(+))and cluster of differentiation 73(CD73^(+))T cells.Patients with low PIK3R1 expression and low CD73^(+)T cell infiltration had significantly better survival.Conclusions:PIK3R1 overexpression is linked to poor prognosis in GC and influences the extent of immune cell infiltration within the tumor microenvironment.A novel prognostic model integrating PIK3R1 and CD73 expression with clinical parameters was established to stratify GC patients into distinct risk groups,offering potential value for personalized therapeutic strategies.
文摘Cerebrovascular diseases are considered to be amongst the most serious public health issues,since they are the third leading cause of death（WHO,2014）and the most common cause of disability worldwide.Its monetary significance is evidenced by the economic burden imposed on health care systems,given that the cost of medical care for a patient that has suffered a stroke is around$25,741US dollars every 5 years（Luengo-Fernandez et al.,2012）.A stroke occurs as a result of a disturbance or interruption of cerebral blood flow that significantly reduces the supply of oxygen and glucose to the neural tissue. Consequently, several cell death mechanisms （secondary lesion mechanisms） such as necrosis, excitotoxicity, free radical production and inflammation are triggered （Castillo, 2000）.
基金Supported by the Program for New Century Excellent Talents in University (No. NCET-05-0684)
文摘AIM: To explore the effect of immunization with copolymer-1 (COP-1) and retinal stem cells (RSCs) transplantation on interferon-gamma (IFN-gamma) levels in a rat experimental glaucoma model. METHODS: An experimental glaucoma was induced by argon laser photocoagulation of the episcleral veins and limbal plexus in the right eye of rats. Immediately following glaucoma induction, rats were immunized with COP-1. RSCs were cultured and transplanted intravitreally into the eyes of glaucoma model animals 1 week post-laser treatment. Six experimental groups were used: COP-1/RSC, PBS/RSC, COP-1/PBS, PBS/PBS, glaucoma model group, and a normal control group. The concentration of IFN-gamma in aqueous humor (AH) and serum was measured by enzyme-linked immunosorbent assay (ELISA) in each of the six groups. Retinal ganglion cell (RGC) survival was assessed by quantifying apoptosis using Hoechst staining. RESULTS: Concentrations of IFN-gamma in AH and serum of rats that had undergone glaucoma induction were higher than those of non-induced control rats. The concentrations of IFN-gamma in AH and serum of the COP-1/RSCs treated group were determined to be 2371.9ng/L and 710.9ng/L, respectively, which were significantly lower than those in the other treated groups (P<0.05). In fact, IFN-gamma levels in the dual treated group were reduced to background levels. The COP-1/RSC group had lower number of apoptotic RGCs than the other three experimental groups (P<0.05). CONCLUSION: The reduced levels of IFN-gamma in AH and serum of the COP-1/RSC group may be related to synergistic effects between RSCs transplantation and COP-1 immune modulation. It is likely that the lower levels of IFN-gamma prevented RGCs glaucomatous apoptasis.
文摘[Objective] This study aimed to construct DNA vaccine of foot-and-mouth disease （FMD）.[Method] Plasmid carriers plESZP1 and pUTK3CP1 with PRV were constructed for FMDV P1 gene expression.Mice were immunized,and their antibody level was detected.The two eukaryotic expression plasmids constructed were transfected into Vero cells.PCR,IFA and Westem-blot were carried out to detect the transcription and expression of the objective gene.Balb/C mice were intramuscularly inoculated with the DNA plasmid which expressed the target gene correctly,and the antibody level in mice was detected by the means of ELISA and serum neutralization （SN）.[Result] DNA plasmid carrying P1 gene which encodes FMDV capsid protein caused specific body fluid immunoreaction in mice,and the antibody level of anti-FMDV had no difference in the mice induced by the two recombinant plasmids.[Conclusion] This study lays a foundation for evaluating the genetically modified vaccine by immunizing animals with recombinant PRV containing the FMDV P1 gene and recombinant virus.
基金supported by a grant from Universidad Anahuac México Norte(No.201425)
文摘Copolymer-1（Cop-1） is a peptide with immunomodulatory properties, approved by the Food and Drug Administration of United States in the treatment of multiple sclerosis. Cop-1 has been shown to exert neuroprotective effects and induce neurogenesis in cerebral ischemia models. Nevertheless, the mechanism involved in the neurogenic action of this compound remains unknown. The choroid plexus（CP） is a network of cells that constitute the interphase between the immune and central nervous systems, with the ability to mediate neurogenesis through the release of cytokines and growth factors. Therefore, the CP could play a role in Cop-1-induced neurogenesis. In order to determine the participation of the CP in the induction of neurogenesis after Cop-1 immunization, we evaluated the gene expression of various growth factors（brain-derived neurotrophic factor, insulin-like growth factor 1, neurotrophin-3） and cytokines（tumor necrosis factor alpha, interferon-gamma, interleukin-4（IL-4）, IL-10 and IL-17）, in the CP at 14 days after ischemia. Furthermore, we analyzed the correlation between the expression of these genes and neurogenesis. Our results showed that Cop-1 was capable of stimulating an upregulation in the expression of the genes encoding for brain-derived neurotrophic factor, insulin-like growth factor 1, neurotrophin-3 and IL-10 in the CP, which correlated with an increase in neurogenesis in the subventricular and subgranular zone. As well, we observed a downregulation of IL-17 gene expression. This study demonstrates the effect of Cop-1 on the expression of growth factors and IL-10 in the CP, in the same way, presents a possible mechanism involved in the neurogenic effect of Cop-1.
基金Supported by the Haihe Laboratory of Cell Ecosystem Innovation Fund,No.22HHXBJC00001the Key Discipline Special Project of Tianjin Municipal Health Commission,No.TJWJ2022XK016.
文摘BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact molecular mechanisms leading to the progression of HCC are still unclear.Research has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor tissues.In this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between them.AIM To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC patients.METHODS In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC patients.Furthermore,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,etc.The statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank test.RESULTS In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival rate.ASH1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated region.Furthermore,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via ASH1L.For the exploration mechanism,we found ASH1L may promote an immunosuppressive microenvironment in HCC and ASH1L affects the expression of the cell junction protein zonula occludens-1,which is potentially relevant to the immune system.CONCLUSION Loss function of microRNA-142-3p induces cancer progression and immune evasion through upregulation of ASH1L in HCC.Both microRNA-142-3p and ASH1L can feature as new biomarker for HCC in the future.
基金supported by grants from the Dongguan Science and Technology of Social Development Program(No.20231800940192)the Talent Development Foundation of the First Dongguan Affiliated Hospital of Guangdong Medical University(No.PU2023002).
文摘Objective:Small cell lung cancer(SCLC)is commonly recognized as the most fatal lung cancer type.Despite substantial advances in immune checkpoint blockade therapies for treating solid cancers,their benefits are limited to a minority of patients with SCLC.In the present study,novel indicators for predicting the outcomes and molecular targets for SCLC treatment were elucidated.Methods:We conducted bioinformatics analysis to identify the key genes associated with tumor-infiltrating lymphocytes in SCLC.The functional role of the key gene identified in SCLC was determined both in vitro and in vivo.Results:A significant correlation was observed between patient survival and CD56dim natural killer(NK)cell proportion.Furthermore,we noted that the hub gene ubiquitin-specific protease 1(USP1)is closely correlated with both CD56dim NK cells and overall survival in SCLC.Bioinformatics analysis revealed that USP1 is upregulated in SCLC.In addition,gene set enrichment analysis revealed that USP1 overexpression hinders NK cell-mediated immune responses.By co-cultivating NK-92 cells with SCLC cells,we demonstrated that NK cell cytotoxicity against SCLC could be improved either via USP1 knock-down or pharmacological inhibition.Furthermore,using a nude-mice xenograft tumor model,we noted that USP1 inhibition effectively suppressed tumor proliferation and increased the expression of NK cell-associated markers.Conclusions:Our study findings highlight the importance of NK cells in regulating SCLC.USP1 overexpression can inhibit NK cell-mediated immunity;therefore,USP1 may serve not only as a prognostic biomarker but also as a potential molecular target of SCLC therapy.
基金supported by the National Natural Science Foundation(82073850)the Hunan Provincial Youth Science Foundation Project(2019JJ50964),China.
文摘Objective:Actin filament-associated protein 1 like 1(AFAP1L1)is an adaptor protein lacking enzymatic and transcriptional activity,but the AFAP1L1 gene functions as an oncogene in colorectal cancer and gastric cancers.This study aims to investigate the role of AFAP1L1 in glioma and to explore changes in AFAP1L1 expression during glioma progression.Methods:Clinical and transcriptomic data of glioma patients were downloaded from The Cancer Genome Atlas(TCGA),the Chinese Glioma Genome Atlas(CGGA),and the Gene Expression Omnibus(GEO)databases to analyze the associations between AFAP1L1 expression and glioma prognosis,somatic mutations,immune cell infiltration,and enriched signaling pathways.Western blotting and real-time polymerase chain reaction(PCR)were used to detect AFAP1L1 messenger RNA(mRNA)and protein expression in glioma patients.Results:Patients with high AFAP1L1 expression had poorer prognosis,and AFAP1L1 was identified as an independent risk factor for glioma.In addition,glioma patients with high AFAP1L1 expression exhibited lower levels of somatic mutations,including amplification of oncogenes such as epidermal growth factor receptor and deletion of tumor suppressor genes such as cyclin-dependent kinase inhibitor 2A(CDKN2A).Estimation of STromal and Immune cells in Malignant Tumours using Expression(ESTIMATE)algorithm analysis showed that AFAP1L1 expression was positively correlated with the immune microenvironment.Tumor immune dysfunction and exclusion(TIDE)analysis indicated that glioma patients with high AFAP1L1 expression responded poorly to immunotherapy.Single cell analysis showed that AFAP1L1 expression was mainly concentrated in glioma cells.Enrichment analysis suggested that AFAP1L1 was potentially associated with small guanosine triphosphatases(GTPases),hypoxia-inducible factor-1(HIF-1),focal adhesion,and mitogen-activated protein kinase(MAPK)signaling pathways.Conclusion:AFAP1L1 is a novel biomarker indicating glioma progression and a potential therapeutic target for glioma.
基金Supported by the National Natural Science Foundation of China(No.81800423)the Guangdong Medical Science and Technology Research project(No.B2022102)。
文摘AIM:Regulatory T cells(Tregs)are a specialized subset of CD4^(+)T cells primarily involved in im⁃munosuppressive functions.AMP-activated protein kinase(AMPK)serves as a metabolic sensor that governs the differen⁃tiation,maturation,and immune functions of Tregs through metabolic reprogramming.However,the impact of AMPKα1(the catalytic subunit of AMPK)knockout specifically in Tregs on the host's immune microenvironment remains largely un⁃explored.METHODS:Histological changes in immune organs were assessed using HE staining.The types of immune cells and their relative population percentages in immune organs and blood were quantified through flow cytometry in both AMPKα1flox/flox(AMPKα1^(fl/fl))mice and Treg-specific AMPKα1 knockout mice(AMPKα1^(fl/fl)Foxp3^(cre)mice).RESULTS:Compared to AMPKα1^(fl/fl)mice,the percentage of eosinophils in the bone marrow of AMPKα1^(fl/fl)Foxp3^(cre)mice was significant⁃ly reduced.Additionally,while the thymus of AMPKα1^(fl/fl)Foxp3^(cre)mice exhibited normal structure,both its size and the ratio of thymus weight to body weight were significantly decreased.The knockout of AMPKα1 in Tregs led to a notable reduction in the total percentage of immature double-negative(DN)cells.Consequently,the percentage of CD4^(+)T cells derived from these DN cells also decreased,even though the percentages of DN1 and DN4 cells were higher in the thymus of AMPKα1^(fl/fl)Foxp3^(cre)mice compared to AMPKα1^(fl/fl)mice.Importantly,the proportion of Siglec-F+CD11b^(+)eosinophils in the thymus was significantly lower in AMPKα1^(fl/fl)Foxp3^(cre)mice.Knockout of AMPKα1 in Tregs resulted in a marked increase in the percentage of CD4^(+)T cells in peripheral blood,alongside a decrease in the proportion of mature CD8^(+)T cells.Similarly,the proportion of CD4^(+)T cells in the spleen of AMPKα1^(fl/fl)Foxp3^(cre)mice was elevated compared to AMPKα1^(fl/fl)mice.In contrast,the proportion of neutrophils significantly decreased,while mononuclear cell proportions increased in the spleen of AMPKα1^(fl/fl)Foxp3^(cre)mice.In lymph nodes,the medullary boundaries in AMPKα1^(fl/fl)Foxp3^(cre)mice were blurred,and the lymphoid follicles were missing,a feature not observed in AMPKα1^(fl/fl)mice.Furthermore,the knockout of AMPKα1 in Tregs reduced the CD3^(+)T cell population,particularly the CD8^(+)T cell population,in lymph nodes.Although the mature Treg cell population was significantly lower in AMPKα1^(fl/fl)Foxp3^(cre)mice,the percentage of CD4^(+)T cells was markedly in⁃creased.In contrast,there was no statistically significant difference in granulocyte populations between AMPKα1^(fl/fl)Foxp3^(cre)and AMPKα1^(fl/fl)mice.CONCLUSION:The populations of mature Tregs,CD8^(+)T cells and eosinophils in various im⁃mune organs were significantly altered in mice with Treg-specific AMPKα1 knockout,suggesting a potential remodeling of the host immune microenvironment in response to inflammatory stimuli.
文摘High expression of pescadillo ribosomal biogenesis factor 1(PES1)has been re-ported across multiple cancer types and is significantly associated with poor prog-nosis.Hu et al in their recent paper described their investigation of PES1 in gastric cancer and head and neck squamous cell carcinoma,demonstrating positive cor-relations between PES1 and programmed death-ligand 1(PD-L1)expression(51.72%for PES1 and 58.62%for PD-L1),as well as associations with lymph node metastasis and tumor invasion depth.However,the relationship between PES1 and PD-L1 remains incompletely defined.To further address this gap,we ana-lyzed The Cancer Genome Atlas gastric adenocarcinoma dataset and found a negative correlation between PES1 expression and CD8+T cell infiltration,along-side a positive correlation with PD-L1 expression.Based on prior findings,we hypothesize that PES1 may regulate PD-L1 through the phosphatidylinositol 3-kinase/protein kinase B pathway or cellular Myc-mediated mechanisms.While these pathways require experimental validation,our observations highlight PES1 as a potential regulator of immune evasion and a promising target for cancer immunotherapy.
基金supported by grants from the National Natural Science Foundation of China(32072403 and 31871945 to Fengming Song,and 32160455 to Yayun Yang)Postdoctoral Fellowship Program of CPSF(GZC20232353 to Yan Bi)the Opening Fund of Yunnan Provincial Key Laboratory of Agricultural Biotechnology to Yan Bi and Yayun Yang.
文摘Posttranslational modifications(PTMs)are essential regulatory mechanisms that play a critical role in plant immunity.Previously,we demonstrated that OsBBI1,a RING finger type E3 ligase,contributes to rice resistance against blast disease.In this study,we identified two Eps15 homology domain(EHD)-containing proteins,OsEHD1 and OsEHD2,as substrates of OsBBI1 and investigated their roles in rice immunity against Magnaporthe oryzae and Xanthomonas oryzae pv.oryzae(Xoo).We found that OsBBI1 ubiquitinated and promoted the degradation of OsEHD1 and OsEHD2 via ubiquitin/26S proteasome system(UPS)pathway.CRISPR/Cas9-mediated knockout of OsEHD1 and OsEHD2 led to enhanced immunity against M.oryzae and Xoo,improved expression of pathogen-induced immunity-associated genes,and strengthened pattern-triggered immunity(PTI),while overexpression of OsEHD1 resulted in opposite phenotypes.Additionally,OsEHD1 and OsEHD2 interacted with three SUMO proteins,OsSUMO3,OsSUMO5,or OsSUMO6,with SUMOylation sites in OsEHD1 and OsEHD2 being critical for these interactions.OsSUMO6 enhanced the stability of OsEHD1 and OsEHD2 to promote their negative immune regulation,whereas OsBBI1 reversed these negative immune functions.This study delineates a regulatory network of OsEHD1 and OsEHD2 proteins in rice immunity,highlighting the balance between OssBBI1-mediated ubiquitination and SUMOylation.
文摘An article recently published in the World Journal of Diabetes,provides valuable insights into using immune biomarkers to identify renal damage in pediatric patients with newly diagnosed type 1 diabetes(T1D).Although these findings are promising,clinical translation of these immune markers into routine diagnostics and preventive care remains challenging.In this letter,we propose building on the authors’work by exploring the integration of immune biomarkers into a more comprehensive dynamic risk stratification model for early renal injury.Com-bining immune system indicators with metabolic and genetic factors could enhance the predictive accuracy and support more personalized interventions.Longitudinal studies are needed to evaluate temporal changes in immune biomarkers and their association with long-term renal outcomes in children with T1Ds.Immunomodulatory therapies targeting early immune dysfunction can prevent or slow the progression of diabetic nephropathy.By incorporating these aspects,we hope to translate immune biomarkers from research into practical clinical tools,ultimately improving patient outcomes and reducing the burden of kidney-related complications in pediatric diabetes.
文摘This editorial delves into the potential of systemic immune indicators(SIIs)as early predictors of renal damage in children with newly diagnosed type 1 diabetes mellitus.By exploring the recent study published by Cao et al,this article aims to highlight the importance of early detection and intervention.This study compre-hensively analyzes various SIIs,examining their correlation with renal compli-cations in newly diagnosed type 1 diabetic children.The findings reveal a sig-nificant association between immune system dysregulation and the onset of renal damage,suggesting that certain immune indicators can be early markers for predicting renal complications.This editorial emphasizes the clinical implications and applications of utilizing SIIs for early detection in pediatric diabetes care.It underscores the importance of innovative diagnostic approaches and illustrates real-world applications and outcomes.Additionally,it addresses the challenges and considerations in adopting these indicators and outlines future research directions to enhance diabetes management in children.
