In 1891,a New York surgeon named William Coley injected cancer patients with live bacteria,observing with fascination as some tumors shrank amid raging fevers.His crude experiments-later deemed reckless-nonetheless re...In 1891,a New York surgeon named William Coley injected cancer patients with live bacteria,observing with fascination as some tumors shrank amid raging fevers.His crude experiments-later deemed reckless-nonetheless revealed a tantalizing truth:The immune system,when properly provoked,could attack cancer.Over a century later,researchers have transformed this observation into a precision strike force.展开更多
To the editor:The liver’s immune-privileged status allows for a unique microenvironment that supports tumour growth and metastasis.In hepatocellular carcinoma(HCC),the balance between cytotoxic T lymphocytes and regu...To the editor:The liver’s immune-privileged status allows for a unique microenvironment that supports tumour growth and metastasis.In hepatocellular carcinoma(HCC),the balance between cytotoxic T lymphocytes and regulatory T cells plays a crucial role in determining patient outcomes.The expression of programmed cell death ligand 1(PD-1)and other immune checkpoint molecules contributes to a pro-tumourigenic microenvironment and is associated with poor prognosis.Additionally,the heterogeneity of the immune microenvironment adds complexity to disease progression and treatment response.展开更多
Polytrauma with significant bone and volumetric muscle loss presents substantial clinical challenges.Although immune responses significantly influence fracture healing post-polytrauma,the cellular and molecular underp...Polytrauma with significant bone and volumetric muscle loss presents substantial clinical challenges.Although immune responses significantly influence fracture healing post-polytrauma,the cellular and molecular underpinnings of polytrauma-induced immune dysregulation require further investigation.While previous studies examined either injury site tissue or systemic tissue(peripheral blood),our study uniquely investigated both systemic and local immune cells at the same time to better understand polytrauma-induced immune dysregulation and associated impaired bone healing.Using single-cell RNA sequencing(scRNA-seq)in a rat polytrauma model,we analyzed blood,bone marrow,and the local defect soft tissue to identify potential cellular and molecular targets involved in immune dysregulation.We identified a trauma-associated immunosuppressive myeloid(TIM)cell population that drives systemic immune dysregulation,immunosuppression,and potentially impaired bone healing.We found CD1d as a global marker for TIM cells in polytrauma.展开更多
Currently,the use of immune checkpoint inhibitors(ICIs)has shown notable clinical efficacy in treating various malignant tumors,significantly improving patient prognosis.However,while ICIs enhance the body’s anti-tum...Currently,the use of immune checkpoint inhibitors(ICIs)has shown notable clinical efficacy in treating various malignant tumors,significantly improving patient prognosis.However,while ICIs enhance the body’s anti-tumor effects,they can also trigger immune-related adverse events(irAEs),with ICI-associated colitis being one of the more prevalent forms.This condition can disrupt treatment,necessitate drug discontinuation,and adversely affect therapeutic outcomes.In severe cases,irAEs may even become life-threatening.A recent case report by Hong et al highlights the importance of vigilance for ICI-associated colitis in patients experiencing symptoms such as diarrhea and abdominal pain,which can arise both during and even after completion of ICI treatment.Early identification,multidisciplinary management,and continuous monitoring of patients are essential steps to further improve outcomes.展开更多
Dysfunction of anti-tumor immune responses is crucial for cancer progression. Immune checkpoint blockade(ICB), which can potentiate T cell responses, is an effective strategy for the normalization of host anti-tumor i...Dysfunction of anti-tumor immune responses is crucial for cancer progression. Immune checkpoint blockade(ICB), which can potentiate T cell responses, is an effective strategy for the normalization of host anti-tumor immunity. In recent years, immune checkpoints, expressed on both tumor cells and immune cells, have been identified;some of them have exhibited potential druggability and have been approved by the US Food and Drug Administration(FDA) for clinical treatment. However, limited responses and immune-related adverse events(ir AEs) cannot be ignored. This review outlines the development and applications of ICBs, potential strategies for overcoming resistance, and future directions for ICB-based cancer immunotherapy.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
The immunomodulatory function of estrogen within the ovary remains a subject of ongoing debate,and the neonatal ovarian immune microenvironment,particularly its modulation by estrogen,has not been comprehensively char...The immunomodulatory function of estrogen within the ovary remains a subject of ongoing debate,and the neonatal ovarian immune microenvironment,particularly its modulation by estrogen,has not been comprehensively characterized.In this study,the effects of 17β-estradiol(E_(2)),a key regulator of immune function,were investigated using single-cell transcriptomic profiling of C57BL/6J neonatal mouse ovaries after E_(2)treatment.Results revealed dynamic alterations in the proportion of immune cell types after E_(2)treatment,accompanied by changes in cytokine and chemokine expression.Detailed analyses of gene expression,cell states,and developmental trajectories across distinct cell types indicated that E_(2)treatment influenced cell differentiation and development.Notably,E_(2)treatment reduced the abundance of macrophages and promoted a phenotypic transition from M1 to M2 macrophages.These findings demonstrate that the neonatal mouse ovarian immune microenvironment is sensitive to estrogenic modulation,which governs both the distribution and functional specialization of resident immune cells,offering novel mechanistic insights into the immunomodulatory roles of estrogen across various immune cell types.展开更多
This paper investigates the effects of graphene quantum dots and mesoporous silica as nanomaterial adjuvants on immune activity in mice both in vitro and in vivo.The two materials have distinct properties;graphene qua...This paper investigates the effects of graphene quantum dots and mesoporous silica as nanomaterial adjuvants on immune activity in mice both in vitro and in vivo.The two materials have distinct properties;graphene quantum dots possess unique optical and electrical characteristics,while mesoporous silica features a regular pore structure.In vitro experiments show differences in their effects on immune cell activation and cytokine secretion;in vivo experiments reveal varying performances in antibody production and immune cell function regulation.Their mechanisms of action and safety profiles also differ,offering distinct advantages in application prospects.These two nanomaterial adjuvants provide new directions for the development of immunology,warranting further exploration.展开更多
Cold tumors,defined by insufficient immune cell infiltration and a highly immunosuppressive tumor microenvironment(TME),exhibit limited responsiveness to conventional immunotherapies.This reviewsystematically summariz...Cold tumors,defined by insufficient immune cell infiltration and a highly immunosuppressive tumor microenvironment(TME),exhibit limited responsiveness to conventional immunotherapies.This reviewsystematically summarizes the mechanisms of immune evasion and the therapeutic strategies for cold tumors as revealed by multiomics technologies.By integrating genomic,transcriptomic,proteomic,metabolomic,and spatialmulti-omics data,the review elucidates key immune evasionmechanisms,including activation of the WNT/β-catenin pathway,transforming growth factor-β(TGF-β)–mediated immunosuppression,metabolic reprogramming(e.g.,lactate accumulation),and aberrant expression of immune checkpoint molecules.Furthermore,this review proposes multi-dimensional therapeutic strategies,such as targeting immunosuppressive pathways(e.g.,programmed death-1(PD-1)/programmed death-ligand 1(PD-L1)inhibitors combined with TGF-βblockade),reshaping the TME through chemokine-based therapies,oncolytic viruses,and vascular normalization,and metabolic interventions(e.g.,inhibition of lactate dehydrogenase A(LDHA)or glutaminase(GLS)).In addition,personalized neoantigen vaccines and engineered cell therapies(e.g.,T cell receptor-engineered T(TCR-T)and natural killer(NK)cells)show promising potential.Emerging evidence also highlights the role of epigenetic regulation(e.g.,histone deacetylase(HDAC)inhibitors)and N6-Methyladenosine(m6A)RNA modifications in reversing immune evasion.Despite the promising insights offered by multi-omics integration in guiding precision immunotherapy,challenges remain in clinical translation,including data heterogeneity,target-specific toxicity,and limitations in preclinical models.Future efforts should focus on coupling dynamic multi-omics technologies with intelligent therapeutic design to convert cold tumors into immunologically active(“hot”)microenvironments,ultimately facilitating breakthroughs in personalized immunotherapy.展开更多
BACKGROUND Colorectal cancer(CRC)is a leading cause of cancer-related mortality worldwide,primarily due to tumor heterogeneity and treatment resistance.The leucine-rich repeat-containing protein 19(LRRC19)has been lin...BACKGROUND Colorectal cancer(CRC)is a leading cause of cancer-related mortality worldwide,primarily due to tumor heterogeneity and treatment resistance.The leucine-rich repeat-containing protein 19(LRRC19)has been linked to immune regulation and tumor suppression,yet its specific role in CRC remains poorly understood.AIM To investigate the tumor-suppressive role of LRRC19 in CRC,focusing on cell cycle,immune microenvironment,and chemotherapy response.METHODS Bioinformatics analyses of Gene Expression Omnibus and The Cancer Genome Atlas databases identified differentially expressed genes in CRC.LRRC19 exp-ression was validated in CRC tissues and cell lines by quantitative PCR,immuno-histochemistry,and Western blotting.Functional assays,including proliferation,soft agar colony formation,flow cytometry,and xenograft models,assessed biological effects.Mechanistic studies with dual-luciferase reporter assays,molecular docking,and drug sensitivity testing explored LRRC19’s interaction with the cyclin-dependent kinase 6(CDK6)/E2F1 axis and oxaliplatin(OXA)response.Single-cell sequencing and immune infiltration analyses assessed its impact on the immune microenvironment.RESULTS LRRC19 expression was significantly downregulated in CRC and associated with poor prognosis.Overexpression of LRRC19 inhibited CRC cell proliferation,induced G0/G1 phase arrest,and suppressed tumor growth in vivo.Mechanistically,LRRC19 suppressed CDK6 transcription by downregulating E2F1,leading to cell cycle arrest.Additionally,LRRC19 promoted immune cell infiltration,particularly B cells and CD4+T cells,while decreasing immunosuppressive cells.LRRC19 also sensitized CRC cells to OXA,enhancing chemotherapy efficacy.CONCLUSION LRRC19 suppresses CRC by targeting the CDK6/E2F1 axis,modulating the immune microenvironment,and enhancing chemotherapy sensitivity,making it a promising therapeutic target for precision medicine in CRC.展开更多
Background:PLK3,which played an important role in cell cycle progression and stress response,was identified as highly expressed in various carcinomas.However,the functions,molecular characteristics,and prognostic valu...Background:PLK3,which played an important role in cell cycle progression and stress response,was identified as highly expressed in various carcinomas.However,the functions,molecular characteristics,and prognostic value of PLK3 in glioma remained unexplored.Methods:We analyzed PLK3 expression in glioma samples from multiple databases.Both overexpression and knockdown of Plk3 were performed to investigate tumor cell growth in glioma,and the transplanted glioma mouse model demonstrated the role of Plk3 on tumor progression.Immunohistochemistry was conducted to detect PLK3 expression and immune cell infiltration.The trans-well assay for PLK3 on the immune cells recruitment was also determined.Additionally,we further evaluated the correlation between PLK3 and PD-1/PD-L1 as well as other immune checkpoints.Results:We found that an increased level of PLK3 was associated with malignancy and poor prognosis of glioma,and further validated that PLK3 promoted glioma progression.PLK3 also played a crucial role in immune response and was involved in Tcell immune suppression.Specifically,we revealed that CD8^(+)and CD4^(+)Tcell infiltration was decreased in Plk3 overexpressed xenografts.Furthermore,it was predicted that PLK3 was synergistic with other checkpoint members in glioma.In general,high expression of PLK3 was associated with a malignant process and poor prognosis in glioma patients.Conclusion:Our findings indicated that PLK3 expression level was highly correlated to the malignancy of gliomas,and we validated that PLK3 could promote the GBM progress in vitro and in vivo.Furthermore,PLK3 played important roles in Tcell and neutrophil immune response in glioma.Besides,the conspicuous association between PLK3 and other immune checkpoints was also observed.Crucially,high-level PLK3 expression was revealed to be related to poor clinical prognosis.These results demonstrated that PLK3 may serve as a prognostic biomarker and a potential target for glioma.展开更多
Background Viral diseases have profoundly influenced the sustainable development of the swine farming industry.With the development of genomics technology,the combination of transcriptome,genetic variation,immune resp...Background Viral diseases have profoundly influenced the sustainable development of the swine farming industry.With the development of genomics technology,the combination of transcriptome,genetic variation,immune response,and QTL mapping data to illustrate the interactions between pathogen and host immune system,will be an effective tool for identification of disease resistance genes in pigs.The immune system of an organism is the source of disease resistance in livestock,consisting of various immune tissues,as well as the immune cells and cytokines they produced.However,comprehensive systematic studies on transcriptome of porcine immune tissues are still rare.Poly(I:C),as a viral mimic,is commonly used to study immune responses of the body during viral infections,and serves as a valuable tool for investigating immune mechanisms in swine.Results WGCNA analysis identified core immune genes across six immune tissues(bone marrow,jejunum,lymph node,PBMC,spleen,thymus)in Landrace pigs,which are also crucial for the development of PBMCs.The examination of the changes in the proportion of immune cells during three developmental stages(1-month-old,4-month-old,7-month-old)shows a shift from innate immunity to humoral immunity.By integrating different epigenetic genomics datasets,we identified several core immune genes and their causal variants,including IFI44,IFIT5,EIF2AK2 and others,which are closely related to immune development and response.Functional validation studies reveal that the IFI44 gene acts as a negative regulator of the antiviral response;its inhibition effect significantly reduced Poly(I:C)-induced cell necrosis,while enhancing apoptosis to combat viral infections.Conclusion Our study elucidated the fundamental transcriptional program in porcine immune tissues and the immunodynamics underlying development of PBMCs,identifying many core immune genes,including IFI44,which plays a critical negative regulator role in the antiviral response,providing valuable insights for breeding programs aimed at enhancing pig disease resistance.展开更多
AIM:To explore the immune cell infiltration and molecular mechanisms of retinal ischemia-reperfusion injury(RIRI)to identify potential therapeutic targets.METHODS:In the bulk RNA-seq analysis,This study performed diff...AIM:To explore the immune cell infiltration and molecular mechanisms of retinal ischemia-reperfusion injury(RIRI)to identify potential therapeutic targets.METHODS:In the bulk RNA-seq analysis,This study performed differential gene expression analysis,weighted gene co-expression network analysis,and protein-protein interaction network analysis to identify hub genes.QuanTIseq was used to determine the composition of infiltrating immune cells.Following the identification of hub genes,single-cell RNA-seq analysis was employed to pinpoint the specific immune cell types expressing these hub genes.Cell-cell communication analysis to explore signaling pathways and interactions between immune cells was further performed.Finally,the expression of these key immune regulators in vivo using quantitative real-time polymerase chain reaction(qRT-PCR)was validated.RESULTS:Bulk RNA-seq analysis identified Stat2,Irf7,Irgm1,Igtp,Parp9,Irgm2,Nlrc5,and Tap1 as hub genes,with strong correlations to immune cell infiltration.Single-cell RNA-seq analysis further revealed six immune cell clusters,showing Irf7 predominantly in microglia and Tap1 in dendritic cells(DCs).And cell-cell communication analysis showed that microglia and DCs play central roles in coordinating immune activity.qRT-PCR validated the upregulation of these genes.CONCLUSION:In the acute phase of RIRI,Irf7 and Tap1 may be the potential therapeutic targets to reduce inflammation and promote neurological function recovery.展开更多
BACKGROUND Understanding the status and function of tumor-infiltrating immune cells is essential for improving immunotherapeutic effects and predicting the clinical response in human patients with carcinoma.However,li...BACKGROUND Understanding the status and function of tumor-infiltrating immune cells is essential for improving immunotherapeutic effects and predicting the clinical response in human patients with carcinoma.However,little is known about tumor-infiltrating immune cells,and the corresponding research results in hepatocellular carcinoma(HCC)are limited.AIM To investigate potential biomarker genes that are important for the development of HCC and to understand how immune cell subsets react throughout this process.METHODS Using single-cell RNA sequencing and T-cell receptor sequencing,the heterogeneity and potential functions of immune cell subpopulations from HCC tissue and normal tissue adjacent to carcinoma,as well as their possible interactions,were analyzed.RESULTS Eight T-cell clusters from patients were analyzed and identified using bioinformatics,including six typical major Tcell clusters and two newly identified T-cell clusters,among which Fc epsilon receptor 1G+T cells were characterized by the upregulation of Fc epsilon receptor 1G,tyrosine kinase binding protein,and T cell receptor delta constant,whereas metallothionein 1E+T cells proliferated significantly in tumors.Differentially expressed genes,such as regulator of cell cycle,cysteine and serine rich nuclear protein 1,SMAD7 and metallothionein 1E,were identified as significantly upregulated in tumors and have potential as biomarkers.In association with T-cell receptor analysis,we inferred the clonal expansion characteristics of each T-cell cluster in HCC patients.CONCLUSION We identified lymphocyte subpopulations and potential biomarker genes critical for HCC development and revealed the clonal amplification of infiltrating T cells.These data provide valuable resources for understanding the response of immune cell subsets in HCC.展开更多
Treatment with immune checkpoint inhibitors(ICIs)is an innovative therapy for managing certain types of malignancy and has the potential to improve overall patient survival significantly.The most widely used ICIs sele...Treatment with immune checkpoint inhibitors(ICIs)is an innovative therapy for managing certain types of malignancy and has the potential to improve overall patient survival significantly.The most widely used ICIs selectively target different receptors comprising programmed cell death-1 receptor,programmed cell death-ligand 1 receptor,and cytotoxic T lymphocyte antigen 4 receptor.The widespread utilization of ICIs over the past several years,however,is frequently accompanied by immune-related adverse events(irAEs)that substantially impact the patient’s quality of life,particularly those affecting the digestive system,including both the upper and lower gastrointestinal tract.Based on a literature search covering databases such as PubMed,Web of Science,Embase,and the Cochrane Library,we present an insight into primary gastrointestinal irAEs,with a special focus on endoscopic manifestations.Additionally,we analyze data regarding the pathogenetic mechanisms,diagnostic approaches,histological characteristics,and proposed therapeutic interventions for managing irAEs involving the gastrointestinal tract.展开更多
BACKGROUND Gestational diabetes mellitus(GDM)has recently been associated with abnormal profiles of inflammatory cells and cytokines,though the findings remain incon-sistent and unclear.AIM To elucidate the peripheral...BACKGROUND Gestational diabetes mellitus(GDM)has recently been associated with abnormal profiles of inflammatory cells and cytokines,though the findings remain incon-sistent and unclear.AIM To elucidate the peripheral immune status in GDM.METHODS We systematically screened databases including Web of Science,PubMed,and EMBASE for eligible studies.Original articles reporting different immune cell levels in GDM compared to normal glucose-tolerance pregnant women were included to extract usable data.The pooled mean difference(MD)with 95%confidence interval(CI)was analyzed as the outcome measure.The Newcastle-Ottawa scale was employed to assess study quality.RESULTS A total of 19 studies involving various immune cell subgroups were included in our analysis.Specifically,total CD4+T cells(WMD=3.08;95%CI:0.81-5.35)were significantly increased in GDM groups.In contrast,total lymphocytes(SMD=0.05;95%CI:-0.16 to 0.26),CD3+T cells(SMD=-0.34;95%CI:-1.01 to 0.32),CD8+T cells(SMD=0.21;95%CI:-0.31 to 0.73),and natural killer T(NKT)Cells(SMD=0.83;95%CI:-1.10 to 2.75)showed no significant changes in GDM.Activation markers(HLA-DR+or CD69+)on CD4+T cells(WMD=0.20;95%CI:0.06-0.34)were increased in GDM patients.Treg cells,a classical subgroup of CD4+T cells,showed a decreasing trend in GDM compared to controls(SMD=-0.83;95%CI:-1.31 to-0.34).These results indicate an abnormal immune status in the peripheral profiles of GDM.CONCLUSION GDM may not only be a dysglycemia-related condition but also an immune disorder characterized by abnormal peripheral immune profiles,including higher levels of CD4+T cells and a reduced population of Treg cells.Tr-eating immune dysregulation could be a new direction for GDM management,although further research is needed to understand the precise mechanisms of immune overactivation in GDM.展开更多
Oral squamous cell carcinoma(OSCC)is the most common malignant tumor in the oral and maxillofacial region,primarily affecting the tongue,gingiva,oral cavity,buccal mucosa,and floor of the mouth.It exhibits high rates ...Oral squamous cell carcinoma(OSCC)is the most common malignant tumor in the oral and maxillofacial region,primarily affecting the tongue,gingiva,oral cavity,buccal mucosa,and floor of the mouth.It exhibits high rates of recurrence and metastasis,contributing to a poor prognosis for patients.Identifying molecular markers associated with OSCC holds significant value for advancing its diagnosis,treatment,and prognosis.Exosome Component 3(EXOSC3)is a protein-coding gene involved in the auto-degradation of E3 ubiquitin ligase COP 1 and rRNA processing in the nucleus and cytoplasmic sol.This gene plays a crucial role in diseases such as colon cancer and non-small cell lung cancer.Bioinformatics analysis revealed that EXOSC3 expression is significantly elevated in OSCC and is associated with poor patient prognosis.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses indicate that EXOSC3 is strongly linked to the cytokine-cytokine receptor interaction,Toll-like receptor signaling pathway,and JAK-STAT signaling pathway.Moreover,immune infiltration analysis demonstrated a significant association between EXOSC3 expression and immune cell subset infiltration,as well as immune checkpoint expression,underscoring its importance in OSCC.However,further research is required to elucidate the specific role of EXOSC3 in OSCC diagnosis and treatment.A comprehensive investigation into the mechanisms of EXOSC3 in OSCC may reveal new potential targets for improving the diagnosis and treatment of this malignancy.展开更多
The concept of neuroimmune interactions has shown significant advancements over the years. Modern research has revealed many areas of connection between fields, which were previously viewed as distinct disciplines. Fo...The concept of neuroimmune interactions has shown significant advancements over the years. Modern research has revealed many areas of connection between fields, which were previously viewed as distinct disciplines. For example, the nervous system can sense changes in the external environment and convey these changes through molecules and mediators with receptors in the immune system to modulate immune responses. Neuromediators can act on different receptors in the same group of cells, producing antipodal effects. Identification of the anti-inflammatory role of glucocorticoids highlighted that the body functions properly in an integrated manner. These interactions and crosstalk are not unidirectional, as the immune system can also influence various aspects of the nervous system, such as synaptic plasticity and fever. Strict integration of neuro-immuno-endocrine circuits is indispensable for homeostasis. Understanding these circuits and molecules can lead to advances in the understanding of various immune diseases, which will offer promising therapeutic options.展开更多
Objective:Intimate partner violence(IPV)among people living with the human immune deficiency virus(PLHIV)poses a significant threat to efforts to reduce the spread of human immune deficiency virus(HIV)and achieve the ...Objective:Intimate partner violence(IPV)among people living with the human immune deficiency virus(PLHIV)poses a significant threat to efforts to reduce the spread of human immune deficiency virus(HIV)and achieve the sustainable development goals.In Ghana,scholarly research on the forms and prevalence of IPV is available,however knowledge of the prevalence of IPV among PLHIV is limited.To understand the prevalence of IPV among PLHIV and the intersectional factors that contribute to it,this study examined the overall prevalence of IPV among PLHIV and the associated sociodemographic factors across ten regions of Ghana.Methods:We administered face-to-face survey questionnaires to 661 randomly selected antiretroviral therapy(ART)clients using Research Electronic Data Capture tools.We used descriptive statistics(mean,standard deviation,minimum,and maximum),pairwise correlation,and multivariate regression analysis to look at the data.Results:The clients of ART experienced various forms of IPV,including sexual,physical,emotional,and economic violence and controlling behaviour.The overall prevalence of IPV among PLHIV was 27.5%.This result,although on par with the global IPV average(27%),is 1.5%higher than the national rate(26%).The Upper West Region had the highest prevalence in all the categories of IPV analysed,followed by Oti Region in second place and the Upper East Region in third,except for the prevalence of sexual violence,where Greater Accra Region ranks second.In specific regions of Ghana,sociodemographic factors shaped by patriarchal and economic considerations contribute to a higher prevalence of IPV among people living with HIV.Conclusion:The findings have implications for developing policies and interventions that address the specific factors associated with HIV-induced IPV in different regions of Ghana.These interventions should also include screening PLHIV receiving ART for their IPV status regardless of gender and deploying culturally appropriate education at the community level to foster empathy towards intimate partners living with HIV.展开更多
Psoriasiform rash is a notable immune-related cutaneous adverse event(ircAE)accounting for approximately 5%of all ircAEs1,2.Patients with cancer and pre-existing psoriasis face elevated risk of disease recurrence or e...Psoriasiform rash is a notable immune-related cutaneous adverse event(ircAE)accounting for approximately 5%of all ircAEs1,2.Patients with cancer and pre-existing psoriasis face elevated risk of disease recurrence or exacerbation after receiving immune checkpoint inhibitors(ICIs).A European multicenter study has reported a reactivation rate of 28.7%in this population3.ICIs also trigger de novo psoriatic lesions,which mirror conventional lesion subtypes(plaque,guttate,erythrodermic,or pustular).展开更多
文摘In 1891,a New York surgeon named William Coley injected cancer patients with live bacteria,observing with fascination as some tumors shrank amid raging fevers.His crude experiments-later deemed reckless-nonetheless revealed a tantalizing truth:The immune system,when properly provoked,could attack cancer.Over a century later,researchers have transformed this observation into a precision strike force.
基金supported by Jiangsu Commission of Health(No.x202308)The Suzhou Gusu Health Talents Scientific Research Project(No.GSWS2021052).
文摘To the editor:The liver’s immune-privileged status allows for a unique microenvironment that supports tumour growth and metastasis.In hepatocellular carcinoma(HCC),the balance between cytotoxic T lymphocytes and regulatory T cells plays a crucial role in determining patient outcomes.The expression of programmed cell death ligand 1(PD-1)and other immune checkpoint molecules contributes to a pro-tumourigenic microenvironment and is associated with poor prognosis.Additionally,the heterogeneity of the immune microenvironment adds complexity to disease progression and treatment response.
文摘Polytrauma with significant bone and volumetric muscle loss presents substantial clinical challenges.Although immune responses significantly influence fracture healing post-polytrauma,the cellular and molecular underpinnings of polytrauma-induced immune dysregulation require further investigation.While previous studies examined either injury site tissue or systemic tissue(peripheral blood),our study uniquely investigated both systemic and local immune cells at the same time to better understand polytrauma-induced immune dysregulation and associated impaired bone healing.Using single-cell RNA sequencing(scRNA-seq)in a rat polytrauma model,we analyzed blood,bone marrow,and the local defect soft tissue to identify potential cellular and molecular targets involved in immune dysregulation.We identified a trauma-associated immunosuppressive myeloid(TIM)cell population that drives systemic immune dysregulation,immunosuppression,and potentially impaired bone healing.We found CD1d as a global marker for TIM cells in polytrauma.
基金Supported by 2021 Key Topic of Qinghai Provincial Health System–Guiding Plan Topic,No.2021-WJZDX-43.
文摘Currently,the use of immune checkpoint inhibitors(ICIs)has shown notable clinical efficacy in treating various malignant tumors,significantly improving patient prognosis.However,while ICIs enhance the body’s anti-tumor effects,they can also trigger immune-related adverse events(irAEs),with ICI-associated colitis being one of the more prevalent forms.This condition can disrupt treatment,necessitate drug discontinuation,and adversely affect therapeutic outcomes.In severe cases,irAEs may even become life-threatening.A recent case report by Hong et al highlights the importance of vigilance for ICI-associated colitis in patients experiencing symptoms such as diarrhea and abdominal pain,which can arise both during and even after completion of ICI treatment.Early identification,multidisciplinary management,and continuous monitoring of patients are essential steps to further improve outcomes.
基金supported by the National Key Research and Development Program of China(No.2022YFE0102100)the National Natural Science Foundation of China(Nos.U22A20307 and 81930041)。
文摘Dysfunction of anti-tumor immune responses is crucial for cancer progression. Immune checkpoint blockade(ICB), which can potentiate T cell responses, is an effective strategy for the normalization of host anti-tumor immunity. In recent years, immune checkpoints, expressed on both tumor cells and immune cells, have been identified;some of them have exhibited potential druggability and have been approved by the US Food and Drug Administration(FDA) for clinical treatment. However, limited responses and immune-related adverse events(ir AEs) cannot be ignored. This review outlines the development and applications of ICBs, potential strategies for overcoming resistance, and future directions for ICB-based cancer immunotherapy.
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 the National Natural Science Foundation of China(32072941)。
文摘The immunomodulatory function of estrogen within the ovary remains a subject of ongoing debate,and the neonatal ovarian immune microenvironment,particularly its modulation by estrogen,has not been comprehensively characterized.In this study,the effects of 17β-estradiol(E_(2)),a key regulator of immune function,were investigated using single-cell transcriptomic profiling of C57BL/6J neonatal mouse ovaries after E_(2)treatment.Results revealed dynamic alterations in the proportion of immune cell types after E_(2)treatment,accompanied by changes in cytokine and chemokine expression.Detailed analyses of gene expression,cell states,and developmental trajectories across distinct cell types indicated that E_(2)treatment influenced cell differentiation and development.Notably,E_(2)treatment reduced the abundance of macrophages and promoted a phenotypic transition from M1 to M2 macrophages.These findings demonstrate that the neonatal mouse ovarian immune microenvironment is sensitive to estrogenic modulation,which governs both the distribution and functional specialization of resident immune cells,offering novel mechanistic insights into the immunomodulatory roles of estrogen across various immune cell types.
文摘This paper investigates the effects of graphene quantum dots and mesoporous silica as nanomaterial adjuvants on immune activity in mice both in vitro and in vivo.The two materials have distinct properties;graphene quantum dots possess unique optical and electrical characteristics,while mesoporous silica features a regular pore structure.In vitro experiments show differences in their effects on immune cell activation and cytokine secretion;in vivo experiments reveal varying performances in antibody production and immune cell function regulation.Their mechanisms of action and safety profiles also differ,offering distinct advantages in application prospects.These two nanomaterial adjuvants provide new directions for the development of immunology,warranting further exploration.
基金The 75th Batch of China Postdoctoral Science Foundation projects(No.2024M754279)Natural Science Foundation of Jiangsu Province(No.BK20240738)+2 种基金Basic Science(Natural Science)Research Project in Universities of Jiangsu Province(No.24KJB360004)Jiangsu Province Chinese Medicine Science and Technology Development Plan Youth Talent Project(No.QN202206)Nanjing University of ChineseMedicine Luo Linxiu Teacher Development Fund Project(No.LLX202310).
文摘Cold tumors,defined by insufficient immune cell infiltration and a highly immunosuppressive tumor microenvironment(TME),exhibit limited responsiveness to conventional immunotherapies.This reviewsystematically summarizes the mechanisms of immune evasion and the therapeutic strategies for cold tumors as revealed by multiomics technologies.By integrating genomic,transcriptomic,proteomic,metabolomic,and spatialmulti-omics data,the review elucidates key immune evasionmechanisms,including activation of the WNT/β-catenin pathway,transforming growth factor-β(TGF-β)–mediated immunosuppression,metabolic reprogramming(e.g.,lactate accumulation),and aberrant expression of immune checkpoint molecules.Furthermore,this review proposes multi-dimensional therapeutic strategies,such as targeting immunosuppressive pathways(e.g.,programmed death-1(PD-1)/programmed death-ligand 1(PD-L1)inhibitors combined with TGF-βblockade),reshaping the TME through chemokine-based therapies,oncolytic viruses,and vascular normalization,and metabolic interventions(e.g.,inhibition of lactate dehydrogenase A(LDHA)or glutaminase(GLS)).In addition,personalized neoantigen vaccines and engineered cell therapies(e.g.,T cell receptor-engineered T(TCR-T)and natural killer(NK)cells)show promising potential.Emerging evidence also highlights the role of epigenetic regulation(e.g.,histone deacetylase(HDAC)inhibitors)and N6-Methyladenosine(m6A)RNA modifications in reversing immune evasion.Despite the promising insights offered by multi-omics integration in guiding precision immunotherapy,challenges remain in clinical translation,including data heterogeneity,target-specific toxicity,and limitations in preclinical models.Future efforts should focus on coupling dynamic multi-omics technologies with intelligent therapeutic design to convert cold tumors into immunologically active(“hot”)microenvironments,ultimately facilitating breakthroughs in personalized immunotherapy.
基金Supported by the Natural Science Foundation of Zhejiang Province,No.LY22H160005。
文摘BACKGROUND Colorectal cancer(CRC)is a leading cause of cancer-related mortality worldwide,primarily due to tumor heterogeneity and treatment resistance.The leucine-rich repeat-containing protein 19(LRRC19)has been linked to immune regulation and tumor suppression,yet its specific role in CRC remains poorly understood.AIM To investigate the tumor-suppressive role of LRRC19 in CRC,focusing on cell cycle,immune microenvironment,and chemotherapy response.METHODS Bioinformatics analyses of Gene Expression Omnibus and The Cancer Genome Atlas databases identified differentially expressed genes in CRC.LRRC19 exp-ression was validated in CRC tissues and cell lines by quantitative PCR,immuno-histochemistry,and Western blotting.Functional assays,including proliferation,soft agar colony formation,flow cytometry,and xenograft models,assessed biological effects.Mechanistic studies with dual-luciferase reporter assays,molecular docking,and drug sensitivity testing explored LRRC19’s interaction with the cyclin-dependent kinase 6(CDK6)/E2F1 axis and oxaliplatin(OXA)response.Single-cell sequencing and immune infiltration analyses assessed its impact on the immune microenvironment.RESULTS LRRC19 expression was significantly downregulated in CRC and associated with poor prognosis.Overexpression of LRRC19 inhibited CRC cell proliferation,induced G0/G1 phase arrest,and suppressed tumor growth in vivo.Mechanistically,LRRC19 suppressed CDK6 transcription by downregulating E2F1,leading to cell cycle arrest.Additionally,LRRC19 promoted immune cell infiltration,particularly B cells and CD4+T cells,while decreasing immunosuppressive cells.LRRC19 also sensitized CRC cells to OXA,enhancing chemotherapy efficacy.CONCLUSION LRRC19 suppresses CRC by targeting the CDK6/E2F1 axis,modulating the immune microenvironment,and enhancing chemotherapy sensitivity,making it a promising therapeutic target for precision medicine in CRC.
基金supported by the Nature Science Foundation of Chongqing(Nos.cstc2016jcyjA0838 and cstc2020jcyj-msxmX0376).
文摘Background:PLK3,which played an important role in cell cycle progression and stress response,was identified as highly expressed in various carcinomas.However,the functions,molecular characteristics,and prognostic value of PLK3 in glioma remained unexplored.Methods:We analyzed PLK3 expression in glioma samples from multiple databases.Both overexpression and knockdown of Plk3 were performed to investigate tumor cell growth in glioma,and the transplanted glioma mouse model demonstrated the role of Plk3 on tumor progression.Immunohistochemistry was conducted to detect PLK3 expression and immune cell infiltration.The trans-well assay for PLK3 on the immune cells recruitment was also determined.Additionally,we further evaluated the correlation between PLK3 and PD-1/PD-L1 as well as other immune checkpoints.Results:We found that an increased level of PLK3 was associated with malignancy and poor prognosis of glioma,and further validated that PLK3 promoted glioma progression.PLK3 also played a crucial role in immune response and was involved in Tcell immune suppression.Specifically,we revealed that CD8^(+)and CD4^(+)Tcell infiltration was decreased in Plk3 overexpressed xenografts.Furthermore,it was predicted that PLK3 was synergistic with other checkpoint members in glioma.In general,high expression of PLK3 was associated with a malignant process and poor prognosis in glioma patients.Conclusion:Our findings indicated that PLK3 expression level was highly correlated to the malignancy of gliomas,and we validated that PLK3 could promote the GBM progress in vitro and in vivo.Furthermore,PLK3 played important roles in Tcell and neutrophil immune response in glioma.Besides,the conspicuous association between PLK3 and other immune checkpoints was also observed.Crucially,high-level PLK3 expression was revealed to be related to poor clinical prognosis.These results demonstrated that PLK3 may serve as a prognostic biomarker and a potential target for glioma.
基金financially supported by the Biological Breeding-National Science and Technology Major Project(No.2023ZD0407106)National Key R&D Program of China(No.2023YFD1300400)Biological Breeding-National Science and Technology Major Project,No.2023ZD0407106,Kai Xing。
文摘Background Viral diseases have profoundly influenced the sustainable development of the swine farming industry.With the development of genomics technology,the combination of transcriptome,genetic variation,immune response,and QTL mapping data to illustrate the interactions between pathogen and host immune system,will be an effective tool for identification of disease resistance genes in pigs.The immune system of an organism is the source of disease resistance in livestock,consisting of various immune tissues,as well as the immune cells and cytokines they produced.However,comprehensive systematic studies on transcriptome of porcine immune tissues are still rare.Poly(I:C),as a viral mimic,is commonly used to study immune responses of the body during viral infections,and serves as a valuable tool for investigating immune mechanisms in swine.Results WGCNA analysis identified core immune genes across six immune tissues(bone marrow,jejunum,lymph node,PBMC,spleen,thymus)in Landrace pigs,which are also crucial for the development of PBMCs.The examination of the changes in the proportion of immune cells during three developmental stages(1-month-old,4-month-old,7-month-old)shows a shift from innate immunity to humoral immunity.By integrating different epigenetic genomics datasets,we identified several core immune genes and their causal variants,including IFI44,IFIT5,EIF2AK2 and others,which are closely related to immune development and response.Functional validation studies reveal that the IFI44 gene acts as a negative regulator of the antiviral response;its inhibition effect significantly reduced Poly(I:C)-induced cell necrosis,while enhancing apoptosis to combat viral infections.Conclusion Our study elucidated the fundamental transcriptional program in porcine immune tissues and the immunodynamics underlying development of PBMCs,identifying many core immune genes,including IFI44,which plays a critical negative regulator role in the antiviral response,providing valuable insights for breeding programs aimed at enhancing pig disease resistance.
基金Supported by the National Natural Science Foundation of China(No.82071312).
文摘AIM:To explore the immune cell infiltration and molecular mechanisms of retinal ischemia-reperfusion injury(RIRI)to identify potential therapeutic targets.METHODS:In the bulk RNA-seq analysis,This study performed differential gene expression analysis,weighted gene co-expression network analysis,and protein-protein interaction network analysis to identify hub genes.QuanTIseq was used to determine the composition of infiltrating immune cells.Following the identification of hub genes,single-cell RNA-seq analysis was employed to pinpoint the specific immune cell types expressing these hub genes.Cell-cell communication analysis to explore signaling pathways and interactions between immune cells was further performed.Finally,the expression of these key immune regulators in vivo using quantitative real-time polymerase chain reaction(qRT-PCR)was validated.RESULTS:Bulk RNA-seq analysis identified Stat2,Irf7,Irgm1,Igtp,Parp9,Irgm2,Nlrc5,and Tap1 as hub genes,with strong correlations to immune cell infiltration.Single-cell RNA-seq analysis further revealed six immune cell clusters,showing Irf7 predominantly in microglia and Tap1 in dendritic cells(DCs).And cell-cell communication analysis showed that microglia and DCs play central roles in coordinating immune activity.qRT-PCR validated the upregulation of these genes.CONCLUSION:In the acute phase of RIRI,Irf7 and Tap1 may be the potential therapeutic targets to reduce inflammation and promote neurological function recovery.
基金Supported by the Scientific Research Topic of Jiangsu Provincial Health Care Commission,No.M2021017the High-level Talent Research Project of the Second Hospital of Nanjing,No.0313504the Nanjing Second Hospital Academic Leader Program,No.0313506.
文摘BACKGROUND Understanding the status and function of tumor-infiltrating immune cells is essential for improving immunotherapeutic effects and predicting the clinical response in human patients with carcinoma.However,little is known about tumor-infiltrating immune cells,and the corresponding research results in hepatocellular carcinoma(HCC)are limited.AIM To investigate potential biomarker genes that are important for the development of HCC and to understand how immune cell subsets react throughout this process.METHODS Using single-cell RNA sequencing and T-cell receptor sequencing,the heterogeneity and potential functions of immune cell subpopulations from HCC tissue and normal tissue adjacent to carcinoma,as well as their possible interactions,were analyzed.RESULTS Eight T-cell clusters from patients were analyzed and identified using bioinformatics,including six typical major Tcell clusters and two newly identified T-cell clusters,among which Fc epsilon receptor 1G+T cells were characterized by the upregulation of Fc epsilon receptor 1G,tyrosine kinase binding protein,and T cell receptor delta constant,whereas metallothionein 1E+T cells proliferated significantly in tumors.Differentially expressed genes,such as regulator of cell cycle,cysteine and serine rich nuclear protein 1,SMAD7 and metallothionein 1E,were identified as significantly upregulated in tumors and have potential as biomarkers.In association with T-cell receptor analysis,we inferred the clonal expansion characteristics of each T-cell cluster in HCC patients.CONCLUSION We identified lymphocyte subpopulations and potential biomarker genes critical for HCC development and revealed the clonal amplification of infiltrating T cells.These data provide valuable resources for understanding the response of immune cell subsets in HCC.
文摘Treatment with immune checkpoint inhibitors(ICIs)is an innovative therapy for managing certain types of malignancy and has the potential to improve overall patient survival significantly.The most widely used ICIs selectively target different receptors comprising programmed cell death-1 receptor,programmed cell death-ligand 1 receptor,and cytotoxic T lymphocyte antigen 4 receptor.The widespread utilization of ICIs over the past several years,however,is frequently accompanied by immune-related adverse events(irAEs)that substantially impact the patient’s quality of life,particularly those affecting the digestive system,including both the upper and lower gastrointestinal tract.Based on a literature search covering databases such as PubMed,Web of Science,Embase,and the Cochrane Library,we present an insight into primary gastrointestinal irAEs,with a special focus on endoscopic manifestations.Additionally,we analyze data regarding the pathogenetic mechanisms,diagnostic approaches,histological characteristics,and proposed therapeutic interventions for managing irAEs involving the gastrointestinal tract.
文摘BACKGROUND Gestational diabetes mellitus(GDM)has recently been associated with abnormal profiles of inflammatory cells and cytokines,though the findings remain incon-sistent and unclear.AIM To elucidate the peripheral immune status in GDM.METHODS We systematically screened databases including Web of Science,PubMed,and EMBASE for eligible studies.Original articles reporting different immune cell levels in GDM compared to normal glucose-tolerance pregnant women were included to extract usable data.The pooled mean difference(MD)with 95%confidence interval(CI)was analyzed as the outcome measure.The Newcastle-Ottawa scale was employed to assess study quality.RESULTS A total of 19 studies involving various immune cell subgroups were included in our analysis.Specifically,total CD4+T cells(WMD=3.08;95%CI:0.81-5.35)were significantly increased in GDM groups.In contrast,total lymphocytes(SMD=0.05;95%CI:-0.16 to 0.26),CD3+T cells(SMD=-0.34;95%CI:-1.01 to 0.32),CD8+T cells(SMD=0.21;95%CI:-0.31 to 0.73),and natural killer T(NKT)Cells(SMD=0.83;95%CI:-1.10 to 2.75)showed no significant changes in GDM.Activation markers(HLA-DR+or CD69+)on CD4+T cells(WMD=0.20;95%CI:0.06-0.34)were increased in GDM patients.Treg cells,a classical subgroup of CD4+T cells,showed a decreasing trend in GDM compared to controls(SMD=-0.83;95%CI:-1.31 to-0.34).These results indicate an abnormal immune status in the peripheral profiles of GDM.CONCLUSION GDM may not only be a dysglycemia-related condition but also an immune disorder characterized by abnormal peripheral immune profiles,including higher levels of CD4+T cells and a reduced population of Treg cells.Tr-eating immune dysregulation could be a new direction for GDM management,although further research is needed to understand the precise mechanisms of immune overactivation in GDM.
文摘Oral squamous cell carcinoma(OSCC)is the most common malignant tumor in the oral and maxillofacial region,primarily affecting the tongue,gingiva,oral cavity,buccal mucosa,and floor of the mouth.It exhibits high rates of recurrence and metastasis,contributing to a poor prognosis for patients.Identifying molecular markers associated with OSCC holds significant value for advancing its diagnosis,treatment,and prognosis.Exosome Component 3(EXOSC3)is a protein-coding gene involved in the auto-degradation of E3 ubiquitin ligase COP 1 and rRNA processing in the nucleus and cytoplasmic sol.This gene plays a crucial role in diseases such as colon cancer and non-small cell lung cancer.Bioinformatics analysis revealed that EXOSC3 expression is significantly elevated in OSCC and is associated with poor patient prognosis.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses indicate that EXOSC3 is strongly linked to the cytokine-cytokine receptor interaction,Toll-like receptor signaling pathway,and JAK-STAT signaling pathway.Moreover,immune infiltration analysis demonstrated a significant association between EXOSC3 expression and immune cell subset infiltration,as well as immune checkpoint expression,underscoring its importance in OSCC.However,further research is required to elucidate the specific role of EXOSC3 in OSCC diagnosis and treatment.A comprehensive investigation into the mechanisms of EXOSC3 in OSCC may reveal new potential targets for improving the diagnosis and treatment of this malignancy.
文摘The concept of neuroimmune interactions has shown significant advancements over the years. Modern research has revealed many areas of connection between fields, which were previously viewed as distinct disciplines. For example, the nervous system can sense changes in the external environment and convey these changes through molecules and mediators with receptors in the immune system to modulate immune responses. Neuromediators can act on different receptors in the same group of cells, producing antipodal effects. Identification of the anti-inflammatory role of glucocorticoids highlighted that the body functions properly in an integrated manner. These interactions and crosstalk are not unidirectional, as the immune system can also influence various aspects of the nervous system, such as synaptic plasticity and fever. Strict integration of neuro-immuno-endocrine circuits is indispensable for homeostasis. Understanding these circuits and molecules can lead to advances in the understanding of various immune diseases, which will offer promising therapeutic options.
基金supported by the Christian Health Association of Ghana under Global Fund New Funding Model 3(NFM 3)HIV/TB Community Systems Strengthening programme(CSS)。
文摘Objective:Intimate partner violence(IPV)among people living with the human immune deficiency virus(PLHIV)poses a significant threat to efforts to reduce the spread of human immune deficiency virus(HIV)and achieve the sustainable development goals.In Ghana,scholarly research on the forms and prevalence of IPV is available,however knowledge of the prevalence of IPV among PLHIV is limited.To understand the prevalence of IPV among PLHIV and the intersectional factors that contribute to it,this study examined the overall prevalence of IPV among PLHIV and the associated sociodemographic factors across ten regions of Ghana.Methods:We administered face-to-face survey questionnaires to 661 randomly selected antiretroviral therapy(ART)clients using Research Electronic Data Capture tools.We used descriptive statistics(mean,standard deviation,minimum,and maximum),pairwise correlation,and multivariate regression analysis to look at the data.Results:The clients of ART experienced various forms of IPV,including sexual,physical,emotional,and economic violence and controlling behaviour.The overall prevalence of IPV among PLHIV was 27.5%.This result,although on par with the global IPV average(27%),is 1.5%higher than the national rate(26%).The Upper West Region had the highest prevalence in all the categories of IPV analysed,followed by Oti Region in second place and the Upper East Region in third,except for the prevalence of sexual violence,where Greater Accra Region ranks second.In specific regions of Ghana,sociodemographic factors shaped by patriarchal and economic considerations contribute to a higher prevalence of IPV among people living with HIV.Conclusion:The findings have implications for developing policies and interventions that address the specific factors associated with HIV-induced IPV in different regions of Ghana.These interventions should also include screening PLHIV receiving ART for their IPV status regardless of gender and deploying culturally appropriate education at the community level to foster empathy towards intimate partners living with HIV.
基金supported by grants from the National Natural Science Foundation of China(Nos.82373372 and U22A20330)Key Project of Research and Development Plan in Heilongjiang Province(Nos.2022ZX06C01 and JD2023SJ40)+1 种基金National Cancer Center Climbing Fund(No.NCC201908A03)Beijing Xisike Clinical Oncology Research Foundation(No.Y-HR2020MS-0900).
文摘Psoriasiform rash is a notable immune-related cutaneous adverse event(ircAE)accounting for approximately 5%of all ircAEs1,2.Patients with cancer and pre-existing psoriasis face elevated risk of disease recurrence or exacerbation after receiving immune checkpoint inhibitors(ICIs).A European multicenter study has reported a reactivation rate of 28.7%in this population3.ICIs also trigger de novo psoriatic lesions,which mirror conventional lesion subtypes(plaque,guttate,erythrodermic,or pustular).
