Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immun...Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immune tolerance of cancer cells.The classical theory holds that prostate apoptosis response-4(PAR-4)is a tumor suppressor protein.However,our recent research has found that PAR-4 has a biological function of promoting cancer in hepatocellular carcinoma(HCC),and our analysis shows that PAR-4 can be modified of lactic acid.These research evidences suggest that PAR-4 lactylation modification may drive immune tolerance in HCC.Therefore,inhibiting PAR-4 lactylation modification is very likely to increase the sensitivity of HCC to immunotherapy.展开更多
Objective:To improve the efficacy of Astragalus membranaceus(Fisch.)Bunge(A.membranaceus,Huang Qi),and to further develop and utilize it,fermentation technology was applied to the stem and leaf of A.membranaceus to en...Objective:To improve the efficacy of Astragalus membranaceus(Fisch.)Bunge(A.membranaceus,Huang Qi),and to further develop and utilize it,fermentation technology was applied to the stem and leaf of A.membranaceus to enhance its immune function.Methods:In this study,we fermented A.membranaceus stem and leaf(ASL)with probiotics and inves-tigated its immune function.Firstly,we screened suitable strains for ASL fermentation and optimized the fermentation process.Secondly,we determined the antioxidant capacity of fermented ASL and its effect on inflammation in mouse monocyte-macrophage cell.Finally,the immunocompromised mice were treated with fermented ASL to investigate the changes in their immune ability.Results:Among the 10 selected probiotics,Lactobacillus plantarum was the most suitable strain for ASL fermentation.After optimization of the fermentation process,the content of saponins in fermented ASL was significantly increased.The fermented ASL exhibited strong anti-inflammatory and antioxidant activities in vitro.The in vivo immune efficacy improved by promoting the development of the spleen and thymus,as well as raising the immunoglobulin M,tumor necrosis factor-α,and interleukin-1β levels of in the serum.Conclusion:This study contributes to developing the non-medicinal parts of A.membranaceus,expands its medicinal resources,highlights the potential of fermentation technology to enhance these parts,and provides a reference for further development.Based on this approach,we can promote using non-me-dicinal parts of herbal medicines,minimize drug waste,and offer a reference for developing non-me-dicinal components in Chinese herbal medicines.展开更多
Hepatocellular carcinoma presents with three distinct immune phenotypes,including immune-desert,immune-excluded,and immune-inflamed,indicating various treatment responses and prognostic outcomes.The clinical applicati...Hepatocellular carcinoma presents with three distinct immune phenotypes,including immune-desert,immune-excluded,and immune-inflamed,indicating various treatment responses and prognostic outcomes.The clinical application of multi-omics parameters is still restricted by the expensive and less accessible assays,although they accurately reflect immune status.A comprehensive evaluation framework based on“easy-to-obtain”multi-model clinical parameters is urgently required,incorporating clinical features to establish baseline patient profiles and disease staging;routine blood tests assessing systemic metabolic and functional status;immune cell subsets quantifying subcluster dynamics;imaging features delineating tumor morphology,spatial configuration,and perilesional anatomical relationships;immunohistochemical markers positioning qualitative and quantitative detection of tumor antigens from the cellular and molecular level.This integrated phenomic approach aims to improve prognostic stratification and clinical decision-making in hepatocellular carcinoma management conveniently and practically.展开更多
BACKGROUND Gastrointestinal(GI)surgery can significantly affect the nutritional status and immune function of patients.This study aimed to investigate the effects of personalized nutritional care on the recovery of im...BACKGROUND Gastrointestinal(GI)surgery can significantly affect the nutritional status and immune function of patients.This study aimed to investigate the effects of personalized nutritional care on the recovery of immune function in patients who underwent postoperative GI surgery.AIM To study examines personalized nutritional care’s impact on immune function recovery,nutritional status,and clinical outcomes after GI surgery.METHODS This observational study included 80 patients who underwent GI surgery between 2021 and 2023.Patients received personalized nutritional care based on their individual needs and surgical outcomes.Immune function markers including lymphocyte subsets,immunoglobulins,and cytokines were measured preoperatively and at regular intervals postoperatively.Nutritional status,clinical outcomes,and quality of life were assessed.RESULTS Patients receiving personalized nutritional care showed significant improvements in immune function markers compared to baseline.At 4 weeks postoperatively,CD4+T-cell counts increased by 25%(P<0.001),while interleukin-6 levels decreased by 40%(P<0.001).Nutritional status,as measured by prealbumin and transferrin levels,improved by 30%(P<0.01).Postoperative complications reduced by 35%compared to historical controls.The quality-of-life scores improved by 40%at 3 months postoperatively.CONCLUSION Personalized nutritional care enhances immune function recovery,improves nutritional status,and reduces complications in patients undergoing postoperative GI surgery,highlighting its crucial role in optimizing patient outcomes following such procedures.展开更多
BACKGROUND Although surgery remains the primary treatment for proximal gastric cancer(PGC),ongoing refinements in surgical strategies are essential to improving clinical outcomes.AIM To investigate the effect of doubl...BACKGROUND Although surgery remains the primary treatment for proximal gastric cancer(PGC),ongoing refinements in surgical strategies are essential to improving clinical outcomes.AIM To investigate the effect of double-tract reconstruction(DTR)on immune function and stress response in patients undergoing laparoscopic proximal gastrectomy(LPG).METHODS In total,78 patients with PGC admitted between August 2020 and August 2024 were enrolled.The research group consisted of 39 patients who underwent DTR+LPG,whereas the control group comprised 39 patients who underwent laparoscopic total gastrectomy with Roux-en-Y esophagojejunostomy.Perioperative indices(intraoperative blood loss,digestive tract anastomosis time,and time to first postoperative flatus),postoperative complications(intestinal obstruction,anastomotic ulcer,diarrhea,dumping syndrome,and gastroesophageal reflux),nutritional parameters(serum albumin,hemoglobin,and body mass index),immune function immunoglobulin(IgG,IgA,and IgM),and stress response indicators(C-reactive protein,interleukin-6,and tumor necrosis factor-α)were collected and analyzed for both groups.RESULTS The intraoperative blood loss was lower(P<0.05),and the time to first postoperative flatus time was shorter(P<0.001)in the research group than in the control group.The two groups had comparable digestive tract anastomosis time(P>0.05).The overall complication rate was significantly lower in the research group than in the control group(P=0.042).Compared with the control group,the research group exhibited notably higher albumin,hemoglobin,and body mass index levels at 2 and 3 months postoperatively,as well as considerably high immunoglobulin(Ig)G,IgA,and IgM levels on postoperative day 1(P<0.05).The postoperative levels of C-reactive protein,interleukin-6,and tumor necrosis factor-αwere also lower in the research group than in the control group(P<0.001).CONCLUSION The combination of DTR and LPG in the treatment of patients with PGC is more effective in enhancing immune function and suppressing stress responses,showing more advantages over laparoscopic total gastrectomy.展开更多
Objective:To investigate the effects of nebulizedα-interferon on immune function in elderly patients with respiratory tract infection.Methods:A total of 120 elderly patients with respiratory tract infection admitted ...Objective:To investigate the effects of nebulizedα-interferon on immune function in elderly patients with respiratory tract infection.Methods:A total of 120 elderly patients with respiratory tract infection admitted to our hospital from June 2023 to June 2024 were selected and randomly divided into an observation group(n=60)and a control group(n=60)using the envelope method.The control group received conventional treatment,while the observation group received additional nebulizedα-interferon therapy based on conventional treatment.After the same treatment period,changes in immune function indicators(immunoglobulins IgG,IgA,IgM)were compared between the two groups.Patients were also followed up for 3 months to observe the frequency of respiratory tract infection recurrences.Results:After treatment,IgA and IgM levels decreased significantly,while IgG levels increased significantly in both groups.The improvement in each indicator was more pronounced in the observation group than in the control group(P<0.05).By the end of the follow-up period,all 120 patients had successfully completed the follow-up,and no patients were lost to follow-up.The frequency of respiratory tract infection recurrences was lower in the observation group than in the control group(P<0.05).Conclusion:Nebulizedα-interferon can improve immune function and reduce the frequency of recurrences in elderly patients with respiratory tract infection.展开更多
The mechanisms of mushroom polysaccharides on immune functions and lipid metabolism of aged mammals have not been fully elucidated.In the present study,after assessing the impacts of one type of Lentinula edodes-deriv...The mechanisms of mushroom polysaccharides on immune functions and lipid metabolism of aged mammals have not been fully elucidated.In the present study,after assessing the impacts of one type of Lentinula edodes-derived polysaccharides,named L2,on immune functions and blood lipid profiles,isobaric tags for relative and absolute quantification(iTRAQ)-based proteomic profiling of the small intestinal tissues from aged mice treated with L2 was performed.L2 reversed immune function declines and modulated the lipid metabolism of aged mice evidenced by increased levels of serum TC,HDL-C,and LDL-C,and reduced levels of serum TG.Moreover,a total of 95 differentially regulated proteins(DRPs) were identified,of which75 were up-regulated and 20 were down-regulated.Most of the DRPs were involved in intracellular and extracellular structure organization,and cellular and metabolic regulation.Particularly,approximately 16 and 9 DRPs participated in the regulation of immune functions and lipid metabolism,respectively.Furthermore,protein-protein interaction analysis highlighted that cadherin-1,plectin,cadherin-17,Ras GTPase-activating-like protein IQGAP2,and ezrin might be key proteins in response to L2 treatment.These findings provide new insights into the biological mechanisms of mushroom polysaccharides in anti-aging from a proteomic perspective.展开更多
Background:Aberrant expression of transcription factors(TFs)is a key mechanism mediating tumor immune escape and therapeutic resistance.The involvement of E26 transformation-specific(ETS)family of TFs in immune regula...Background:Aberrant expression of transcription factors(TFs)is a key mechanism mediating tumor immune escape and therapeutic resistance.The involvement of E26 transformation-specific(ETS)family of TFs in immune regulation is not fully understood.The study aimed to elucidate the function of E-twenty-six variant 4(ETV4)in tumor immune evasion and its potential as a predictive biomarker for immunotherapy in melanoma.Methods:The expression patterns of ETS family TFs were analyzed in melanoma and hepatocellular carcinoma(HCC).Single-cell RNA sequencing(scRNA-seq)was used to dissect the cellular expression and function of ETV4 in the tumor microenvironment.Functional studies and murine models were employed to investigate the role of ETV4 in T cell-mediated tumor killing and tumor growth.The correlation between ETV4 expression level and patient responsiveness to programmed cell death protein 1(PD-1)blockade therapy was evaluated.Results:TFs in the ETS family were found to effectively stratify melanoma and HCC patients into prognostic subgroups.In melanoma,the polyoma enhancer activator 3(PEA3)subfamily,particularly ETV4 and ETV5,showed a negative correlation with immune infiltration.scRNA-seq analysis showed that ETV4 is preferentially expressed in melanoma cells and involves in mediating tumor-immunocyte interactions.Functional studies demonstrated that ETV4 impairs T cell-mediated tumor killing by transcriptionally upregulating programmed death-ligand 1(PD-L1).In immunocompetent murine models,ETV4 downregulation significantly suppressed tumor growth.Furthermore,high ETV4 expression correlated with poor responses to anti-PD-1 therapy.Conclusion:Our findings identify ETV4 as a key transcriptional regulator of immune evasion in melanoma by controlling PD-L1 expression.ETV4 may act as a predictive biomarker for immunotherapy outcomes.展开更多
Objective:To analyze the efficacy of whole-course local simultaneous integrated boost intensity-modulated radiotherapy(SIB-IMRT)on patients with locally advanced esophageal squamous cell carcinoma(ESCC).Methods:88 pat...Objective:To analyze the efficacy of whole-course local simultaneous integrated boost intensity-modulated radiotherapy(SIB-IMRT)on patients with locally advanced esophageal squamous cell carcinoma(ESCC).Methods:88 patients with ESCC admitted to the hospital between October 2022 and October 2024 were selected and randomly divided into two groups using a random number table.The experimental group received SIB-IMRT treatment,while the control group received conventional intensity-modulated radiotherapy(C-IMRT).The objective remission rate,immune function,tumor markers,and adverse reaction rate were compared between the two groups.Results:The objective remission rate in the experimental group was higher than that in the control group(P<0.05).Before treatment,there was no difference in immune function levels and tumor marker levels between the two groups(P>0.05).After treatment,the immune function levels in the experimental group were better than those in the control group,and the tumor marker levels were lower than those in the control group(P<0.05).The adverse reaction rate in the experimental group was lower than that in the control group(P<0.05).Conclusion:SIB-IMRT can improve the objective remission rate of patients with ESCC,protect their immune function,down-regulate tumor marker levels,and prevent side effects after treatment.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
Microglia are the resident macrophages of the central nervous system.They act as the first line of defense against pathogens and play essential roles in neuroinflammation and tissue repair after brain insult or in neu...Microglia are the resident macrophages of the central nervous system.They act as the first line of defense against pathogens and play essential roles in neuroinflammation and tissue repair after brain insult or in neurodegenerative and demyelinating diseases(Borst et al.,2021).Together with infiltrating monocyte-derived macrophages,microglia also play a critical role for brain tumor development,since immunosuppressive interactions between tumor cells and tumor-associated microglia and macrophages(TAM)are linked to malignant progression.This mechanism is of particular relevance in glioblastoma(GB),the deadliest form of brain cancer with a median overall survival of less than 15 months(Khan et al.,2023).Therefore,targeting microglia and macrophage activation is a promising strategy for therapeutic interference in brain disease.展开更多
Small intestinal villi are essential for nutrient absorption,and their impairment can lead to malabsorption.Small intestinal villous atrophy(VA)encompasses a heterogeneous group of disorders,including immune-mediated ...Small intestinal villi are essential for nutrient absorption,and their impairment can lead to malabsorption.Small intestinal villous atrophy(VA)encompasses a heterogeneous group of disorders,including immune-mediated conditions(e.g.,celiac disease,autoimmune enteropathy,inborn errors of immunity),lymphoproliferative disorders(e.g.,enteropathy-associated T-cell lymphoma),infectious causes(e.g.,tropical sprue,Whipple’s disease),iatrogenic factors(e.g.,Olmesartanassociated enteropathy,graft-vs-host disease),as well as inflammatory and idiopathic types.These disorders are often rare and challenging to distinguish due to overlapping clinical,serological,endoscopic,and histopathological features.Through a systematic literature search using keywords such as small intestinal VA,malabsorption,and specific enteropathies,this review provides a comprehensive overview of diagnostic clues for VA and malabsorption.We systematically summarize the pathological characteristics of each condition to assist pathologists and clinicians in accurately identifying the underlying etiologies.Current studies still have many limitations and lack broader and deeper investigations into these diseases.Therefore,future research should focus on the development of novel diagnostic tools,predictive models,therapeutic targets,and mechanistic molecular studies to refine both diagnosis and management strategies.展开更多
Background:While the treatment of metastatic renal cell carcinoma(mRCC)is evolving due to immune checkpoint inhibitors(ICIs),optimal strategies for later lines of therapy have yet to be defined.The combination of lenv...Background:While the treatment of metastatic renal cell carcinoma(mRCC)is evolving due to immune checkpoint inhibitors(ICIs),optimal strategies for later lines of therapy have yet to be defined.The combination of lenvatinib and everolimus represents a viable option,and the present review aimed to summarize its activity,effectiveness,and safety.Methods:A systematic review of the literature was conducted using PubMed,targeting studies published between 2018 and 2025.Eligible studies included English-language prospective and retrospective trials reporting survival outcomes in mRCC patients treated with lenvatinib and everolimus after at least one ICI-containing regimen.Results:Nine studies met the inclusion criteria,encompassing a total of 441 patients.The lenvatinib and everolimus combination was primarily used in the third and subsequent lines of therapy.Median overall survival ranged from 7.5 to 24.5 months,while median progression-free survival was more consistent,between 6.1 and 6.7 months,except for one study reporting 12.9 months.Objective response rates varied widely(14.0%–55.7%).Adverse events of grade≥3 did not exceed the expected rate,with diarrhoea and proteinuria as the most reported events.Dose reductions and treatment discontinuations due to toxicity occurred but were generally lower than in prior pivotal trials.Conclusions:Real-world evidence suggests that lenvatinib and everolimus represent an effective and safe option after ICI failure in mRCC patients.Nevertheless,the lack of randomized phase III trials and the heterogeneity of existing studies highlight the need for more robust prospective research to guide post-ICI therapeutic strategies.展开更多
The intricate interactions between immune cells and tumors exert a profound influence on cancer progression and therapeutic efficacy.Within the tumor microenvironment,exosomes have emerged as pivotal mediators of inte...The intricate interactions between immune cells and tumors exert a profound influence on cancer progression and therapeutic efficacy.Within the tumor microenvironment,exosomes have emerged as pivotal mediators of intercellular communication,with their cargo of non-coding RNAs(ncRNAs)serving as key regulatory elements.This review examines the multifaceted roles of immune cell-derived exosomal ncRNAs in tumor biology.The involvement of various immune cells,including T cells,B cells,natural killer cells,macrophages,neutrophils,and myeloid-derived suppressor cells,in utilizing exosomal ncRNAs to regulate tumor initiation and progression is explored.Additionally,the biogenesis and delivery mechanisms of these immune cell-derived exosomal ncRNAs are discussed,alongside their potential clinical applications in cancer.展开更多
Objective:Grifola frondosa,a medicinal mushroom,is widely used to enhance immunity and treat cancer.Polysaccharides are its primary active components.We aimed to investigate the effects of the alkaloid G.frondosa poly...Objective:Grifola frondosa,a medicinal mushroom,is widely used to enhance immunity and treat cancer.Polysaccharides are its primary active components.We aimed to investigate the effects of the alkaloid G.frondosa polysaccharide(GFP)extract on immunity and gut microbiota.Methods:Alkaloid GFP was extracted using an alkaline extraction method,followed by hollow-fiber microfiltration.The molecular weight of alkaloid GFP was determined by high-performance gel permeation chromatography(HPGPC).Monosaccharide composition was analyzed by pre-column derivatization combined with high-performance liquid chromatography(HPLC).Methylation analysis was performed to characterize glycosidic linkages in alkaloid GFP.The immune function of alkaloid GFP was assessed in a cyclophosphamide(CTX)-induced immunosuppressive mouse model.Splenic lymphocyte proliferation,macrophage phagocytic capacity,and natural killer(NK)cell cytotoxicity were evaluated.The effect of alkaloid GFP on gut microbiota was assessed by 16S rRNA sequencing.Results:The molecular weight distribution of alkaloid GFP ranged from 17 to 18 kDa.The alkaloid GFP contained aβ-(1→6)-glucan backbone branched at O-3 byβ-1,3-D-Glcp.Oral administration of alkaloid GFP mitigated the effects of CTX on spleen index,splenic lymphocyte proliferation,and peritoneal macrophage phagocytosis.Additionally,alkaloid GFP improved the gut microbiota composition of immunosuppressed mice,increasing the relative abundances of Ligilactobacillus and Lactobacillus.Conclusions:Alkaloid GFP demonstrated immune-enhancing effects and gut microbiota regulatory activity,providing a basis for developing related health food ingredients.展开更多
Background Tryptophan is essential for nutrition,immunity and neural activity,but cannot be synthesized endogenously.Certain natural products influence host health by modulating the gut microbiota to promote the produ...Background Tryptophan is essential for nutrition,immunity and neural activity,but cannot be synthesized endogenously.Certain natural products influence host health by modulating the gut microbiota to promote the production of tryptophan metabolites.Sanguinarine(SAN)enhances broiler immunity,however,its low bioavailability and underlying mechanisms remain unclear.This study aimed to decode the mechanisms by which sanguinarine enhances intestinal immune function in broilers.Methods Liquid chromatography-tandem mass spectrometry(LC-MS/MS)was employed to identify the main metabolites of sanguinarine in the intestine.Subsequently,equal concentrations of sanguinarine and its metabolites were separately added to the diets.The effects of sanguinarine and its metabolites on the intestinal immune function of broiler chickens were evaluated using 16S rRNA gene amplicon sequencing and tryptophan metabolomics approaches.Results We determined that dihydrosanguinarine(DHSA)is the main metabolite of sanguinarine in the intestine.Both compounds increased average daily gain and reduced feed efficiency,thereby improving growth performance.They also enhanced ileal villus height and the villus-to-crypt(V/C)ratio while decreasing crypt depth and upregulating the mRNA expression of tight junction proteins ZO-1,occludin and claudin-1.Furthermore,both compounds promoted the proliferation of intestinal Lactobacillus species,a tryptophan-metabolizing bacterium,stimulated short-chain fatty acid production,and lowered intestinal pH.They regulated tryptophan metabolism by increasing the diversity and content of indole tryptophan metabolites,activating the aryl hydrocarbon receptor(AhR)pathway,and elevating the mRNA levels of CYP1A1,CYP1B1,SLC3A1,IDO2 and TPH1.Inflammatory cytokines IL-1β and IL-6 were inhibited,while anti-inflammatory cytokines IL-10 and IL-22,serum SIgA concentration,and intestinal MUC2 expression were increased.Notably,DHSA exhibited a more pronounced effect on enhancing immune function compared to SAN.Conclusions SAN is converted to DHSA in vivo,which increases its bioavailability.DHSA regulates tryptophan metabolism by activating the AhR pathway and modulating immune-related factors through changes in the gut microbiota.Notably,DHSA significantly increases the abundance of Lactobacillus,a key tryptophan-metabolizing bacterium,thereby enhancing intestinal immune function and improving broiler growth performance.展开更多
BACKGROUND Autoimmune liver diseases,including primary biliary cholangitis(PBC),autoi-mmune hepatitis(AIH),and their overlap syndrome(OS),involve immune-mediated liver injury,with OS occurring in 1.2%-25%of PBC patien...BACKGROUND Autoimmune liver diseases,including primary biliary cholangitis(PBC),autoi-mmune hepatitis(AIH),and their overlap syndrome(OS),involve immune-mediated liver injury,with OS occurring in 1.2%-25%of PBC patients.OS carries a higher risk of cirrhosis,hepatocellular carcinoma,and reduced survival.While its pathogenesis remains unclear,gut microbiota dysbiosis and serum metabolite alterations may play key roles.This study uses 16S rRNA sequencing and liquid chromatography-mass spec-trometry(LC-MS)metabolomics to compare gut microbiota and serum metabolites among PBC,AIH,and OS patients,and explores their associations with liver function.AIM To differentiate OS from PBC and AIH based on gut microbiota,serum metabolites,and liver function.METHODS Gut microbiota profiles were analyzed using 16S rRNA sequencing,while untargeted serum metabolomics was conducted via LC-MS.Comparative analyses were performed to identify differences in microbial composition and serum metabolite levels among PBC,AIH,and OS groups.Correlation analyses and network visualization tech-niques were applied to elucidate the interactions among liver function parameters,gut microbiota,and serum metabolites in OS patients.RESULTS Compared to patients with PBC or AIH,OS patients demonstrated significantly reduced microbial diversity and richness.Notable taxonomic shifts included decreased abundances of Firmicutes,Bacteroidetes,and Actinobacteria,alongside increased levels of Proteobacteria and Verrucomicrobia.Distinct serum metabolites,such as pentadecanoic acid and aminoimidazole carboxamide ribonucleotide,were identified in OS patients.Correlation analysis revealed that aspartate aminotransferase(AST)levels were negatively associated with the bacterial genus Fusicatenibacter and the metabolite L-Tyrosine.A microbial-metabolite network diagram further confirmed a strong association between Fusicatenibacter and L-Tyrosine in OS patients.CONCLUSION OS patients show decreased gut microbiota diversity and unique serum metabolites.Multi-omics linked AST,Fusicatenibacter,and L-Tyrosine,revealing OS mechanisms and diagnostic potential.展开更多
Mood disorders include a set of psychiatric manifestations of increasing prevalence in our society,being mainly represented by major depressive disorder(MDD)and bipolar disorder(BD).The etiopathogenesis of mood disord...Mood disorders include a set of psychiatric manifestations of increasing prevalence in our society,being mainly represented by major depressive disorder(MDD)and bipolar disorder(BD).The etiopathogenesis of mood disorders is extremely complex,with a wide spectrum of biological,psychological,and sociocultural factors being responsible for their appearance and development.In this sense,immune system dysfunction represents a key mechanism in the onset and pathophysiology of mood disorders,worsening mainly the central nervous system(neuroinflammation)and the periphery of the body(systemic inflammation).However,these alterations cannot be understood separately,but as part of a complex picture in which different factors and systems interact with each other.Psychoneuroimmunoendocrinology(PNIE)is the area responsible for studying the relationship between these elements and the impact of mind–body integration,placing the immune system as part of a whole.Thus,the dysfunction of the immune system is capable of influencing and activating different mechanisms that promote disruption of the psyche,damage to the nervous system,alterations to the endocrine and metabolic systems,and disruption of the microbiota and intestinal ecosystem,as well as of other organs and,in turn,all these mechanisms are responsible for inducing and enhancing the immune dysfunction.Similarly,the clinical approach to these patients is usually multidisciplinary,and the therapeutic arsenal includes different pharmacological(for example,antidepressants,antipsychotics,and lithium)and non-pharmacological(i.e.,psychotherapy,lifestyle,and electroconvulsive therapy)treatments.These interventions also modulate the immune system and other elements of the PNIE in these patients,which may be interesting to understand the therapeutic success or failure of these approaches.In this sense,this review aims to delve into the relationship between immune dysfunction and mood disorders and their integration in the complex context of PNIE.Likewise,an attempt will be made to explore the effects on the immune system of different strategies available in the clinical approach to these patients,in order to identify the mechanisms described and their possible uses as biomarkers.展开更多
Lymph node dissection(lymphadenectomy)remains a critical component of pancreatic cancer surgery,contributing to accurate staging and guiding adjuvant therapy.The debate between standard and extended lymphadenectomy pe...Lymph node dissection(lymphadenectomy)remains a critical component of pancreatic cancer surgery,contributing to accurate staging and guiding adjuvant therapy.The debate between standard and extended lymphadenectomy persists,with evidence showing no significant survival advantage of extended dissection over the standard approach.Extended lymphadenectomy,while increasing the number of lymph nodes retrieved,is associated with longer operative times,greater blood loss,and higher morbidity.More importantly,lymph nodes serve as critical immune hubs,and excessive removal may compromise systemic immune surveillance,which is vital in the context of emerging immunotherapies for pan-creatic cancer.This minireview synthesizes the oncological and immunological perspectives on lymphadenectomy,advocating for a personalized approach to lymph node management in pancreatic cancer surgery,focusing on balancing oncologic outcomes with immune preservation.展开更多
Mimicking the electric microenvironment of natural tissue is a promising strategy for developing biomedical implants. However, current research has not taken biomimetic electrical functional units into consideration w...Mimicking the electric microenvironment of natural tissue is a promising strategy for developing biomedical implants. However, current research has not taken biomimetic electrical functional units into consideration when designing biomedical implants. In this research, ordered structures with Schottky heterojunction functional unit (OSSH) were constructed on titanium implant surfaces for bone regeneration regulation. The Schottky heterojunction functional unit is composed of periodically distributed titanium microdomain and titanium oxide microdomain with different carrier densities and surface potentials. The OSSH regulates the M2-type polarization of macrophages to a regenerative immune response by activating the PI3K-AKT-mTOR signal pathway and further promotes osteogenic differentiation of rat bone marrow mesenchymal stem cells. This work provides fundamental insights into the biological effects driven by the Schottky heterojunction functional units that can electrically modulate osteogenesis.展开更多
基金supported by the National Natural Science Foundation of China(Nos.82573045,82460602,82560459)the Hainan Provincial Graduate Student Innovative Research Project(No.Qhys2024-440).
文摘Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immune tolerance of cancer cells.The classical theory holds that prostate apoptosis response-4(PAR-4)is a tumor suppressor protein.However,our recent research has found that PAR-4 has a biological function of promoting cancer in hepatocellular carcinoma(HCC),and our analysis shows that PAR-4 can be modified of lactic acid.These research evidences suggest that PAR-4 lactylation modification may drive immune tolerance in HCC.Therefore,inhibiting PAR-4 lactylation modification is very likely to increase the sensitivity of HCC to immunotherapy.
基金funded by the National Natural Science Foundation of China(82174093).
文摘Objective:To improve the efficacy of Astragalus membranaceus(Fisch.)Bunge(A.membranaceus,Huang Qi),and to further develop and utilize it,fermentation technology was applied to the stem and leaf of A.membranaceus to enhance its immune function.Methods:In this study,we fermented A.membranaceus stem and leaf(ASL)with probiotics and inves-tigated its immune function.Firstly,we screened suitable strains for ASL fermentation and optimized the fermentation process.Secondly,we determined the antioxidant capacity of fermented ASL and its effect on inflammation in mouse monocyte-macrophage cell.Finally,the immunocompromised mice were treated with fermented ASL to investigate the changes in their immune ability.Results:Among the 10 selected probiotics,Lactobacillus plantarum was the most suitable strain for ASL fermentation.After optimization of the fermentation process,the content of saponins in fermented ASL was significantly increased.The fermented ASL exhibited strong anti-inflammatory and antioxidant activities in vitro.The in vivo immune efficacy improved by promoting the development of the spleen and thymus,as well as raising the immunoglobulin M,tumor necrosis factor-α,and interleukin-1β levels of in the serum.Conclusion:This study contributes to developing the non-medicinal parts of A.membranaceus,expands its medicinal resources,highlights the potential of fermentation technology to enhance these parts,and provides a reference for further development.Based on this approach,we can promote using non-me-dicinal parts of herbal medicines,minimize drug waste,and offer a reference for developing non-me-dicinal components in Chinese herbal medicines.
文摘Hepatocellular carcinoma presents with three distinct immune phenotypes,including immune-desert,immune-excluded,and immune-inflamed,indicating various treatment responses and prognostic outcomes.The clinical application of multi-omics parameters is still restricted by the expensive and less accessible assays,although they accurately reflect immune status.A comprehensive evaluation framework based on“easy-to-obtain”multi-model clinical parameters is urgently required,incorporating clinical features to establish baseline patient profiles and disease staging;routine blood tests assessing systemic metabolic and functional status;immune cell subsets quantifying subcluster dynamics;imaging features delineating tumor morphology,spatial configuration,and perilesional anatomical relationships;immunohistochemical markers positioning qualitative and quantitative detection of tumor antigens from the cellular and molecular level.This integrated phenomic approach aims to improve prognostic stratification and clinical decision-making in hepatocellular carcinoma management conveniently and practically.
文摘BACKGROUND Gastrointestinal(GI)surgery can significantly affect the nutritional status and immune function of patients.This study aimed to investigate the effects of personalized nutritional care on the recovery of immune function in patients who underwent postoperative GI surgery.AIM To study examines personalized nutritional care’s impact on immune function recovery,nutritional status,and clinical outcomes after GI surgery.METHODS This observational study included 80 patients who underwent GI surgery between 2021 and 2023.Patients received personalized nutritional care based on their individual needs and surgical outcomes.Immune function markers including lymphocyte subsets,immunoglobulins,and cytokines were measured preoperatively and at regular intervals postoperatively.Nutritional status,clinical outcomes,and quality of life were assessed.RESULTS Patients receiving personalized nutritional care showed significant improvements in immune function markers compared to baseline.At 4 weeks postoperatively,CD4+T-cell counts increased by 25%(P<0.001),while interleukin-6 levels decreased by 40%(P<0.001).Nutritional status,as measured by prealbumin and transferrin levels,improved by 30%(P<0.01).Postoperative complications reduced by 35%compared to historical controls.The quality-of-life scores improved by 40%at 3 months postoperatively.CONCLUSION Personalized nutritional care enhances immune function recovery,improves nutritional status,and reduces complications in patients undergoing postoperative GI surgery,highlighting its crucial role in optimizing patient outcomes following such procedures.
文摘BACKGROUND Although surgery remains the primary treatment for proximal gastric cancer(PGC),ongoing refinements in surgical strategies are essential to improving clinical outcomes.AIM To investigate the effect of double-tract reconstruction(DTR)on immune function and stress response in patients undergoing laparoscopic proximal gastrectomy(LPG).METHODS In total,78 patients with PGC admitted between August 2020 and August 2024 were enrolled.The research group consisted of 39 patients who underwent DTR+LPG,whereas the control group comprised 39 patients who underwent laparoscopic total gastrectomy with Roux-en-Y esophagojejunostomy.Perioperative indices(intraoperative blood loss,digestive tract anastomosis time,and time to first postoperative flatus),postoperative complications(intestinal obstruction,anastomotic ulcer,diarrhea,dumping syndrome,and gastroesophageal reflux),nutritional parameters(serum albumin,hemoglobin,and body mass index),immune function immunoglobulin(IgG,IgA,and IgM),and stress response indicators(C-reactive protein,interleukin-6,and tumor necrosis factor-α)were collected and analyzed for both groups.RESULTS The intraoperative blood loss was lower(P<0.05),and the time to first postoperative flatus time was shorter(P<0.001)in the research group than in the control group.The two groups had comparable digestive tract anastomosis time(P>0.05).The overall complication rate was significantly lower in the research group than in the control group(P=0.042).Compared with the control group,the research group exhibited notably higher albumin,hemoglobin,and body mass index levels at 2 and 3 months postoperatively,as well as considerably high immunoglobulin(Ig)G,IgA,and IgM levels on postoperative day 1(P<0.05).The postoperative levels of C-reactive protein,interleukin-6,and tumor necrosis factor-αwere also lower in the research group than in the control group(P<0.001).CONCLUSION The combination of DTR and LPG in the treatment of patients with PGC is more effective in enhancing immune function and suppressing stress responses,showing more advantages over laparoscopic total gastrectomy.
文摘Objective:To investigate the effects of nebulizedα-interferon on immune function in elderly patients with respiratory tract infection.Methods:A total of 120 elderly patients with respiratory tract infection admitted to our hospital from June 2023 to June 2024 were selected and randomly divided into an observation group(n=60)and a control group(n=60)using the envelope method.The control group received conventional treatment,while the observation group received additional nebulizedα-interferon therapy based on conventional treatment.After the same treatment period,changes in immune function indicators(immunoglobulins IgG,IgA,IgM)were compared between the two groups.Patients were also followed up for 3 months to observe the frequency of respiratory tract infection recurrences.Results:After treatment,IgA and IgM levels decreased significantly,while IgG levels increased significantly in both groups.The improvement in each indicator was more pronounced in the observation group than in the control group(P<0.05).By the end of the follow-up period,all 120 patients had successfully completed the follow-up,and no patients were lost to follow-up.The frequency of respiratory tract infection recurrences was lower in the observation group than in the control group(P<0.05).Conclusion:Nebulizedα-interferon can improve immune function and reduce the frequency of recurrences in elderly patients with respiratory tract infection.
基金supported by the Key-Area Research and Development Program of Guangdong Province (2021B0707060001)the Program for Scientific Research Start-Up Funds of Guangdong Ocean UniversityChina Postdoctoral Science Foundation (2016T90787)。
文摘The mechanisms of mushroom polysaccharides on immune functions and lipid metabolism of aged mammals have not been fully elucidated.In the present study,after assessing the impacts of one type of Lentinula edodes-derived polysaccharides,named L2,on immune functions and blood lipid profiles,isobaric tags for relative and absolute quantification(iTRAQ)-based proteomic profiling of the small intestinal tissues from aged mice treated with L2 was performed.L2 reversed immune function declines and modulated the lipid metabolism of aged mice evidenced by increased levels of serum TC,HDL-C,and LDL-C,and reduced levels of serum TG.Moreover,a total of 95 differentially regulated proteins(DRPs) were identified,of which75 were up-regulated and 20 were down-regulated.Most of the DRPs were involved in intracellular and extracellular structure organization,and cellular and metabolic regulation.Particularly,approximately 16 and 9 DRPs participated in the regulation of immune functions and lipid metabolism,respectively.Furthermore,protein-protein interaction analysis highlighted that cadherin-1,plectin,cadherin-17,Ras GTPase-activating-like protein IQGAP2,and ezrin might be key proteins in response to L2 treatment.These findings provide new insights into the biological mechanisms of mushroom polysaccharides in anti-aging from a proteomic perspective.
基金funded by the National Natural Science Foundation of China(Grant Nos.82204517 to T.Z.and 82404756 to J.Z.)the Science and Technology Program in Medicine and Health of Zhejiang Province(Grant No.2023KY726 to T.Z.).
文摘Background:Aberrant expression of transcription factors(TFs)is a key mechanism mediating tumor immune escape and therapeutic resistance.The involvement of E26 transformation-specific(ETS)family of TFs in immune regulation is not fully understood.The study aimed to elucidate the function of E-twenty-six variant 4(ETV4)in tumor immune evasion and its potential as a predictive biomarker for immunotherapy in melanoma.Methods:The expression patterns of ETS family TFs were analyzed in melanoma and hepatocellular carcinoma(HCC).Single-cell RNA sequencing(scRNA-seq)was used to dissect the cellular expression and function of ETV4 in the tumor microenvironment.Functional studies and murine models were employed to investigate the role of ETV4 in T cell-mediated tumor killing and tumor growth.The correlation between ETV4 expression level and patient responsiveness to programmed cell death protein 1(PD-1)blockade therapy was evaluated.Results:TFs in the ETS family were found to effectively stratify melanoma and HCC patients into prognostic subgroups.In melanoma,the polyoma enhancer activator 3(PEA3)subfamily,particularly ETV4 and ETV5,showed a negative correlation with immune infiltration.scRNA-seq analysis showed that ETV4 is preferentially expressed in melanoma cells and involves in mediating tumor-immunocyte interactions.Functional studies demonstrated that ETV4 impairs T cell-mediated tumor killing by transcriptionally upregulating programmed death-ligand 1(PD-L1).In immunocompetent murine models,ETV4 downregulation significantly suppressed tumor growth.Furthermore,high ETV4 expression correlated with poor responses to anti-PD-1 therapy.Conclusion:Our findings identify ETV4 as a key transcriptional regulator of immune evasion in melanoma by controlling PD-L1 expression.ETV4 may act as a predictive biomarker for immunotherapy outcomes.
文摘Objective:To analyze the efficacy of whole-course local simultaneous integrated boost intensity-modulated radiotherapy(SIB-IMRT)on patients with locally advanced esophageal squamous cell carcinoma(ESCC).Methods:88 patients with ESCC admitted to the hospital between October 2022 and October 2024 were selected and randomly divided into two groups using a random number table.The experimental group received SIB-IMRT treatment,while the control group received conventional intensity-modulated radiotherapy(C-IMRT).The objective remission rate,immune function,tumor markers,and adverse reaction rate were compared between the two groups.Results:The objective remission rate in the experimental group was higher than that in the control group(P<0.05).Before treatment,there was no difference in immune function levels and tumor marker levels between the two groups(P>0.05).After treatment,the immune function levels in the experimental group were better than those in the control group,and the tumor marker levels were lower than those in the control group(P<0.05).The adverse reaction rate in the experimental group was lower than that in the control group(P<0.05).Conclusion:SIB-IMRT can improve the objective remission rate of patients with ESCC,protect their immune function,down-regulate tumor marker levels,and prevent side effects after treatment.
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Deutsche Forschungsgemeinschaft(DFG,German Research Foundation),project numbers 324633948 and 409784463(DFG grants Hi 678/9-3 and Hi 678/10-2,FOR2953)to HHBundesministerium für Bildung und Forschung-BMBF,project number 16LW0463K to HT.
文摘Microglia are the resident macrophages of the central nervous system.They act as the first line of defense against pathogens and play essential roles in neuroinflammation and tissue repair after brain insult or in neurodegenerative and demyelinating diseases(Borst et al.,2021).Together with infiltrating monocyte-derived macrophages,microglia also play a critical role for brain tumor development,since immunosuppressive interactions between tumor cells and tumor-associated microglia and macrophages(TAM)are linked to malignant progression.This mechanism is of particular relevance in glioblastoma(GB),the deadliest form of brain cancer with a median overall survival of less than 15 months(Khan et al.,2023).Therefore,targeting microglia and macrophage activation is a promising strategy for therapeutic interference in brain disease.
基金Supported by National High-Level Hospital Clinical Research Funding,No.2022-PUMCH-B-022,and No.2022-PUMCH-D-002CAMS Innovation Fund for Medical Sciences,No.CIFMS 2021-1-I2M-003Undergraduate Innovation Program,No.2024dcxm025.
文摘Small intestinal villi are essential for nutrient absorption,and their impairment can lead to malabsorption.Small intestinal villous atrophy(VA)encompasses a heterogeneous group of disorders,including immune-mediated conditions(e.g.,celiac disease,autoimmune enteropathy,inborn errors of immunity),lymphoproliferative disorders(e.g.,enteropathy-associated T-cell lymphoma),infectious causes(e.g.,tropical sprue,Whipple’s disease),iatrogenic factors(e.g.,Olmesartanassociated enteropathy,graft-vs-host disease),as well as inflammatory and idiopathic types.These disorders are often rare and challenging to distinguish due to overlapping clinical,serological,endoscopic,and histopathological features.Through a systematic literature search using keywords such as small intestinal VA,malabsorption,and specific enteropathies,this review provides a comprehensive overview of diagnostic clues for VA and malabsorption.We systematically summarize the pathological characteristics of each condition to assist pathologists and clinicians in accurately identifying the underlying etiologies.Current studies still have many limitations and lack broader and deeper investigations into these diseases.Therefore,future research should focus on the development of novel diagnostic tools,predictive models,therapeutic targets,and mechanistic molecular studies to refine both diagnosis and management strategies.
文摘Background:While the treatment of metastatic renal cell carcinoma(mRCC)is evolving due to immune checkpoint inhibitors(ICIs),optimal strategies for later lines of therapy have yet to be defined.The combination of lenvatinib and everolimus represents a viable option,and the present review aimed to summarize its activity,effectiveness,and safety.Methods:A systematic review of the literature was conducted using PubMed,targeting studies published between 2018 and 2025.Eligible studies included English-language prospective and retrospective trials reporting survival outcomes in mRCC patients treated with lenvatinib and everolimus after at least one ICI-containing regimen.Results:Nine studies met the inclusion criteria,encompassing a total of 441 patients.The lenvatinib and everolimus combination was primarily used in the third and subsequent lines of therapy.Median overall survival ranged from 7.5 to 24.5 months,while median progression-free survival was more consistent,between 6.1 and 6.7 months,except for one study reporting 12.9 months.Objective response rates varied widely(14.0%–55.7%).Adverse events of grade≥3 did not exceed the expected rate,with diarrhoea and proteinuria as the most reported events.Dose reductions and treatment discontinuations due to toxicity occurred but were generally lower than in prior pivotal trials.Conclusions:Real-world evidence suggests that lenvatinib and everolimus represent an effective and safe option after ICI failure in mRCC patients.Nevertheless,the lack of randomized phase III trials and the heterogeneity of existing studies highlight the need for more robust prospective research to guide post-ICI therapeutic strategies.
基金supported by the National Natural Science Foundation of China(No.82203056)the Natural Science Foundation of Liaoning Province(No.2023-BS-167)+1 种基金the Science and Technology Talent Innovation Support Plan of Dalian(NO.2022RQ091)the“1+X”program for Clinical Competency enhancement-Clinical Research Incubation Project of the Second Hospital of Dalian Medical University(No.2022LCYJYB01)。
文摘The intricate interactions between immune cells and tumors exert a profound influence on cancer progression and therapeutic efficacy.Within the tumor microenvironment,exosomes have emerged as pivotal mediators of intercellular communication,with their cargo of non-coding RNAs(ncRNAs)serving as key regulatory elements.This review examines the multifaceted roles of immune cell-derived exosomal ncRNAs in tumor biology.The involvement of various immune cells,including T cells,B cells,natural killer cells,macrophages,neutrophils,and myeloid-derived suppressor cells,in utilizing exosomal ncRNAs to regulate tumor initiation and progression is explored.Additionally,the biogenesis and delivery mechanisms of these immune cell-derived exosomal ncRNAs are discussed,alongside their potential clinical applications in cancer.
基金supported by Infinitus Co.,Ltd(2019009)the Scientific and Technologic Foundation of Jilin Province(No.20230202050NC).
文摘Objective:Grifola frondosa,a medicinal mushroom,is widely used to enhance immunity and treat cancer.Polysaccharides are its primary active components.We aimed to investigate the effects of the alkaloid G.frondosa polysaccharide(GFP)extract on immunity and gut microbiota.Methods:Alkaloid GFP was extracted using an alkaline extraction method,followed by hollow-fiber microfiltration.The molecular weight of alkaloid GFP was determined by high-performance gel permeation chromatography(HPGPC).Monosaccharide composition was analyzed by pre-column derivatization combined with high-performance liquid chromatography(HPLC).Methylation analysis was performed to characterize glycosidic linkages in alkaloid GFP.The immune function of alkaloid GFP was assessed in a cyclophosphamide(CTX)-induced immunosuppressive mouse model.Splenic lymphocyte proliferation,macrophage phagocytic capacity,and natural killer(NK)cell cytotoxicity were evaluated.The effect of alkaloid GFP on gut microbiota was assessed by 16S rRNA sequencing.Results:The molecular weight distribution of alkaloid GFP ranged from 17 to 18 kDa.The alkaloid GFP contained aβ-(1→6)-glucan backbone branched at O-3 byβ-1,3-D-Glcp.Oral administration of alkaloid GFP mitigated the effects of CTX on spleen index,splenic lymphocyte proliferation,and peritoneal macrophage phagocytosis.Additionally,alkaloid GFP improved the gut microbiota composition of immunosuppressed mice,increasing the relative abundances of Ligilactobacillus and Lactobacillus.Conclusions:Alkaloid GFP demonstrated immune-enhancing effects and gut microbiota regulatory activity,providing a basis for developing related health food ingredients.
基金funded by National Key R&D Program of China(2023YFD1301200)the science and technology innovation Program of Hunan Province(2021RC3091).
文摘Background Tryptophan is essential for nutrition,immunity and neural activity,but cannot be synthesized endogenously.Certain natural products influence host health by modulating the gut microbiota to promote the production of tryptophan metabolites.Sanguinarine(SAN)enhances broiler immunity,however,its low bioavailability and underlying mechanisms remain unclear.This study aimed to decode the mechanisms by which sanguinarine enhances intestinal immune function in broilers.Methods Liquid chromatography-tandem mass spectrometry(LC-MS/MS)was employed to identify the main metabolites of sanguinarine in the intestine.Subsequently,equal concentrations of sanguinarine and its metabolites were separately added to the diets.The effects of sanguinarine and its metabolites on the intestinal immune function of broiler chickens were evaluated using 16S rRNA gene amplicon sequencing and tryptophan metabolomics approaches.Results We determined that dihydrosanguinarine(DHSA)is the main metabolite of sanguinarine in the intestine.Both compounds increased average daily gain and reduced feed efficiency,thereby improving growth performance.They also enhanced ileal villus height and the villus-to-crypt(V/C)ratio while decreasing crypt depth and upregulating the mRNA expression of tight junction proteins ZO-1,occludin and claudin-1.Furthermore,both compounds promoted the proliferation of intestinal Lactobacillus species,a tryptophan-metabolizing bacterium,stimulated short-chain fatty acid production,and lowered intestinal pH.They regulated tryptophan metabolism by increasing the diversity and content of indole tryptophan metabolites,activating the aryl hydrocarbon receptor(AhR)pathway,and elevating the mRNA levels of CYP1A1,CYP1B1,SLC3A1,IDO2 and TPH1.Inflammatory cytokines IL-1β and IL-6 were inhibited,while anti-inflammatory cytokines IL-10 and IL-22,serum SIgA concentration,and intestinal MUC2 expression were increased.Notably,DHSA exhibited a more pronounced effect on enhancing immune function compared to SAN.Conclusions SAN is converted to DHSA in vivo,which increases its bioavailability.DHSA regulates tryptophan metabolism by activating the AhR pathway and modulating immune-related factors through changes in the gut microbiota.Notably,DHSA significantly increases the abundance of Lactobacillus,a key tryptophan-metabolizing bacterium,thereby enhancing intestinal immune function and improving broiler growth performance.
基金Supported by WBE Liver Foundation,No.WBE20220182022 Young and Middle-aged Talents Incubation Project(Youth Innovation)of Beijing Youan Hospital,Capital Medical University,No.BJYAYY-YN-2022-092023 Young and Middle-aged Talents Incubation Project(Youth Innovation)of Beijing Youan Hospital,Capital Medical University,No.BJYAYYYN2023-14.
文摘BACKGROUND Autoimmune liver diseases,including primary biliary cholangitis(PBC),autoi-mmune hepatitis(AIH),and their overlap syndrome(OS),involve immune-mediated liver injury,with OS occurring in 1.2%-25%of PBC patients.OS carries a higher risk of cirrhosis,hepatocellular carcinoma,and reduced survival.While its pathogenesis remains unclear,gut microbiota dysbiosis and serum metabolite alterations may play key roles.This study uses 16S rRNA sequencing and liquid chromatography-mass spec-trometry(LC-MS)metabolomics to compare gut microbiota and serum metabolites among PBC,AIH,and OS patients,and explores their associations with liver function.AIM To differentiate OS from PBC and AIH based on gut microbiota,serum metabolites,and liver function.METHODS Gut microbiota profiles were analyzed using 16S rRNA sequencing,while untargeted serum metabolomics was conducted via LC-MS.Comparative analyses were performed to identify differences in microbial composition and serum metabolite levels among PBC,AIH,and OS groups.Correlation analyses and network visualization tech-niques were applied to elucidate the interactions among liver function parameters,gut microbiota,and serum metabolites in OS patients.RESULTS Compared to patients with PBC or AIH,OS patients demonstrated significantly reduced microbial diversity and richness.Notable taxonomic shifts included decreased abundances of Firmicutes,Bacteroidetes,and Actinobacteria,alongside increased levels of Proteobacteria and Verrucomicrobia.Distinct serum metabolites,such as pentadecanoic acid and aminoimidazole carboxamide ribonucleotide,were identified in OS patients.Correlation analysis revealed that aspartate aminotransferase(AST)levels were negatively associated with the bacterial genus Fusicatenibacter and the metabolite L-Tyrosine.A microbial-metabolite network diagram further confirmed a strong association between Fusicatenibacter and L-Tyrosine in OS patients.CONCLUSION OS patients show decreased gut microbiota diversity and unique serum metabolites.Multi-omics linked AST,Fusicatenibacter,and L-Tyrosine,revealing OS mechanisms and diagnostic potential.
基金supported by the Instituto de Salud Carlos III(EstataldeI+D+I2020-2027)co-financed by the European Development Regional Fund“A way to achieve Europe”P2022/BMD-7321(Comunidad de Madrid)and ProACapital,Halekulani S.L.and MJR.
文摘Mood disorders include a set of psychiatric manifestations of increasing prevalence in our society,being mainly represented by major depressive disorder(MDD)and bipolar disorder(BD).The etiopathogenesis of mood disorders is extremely complex,with a wide spectrum of biological,psychological,and sociocultural factors being responsible for their appearance and development.In this sense,immune system dysfunction represents a key mechanism in the onset and pathophysiology of mood disorders,worsening mainly the central nervous system(neuroinflammation)and the periphery of the body(systemic inflammation).However,these alterations cannot be understood separately,but as part of a complex picture in which different factors and systems interact with each other.Psychoneuroimmunoendocrinology(PNIE)is the area responsible for studying the relationship between these elements and the impact of mind–body integration,placing the immune system as part of a whole.Thus,the dysfunction of the immune system is capable of influencing and activating different mechanisms that promote disruption of the psyche,damage to the nervous system,alterations to the endocrine and metabolic systems,and disruption of the microbiota and intestinal ecosystem,as well as of other organs and,in turn,all these mechanisms are responsible for inducing and enhancing the immune dysfunction.Similarly,the clinical approach to these patients is usually multidisciplinary,and the therapeutic arsenal includes different pharmacological(for example,antidepressants,antipsychotics,and lithium)and non-pharmacological(i.e.,psychotherapy,lifestyle,and electroconvulsive therapy)treatments.These interventions also modulate the immune system and other elements of the PNIE in these patients,which may be interesting to understand the therapeutic success or failure of these approaches.In this sense,this review aims to delve into the relationship between immune dysfunction and mood disorders and their integration in the complex context of PNIE.Likewise,an attempt will be made to explore the effects on the immune system of different strategies available in the clinical approach to these patients,in order to identify the mechanisms described and their possible uses as biomarkers.
文摘Lymph node dissection(lymphadenectomy)remains a critical component of pancreatic cancer surgery,contributing to accurate staging and guiding adjuvant therapy.The debate between standard and extended lymphadenectomy persists,with evidence showing no significant survival advantage of extended dissection over the standard approach.Extended lymphadenectomy,while increasing the number of lymph nodes retrieved,is associated with longer operative times,greater blood loss,and higher morbidity.More importantly,lymph nodes serve as critical immune hubs,and excessive removal may compromise systemic immune surveillance,which is vital in the context of emerging immunotherapies for pan-creatic cancer.This minireview synthesizes the oncological and immunological perspectives on lymphadenectomy,advocating for a personalized approach to lymph node management in pancreatic cancer surgery,focusing on balancing oncologic outcomes with immune preservation.
基金supported by the National Natural Science Foundation of China(Nos.52072127,52201297,U21A2055,and U22A20160)the China Postdoctoral Science Foundation(No.2022M711200)the Royal Society(No.IEC/NSFC/191344)(UK).
文摘Mimicking the electric microenvironment of natural tissue is a promising strategy for developing biomedical implants. However, current research has not taken biomimetic electrical functional units into consideration when designing biomedical implants. In this research, ordered structures with Schottky heterojunction functional unit (OSSH) were constructed on titanium implant surfaces for bone regeneration regulation. The Schottky heterojunction functional unit is composed of periodically distributed titanium microdomain and titanium oxide microdomain with different carrier densities and surface potentials. The OSSH regulates the M2-type polarization of macrophages to a regenerative immune response by activating the PI3K-AKT-mTOR signal pathway and further promotes osteogenic differentiation of rat bone marrow mesenchymal stem cells. This work provides fundamental insights into the biological effects driven by the Schottky heterojunction functional units that can electrically modulate osteogenesis.
