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 Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact mo...BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact molecular mechanisms leading to the progression of HCC are still unclear.Research has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor tissues.In this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between them.AIM To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC patients.METHODS In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC patients.Furthermore,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,etc.The statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank test.RESULTS In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival rate.ASH1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated region.Furthermore,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via ASH1L.For the exploration mechanism,we found ASH1L may promote an immunosuppressive microenvironment in HCC and ASH1L affects the expression of the cell junction protein zonula occludens-1,which is potentially relevant to the immune system.CONCLUSION Loss function of microRNA-142-3p induces cancer progression and immune evasion through upregulation of ASH1L in HCC.Both microRNA-142-3p and ASH1L can feature as new biomarker for HCC in the future.展开更多
Objective: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
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
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
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 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
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
This study investigates the properties of high-purity starches extracted from Polygonum multiflorum(PMS)and Smilax glabra(SGS).The starches were characterized by scanning electron microscopy,Fouriertransform infrared ...This study investigates the properties of high-purity starches extracted from Polygonum multiflorum(PMS)and Smilax glabra(SGS).The starches were characterized by scanning electron microscopy,Fouriertransform infrared spectroscopy,X-ray diffraction,high-performance anion-exchange chromatography,and differential scanning calorimetry.Significant differences were observed in their morphological,physicochemical,and functional properties.PMS had a smaller particle size(13.68 μm),irregular polygonal shape,A-type,lower water absorption(62.67 %),and higher oil absorption(51.17 %).In contrast,SGS exhibited larger particles(31.75 μm),a nearly spherical shape,B-type,higher crystallinity(50.66 %),and greater amylose content(21.54 %),with superior thermal stability,shear resistance,and gelatinization enthalpy.SGS also contained higher resistant starch(83.28 %) and longer average chain length(20.58 %),but showed lower solubility,swelling power,light transmittance,and freeze-thaw stability.The physicochemical properties differences in crystal pattern and particle morphology between PMS and SGS lead to distinct behaviors during in vitro digestion and fermentation.These findings highlight the potential of medicinal plant starches in functional ingredients and industrial processes.展开更多
Gauss radial basis functions(GRBF)are frequently employed in data fitting and machine learning.Their linear independence property can theoretically guarantee the avoidance of data redundancy.In this paper,one of the m...Gauss radial basis functions(GRBF)are frequently employed in data fitting and machine learning.Their linear independence property can theoretically guarantee the avoidance of data redundancy.In this paper,one of the main contributions is proving this property using linear algebra instead of profound knowledge.This makes it easy to read and understand this fundamental fact.The proof of linear independence of a set of Gauss functions relies on the constructing method for one-dimensional space and on the deducing method for higher dimensions.Additionally,under the condition of preserving the same moments between the original function and interpolating function,both the interpolating existence and uniqueness are proven for GRBF in one-dimensional space.The final work demonstrates the application of the GRBF method to locate lunar olivine.By combining preprocessed data using GRBF with the removing envelope curve method,a program is created to find the position of lunar olivine based on spectrum data,and the numerical experiment shows that it is an effective scheme.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
Enterovirus A71(EV-A71)is the major causative pathogen for severe hand-foot-mouth disease(HFMD),a predominantly childhood-associated communicable disease.The mechanisms that children manifest severe disease progressio...Enterovirus A71(EV-A71)is the major causative pathogen for severe hand-foot-mouth disease(HFMD),a predominantly childhood-associated communicable disease.The mechanisms that children manifest severe disease progression while adults typically exhibit milder or asymptomatic infections remain incompletely characterized,which hinders the development of effective therapy against this disease.Herein,using the newborn mouse model of EV-A71 infection,we uncovered that the underdevelopment of T cells closely associated with the severity of EV-A71 infection,and EV-A71 infection dramatically impaired T-cell immune response.Moreover,the dysfunction of T-cell immunity contributes to the pathogenesis of EV-A71 infection,as the loss of T cells made neonatal mice highly vulnerable to EV-A71 infection.To further assess the relationship between T-cell immunity and HFMD,we enrolled a cohort of 145 pediatric patients with laboratory-confirmed EV-A71 infection and found that the compromised T-cell immune response is associated with the severity of EV-A71-caused HFMD in these children.Furthermore,we found that the treatment of newborn mice with Astragaloside A,a saponin from the medicinal herb Astragalus membranaceus,showed potent in vivo therapeutic efficacy against EV-A71 infection in a T-cell-dependent manner.In conclusion,these findings uncover the interaction between EV-A71 infection and T-cell immunity,provide novel insights onto the physiological impacts of T cells on the pathogenesis of EV-A71 infection and HFMD,and find a promising immunotherapeutic strategy to treat this viral disease.展开更多
Skin cutaneous melanoma(SKCM),a highly invasive malignant tumor originating from skin melanocytes,poses a significant threat to public health[1,2].Its development is closely associated with multiple factors,such as ul...Skin cutaneous melanoma(SKCM),a highly invasive malignant tumor originating from skin melanocytes,poses a significant threat to public health[1,2].Its development is closely associated with multiple factors,such as ultraviolet radiation,gene mutations,and immune escape.Among these,imbalance in the immune surveillance and clearance of tumor cells is a crucial link to disease progression[3,4].Tripartite motif-containing 27,which belongs to the TRIM protein family and is encoded by the TRIM27 gene,contains the RING,B-box,and coiled-coil domains.It participates in biological processes such as cell-cycle regulation,signal transduction,and immune response mainly by modifying target proteins through ubiquitination.Notably,increasing evidence indicates that TRIM27 is closely associated with the tumor immune microenvironment and contributes to cancer immune escape via multiple mechanisms,thereby promoting tumor development[5].However,the role of TRIM27 in SKCM remains unclear,thus prompting our investigation to elucidate this.展开更多
Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in s...Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.展开更多
Microglia,the resident immune cells of the central nervous system,exhibit a wide array of functional states,even in their so-called“homeostatic”condition,when they are not actively responding to overt pathological s...Microglia,the resident immune cells of the central nervous system,exhibit a wide array of functional states,even in their so-called“homeostatic”condition,when they are not actively responding to overt pathological stimuli.These functional states can be visualized using a combination of multi-omics techniques(e.g.,gene and protein expression,posttranslational modifications,mRNA profiling,and metabolomics),and,in the case of homeostatic microglia,are largely defined by the global(e.g.,genetic variations,organism’s age,sex,circadian rhythms,and gut microbiota)as well as local(specific area of the brain,immediate microglial surrounding,neuron-glia interactions and synaptic density/activity)signals(Paolicelli et al.,2022).While phenomics(i.e.,ultrastructural microglial morphology and motility)is also one of the key microglial state-defining parameters,it is known that cells with similar morphology can belong to different functional states.展开更多
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.
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 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 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 the National Natural Science Foundation of China (No.82174074)。
文摘This study investigates the properties of high-purity starches extracted from Polygonum multiflorum(PMS)and Smilax glabra(SGS).The starches were characterized by scanning electron microscopy,Fouriertransform infrared spectroscopy,X-ray diffraction,high-performance anion-exchange chromatography,and differential scanning calorimetry.Significant differences were observed in their morphological,physicochemical,and functional properties.PMS had a smaller particle size(13.68 μm),irregular polygonal shape,A-type,lower water absorption(62.67 %),and higher oil absorption(51.17 %).In contrast,SGS exhibited larger particles(31.75 μm),a nearly spherical shape,B-type,higher crystallinity(50.66 %),and greater amylose content(21.54 %),with superior thermal stability,shear resistance,and gelatinization enthalpy.SGS also contained higher resistant starch(83.28 %) and longer average chain length(20.58 %),but showed lower solubility,swelling power,light transmittance,and freeze-thaw stability.The physicochemical properties differences in crystal pattern and particle morphology between PMS and SGS lead to distinct behaviors during in vitro digestion and fermentation.These findings highlight the potential of medicinal plant starches in functional ingredients and industrial processes.
基金Supported by the National Basic Research Program of China(2012CB025904)Zhengzhou Shengda University of Economics,Business and Management(SD-YB2025085)。
文摘Gauss radial basis functions(GRBF)are frequently employed in data fitting and machine learning.Their linear independence property can theoretically guarantee the avoidance of data redundancy.In this paper,one of the main contributions is proving this property using linear algebra instead of profound knowledge.This makes it easy to read and understand this fundamental fact.The proof of linear independence of a set of Gauss functions relies on the constructing method for one-dimensional space and on the deducing method for higher dimensions.Additionally,under the condition of preserving the same moments between the original function and interpolating function,both the interpolating existence and uniqueness are proven for GRBF in one-dimensional space.The final work demonstrates the application of the GRBF method to locate lunar olivine.By combining preprocessed data using GRBF with the removing envelope curve method,a program is created to find the position of lunar olivine based on spectrum data,and the numerical experiment shows that it is an effective scheme.
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.
基金supported by the National Natural Science Foundation of China(32200130 to Chong Wang and 82372228 to Yi Xu)the 2023-2024 Annual Scientific Research Project of Traditional Chinese Medicine from Hubei Provincial Administration of Traditional Chinese Medicine(ZY2023Q050 to Chong Wang)Hubei Province Natural Science Funds(2023AFA008 to Xi Zhou).
文摘Enterovirus A71(EV-A71)is the major causative pathogen for severe hand-foot-mouth disease(HFMD),a predominantly childhood-associated communicable disease.The mechanisms that children manifest severe disease progression while adults typically exhibit milder or asymptomatic infections remain incompletely characterized,which hinders the development of effective therapy against this disease.Herein,using the newborn mouse model of EV-A71 infection,we uncovered that the underdevelopment of T cells closely associated with the severity of EV-A71 infection,and EV-A71 infection dramatically impaired T-cell immune response.Moreover,the dysfunction of T-cell immunity contributes to the pathogenesis of EV-A71 infection,as the loss of T cells made neonatal mice highly vulnerable to EV-A71 infection.To further assess the relationship between T-cell immunity and HFMD,we enrolled a cohort of 145 pediatric patients with laboratory-confirmed EV-A71 infection and found that the compromised T-cell immune response is associated with the severity of EV-A71-caused HFMD in these children.Furthermore,we found that the treatment of newborn mice with Astragaloside A,a saponin from the medicinal herb Astragalus membranaceus,showed potent in vivo therapeutic efficacy against EV-A71 infection in a T-cell-dependent manner.In conclusion,these findings uncover the interaction between EV-A71 infection and T-cell immunity,provide novel insights onto the physiological impacts of T cells on the pathogenesis of EV-A71 infection and HFMD,and find a promising immunotherapeutic strategy to treat this viral disease.
基金supported by the Natural Science Foundation of Hebei Province(Grant number:C2025405060).
文摘Skin cutaneous melanoma(SKCM),a highly invasive malignant tumor originating from skin melanocytes,poses a significant threat to public health[1,2].Its development is closely associated with multiple factors,such as ultraviolet radiation,gene mutations,and immune escape.Among these,imbalance in the immune surveillance and clearance of tumor cells is a crucial link to disease progression[3,4].Tripartite motif-containing 27,which belongs to the TRIM protein family and is encoded by the TRIM27 gene,contains the RING,B-box,and coiled-coil domains.It participates in biological processes such as cell-cycle regulation,signal transduction,and immune response mainly by modifying target proteins through ubiquitination.Notably,increasing evidence indicates that TRIM27 is closely associated with the tumor immune microenvironment and contributes to cancer immune escape via multiple mechanisms,thereby promoting tumor development[5].However,the role of TRIM27 in SKCM remains unclear,thus prompting our investigation to elucidate this.
基金supported by the National Natural Science Foundation of China,Nos.82072165 and 82272256(both to XM)the Key Project of Xiangyang Central Hospital,No.2023YZ03(to RM)。
文摘Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.
基金supported by Deutsche Forschungsgemeinschaft,German Research Foundation grant GA 654/13-2 to OG.
文摘Microglia,the resident immune cells of the central nervous system,exhibit a wide array of functional states,even in their so-called“homeostatic”condition,when they are not actively responding to overt pathological stimuli.These functional states can be visualized using a combination of multi-omics techniques(e.g.,gene and protein expression,posttranslational modifications,mRNA profiling,and metabolomics),and,in the case of homeostatic microglia,are largely defined by the global(e.g.,genetic variations,organism’s age,sex,circadian rhythms,and gut microbiota)as well as local(specific area of the brain,immediate microglial surrounding,neuron-glia interactions and synaptic density/activity)signals(Paolicelli et al.,2022).While phenomics(i.e.,ultrastructural microglial morphology and motility)is also one of the key microglial state-defining parameters,it is known that cells with similar morphology can belong to different functional states.
