In recent years,the field of neuroimmunology has witnessed a profound paradigm shift.Research has expanded beyond the traditional focus on the central nervous system to unravel the dynamic interplay between peripheral...In recent years,the field of neuroimmunology has witnessed a profound paradigm shift.Research has expanded beyond the traditional focus on the central nervous system to unravel the dynamic interplay between peripheral immunity and neural networks.Cutting-edge methodologies have unmasked a tripartite communication axis enabling peripheral immune signals to mediate the CNS:(1)neural communication via vagal afferents,(2)humoral signaling through circumventricular organ cytokine diffusion,and(3)cellular interactions involving bone marrow-derived macrophages[1].展开更多
Objective:The incidence and mortality of colorectal carcinoma(CRC)continue to rise globally,highlighting the need to identify modifiable risk factors for early detection and prevention.Previous studies have demonstrat...Objective:The incidence and mortality of colorectal carcinoma(CRC)continue to rise globally,highlighting the need to identify modifiable risk factors for early detection and prevention.Previous studies have demonstrated significant associations between CRC risk and various serum metabolites as well as inflammatory cytokines;however,due to limitations in study design and potential confounding factors,the causal relationships remain unclear.This study aims to investigate the causal relationships between inflammatory cytokines,serum metabolites,and CRC risk,providing a theoretical basis for the development of novel early diagnostic biomarkers and therapeutic targets.Methods:A two-sample Mendelian randomization(MR)design was applied using summary statistics from genome-wide association studies(GWAS).Instrumental variables(IVs)were derived from:1)metabolomics GWAS data of 1400 serum metabolites(n=8299);2)cytokine GWAS data of 91 inflammatory factors(n=14824);and 3)CRC risk data from the FinnGen consortium(6847 cases and 314193 controls).The primary analysis was conducted using the inverse-variance weighted(IVW)method,with sensitivity analyses performed using MR Egger regression and the weighted median method.Effect estimates including odds ratios(OR),95%confidence intervals(CI),and false discovery rates(FDR)were calculated.Results:MR analysis indicated that higher levels of axin-1(AXIN1)(OR=0.84195%CI 0.714 to 0.991)and Fms-related tyrosine kinase 3 ligand(Flt3L)(OR=0.916,95%CI 0.844 to 0.994)were associated with a reduced risk of CRC.In contrast,higher levels of Delta/Notchlike epidermal growth factor-related receptor(DNER)(OR=1.119,95%CI 1.009 to 1.241)and vascular endothelial growth factor A(VEGF-A)(OR=1.078,95%CI 1.011 to 1.150)were associated with an increased risk of CRC(all P<0.05).Metabolomics association analysis further identified 144 serum metabolites significantly correlated with these four key inflammatory cytokines(FDR<0.05),suggesting that they may regulate CRC risk through inflammatory pathways.Conclusion:Specific inflammatory cytokines and serum metabolites have causal relationships with the risk of CRC.These findings provide insights for further exploration of potential risk factors and the development of effective prevention strategies for CRC.展开更多
Objective Sepsis patients exhibit diverse immune states,making it crucial to identify subtypes with distinct inflammatory profiles through Th1/Th2 cytokine data for personalized treatment and improved prognosis.Method...Objective Sepsis patients exhibit diverse immune states,making it crucial to identify subtypes with distinct inflammatory profiles through Th1/Th2 cytokine data for personalized treatment and improved prognosis.Methods We retrieved data from sepsis patients who underwent Th1/Th2 cytokine testing in Nanfang Hospital,Southern Medical University from June 1,2020,to February 1,2022.An unsupervised K-means clustering method classified participants based on Th1/Th2 cytokine levels,with the primary outcome being the 7-day mortality rate post-ICU admission.Cox proportional hazards and Restricted Mean Survival Time(RMST)analyses were utilized to explore survival outcomes.Results A total of 321 sepsis patients were included.IL-6(HR 1.69,95%CI:1.22,2.34)and IL-10(HR 1.81,95%CI:1.37,2.40)emerged as independent predictors of 7-day mortality.Unsupervised K-means clustering revealed 3 inflammatory/immune subgroups:Cluster 1(n=166,low inflammatory response),Cluster 2(n=99,moderate inflammatory response with immune suppression),and Cluster 3(n=56,strong inflammatory and immune suppression).Compared to Cluster 1,Clusters 2 and 3 had higher 7-day mortality risks(14.4%vs 23.2%,HR=4.30,95%CI:1.51-12.26;14.4%vs 35.7%,HR=7.32,95%CI:2.57-20.79).Conclusion Septic patients in a protective immune response state(Cluster 1)exhibit better short-term prognoses,suggesting the importance of understanding inflammatory/immune states for precise treatment and improved outcomes.展开更多
Background Sphingolipids(SL)are key regulators of inflammatory processes,yet their roles in dairy cows remain poorly understood.This study investigated the effects of inflammation(plasma haptoglobin concentration),ket...Background Sphingolipids(SL)are key regulators of inflammatory processes,yet their roles in dairy cows remain poorly understood.This study investigated the effects of inflammation(plasma haptoglobin concentration),ketosis,and mastitis on plasma SL profiles in Holstein cows sampled seven days postpartum.From a cohort of 427 cows across 25 farms,80 animals were classified into four groups:inflammation(n=20),ketosis(n=19),mastitis(n=21),and healthy controls(n=20).Plasma SL were quantified by targeted HPLC-MS/MS,while cytokines were quantified with a 15-plex bead-based assay.Both univariate and multivariate analyses were applied to assess pathological effects,along with SL ratios and correlations between SL and cytokines.Results Systemic inflammation detected through the haptoglobin measure induced the most pronounced alterations in SL metabolism,characterized by elevated dihydrosphingomyelins(DHSM)and lactosylceramides(Lac Cer),higher C22-24:C16 ratios,and lower unsaturated:saturated ratios in ceramides(Cer)and sphingomyelins(SM).Although total Cer,SM,and the Cer:SM ratio remained unchanged,specific reductions were observed in both Cer and SM in C14,Cer C18:1,SM C16:1,and SM C23:1,whereas SM C25:0 and C26:0 increased.Sphingosine-1-phosphate(So1P)was positively correlated with IL-10 as well as IL-1α and TNFα,while C18-20 Cer correlated positively with multiple pro-inflammatory cytokines and chemokines such as CXCL8 and CCL2.Ketosis induced subtler changes,primarily an increase in plasma DHSM and DHSM:SM ratio(driven by C16:0),an increase in C22-24:C16 DHCer ratio,and a decrease in both Lac So:Lac Cer and unsaturated:saturated ratios in C23-SM.In this group,So1P correlated positively with CXCL8 and CCL2.Moreover C18-20 Cer and DHCer were positively associated with CXCL8,CCL2,CCL3,and CCL4,which also showed correlations with most Lac Cer species.Analysis of chronic mastitis cases yielded a clear separation from controls in multivariate analysis but only minimal changes in SL concentrations and ratios,maybe due to the localized nature of the inflammatory response.Conclusions In summary,heightened inflammatory response in early post-partum is associated with the strongest systemic effects on SL metabolism,followed by ketosis,while mastitis induced only modest alterations.These findings highlight condition-specific patterns of SL regulation postpartum and suggest potential immunometabolic biomarkers of disease.展开更多
AIM:To investigate the potential causal associations between 41 inflammatory cytokines and myopia using a two-sample Mendelian randomization(MR)approach.METHODS:Publicly available genome-wide association study(GWAS)da...AIM:To investigate the potential causal associations between 41 inflammatory cytokines and myopia using a two-sample Mendelian randomization(MR)approach.METHODS:Publicly available genome-wide association study(GWAS)datasets were utilized for this two-sample MR analysis.Inflammatory cytokine-related GWAS data were extracted from The University of Bristol’s Research Data Repository,and myopia-related GWAS data were obtained from the FinnGen project.Single nucleotide polymorphisms(SNPs)associated with inflammatory cytokines were systematically selected as instrumental variables(IVs)based on three rigorous criteria:relevance,independence,and exclusion of pleiotropy.Five MR methods were employed for causal inference:the inverse-variance weighted(IVW)method as the primary analysis,supplemented by MREgger regression,weighted median estimator,simple mode,and weighted mode approaches.Sensitivity analyses were performed to evaluate the robustness of the causal estimates.RESULTS:A total of 773 myopia-associated SNPs were identified.MR analysis revealed that higher levels of macrophage inflammatory protein 1-α(MIP-1α)were associated with a 17%reduced risk of myopia[odds ratio(OR)=0.83;95%confidence interval(CI):0.69-0.99;P<0.05].In contrast,elevated levels of eotaxin(OR=1.26;95%CI:1.07-1.47;P<0.01),stromal cell-derived factor-1α(SDF-1α;OR=1.68;95%CI:1.08-2.62;P<0.05),and interleukin-2 receptor subunit alpha(IL-2Rα;OR=1.25;95%CI:1.01-1.53;P<0.05)were significantly associated with an increased risk of myopia.Sensitivity analyses confirmed the reliability of these results.CONCLUSION:This study provides evidence supporting a causal relationship between specific inflammatory cytokines and myopia.MIP-1αmay act as a protective factor against myopia,while eotaxin,SDF-1α,and IL-2Rαare potential risk factors for myopia.These findings emphasize the critical role of inflammatory pathways in the pathogenesis of myopia,offering novel insights for the development of preventive and therapeutic strategies for myopia.展开更多
Objective The aim of this study was to analyze the correlation between the levels of 12 cytokines in the cervical microenvironment and cervical intraepithelial neoplasia in patients with high-risk human papillomavirus...Objective The aim of this study was to analyze the correlation between the levels of 12 cytokines in the cervical microenvironment and cervical intraepithelial neoplasia in patients with high-risk human papillomavirus(HR-HPV)infection.Methods Female patients(n=73)with HR-HPV infection were enrolled and divided into a high-grade squamous intraepithelial lesion(HSIL)group(n=33)and a non-HSIL(N-HSIL)group(n=40),which include low-grade squamous intraepithelial lesions and inflammation.Healthy screening subjects(n=31)with negative HR-HPV results were enrolled as a control group.We examined contemporaneous plasma and secretory cytokines from 25 study subjects to investigate the difference between systemic cytokine profiles and the local microenvironment immunity using the Wilcoxon matched-pairs signed rank test.The 12 cytokines from cervical secretions were compared between the three groups using the Mann-Whitney test,and logistic regression was used to analyze HSIL and N-HSIL.Results There were statistical differences in eight cytokines(IL-2,IL-6,TNF-α,IFN-γ,IL-1β,IL-12p70,IFN-α,and IL-8)between cervical secretion and plasma of the same patient,and seven cytokines were statistically different between the control and other two groups.We selected four independent variables(TNF-α,IFN-γ,IL-12p70,and IFN-α)commonly identified by univariate regression analysis and non-parametric tests for multivariate logistic regression analysis.Based on this model,HSIL could be predicted in patients with HR-HPV infection,with the area under the curve being 0.76.Conclusion The systemic cytokine profile cannot reflect the local microenvironment immunity,and the occurrence of HSIL is related to the cytokine levels in the cervical microenvironment.展开更多
Background:Fever is characterized by an upregulation of the thermoregulatory set-point after the body encounters any pathological challenge.It is accompanied by uncomfortable sickness behaviors and may be harmful in p...Background:Fever is characterized by an upregulation of the thermoregulatory set-point after the body encounters any pathological challenge.It is accompanied by uncomfortable sickness behaviors and may be harmful in patients with other comor-bidities.We have explored the impact of an Ayurvedic medicine,Fevogrit,in an endo-toxin(lipopolysaccharide)-induced fever model in Wistar rats.Methods:Active phytoconstituents of Fevogrit were identified and quantified using ultra-high-performance liquid chromatography(UHPLC)platform.For the in-vivo study,fever was induced in male Wistar rats by the intraperitoneal administration of lipopolysaccharide(LPS),obtained from Escherichia coli.The animals were allocated to normal control,disease control,Paracetamol treated and Fevogrit treated groups.The rectal temperature of animals was recorded at different time points using a digital thermometer.At the 6-h time point,levels of TNF-α,IL-1βand IL-6 cytokines were analyzed in serum.Additionally,the mRNA expression of these cytokines was deter-mined in hypothalamus,24 h post-LPS administration.Results:UHPLC analysis of Fevogrit revealed the presence of picroside I,picroside II,vanillic acid,cinnamic acid,magnoflorine and cordifolioside A,as bioactive constitu-ents with known anti-inflammatory properties.Fevogrit treatment efficiently reduces the LPS-induced rise in the rectal temperature of animals.The levels and gene ex-pression of TNF-α,IL-1βand IL-6 in serum and hypothalamus,respectively,was also significantly reduced by Fevogrit treatment.Conclusion:The findings of the study demonstrated that Fevogrit can suppress LPS-induced fever by inhibiting peripheral or central inflammatory signaling pathways and could well be a viable treatment for infection-induced increase in body temperatures.展开更多
Background:One-third of veterans returning from the 1990–1991 Gulf War reported a myriad of symptoms including cognitive dysfunction,skin rashes,musculoskeletal discomfort,and fatigue.This symptom cluster is now refe...Background:One-third of veterans returning from the 1990–1991 Gulf War reported a myriad of symptoms including cognitive dysfunction,skin rashes,musculoskeletal discomfort,and fatigue.This symptom cluster is now referred to as Gulf War Illness(GWI).As the underlying mechanisms of GWI have yet to be fully elucidated,diagnosis and treatment are based on symptomatic presentation.One confounding factor tied to the illness is the high presence of post-traumatic stress disorder(PTSD).Previous research efforts have demonstrated that both GWI and PTSD are associated with immunological dysfunction.As such,this research endeavor aimed to provide insight into the complex relationship between GWI symptoms,cytokine presence,and immune cell populations to pinpoint the impact of PTSD on these measures in GWI.Methods:Symptom measures were gathered through the Multidimensional fatigue inventory(MFI)and 36-item short form health survey(SF-36)scales and biological measures were obtained through cytokine&cytometry analysis.Subgrouping was conducted using Davidson Trauma Scale scores and the Structured Clinical Interview for Diagnostic and statistical manual of mental disorders(DSM)-5,into GWI with high probability of PTSD symptoms(GWIH)and GWI with low probability of PTSD symptoms(GWIL).Data was analyzed using analysis of variance(ANOVA)statistical analysis along with correlation graph analysis.We mapped correlations between immune cells and cytokine signaling measures,hormones and GWI symptom measures to identify patterns in regulation between the GWIH,GWIL,and healthy control groups.Results:GWI with comorbid PTSD symptoms resulted in poorer health outcomes compared with both healthy control(HC)and the GWIL subgroup.Significant differences were found in basophil levels of GWI compared with HC at peak exercise regardless of PTSD symptom comorbidity(ANOVA F=4.7,P=0.01)indicating its potential usage as a biomarker for general GWI from control.While the unique identification of GWI with PTSD symptoms was less clear,the GWIL subgroup was found to be delineated from both GWIH and HC on measures of IL-15 across an exercise challenge(ANOVA F>3.75,P<0.03).Additional differences in natural killer(NK)cell numbers and function highlight IL-15 as a potential biomarker of GWI in the absence of PTSD symptoms.Conclusions:We conclude that disentangling GWI and PTSD by defining trauma-based subgroups may aid in the identification of unique GWI biosignatures that can help to improve diagnosis and target treatment of GWI more effectively.展开更多
Background Changes in macrophage function are crucial contributors to hepatic inflammation and fibrosis.However,the role of macrophages in the development of liver fibrosis in dairy cows with ketosis remains unclear.T...Background Changes in macrophage function are crucial contributors to hepatic inflammation and fibrosis.However,the role of macrophages in the development of liver fibrosis in dairy cows with ketosis remains unclear.This study integrated proteomics and cytokine array approach to identify the multifactorial and multicellular interaction effects driving liver fibrosis in dairy cows with ketosis and analyze the mechanism by which the proinflammatory shift in macrophages contributes to liver fibrosis.Results Histopathological analysis revealed liver injury,including severe steatosis,infiltration of inflammatory cells,an increase in lipid deposition,and a decrease in glycogen expression in ketotic cows.Moreover,the number of mitochondria considerably increased in hepatocytes.The activation of the dynamin-related protein 1/mitochondrial fission factor(DRP1/MFF)pathway induced excessive mitochondrial fission,and the inhibition of the nuclear factor erythroid 2-related factor 2/heme oxygenase 1(Nrf2/HO-1)pathway led to the accumulation of intracellular reactive oxygen species(ROS).Proteomic analysis revealed the activation of extracellular matrix(ECM)-related functions and the NF-κB pathway in the liver,whereas cytokine array analysis revealed that the cytokine network was dysregulated.The accumulation of ROS triggered NF-κB nuclear translocation,inducing a proinflammatory shift in macrophages and liver inflammation.M1 polarization of macrophages promotes the release of proinflammatory mediators,which stimulated hepatic stellate cells(HSCs)activation,leading to ECM deposition,ultimately contributing to liver fibrosis.Conclusions To summarize,our study revealed the multifactorial and multicellular interaction effects driving liver fibrosis.Our results preliminarily showed that increased mitochondrial fission and inhibition of the Nrf2/HO-1 pathway are key factors in activating macrophages,which can lead to liver fibrosis in dairy cows with ketosis.展开更多
BACKGROUND Liver hepatocellular carcinoma(LIHC)is a highly aggressive cancer with poor prognosis due to its complex tumor microenvironment(TME)and immune evasion.Regulatory T cells(Tregs)play a critical role in tumor ...BACKGROUND Liver hepatocellular carcinoma(LIHC)is a highly aggressive cancer with poor prognosis due to its complex tumor microenvironment(TME)and immune evasion.Regulatory T cells(Tregs)play a critical role in tumor progression.Suppressor of cytokine signaling 2(SOCS2),a key immune regulator,may modulate Treg activity and impact LIHC growth and metastasis.AIM To explore how the SOCS2 affects Treg activity in LIHC and its impact on tumor growth and metastasis.METHODS LIHC transcriptome data from The Cancer Genome Atlas database were analyzed using Gene Set Enrichment Analysis,Estimation of Stromal and Immune Cells in Malignant Tumors Using Expression Data,and Cell-Type Identification by Estimating Relative Subsets of RNA Transcripts to evaluate immune pathways and Treg infiltration.Key prognostic genes were identified using Weighted Gene Coexpression Network Analysis and machine learning.In vitro,co-culture experiments,migration assays,apoptosis detection,and enzyme-linked immunosorbent assay were conducted.In vivo,tumor growth,metastasis,and apoptosis were assessed using subcutaneous and lung metastasis mouse models with hematoxylin and eosin staining,Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling,and immunohistochemistry analyses.RESULTS SOCS2 overexpression inhibited Treg cell activity,reducing LIHC cell migration and invasion while increasing apoptosis.In vivo,SOCS2 suppressed tumor growth and metastasis,confirming its therapeutic potential.CONCLUSION SOCS2 modulates CD4+T function in the TME,contributing to LIHC progression.Targeting SOCS2 presents a potential therapeutic strategy for treating LIHC.展开更多
BACKGROUND Multiple lines of evidence have indicated that pro-inflammatory cytokines play a role in the pathophysiology of gastric carcinoma(GC).AIM To identify potential serum cytokine-based biomarkers for GC diagnos...BACKGROUND Multiple lines of evidence have indicated that pro-inflammatory cytokines play a role in the pathophysiology of gastric carcinoma(GC).AIM To identify potential serum cytokine-based biomarkers for GC diagnosis.METHODS The study cohort comprised 50 patients diagnosed with GC and 50 healthy control subjects.A panel of 7 pro-inflammatory cytokines,including interleukin(IL)-1β,IL-2,IL-6,IL-8,IL-12,tumor necrosis factor-α,and interferon-γ(IFN-γ)were quantified using multiplex Luminex assays.Comparative analyses were conducted to evaluate cytokine levels between the GC patients and healthy controls.The diagnostic potential of serum pro-inflammatory cytokines in differentiating GC patients from healthy individuals was assessed through receiver operating characteristic(ROC)curve analysis.The correlation between serum cytokine levels and disease severity,as classified by the tumor-node-metastasis staging system,was analyzed using Spearman's rank correlation coefficient.RESULTS In comparison to the control group,patients with GC demonstrated significantly elevated serum levels of IL-1β(t=-4.089,P<0.001),IL-6(t=-3.983,P<0.001),IL8(t=-5.460,P<0.001),and IFN-γ(t=-2.856,P=0.005).ROC curve analysis indicated that the area under the curve values for IL-1β,IL-6,and IL-8 exceeded 0.7,effectively distinguishing GC patients from healthy controls.Additionally,serum levels of IL-1β(r=0.424,P=0.012)and IL-6(r=0.742,P<0.001)were positively correlated with the T stage in GC patients.Similarly,serum concentrations of IL-1β(r=0.356,P=0.039)and IL-6(r=0.441,P=0.008)exhibited a positive association with the N stage in these patients.CONCLUSION These findings suggest that circulating pro-inflammatory cytokines,such as IL-1β,IL-6,and IL-8,may serve as potential biomarkers for the diagnosis of GC.展开更多
Background:Non-human primates(NPHs),such as rhesus macaques,cynomol-gus monkeys,and Assamese macaques,play a crucial role in biomedical research.However,baseline cytokine and electrolyte data for these three species,p...Background:Non-human primates(NPHs),such as rhesus macaques,cynomol-gus monkeys,and Assamese macaques,play a crucial role in biomedical research.However,baseline cytokine and electrolyte data for these three species,particularly data stratified by age and sex,are limited.Therefore,the aim of this study was to establish and analyze age-and sex-specific cytokine and electrolyte profiles in these three species.Methods:This study included 40 rhesus macaques(21 males,19 females),33 cyn-omolgus monkeys(17 males,16 females),and 45 Assamese macaques(25 males,20 females)classified by age(1-5 years,6-12 years,>13 years)and sex.The levels of 23 immune function indicators and 5 electrolyte indicators were measured.Results:Among the three monkey species,the levels of sCD40L,IL-18,MCP-1,MIP-1β,TGFa,K^(+),Na^(+),and Cl^(-)exhibited species-,sex-,and age-related differences.Comparison within the same species,sex had no significant impact on cytokine levels in NHPs but did affect electrolyte levels,particularly Cl^(-)and Na^(+)levels,in cynomol-gus monkeys and Assamese macaques.Electrolyte levels in NHPs were not affected by age,whereas the levels of certain cytokines,particularly sCD40L,GM-CSF,and IL-10,varied with age.The remaining 21 cytokines demonstrated no significant age-related changes.Conclusions:Significant variations in cytokine and electrolyte levels exist among dif-ferent monkey species,sexes,and age groups.This research provides valuable re-sources for NHP researchers and sets the stage for further exploring the impacts of sex and age on NHP physiology and immune function.展开更多
This editorial critically analyses the recent article by Jung et al,which investigates the utility of 4-hour serum amylase and lipase as early blood markers for postendoscopic retrograde cholangiopancreatography(ERCP)...This editorial critically analyses the recent article by Jung et al,which investigates the utility of 4-hour serum amylase and lipase as early blood markers for postendoscopic retrograde cholangiopancreatography(ERCP)acute pancreatitis prediction.Although these enzymes are valuable for the early diagnosis of post-ERCP pancreatitis,they lack specificity for disease etiology and provide limited insight into the molecular mechanisms underlying disease progression.Several cytokines,notably interleukin(IL)-6,tumor necrosis factor-alpha,and IL-8,are increased in post-ERCP pancreatitis and may serve as potential predictors for disease severity.The incorporation of these biomarkers in early enzymatic biomarkers and established prognostic scoring systems could further enhance their accuracy and allow for earlier,more effective management of patients with post-ERCP pancreatitis.展开更多
Gastric carcinoma(GC)is one of the most common and deadly cancers worldwide,ranking fifth in incidence and third in cancer-related mortality.Despite significant advancements in surgical techniques and chemotherapy,the...Gastric carcinoma(GC)is one of the most common and deadly cancers worldwide,ranking fifth in incidence and third in cancer-related mortality.Despite significant advancements in surgical techniques and chemotherapy,the overall prognosis for GC remains poor,primarily due to late-stage diagnosis.Current diagnostic tools,such as endoscopy and biopsy,are invasive and are often utilized only after symptoms arise,leading to missed opportunities for early intervention.Traditional serum tumour markers,such as carcinoembryonic antigen and carbohydrate antigen 19-9,demonstrate limited sensitivity and specificity,particularly in the disease's early stages.GC often diagnosed at advanced stages due to a lack of early,specific biomarkers.Chronic inflammation plays a significant role in gastric carcinogenesis,particularly in cases of Helicobacter pylori-associated gastritis.Pro-inflammatory cytokines have gained attention as potential noninvasive serum biomarkers for early diagnosis and disease monitoring.In recent years,numerous studies have explored the potential of serum cytokines-such as interleukin(IL)-6,tumour necrosis factor-alpha,IL-8 and interferon-gamma-as biomarkers for detecting gastric cancer.Future research integrating cytokine profiling with imaging,endoscopic,or genomic data may revolutionize how we screen and manage GC.展开更多
Chemoresistance remains a major challenge in non-small cell lung cancer,especially for cisplatin(DDP)-based therapies,which are a mainstay of treatment.In their study,Dai et al investigate how inflammatory cytokines w...Chemoresistance remains a major challenge in non-small cell lung cancer,especially for cisplatin(DDP)-based therapies,which are a mainstay of treatment.In their study,Dai et al investigate how inflammatory cytokines within the tumor microenvironment contribute to DDP resistance.By analyzing tumor samples from 20 non-small cell lung cancer patients and two resistant cell lines(A549/DDP and SK-MES-1/DDP),the authors show that increased levels of interleukin(IL)-6,IL-8,and tumor necrosis factor-αare linked to resistance.Logistic regression identifies IL-6 and IL-8 as key risk factors.Functional experiments using tocilizumab,an IL-6 receptor antagonist,demonstrate a reduction in DDP half maximum inhibitory concentration,higher apoptosis rates,and decreased migration and invasion in resistant cells.Although the study has certain limitations,such as the analysis of only five inflammatory cytokines in a small,non-stratified patient cohort;it demonstrates that targeting the IL-6 cytokine axis may help overcome DDP resistance.Overall,the study highlights the inflammatory component of the tumor microenvironment as a modifiable driver of chemoresistance and provide a rationale for integrating cytokine blockade into platinum-based chemotherapy regimens to enhance therapeutic response.展开更多
BACKGROUND Cancer-induced incomplete bowel obstruction presents numerous clinical cha-llenges,notably pain management and inflammation control.Conventional thera-pies provide limited relief,prompting investigation int...BACKGROUND Cancer-induced incomplete bowel obstruction presents numerous clinical cha-llenges,notably pain management and inflammation control.Conventional thera-pies provide limited relief,prompting investigation into complementary approa-ches.This study compares the efficacy of bottle gourd moxibustion combined with umbilical therapy(BGM-UT)plus standard palliative care vs standard Wes-tern palliative care alone in symptom alleviation and inflammation reduction.AIM To compare the efficacy of BGM-UT plus standard palliative care vs standard pa-lliative care alone in reducing inflammatory cytokine levels,alleviating symp-toms,and improving gastrointestinal recovery in cancer-induced incomplete bowel obstruction.METHODS A retrospective analysis was conducted on 109 patients aged 18-75 years with cancer-induced incomplete bowel obstruction treated at the Foshan Hospital of Traditional Chinese Medicine between October 2023 and September 2024.The participants were categorized into two groups:(1)Regular group receiving stan-dard palliative care;and(2)BGM-UT group receiving additional moxibustion therapy.The inclusion criteria included ongoing opioid use and a Karnofsky per-formance status score below 60.The treatments were evaluated for 3 weeks in terms of opioid consumption,gastrointestinal function recovery,brief pain inven-tory scores,traditional Chinese medicine symptom scores,and inflammatory cytokine levels.RESULTS Initially,the groups were demographically and clinically comparable.Post-treatment,the BGM-UT group showed significant reductions in opioid intake(P=0.027),improved gastrointestinal recovery times,and enhanced pain management as reflected by their lower brief pain inventory scores(P<0.05).Similarly,the improvement in traditional Chinese medicine scores was greater in the BGM-UT group than in the regular group(P<0.05).Inflam-matory markers including interleukin-6,tumor necrosis factor-α,and C-reactive protein decreased significantly in the BGM-UT group,indicating the superior anti-inflammatory effects of this treatment(P<0.05).CONCLUSION The addition of BGM-UT to standard palliative care enhances pain relief,accelerates gastrointestinal recovery,and effectively reduces inflammatory cytokine levels in patients with cancer-induced incomplete bowel obstruction.This combination therapy offers a promising complementary approach to managing this challenging condition.Further prospective studies are warranted to validate these findings and explore underlying mechanisms.展开更多
While viral infections can disturb the host gut microbiome,the dynamic alterations in microbial composition following infection remain poorly characterized.This study identified SRV-8-infected monkeys and classified t...While viral infections can disturb the host gut microbiome,the dynamic alterations in microbial composition following infection remain poorly characterized.This study identified SRV-8-infected monkeys and classified them into five groups based on infection progression.16S rRNA amplicon sequencing revealed significant alterations in the relative and inferred absolute abundance of bacterial genera UCG-002,Agathobacter,Coprococcus,and Holdemanella during the early stage of SRV-8 infection,coinciding with provirus formation.These microbial shifts were accompanied by functional modifications in bacterial communities at the same stage.In contrast,ITS amplicon sequencing indicated no significant differences in fungal composition between healthy wild-type and SRV-8-infected monkeys.Spearman correlation analyses demonstrated close interactions between intestinal bacteria and fungi following SRV-8 infection.Additionally,SRV-8 seropositive groups exhibited significantly elevated mRNA expression levels of pro-inflammatory(TNF-α,IFN-γ,IL-1β,and IL-6)and anti-inflammatory(IL-10)cytokine genes,highlighting close associations between inflammatory cytokines and immune responses.Overall,these findings provide a comprehensive characterization of bacterial and fungal microbiota dynamics and inflammatory cytokine responses associated with SRV-8 infection,clarifying the pathobiological mechanisms underlying SRV-8 infection from the perspective of the gut microbiome.展开更多
Anti-inflammatory activity ofRubus idaeus L. and possible mechanisms involved were explored in lipopolysaccharide （LPS）-treated RAW 264.7 cells. The effects of ethanol extract of R. idaeus on the levels of pro-infla...Anti-inflammatory activity ofRubus idaeus L. and possible mechanisms involved were explored in lipopolysaccharide （LPS）-treated RAW 264.7 cells. The effects of ethanol extract of R. idaeus on the levels of pro-inflammatory cytokines, including tumor necrosis factor-alfa （TNF-α）, interleukin-6 （IL-6） and interleukin-1 beta （IL-1β）, as well as pro-inflammatory mediators, such as nitric oxide （NO）, inducible nitric oxide synthase （iNOS） and cyclooxygenase-2 （COX-2） were studied by Sandwich ELISA, real-time PCR, and Western blot analysis. Moreover, the effects of ethanol extract of R. idaeus on anti-inflammatory cytokine interleukin-10 （IL-10） and anti-inflammatory mediator heme oxygenase-1 （HO-1） were also investigated using the same methods. Furthermore, nuclear factor-gB （NF-κB） level was assayed by immunocytochemistry. The results showed that the production of IL-1β, IL-6, NO, TNF-α and COX-2 in LPS-treated cells could be significantly inhibited （P〈0.01 or P〈0.05） by ethanol extract ofR. idaeus compared with that in the cells treated with LPS only. Meanwhile, the production of NF-r,B was also inhibited by the extract. Based on these results, the anti-inflammatory activity ofR. idaeus was attributed to the down-regulation of IL-6, IL-1β and TNF-α levels as well as gene expression of iNOS and COX-2 through the suppression of NF-κB activation, and induction of anti-inflammatory cytokine IL- 10 and anti-inflammatory mediator HO- 1.展开更多
Inflammatory events occurring in the distal part of an injured peripheral nerve have, nowadays, a great resonance. Investigating the timing of action of the several cytokines in the important stages of Wallerian degen...Inflammatory events occurring in the distal part of an injured peripheral nerve have, nowadays, a great resonance. Investigating the timing of action of the several cytokines in the important stages of Wallerian degeneration helps to understand the regenerative process and design pharmacologic intervention that promotes and expedites recovery. The complex and synergistic action of inflammatory cytokines finally promotes axonal regeneration. Cytokines can be divided into pro- and anti-inflammatory cytokines that upregulate and downregulate, respectively, the production of inflammatory mediators. While pro-inflammatory cytokines are expressed in the first phase of Wallerian degeneration and promote the recruitment of macrophages, anti-inflammatory cytokines are expressed after this recruitment and downregulate the production of all cytokines, thus determining the end of the process. In this review, we describe the major inflammatory cytokines involved in Wallerian degeneration and the early phases of nerve regeneration. In particular, we focus on interleukin-1, interleukin-2, interleukin-6, tumor necrosis factor-β, interleukin-10 and transforming growth factor-β.展开更多
基金supported by the STI2030-Major Projects(2021ZD0200600)the National Natural Science Foundation of China(81971269).
文摘In recent years,the field of neuroimmunology has witnessed a profound paradigm shift.Research has expanded beyond the traditional focus on the central nervous system to unravel the dynamic interplay between peripheral immunity and neural networks.Cutting-edge methodologies have unmasked a tripartite communication axis enabling peripheral immune signals to mediate the CNS:(1)neural communication via vagal afferents,(2)humoral signaling through circumventricular organ cytokine diffusion,and(3)cellular interactions involving bone marrow-derived macrophages[1].
基金supported by the Natural Science Foundation of Hunan Province (2022JJ30987)the Key Research and Development Project of Hunan Province (2024JK2107),China。
文摘Objective:The incidence and mortality of colorectal carcinoma(CRC)continue to rise globally,highlighting the need to identify modifiable risk factors for early detection and prevention.Previous studies have demonstrated significant associations between CRC risk and various serum metabolites as well as inflammatory cytokines;however,due to limitations in study design and potential confounding factors,the causal relationships remain unclear.This study aims to investigate the causal relationships between inflammatory cytokines,serum metabolites,and CRC risk,providing a theoretical basis for the development of novel early diagnostic biomarkers and therapeutic targets.Methods:A two-sample Mendelian randomization(MR)design was applied using summary statistics from genome-wide association studies(GWAS).Instrumental variables(IVs)were derived from:1)metabolomics GWAS data of 1400 serum metabolites(n=8299);2)cytokine GWAS data of 91 inflammatory factors(n=14824);and 3)CRC risk data from the FinnGen consortium(6847 cases and 314193 controls).The primary analysis was conducted using the inverse-variance weighted(IVW)method,with sensitivity analyses performed using MR Egger regression and the weighted median method.Effect estimates including odds ratios(OR),95%confidence intervals(CI),and false discovery rates(FDR)were calculated.Results:MR analysis indicated that higher levels of axin-1(AXIN1)(OR=0.84195%CI 0.714 to 0.991)and Fms-related tyrosine kinase 3 ligand(Flt3L)(OR=0.916,95%CI 0.844 to 0.994)were associated with a reduced risk of CRC.In contrast,higher levels of Delta/Notchlike epidermal growth factor-related receptor(DNER)(OR=1.119,95%CI 1.009 to 1.241)and vascular endothelial growth factor A(VEGF-A)(OR=1.078,95%CI 1.011 to 1.150)were associated with an increased risk of CRC(all P<0.05).Metabolomics association analysis further identified 144 serum metabolites significantly correlated with these four key inflammatory cytokines(FDR<0.05),suggesting that they may regulate CRC risk through inflammatory pathways.Conclusion:Specific inflammatory cytokines and serum metabolites have causal relationships with the risk of CRC.These findings provide insights for further exploration of potential risk factors and the development of effective prevention strategies for CRC.
文摘Objective Sepsis patients exhibit diverse immune states,making it crucial to identify subtypes with distinct inflammatory profiles through Th1/Th2 cytokine data for personalized treatment and improved prognosis.Methods We retrieved data from sepsis patients who underwent Th1/Th2 cytokine testing in Nanfang Hospital,Southern Medical University from June 1,2020,to February 1,2022.An unsupervised K-means clustering method classified participants based on Th1/Th2 cytokine levels,with the primary outcome being the 7-day mortality rate post-ICU admission.Cox proportional hazards and Restricted Mean Survival Time(RMST)analyses were utilized to explore survival outcomes.Results A total of 321 sepsis patients were included.IL-6(HR 1.69,95%CI:1.22,2.34)and IL-10(HR 1.81,95%CI:1.37,2.40)emerged as independent predictors of 7-day mortality.Unsupervised K-means clustering revealed 3 inflammatory/immune subgroups:Cluster 1(n=166,low inflammatory response),Cluster 2(n=99,moderate inflammatory response with immune suppression),and Cluster 3(n=56,strong inflammatory and immune suppression).Compared to Cluster 1,Clusters 2 and 3 had higher 7-day mortality risks(14.4%vs 23.2%,HR=4.30,95%CI:1.51-12.26;14.4%vs 35.7%,HR=7.32,95%CI:2.57-20.79).Conclusion Septic patients in a protective immune response state(Cluster 1)exhibit better short-term prognoses,suggesting the importance of understanding inflammatory/immune states for precise treatment and improved outcomes.
基金partly funded by APIS-GENEsupported by a grant Bonus QualitéRecherche(BQR)s from ENVT。
文摘Background Sphingolipids(SL)are key regulators of inflammatory processes,yet their roles in dairy cows remain poorly understood.This study investigated the effects of inflammation(plasma haptoglobin concentration),ketosis,and mastitis on plasma SL profiles in Holstein cows sampled seven days postpartum.From a cohort of 427 cows across 25 farms,80 animals were classified into four groups:inflammation(n=20),ketosis(n=19),mastitis(n=21),and healthy controls(n=20).Plasma SL were quantified by targeted HPLC-MS/MS,while cytokines were quantified with a 15-plex bead-based assay.Both univariate and multivariate analyses were applied to assess pathological effects,along with SL ratios and correlations between SL and cytokines.Results Systemic inflammation detected through the haptoglobin measure induced the most pronounced alterations in SL metabolism,characterized by elevated dihydrosphingomyelins(DHSM)and lactosylceramides(Lac Cer),higher C22-24:C16 ratios,and lower unsaturated:saturated ratios in ceramides(Cer)and sphingomyelins(SM).Although total Cer,SM,and the Cer:SM ratio remained unchanged,specific reductions were observed in both Cer and SM in C14,Cer C18:1,SM C16:1,and SM C23:1,whereas SM C25:0 and C26:0 increased.Sphingosine-1-phosphate(So1P)was positively correlated with IL-10 as well as IL-1α and TNFα,while C18-20 Cer correlated positively with multiple pro-inflammatory cytokines and chemokines such as CXCL8 and CCL2.Ketosis induced subtler changes,primarily an increase in plasma DHSM and DHSM:SM ratio(driven by C16:0),an increase in C22-24:C16 DHCer ratio,and a decrease in both Lac So:Lac Cer and unsaturated:saturated ratios in C23-SM.In this group,So1P correlated positively with CXCL8 and CCL2.Moreover C18-20 Cer and DHCer were positively associated with CXCL8,CCL2,CCL3,and CCL4,which also showed correlations with most Lac Cer species.Analysis of chronic mastitis cases yielded a clear separation from controls in multivariate analysis but only minimal changes in SL concentrations and ratios,maybe due to the localized nature of the inflammatory response.Conclusions In summary,heightened inflammatory response in early post-partum is associated with the strongest systemic effects on SL metabolism,followed by ketosis,while mastitis induced only modest alterations.These findings highlight condition-specific patterns of SL regulation postpartum and suggest potential immunometabolic biomarkers of disease.
文摘AIM:To investigate the potential causal associations between 41 inflammatory cytokines and myopia using a two-sample Mendelian randomization(MR)approach.METHODS:Publicly available genome-wide association study(GWAS)datasets were utilized for this two-sample MR analysis.Inflammatory cytokine-related GWAS data were extracted from The University of Bristol’s Research Data Repository,and myopia-related GWAS data were obtained from the FinnGen project.Single nucleotide polymorphisms(SNPs)associated with inflammatory cytokines were systematically selected as instrumental variables(IVs)based on three rigorous criteria:relevance,independence,and exclusion of pleiotropy.Five MR methods were employed for causal inference:the inverse-variance weighted(IVW)method as the primary analysis,supplemented by MREgger regression,weighted median estimator,simple mode,and weighted mode approaches.Sensitivity analyses were performed to evaluate the robustness of the causal estimates.RESULTS:A total of 773 myopia-associated SNPs were identified.MR analysis revealed that higher levels of macrophage inflammatory protein 1-α(MIP-1α)were associated with a 17%reduced risk of myopia[odds ratio(OR)=0.83;95%confidence interval(CI):0.69-0.99;P<0.05].In contrast,elevated levels of eotaxin(OR=1.26;95%CI:1.07-1.47;P<0.01),stromal cell-derived factor-1α(SDF-1α;OR=1.68;95%CI:1.08-2.62;P<0.05),and interleukin-2 receptor subunit alpha(IL-2Rα;OR=1.25;95%CI:1.01-1.53;P<0.05)were significantly associated with an increased risk of myopia.Sensitivity analyses confirmed the reliability of these results.CONCLUSION:This study provides evidence supporting a causal relationship between specific inflammatory cytokines and myopia.MIP-1αmay act as a protective factor against myopia,while eotaxin,SDF-1α,and IL-2Rαare potential risk factors for myopia.These findings emphasize the critical role of inflammatory pathways in the pathogenesis of myopia,offering novel insights for the development of preventive and therapeutic strategies for myopia.
基金supported by the National Key Research and Development Program of China(2023YFC2308800)the Natural Science Foundation of Shanghai(25ZR1402053)the Key Discipline of Public Health of the Shanghai Municipal Health Commission(Grant No.GWVI-11.1-07).
文摘Objective The aim of this study was to analyze the correlation between the levels of 12 cytokines in the cervical microenvironment and cervical intraepithelial neoplasia in patients with high-risk human papillomavirus(HR-HPV)infection.Methods Female patients(n=73)with HR-HPV infection were enrolled and divided into a high-grade squamous intraepithelial lesion(HSIL)group(n=33)and a non-HSIL(N-HSIL)group(n=40),which include low-grade squamous intraepithelial lesions and inflammation.Healthy screening subjects(n=31)with negative HR-HPV results were enrolled as a control group.We examined contemporaneous plasma and secretory cytokines from 25 study subjects to investigate the difference between systemic cytokine profiles and the local microenvironment immunity using the Wilcoxon matched-pairs signed rank test.The 12 cytokines from cervical secretions were compared between the three groups using the Mann-Whitney test,and logistic regression was used to analyze HSIL and N-HSIL.Results There were statistical differences in eight cytokines(IL-2,IL-6,TNF-α,IFN-γ,IL-1β,IL-12p70,IFN-α,and IL-8)between cervical secretion and plasma of the same patient,and seven cytokines were statistically different between the control and other two groups.We selected four independent variables(TNF-α,IFN-γ,IL-12p70,and IFN-α)commonly identified by univariate regression analysis and non-parametric tests for multivariate logistic regression analysis.Based on this model,HSIL could be predicted in patients with HR-HPV infection,with the area under the curve being 0.76.Conclusion The systemic cytokine profile cannot reflect the local microenvironment immunity,and the occurrence of HSIL is related to the cytokine levels in the cervical microenvironment.
基金This study was supported by internal funds from Patanjali Research Foundation Trust,Haridwar,India。
文摘Background:Fever is characterized by an upregulation of the thermoregulatory set-point after the body encounters any pathological challenge.It is accompanied by uncomfortable sickness behaviors and may be harmful in patients with other comor-bidities.We have explored the impact of an Ayurvedic medicine,Fevogrit,in an endo-toxin(lipopolysaccharide)-induced fever model in Wistar rats.Methods:Active phytoconstituents of Fevogrit were identified and quantified using ultra-high-performance liquid chromatography(UHPLC)platform.For the in-vivo study,fever was induced in male Wistar rats by the intraperitoneal administration of lipopolysaccharide(LPS),obtained from Escherichia coli.The animals were allocated to normal control,disease control,Paracetamol treated and Fevogrit treated groups.The rectal temperature of animals was recorded at different time points using a digital thermometer.At the 6-h time point,levels of TNF-α,IL-1βand IL-6 cytokines were analyzed in serum.Additionally,the mRNA expression of these cytokines was deter-mined in hypothalamus,24 h post-LPS administration.Results:UHPLC analysis of Fevogrit revealed the presence of picroside I,picroside II,vanillic acid,cinnamic acid,magnoflorine and cordifolioside A,as bioactive constitu-ents with known anti-inflammatory properties.Fevogrit treatment efficiently reduces the LPS-induced rise in the rectal temperature of animals.The levels and gene ex-pression of TNF-α,IL-1βand IL-6 in serum and hypothalamus,respectively,was also significantly reduced by Fevogrit treatment.Conclusion:The findings of the study demonstrated that Fevogrit can suppress LPS-induced fever by inhibiting peripheral or central inflammatory signaling pathways and could well be a viable treatment for infection-induced increase in body temperatures.
基金suppor ted by the US Depar tment of Defense Congressionally Directed Medical Research Program (CDMRP)awards (http://cdmrp.army.mil/) W81XWH-16-1-0632 (Craddock PI),W81XWH-16-1-0552 (Craddock PI),W81XWH-18-1-0549 (Sullivan PI),W81XWH-13-2-0072 (Sullivan PI),and W81XWH-09-2-0071 (Klimas PI)a Veterans Affairs Merit Award (4987.69) to Dr.Nancy Klimas。
文摘Background:One-third of veterans returning from the 1990–1991 Gulf War reported a myriad of symptoms including cognitive dysfunction,skin rashes,musculoskeletal discomfort,and fatigue.This symptom cluster is now referred to as Gulf War Illness(GWI).As the underlying mechanisms of GWI have yet to be fully elucidated,diagnosis and treatment are based on symptomatic presentation.One confounding factor tied to the illness is the high presence of post-traumatic stress disorder(PTSD).Previous research efforts have demonstrated that both GWI and PTSD are associated with immunological dysfunction.As such,this research endeavor aimed to provide insight into the complex relationship between GWI symptoms,cytokine presence,and immune cell populations to pinpoint the impact of PTSD on these measures in GWI.Methods:Symptom measures were gathered through the Multidimensional fatigue inventory(MFI)and 36-item short form health survey(SF-36)scales and biological measures were obtained through cytokine&cytometry analysis.Subgrouping was conducted using Davidson Trauma Scale scores and the Structured Clinical Interview for Diagnostic and statistical manual of mental disorders(DSM)-5,into GWI with high probability of PTSD symptoms(GWIH)and GWI with low probability of PTSD symptoms(GWIL).Data was analyzed using analysis of variance(ANOVA)statistical analysis along with correlation graph analysis.We mapped correlations between immune cells and cytokine signaling measures,hormones and GWI symptom measures to identify patterns in regulation between the GWIH,GWIL,and healthy control groups.Results:GWI with comorbid PTSD symptoms resulted in poorer health outcomes compared with both healthy control(HC)and the GWIL subgroup.Significant differences were found in basophil levels of GWI compared with HC at peak exercise regardless of PTSD symptom comorbidity(ANOVA F=4.7,P=0.01)indicating its potential usage as a biomarker for general GWI from control.While the unique identification of GWI with PTSD symptoms was less clear,the GWIL subgroup was found to be delineated from both GWIH and HC on measures of IL-15 across an exercise challenge(ANOVA F>3.75,P<0.03).Additional differences in natural killer(NK)cell numbers and function highlight IL-15 as a potential biomarker of GWI in the absence of PTSD symptoms.Conclusions:We conclude that disentangling GWI and PTSD by defining trauma-based subgroups may aid in the identification of unique GWI biosignatures that can help to improve diagnosis and target treatment of GWI more effectively.
基金supported by the National Natural Science Foundation of China(32125038 and 32402957)China National Postdoctoral Program for Innovative Talents(BX20240417)+1 种基金China Postdoctoral Science Foundation funded project(2024M753563)National Key Research and Development Program of China(2023YFD1801100).
文摘Background Changes in macrophage function are crucial contributors to hepatic inflammation and fibrosis.However,the role of macrophages in the development of liver fibrosis in dairy cows with ketosis remains unclear.This study integrated proteomics and cytokine array approach to identify the multifactorial and multicellular interaction effects driving liver fibrosis in dairy cows with ketosis and analyze the mechanism by which the proinflammatory shift in macrophages contributes to liver fibrosis.Results Histopathological analysis revealed liver injury,including severe steatosis,infiltration of inflammatory cells,an increase in lipid deposition,and a decrease in glycogen expression in ketotic cows.Moreover,the number of mitochondria considerably increased in hepatocytes.The activation of the dynamin-related protein 1/mitochondrial fission factor(DRP1/MFF)pathway induced excessive mitochondrial fission,and the inhibition of the nuclear factor erythroid 2-related factor 2/heme oxygenase 1(Nrf2/HO-1)pathway led to the accumulation of intracellular reactive oxygen species(ROS).Proteomic analysis revealed the activation of extracellular matrix(ECM)-related functions and the NF-κB pathway in the liver,whereas cytokine array analysis revealed that the cytokine network was dysregulated.The accumulation of ROS triggered NF-κB nuclear translocation,inducing a proinflammatory shift in macrophages and liver inflammation.M1 polarization of macrophages promotes the release of proinflammatory mediators,which stimulated hepatic stellate cells(HSCs)activation,leading to ECM deposition,ultimately contributing to liver fibrosis.Conclusions To summarize,our study revealed the multifactorial and multicellular interaction effects driving liver fibrosis.Our results preliminarily showed that increased mitochondrial fission and inhibition of the Nrf2/HO-1 pathway are key factors in activating macrophages,which can lead to liver fibrosis in dairy cows with ketosis.
基金Supported by Wu Jieping Medical Foundation,No.320.6750.2021-06-30Guangdong Basic and Applied Basic Research Foundation,No.2019A1515110120National Natural Science Foundation of China,No.82002974。
文摘BACKGROUND Liver hepatocellular carcinoma(LIHC)is a highly aggressive cancer with poor prognosis due to its complex tumor microenvironment(TME)and immune evasion.Regulatory T cells(Tregs)play a critical role in tumor progression.Suppressor of cytokine signaling 2(SOCS2),a key immune regulator,may modulate Treg activity and impact LIHC growth and metastasis.AIM To explore how the SOCS2 affects Treg activity in LIHC and its impact on tumor growth and metastasis.METHODS LIHC transcriptome data from The Cancer Genome Atlas database were analyzed using Gene Set Enrichment Analysis,Estimation of Stromal and Immune Cells in Malignant Tumors Using Expression Data,and Cell-Type Identification by Estimating Relative Subsets of RNA Transcripts to evaluate immune pathways and Treg infiltration.Key prognostic genes were identified using Weighted Gene Coexpression Network Analysis and machine learning.In vitro,co-culture experiments,migration assays,apoptosis detection,and enzyme-linked immunosorbent assay were conducted.In vivo,tumor growth,metastasis,and apoptosis were assessed using subcutaneous and lung metastasis mouse models with hematoxylin and eosin staining,Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling,and immunohistochemistry analyses.RESULTS SOCS2 overexpression inhibited Treg cell activity,reducing LIHC cell migration and invasion while increasing apoptosis.In vivo,SOCS2 suppressed tumor growth and metastasis,confirming its therapeutic potential.CONCLUSION SOCS2 modulates CD4+T function in the TME,contributing to LIHC progression.Targeting SOCS2 presents a potential therapeutic strategy for treating LIHC.
文摘BACKGROUND Multiple lines of evidence have indicated that pro-inflammatory cytokines play a role in the pathophysiology of gastric carcinoma(GC).AIM To identify potential serum cytokine-based biomarkers for GC diagnosis.METHODS The study cohort comprised 50 patients diagnosed with GC and 50 healthy control subjects.A panel of 7 pro-inflammatory cytokines,including interleukin(IL)-1β,IL-2,IL-6,IL-8,IL-12,tumor necrosis factor-α,and interferon-γ(IFN-γ)were quantified using multiplex Luminex assays.Comparative analyses were conducted to evaluate cytokine levels between the GC patients and healthy controls.The diagnostic potential of serum pro-inflammatory cytokines in differentiating GC patients from healthy individuals was assessed through receiver operating characteristic(ROC)curve analysis.The correlation between serum cytokine levels and disease severity,as classified by the tumor-node-metastasis staging system,was analyzed using Spearman's rank correlation coefficient.RESULTS In comparison to the control group,patients with GC demonstrated significantly elevated serum levels of IL-1β(t=-4.089,P<0.001),IL-6(t=-3.983,P<0.001),IL8(t=-5.460,P<0.001),and IFN-γ(t=-2.856,P=0.005).ROC curve analysis indicated that the area under the curve values for IL-1β,IL-6,and IL-8 exceeded 0.7,effectively distinguishing GC patients from healthy controls.Additionally,serum levels of IL-1β(r=0.424,P=0.012)and IL-6(r=0.742,P<0.001)were positively correlated with the T stage in GC patients.Similarly,serum concentrations of IL-1β(r=0.356,P=0.039)and IL-6(r=0.441,P=0.008)exhibited a positive association with the N stage in these patients.CONCLUSION These findings suggest that circulating pro-inflammatory cytokines,such as IL-1β,IL-6,and IL-8,may serve as potential biomarkers for the diagnosis of GC.
基金National Resources Center for Non Human PrimatesNational Key R&D Project of China,Grant/Award Number:2021YFF0702804。
文摘Background:Non-human primates(NPHs),such as rhesus macaques,cynomol-gus monkeys,and Assamese macaques,play a crucial role in biomedical research.However,baseline cytokine and electrolyte data for these three species,particularly data stratified by age and sex,are limited.Therefore,the aim of this study was to establish and analyze age-and sex-specific cytokine and electrolyte profiles in these three species.Methods:This study included 40 rhesus macaques(21 males,19 females),33 cyn-omolgus monkeys(17 males,16 females),and 45 Assamese macaques(25 males,20 females)classified by age(1-5 years,6-12 years,>13 years)and sex.The levels of 23 immune function indicators and 5 electrolyte indicators were measured.Results:Among the three monkey species,the levels of sCD40L,IL-18,MCP-1,MIP-1β,TGFa,K^(+),Na^(+),and Cl^(-)exhibited species-,sex-,and age-related differences.Comparison within the same species,sex had no significant impact on cytokine levels in NHPs but did affect electrolyte levels,particularly Cl^(-)and Na^(+)levels,in cynomol-gus monkeys and Assamese macaques.Electrolyte levels in NHPs were not affected by age,whereas the levels of certain cytokines,particularly sCD40L,GM-CSF,and IL-10,varied with age.The remaining 21 cytokines demonstrated no significant age-related changes.Conclusions:Significant variations in cytokine and electrolyte levels exist among dif-ferent monkey species,sexes,and age groups.This research provides valuable re-sources for NHP researchers and sets the stage for further exploring the impacts of sex and age on NHP physiology and immune function.
文摘This editorial critically analyses the recent article by Jung et al,which investigates the utility of 4-hour serum amylase and lipase as early blood markers for postendoscopic retrograde cholangiopancreatography(ERCP)acute pancreatitis prediction.Although these enzymes are valuable for the early diagnosis of post-ERCP pancreatitis,they lack specificity for disease etiology and provide limited insight into the molecular mechanisms underlying disease progression.Several cytokines,notably interleukin(IL)-6,tumor necrosis factor-alpha,and IL-8,are increased in post-ERCP pancreatitis and may serve as potential predictors for disease severity.The incorporation of these biomarkers in early enzymatic biomarkers and established prognostic scoring systems could further enhance their accuracy and allow for earlier,more effective management of patients with post-ERCP pancreatitis.
文摘Gastric carcinoma(GC)is one of the most common and deadly cancers worldwide,ranking fifth in incidence and third in cancer-related mortality.Despite significant advancements in surgical techniques and chemotherapy,the overall prognosis for GC remains poor,primarily due to late-stage diagnosis.Current diagnostic tools,such as endoscopy and biopsy,are invasive and are often utilized only after symptoms arise,leading to missed opportunities for early intervention.Traditional serum tumour markers,such as carcinoembryonic antigen and carbohydrate antigen 19-9,demonstrate limited sensitivity and specificity,particularly in the disease's early stages.GC often diagnosed at advanced stages due to a lack of early,specific biomarkers.Chronic inflammation plays a significant role in gastric carcinogenesis,particularly in cases of Helicobacter pylori-associated gastritis.Pro-inflammatory cytokines have gained attention as potential noninvasive serum biomarkers for early diagnosis and disease monitoring.In recent years,numerous studies have explored the potential of serum cytokines-such as interleukin(IL)-6,tumour necrosis factor-alpha,IL-8 and interferon-gamma-as biomarkers for detecting gastric cancer.Future research integrating cytokine profiling with imaging,endoscopic,or genomic data may revolutionize how we screen and manage GC.
文摘Chemoresistance remains a major challenge in non-small cell lung cancer,especially for cisplatin(DDP)-based therapies,which are a mainstay of treatment.In their study,Dai et al investigate how inflammatory cytokines within the tumor microenvironment contribute to DDP resistance.By analyzing tumor samples from 20 non-small cell lung cancer patients and two resistant cell lines(A549/DDP and SK-MES-1/DDP),the authors show that increased levels of interleukin(IL)-6,IL-8,and tumor necrosis factor-αare linked to resistance.Logistic regression identifies IL-6 and IL-8 as key risk factors.Functional experiments using tocilizumab,an IL-6 receptor antagonist,demonstrate a reduction in DDP half maximum inhibitory concentration,higher apoptosis rates,and decreased migration and invasion in resistant cells.Although the study has certain limitations,such as the analysis of only five inflammatory cytokines in a small,non-stratified patient cohort;it demonstrates that targeting the IL-6 cytokine axis may help overcome DDP resistance.Overall,the study highlights the inflammatory component of the tumor microenvironment as a modifiable driver of chemoresistance and provide a rationale for integrating cytokine blockade into platinum-based chemotherapy regimens to enhance therapeutic response.
基金Supported by Medical Research Project of Foshan Health Bureau in 2024,No.20240243.
文摘BACKGROUND Cancer-induced incomplete bowel obstruction presents numerous clinical cha-llenges,notably pain management and inflammation control.Conventional thera-pies provide limited relief,prompting investigation into complementary approa-ches.This study compares the efficacy of bottle gourd moxibustion combined with umbilical therapy(BGM-UT)plus standard palliative care vs standard Wes-tern palliative care alone in symptom alleviation and inflammation reduction.AIM To compare the efficacy of BGM-UT plus standard palliative care vs standard pa-lliative care alone in reducing inflammatory cytokine levels,alleviating symp-toms,and improving gastrointestinal recovery in cancer-induced incomplete bowel obstruction.METHODS A retrospective analysis was conducted on 109 patients aged 18-75 years with cancer-induced incomplete bowel obstruction treated at the Foshan Hospital of Traditional Chinese Medicine between October 2023 and September 2024.The participants were categorized into two groups:(1)Regular group receiving stan-dard palliative care;and(2)BGM-UT group receiving additional moxibustion therapy.The inclusion criteria included ongoing opioid use and a Karnofsky per-formance status score below 60.The treatments were evaluated for 3 weeks in terms of opioid consumption,gastrointestinal function recovery,brief pain inven-tory scores,traditional Chinese medicine symptom scores,and inflammatory cytokine levels.RESULTS Initially,the groups were demographically and clinically comparable.Post-treatment,the BGM-UT group showed significant reductions in opioid intake(P=0.027),improved gastrointestinal recovery times,and enhanced pain management as reflected by their lower brief pain inventory scores(P<0.05).Similarly,the improvement in traditional Chinese medicine scores was greater in the BGM-UT group than in the regular group(P<0.05).Inflam-matory markers including interleukin-6,tumor necrosis factor-α,and C-reactive protein decreased significantly in the BGM-UT group,indicating the superior anti-inflammatory effects of this treatment(P<0.05).CONCLUSION The addition of BGM-UT to standard palliative care enhances pain relief,accelerates gastrointestinal recovery,and effectively reduces inflammatory cytokine levels in patients with cancer-induced incomplete bowel obstruction.This combination therapy offers a promising complementary approach to managing this challenging condition.Further prospective studies are warranted to validate these findings and explore underlying mechanisms.
基金supported by the National Science and Technology Innovation 2030 Major Program(2021ZD0200900)National Key Research and Development Program of China(2022YFF0710901)+3 种基金National Natural Science Foundation of China(82021001,31825018)Biological Resources Program of the Chinese Academy of Sciences(KFJBRP-005)111 Project D18007a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)。
文摘While viral infections can disturb the host gut microbiome,the dynamic alterations in microbial composition following infection remain poorly characterized.This study identified SRV-8-infected monkeys and classified them into five groups based on infection progression.16S rRNA amplicon sequencing revealed significant alterations in the relative and inferred absolute abundance of bacterial genera UCG-002,Agathobacter,Coprococcus,and Holdemanella during the early stage of SRV-8 infection,coinciding with provirus formation.These microbial shifts were accompanied by functional modifications in bacterial communities at the same stage.In contrast,ITS amplicon sequencing indicated no significant differences in fungal composition between healthy wild-type and SRV-8-infected monkeys.Spearman correlation analyses demonstrated close interactions between intestinal bacteria and fungi following SRV-8 infection.Additionally,SRV-8 seropositive groups exhibited significantly elevated mRNA expression levels of pro-inflammatory(TNF-α,IFN-γ,IL-1β,and IL-6)and anti-inflammatory(IL-10)cytokine genes,highlighting close associations between inflammatory cytokines and immune responses.Overall,these findings provide a comprehensive characterization of bacterial and fungal microbiota dynamics and inflammatory cytokine responses associated with SRV-8 infection,clarifying the pathobiological mechanisms underlying SRV-8 infection from the perspective of the gut microbiome.
文摘Anti-inflammatory activity ofRubus idaeus L. and possible mechanisms involved were explored in lipopolysaccharide （LPS）-treated RAW 264.7 cells. The effects of ethanol extract of R. idaeus on the levels of pro-inflammatory cytokines, including tumor necrosis factor-alfa （TNF-α）, interleukin-6 （IL-6） and interleukin-1 beta （IL-1β）, as well as pro-inflammatory mediators, such as nitric oxide （NO）, inducible nitric oxide synthase （iNOS） and cyclooxygenase-2 （COX-2） were studied by Sandwich ELISA, real-time PCR, and Western blot analysis. Moreover, the effects of ethanol extract of R. idaeus on anti-inflammatory cytokine interleukin-10 （IL-10） and anti-inflammatory mediator heme oxygenase-1 （HO-1） were also investigated using the same methods. Furthermore, nuclear factor-gB （NF-κB） level was assayed by immunocytochemistry. The results showed that the production of IL-1β, IL-6, NO, TNF-α and COX-2 in LPS-treated cells could be significantly inhibited （P〈0.01 or P〈0.05） by ethanol extract ofR. idaeus compared with that in the cells treated with LPS only. Meanwhile, the production of NF-r,B was also inhibited by the extract. Based on these results, the anti-inflammatory activity ofR. idaeus was attributed to the down-regulation of IL-6, IL-1β and TNF-α levels as well as gene expression of iNOS and COX-2 through the suppression of NF-κB activation, and induction of anti-inflammatory cytokine IL- 10 and anti-inflammatory mediator HO- 1.
基金supported by Regione Piemonte founding(RSF-4097-2009)
文摘Inflammatory events occurring in the distal part of an injured peripheral nerve have, nowadays, a great resonance. Investigating the timing of action of the several cytokines in the important stages of Wallerian degeneration helps to understand the regenerative process and design pharmacologic intervention that promotes and expedites recovery. The complex and synergistic action of inflammatory cytokines finally promotes axonal regeneration. Cytokines can be divided into pro- and anti-inflammatory cytokines that upregulate and downregulate, respectively, the production of inflammatory mediators. While pro-inflammatory cytokines are expressed in the first phase of Wallerian degeneration and promote the recruitment of macrophages, anti-inflammatory cytokines are expressed after this recruitment and downregulate the production of all cytokines, thus determining the end of the process. In this review, we describe the major inflammatory cytokines involved in Wallerian degeneration and the early phases of nerve regeneration. In particular, we focus on interleukin-1, interleukin-2, interleukin-6, tumor necrosis factor-β, interleukin-10 and transforming growth factor-β.
