Interleukin-1β:Friend or foe for gastrointestinal cancers

Gastrointestinal(GI)cancer is a malignancy arising in the digestive system and accounts for approximately a third of increasing global cancer-related mortality,especially in the colorectum,esophagus,stomach,and liver.Interleukin-1β(IL-1β)is a leukocytic pyrogen recognized as a tumor progression-related cytokine.IL-1βsecretion and maturation in inflammatory responses could be regulated by nuclear factor-kappaB-dependent expression of NLR family pyrin domain containing 3,inflammasome formation,and activation of IL-1 converting enzyme.Several studies have documented the pro-tumorigenic effects of IL-1β in tumor microenvironments,promoting proliferation and metastatic potential of cancer cells in vitro and tumorigenesis in vivo.The application of IL-1β inhibitors is also promising for targeted therapy development in some cancer types.However,as a leukocytic pro-inflammatory cytokine,IL-1β may also possess anti-tumorigenic effects and be type-specific in different cancers.This editorial discusses the up-to-date roles of IL-1β in GI cancers,including underlying mechanisms and down-stream signaling pathways.Understanding and clarifying the roles of IL-1β would significantly benefit future therapeutic targeting and help improve therapeutic outcomes in patients suffering from GI cancer.

Low interleukin-10 level indicates a good prognosis in Salmonella enterica serovar typhimurium-induced pediatric hemophagocytic lymphohistiocytosis:A case report

BACKGROUND Secondary hemophagocytic lymphohistiocytosis(sHLH)triggered by Salmonella enterica serovar Typhimurium is rare in pediatric patients.There is no consensus on how to treat S.typhimurium-triggered sHLH.CASE SUMMARY A 9-year-old boy with intermittent fever for 3 d presented to our hospital with positive results for S.typhimurium,human rhinovirus,and Mycoplasma pneumoniae infections.At the time of admission to our institution,the patient’s T helper 1/T helper 2 cytokine levels were 326 pg/mL for interleukin 6(IL-6),9.1 pg/mL for IL-10,and 246.7 pg/mL for interferon-gamma(IFN-γ),for which the ratio of IL-10 to IFN-γwas 0.04.In this study,the patient received meropenem,linezolid,and cefoperazone/sulbactam in combination with high-dose methylprednisolone therapy(10 mg/kg/d for 3 d)and antishock supportive treatment twice.After careful evaluation,this patient did not receive HLH chemotherapy and recovered well.CONCLUSION S.Typhimurium infection-triggered sHLH patient had a ratio of IL-10 to IFN-γ≤1.33,an IL-10 concentration≤10.0 pg/mL,and/or an IFN-γconcentration≤225 pg/mL at admission.Early antimicrobial and supportive treatment was sufficient,and the HLH-94/2004 protocol was not necessary under these conditions.

Effects of interleukin-10 treated macrophages on bone marrow mesenchymal stem cells via signal transducer and activator of transcription 3 pathway

BACKGROUND Alveolar bone defects caused by inflammation are an urgent issue in oral implant surgery that must be solved.Regulating the various phenotypes of macrophages to enhance the inflammatory environment can significantly affect the progression of diseases and tissue engineering repair process.AIM To assess the influence of interleukin-10(IL-10)on the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)following their interaction with macrophages in an inflammatory environment.METHODS IL-10 modulates the differentiation of peritoneal macrophages in Wistar rats in an inflammatory environment.In this study,we investigated its impact on the proliferation,migration,and osteogenesis of BMSCs.The expression levels of signal transducer and activator of transcription 3(STAT3)and its activated form,phos-phorylated-STAT3,were examined in IL-10-stimulated macrophages.Subsequently,a specific STAT3 signaling inhibitor was used to impede STAT3 signal activation to further investigate the role of STAT3 signaling.RESULTS IL-10-stimulated macrophages underwent polarization to the M2 type through substitution,and these M2 macrophages actively facilitated the osteogenic differentiation of BMSCs.Mechanistically,STAT3 signaling plays a crucial role in the process by which IL-10 influences macrophages.Specifically,IL-10 stimulated the activation of the STAT3 signaling pathway and reduced the macrophage inflammatory response,as evidenced by its diminished impact on the osteogenic differentiation of BMSCs.CONCLUSION Stimulating macrophages with IL-10 proved effective in improving the inflammatory environment and promoting the osteogenic differentiation of BMSCs.The IL-10/STAT3 signaling pathway has emerged as a key regulator in the macrophage-mediated control of BMSCs’osteogenic differentiation.

Effect of flurbiprofen combined with prednisolone on interleukin-6 in elderly surgery patients

Objective: To determine the effect of flurbiprofen combined with prednisolone on interleukin-6 in elderly surgery patients. Methods: In this double-blind randomized controlled study, patients aged 65 to 80 who were undergoing spinal fusion surgery for disc herniation were administered flurbiprofen 100 mg (P group, flurbiprofen group), prednisolone 0.6 mg/kg (D group, prednisolone group), prednisolone 0.6 mg/kg plus flurbiprofen 100 mg (P + D group, flurbiprofen + prednisolone group) or normal saline (S group, saline group) 15 minutes before the induction of anesthesia. Plasma samples were collected before surgery (T0) and on day 1 (T1), day 2 (T2) and day 3 (T3) following surgery. At the same time, systemic inflammatory response syndrome (SIRS) was assessed by SIRS criteria. The levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) for collected samples were measured. Results: Other groups had significantly lower levels of IL-6, CRP and occurrence of SIRS than S group (p < 0.05). Compared to groups P and D, the levels of IL-6 and CRP in P + D group were significantly lower on T1 (p < 0.05). Peak levels of IL-6 in all groups were presented on T1 (p 0.05). The levels of CRP within three days were significantly different but did not show peak levels (p > 0.05). Conclusion: Compared to prednisolone or flurbiprofen, combining flurbiprofen with prednisolone in elderly surgery patients led to an increased suppression of IL-6.

Neutrophil-derived interleukin-17A participates in neuroinflammation induced by traumatic brain injury

After brain injury, infiltration and abnormal activation of neutrophils damages brain tissue and worsens inflammation, but the mediators that connect activated neutrophils with neuroinflammation have not yet been fully clarified. To identify regulators of neutrophil-mediated neuroinflammation after traumatic brain injury, a mouse model of traumatic brain injury was established by controlled cortical impact. At 7 days post-injury(sub-acute phase), genome-wide transcriptomic data showed that interleukin 17 A-associated signaling pathways were markedly upregulated, suggesting that interleukin 17 A may be involved in neuroinflammation. Double immunofluorescence staining showed that interleukin 17 A was largely secreted by neutrophils rather than by glial cells and neurons. Furthermore, nuclear factor-kappaB and Stat3, both of which are important effectors in interleukin 17 A-mediated proinflammatory responses, were significantly activated. Collectively, our findings suggest that neutrophil-derived interleukin 17 A participates in neutrophil-mediated neuroinflammation during the subacute phase of traumatic brain injury. Therefore, interleukin 17 A may be a promising therapeutic target for traumatic brain injury.

Interleukin-1:an important target for perinatal neuroprotection?

Perinatal inflammation is a significant risk factor for lifelong neurodevelopmental impairments such as cerebral palsy.Extensive clinical and preclinical evidence links the severity and pattern of perinatal inflammation to impaired maturation of white and grey matters and reduced brain growth.Multiple pathways are involved in the pathogenesis of perinatal inflammation.However,studies of human and experimental perinatal encephalopathy have demonstrated a strong causative link between perinatal encephalopathy and excessive production of the pro-inflammatory effector cytokine interleukin-1.In this review,we summarize clinical and preclinical evidence that underpins interleukin-1 as a critical factor in initiating and perpatuating systemic and central nervous system inflammation and subsequent perinatal brain injury.We also highlight the important role of endogenous interleukin-1 receptor antagonist in mitigating interleukin-1-driven neuroinflammation and tissue damage,and summarize outcomes from clinical and mechanistic animal studies that establish the commercially available interleukin-1 receptor antagonist,anakinra,as a safe and effective therapeutic intervention.We reflect on the evidence supporting clinical translation of interleukin-1 receptor antagonist for infants at the greatest risk of perinatal inflammation and impaired neurodevelopment,and suggest a path to advance interleukin-1 receptor antagonist along the translational path for perinatal neuroprotection.

Drug-induced entero-colitis due to interleukin-17 inhibitor use;capsule endoscopic findings and pathological characteristics:A case report

BACKGROUND Interleukin-17(IL-17)inhibitors are known to cause exacerbation or new onset of inflammatory bowel disease upon administration.However,few reports have described characteristic endoscopic and histopathologic findings,and no small intestinal lesions have been reported so far.CASE SUMMARY A woman in her 60s with psoriasis was administered ixekizumab(IXE),an anti-IL-17A antibody,for the treatment of psoriasis.Twenty months after commencing treatment,the patient visited our hospital because of persistent diarrhea.Blood tests performed at the time of the visit revealed severe inflammation,and colonoscopy revealed multiple round ulcers throughout the colon.A tissue biopsy of the ulcer revealed infiltration of inflammatory cells and granuloma-like findings in the submucosal layer.Capsule endoscopy revealed multiple jejunal erosions.After the withdrawal of IXE,the symptoms gradually improved,and ulcer reduction and scarring of the colon were endoscopically confirmed.CONCLUSION To the best of our knowledge,17 reports have documented IL-17 inhibitorinduced entero-colitis with endoscopic images,endoscopic findings,and pathological characteristics,including the present case.Nine of these cases showed diffuse loss of vascular pattern,coarse mucosa/ulcer formation in the left colon,and endoscopic findings similar to those of ulcerative colitis.In the remaining eight cases,discontinuous erosions and ulcerations from the terminal ileum to the rectum were seen,with endoscopic findings similar to those of Crohn’s disease.In this case,the findings were confirmed by capsule endoscopy,which has not been previously reported.

6-Gingerol, asarinin, and deoxyschizandrin improve bronchial epithelium functions in an interleukin-13einduced BEAS-2B cell model

Objective:To explore the effects of 6-gingerol,asarinin,and deoxyschizandrindthe main components of Zingiber officinale(Willd.)Rosc.(Gan Jiang),Asarum heterotropoides f.var.mandshuricum(Maxim.)(Xi Xin),and Schisandra chinensis(Turcz.)Baill.(Wu Wei Zi),respectivelydon an interleukin(IL)-13einduced BEAS-2B cell model in vitro.Methods:The BEAS-2B cell model was established using 25 ng/mL IL-13 combined with 1%fetal bovine serum(FBS)in vitro.Mitoquinone mesylate(Mito-Q)treatment was used as a positive control group,and different concentrations of 6-gingerol,asarinin,and deoxyschizandrin were used to treat the models.The level of reactive oxygen species(ROS)production was detected by flow cytometry.The expression levels of LC3B,Beclin1,adenosine 50-monophosphate(AMP)eactivated protein kinase(AMPK),phosphory-lated-AMPeactivated protein kinase(P-AMPK),dynamin-related protein 1(DRP1),and mitochondrial fusion protein 2(MFN2)were detected by Western blot.Mitochondrial membrane potential(MMP)assay kit with JC-1 was utilized to detect the level of MMP.Results:The BEAS-2B cells exposed to 25 ng/mL IL-13 with 1%FBS showed an increased ROS level and a decreased MMP.6-Gingerol,asarinin,and deoxyschizandrin were able to downregulate ROS level and upregulate the MMP in the BEAS-2B model.Asarinin and deoxyschizandrin reduced the expression of autophagy protein LC3B,while deoxyschizandrin significantly increased the expression of DRP1 in the BEAS-2B model.Conclusion:6-Gingerol,asarinin,and deoxyschizandrin can reduce ROS generation and increase MMP,but have different regulatory effects on the expression of autophagy protein and mitochondrial mitotic protein.The three components have both synergistic and complementary effects in classic medicine compatibility.This study may provide an innovative strategy to reduce the lung inflammation related to IL-13.

Correction to “Interleukin-34 promotes the proliferation and epithelial-mesenchymal transition of gastric cancer cells”

Correction to“Interleukin-34 promotes the proliferation and epithelialmesenchymal transition of gastric cancer cells”.In this article,we found the following error in Figure 3A:The panel image"24 h,sh-RNA1"in the AGS cells wound healing assay was incorrectly inserted during the preparation of the submission;the correct figure is provided in this correction.

Effect of T-regulatory cells and interleukin-35, interleukin-10, and transforming growth factor-beta on diffuse large B-cell lymphoma

BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is an aggressive non-Hodgkin lymphoma that affects B lymphocytes.It can develop in the lymph nodes and can be localized or generalized.Despite DLBCL being considered potentially curable,little research has been conducted on the relationship between the body's immune response and DLBCL.AIM To study the expression and significance of T-regulatory cells(Tregs)interleukin(IL)-35,IL-10,and transforming growth factor-beta(TGF-β)in DLBCL.METHODS Data from 82 patients with DLBCL who were initially admitted to The First Affiliated Hospital of Ningbo University(Zhejiang Province,China)between January 2017 and June 2022 and treated with standard first-line regimens were reviewed.Three patients were lost to follow-up;thus,79 patients were included in the statistical analysis and then divided into three groups according to the evaluation of clinical efficacy:Incipient(new-onset and treatment-naïve),effectively treated,and relapsed-refractory.Thirty healthy individuals were included in the control group.The expression of peripheral blood T lymphocytes and their associated factors IL-35,IL-10,and TGF-βin the four groups were observed.RESULTS In contrast to the successfully treated and normal control groups,both the incipient and relapse-refractory groups exhibited greater proportions of CD4-positive(+)Tregs(P<0.05),whereas the proportion of CD8+Tregs did not differ substantially between the groups.Serum levels of IL-35 and IL-10 in the incipient and relapsed-refractory groups were higher than those in the effectively treated and normal control groups(P<0.05).There was no statistically significant distinction in the expression level of TGF-βbetween the groups(P>0.05).The correlation between IL-35 and IL-10 concentrations was significantly positive,with a correlation coefficient of 0.531(P<0.05).The correlation between IL-35 and TGF-βconcentration was significantly positive,with a correlation coefficient of 0.375(P<0.05).The correlation between IL-10 and TGF-βconcentration was significantly positive,with a correlation coefficient of 0.185(P<0.05).The expression concentrations of IL-35,IL-10 and TGF-βwere apparently and positively correlated(P<0.05).CONCLUSION Tregs IL-35,and IL-10 may be closely associated with the occurrence and development of DLBCL and the detection of related indices may be helpful in the analysis of disease prognosis.

Hepatic vagotomy blunts liver regeneration after hepatectomy by downregulating the expression of interleukin-22

BACKGROUND Rapid regeneration of the residual liver is one of the key determinants of successful partial hepatectomy(PHx).At present,there is a lack of recognized safe,effective,and stable drugs to promote liver regeneration.It has been reported that vagus nerve signaling is beneficial to liver regeneration,but the potential mechanism at play here is not fully understood.AIM To explore the effect and mechanism of hepatic vagus nerve in liver regeneration after PHx.METHODS A PHx plus hepatic vagotomy(Hv)mouse model was established.The effect of Hv on liver regeneration after PHx was determined by comparing the liver regeneration levels of the PHx-Hv group and the PHx-sham group mice.In order to further investigate the role of interleukin(IL)-22 in liver regeneration inhibition mediated by Hv,the levels of IL-22 in the PHx-Hv group and the PHx-sham group was measured.The degree of liver injury in the PHx-Hv group and the PHx-sham group mice was detected to determine the role of the hepatic vagus nerve in liver injury after PHx.RESULTS Compared to control-group mice,Hv mice showed severe liver injury and weakened liver regeneration after PHx.Further research found that Hv downregulates the production of IL-22 induced by PHx and blocks activation of the signal transducer and activator of transcription 3(STAT3)pathway then reduces the expression of various mitogenic and anti-apoptotic proteins after PHx.Exogenous IL-22 reverses the inhibition of liver regeneration induced by Hv and alleviates liver injury,while treatment with IL-22 binding protein(an inhibitor of IL-22 signaling)reduce the concentration of IL-22 induced by PHx,inhibits the activation of the STAT3 signaling pathway in the liver after PHx,thereby hindering liver regeneration and aggravating liver injury in PHx-sham mice.CONCLUSION Hv attenuates liver regeneration after hepatectomy,and the mechanism may be related to the fact that Hv downregulates the production of IL-22,then blocks activation of the STAT3 pathway.

Clinical analysis between serum 25-hydroxyvitamin D3, interleukin-6 levels and febrile convulsion in children

Objective:To investigate the relation between febrile convulsions and 25hydroxy-vitamin D_(3)[25-(OH)D_(3)]and interleukin-6(IL-6)levels in children.Methods:241 children(divided into simple febrile convulsions and complex febrile convulsions),who were diagnosed with febrile convulsions at the Women and Children's Medical Center of Hainan Province from January 2017 to October 2022,were selected into the febrile convulsions group;100 healthy children,who had no uncomfortable symptoms and attended the outpatient clinic of the Women and Children's Medical Center of Hainan Province for physical examination,for the control group.All the subjects measured the serum 25-(OH)D_(3) and IL-6 levels,and clinical information,such as age,gender and season,was recorded.Results:1)Serum 25-(OH)D_(3) levels in the febrile convulsion group were significantly lower than in the healthy control group(78.77±20.37 nmol/L versus 96.55±29.74 nmol/L,respectively),and there was a statistically significant between the two groups(t value-6.359,P<0.001).Serum IL-6 levels in the febrile convulsion group were significantly higher than in the healthy control group,and there was a statistically significant between the two groups(Z value of-14.291,P<0.001).2)Serum 25-(OH)D_(3) levels in children with complex febrile convulsions were significantly lower than those in children with simple febrile convulsions,and the difference between the two groups was statistically significant(t-value of 6.612,P<0.05).IL-6 levels were higher in children with complex febrile convulsions than in children with simple febrile convulsions,and the difference between the two groups was statistically significant(Z value-10.151,P<0.001).The difference in the severity of febrile convulsions was statistically significant in serum 25-(OH)D_(3) levels(x^(2)=29.83,P<0.001).3)The results of correlation analysis showed that serum 25-(OH)D_(3) level was negatively correlated with febrile convulsion(γ=-0.393,P<0.05);serum 25-(OH)D_(3) level was positively correlated with that(γs=0.328,P<0.05).4)The correlation analysis results showed that the serum 25-(OH)D_(3) level was negatively correlated with the clinical characteristics of febrile convulsion(γ=-0.393,P<0.05).However,serum IL-6 water is positively correlated with it(γs=0.328,P<0.05).4)In contrast,there was no statistically significant difference in serum 25-(OH)D_(3) levels among children with febrile convulsions in different seasons(P>0.05).Conclusions:There is a correlation between febrile convulsion and serum levels of 25-(OH)D_(3) and IL-6.25-(OH)D_(3) and IL-6 may participate in the pathogenesis of febrile convulsion.

The role of Interleukin-1 family in cardiovascular disease and its research progress

The interleukin-1 family is a group of important cytokines that play a key regulatory role in the immune and inflammatory response(including infectious and non-bacterial injuries).Nowadays,the interleukin-1 family mainly includes 11 cytokines and has multiple roles in the pathology and physiology of inflammation.Moreover,accumulating number of research show that the interleukin-1 family and its receptors are involved in the occurrence and development of cardiovascular diseases.Therefore,we show here the review involving hotspots of the interleukin-1 family in the process of inflammation and its target therapy in cardiovascular diseases,including atherosclerosis,myocardial infarction and heart failure.

Association between Metabolic Syndrome Components and Serum High-Sensitivity C-Reactive Protein or Interleukin-6 Levels among Congolese Adults

Metabolic syndrome (MetS) and its components have been linked to elevated serum levels of inflammatory biomarkers such as C-reactive protein, interleukin-6, interleukin-1β and tumor necrosis factor alpha. The aim of our study was to address the association between MetS components with serum hs-CRP and IL-6 levels among Congolese adults. A total of 357 participants (aged 30 - 87 years) were included in this cross-sectional study. Anthropometrics were collected and fasting blood sampled for assessment of fasting blood glycaemia (FBG), lipids and inflammatory parameters using commercially available assays. NCEP-ATPIII criteria were used to define MetS. The Median (IQR) hs-CRP and IL-6 levels were higher in participants with MetS than in those without ([7 (4, 14) versus 6 (4, 8)] mg/L;p = 0.092 and [23.8 (20.9, 27.6) versus 22.3 (19.5, 25.0)] pg/mL;p = 0.002). hs-CRP and IL-6 levels were significantly higher in females with MetS than in those without, but not in males. Among participants, only TG was correlated with hs-CRP (r = 0.149, p = 0.007), and a significant correlation was observed between TG (r = 0.116, p = 0.037), FBG (r = 0.208, p = 0.000), HDL-C (r = −0.119, p = 0.034) and SBP (r = 0.143, p = 0.010) and IL-6. In males, hs-CRP levels were positively correlated with TG (0.316;p = 0.000), negatively with HDL-C (r = −0.290, p = 0.0022), without such correlations in females. In Ames, IL-6 levels were positively correlated with FBG (r = 0.202;p = 0.035), and negatively with HDL-C (r = −0.249, p = 0.009). Significant correlations between IL-6 levels and FBG (r = 0.214;p = 0.000) or SBP (r = 0.227, p = 0.000) were observed in females. Logistic regression analysis was carried out to identify the relationship between MetS components and hs-CRP or IL-6. Values of area under receiver-operating characteristic (ROC) curves suggest potential use of serum hs-CRP (AUC = 0.675) and IL-6 (AUC = 0.656) as diagnostic biomarkers of MetS. Combination of hs-CRP and IL-6 improved diagnosis accuracy, yielding a 0.698 ROC curve area. MetS components are associated with hs-CRP and IL-6 levels among adults Congolese. Combining the two biomarkers hs-CRP and IL-6 improves Mets diagnostic accuracy compared to hs-CRP or IL-6 alone.

瑞芬太尼调节IL-10/β-内啡肽信号通路对坐骨神经损伤大鼠疼痛的影响

目的探讨瑞芬太尼对坐骨神经损伤(SNI)大鼠疼痛的影响及作用机制。方法建立SNI大鼠模型,大鼠分为假手术组、模型组、瑞芬太尼低剂量组(5μg·kg^(-1)·min^(-1))、瑞芬太尼高剂量组(20μg·kg^(-1)·min^(-1))和瑞芬太尼+抑制剂组(20μg·kg^(-1)·min^(-1)的瑞芬太尼+10μL IL-10抗体),评估大鼠疼痛阈值,统计坐骨神经指数(SFI),Masson染液评价靶肌肉萎缩情况,酶联免疫吸附法(ELISA)检测白介素(IL)-1β、IL-6、肿瘤坏死因子(TNF)-α的含量,免疫荧光检测微管相关蛋白(MAP2)的表达,Western blot检测IL-10、β-内啡肽蛋白表达。结果与假手术组比较,模型组大鼠疼痛阈值、SFI和IL-10、β-内啡肽蛋白的表达水平下降,肌肉萎缩、IL-1β、IL-6、TNF-α、MAP2表达增加(P<0.05);与模型组比较,瑞芬太尼低、高剂量组大鼠疼痛阈值、SFI和IL-10、β-内啡肽蛋白的表达水平升高,肌肉萎缩、IL-1β、IL-6、TNF-α、MAP2表达降低,且呈剂量依赖性(P<0.05);与瑞芬太尼高剂量组比较,瑞芬太尼+抑制剂组大鼠疼痛阈值、SFI和IL-10、β-内啡肽蛋白的表达水平下降,肌肉萎缩、IL-1β、IL-6、TNF-α、MAP2表达增加(P<0.05)。结论瑞芬太尼可能通过激活IL-10/β-内啡肽信号通路抑制SNI大鼠的疼痛行为。

血清中Interleukin-18含量的检测对结肠癌预后判断的价值

目的 探讨结肠癌患者血清中白细胞介素 18(IL 18)水平与预后的关系。方法 收集 10 6例结肠癌患者和 60例健康成人的血清 ,采用酶联免疫吸附反应 (ELISA )检测IL 18的水平。结果 1997年 6月及以前的血清 5 9份 ,IL 18的平均含量为3 3 8.46pg/ml ;1997年 6月以后的血清 47份 ,IL 18的平均含量为 3 2 8.85 pg/ml ;2组比较无显著性差异 (P <0 .0 5 ) ;结肠癌组患者血清IL 18的含量 ( 3 46.5 3 pg/ml± 3 1.2 3pg/ml)明显高于正常对照组 ( 2 3 3 .3 2 pg/ml± 2 2 .5 4pg/ml) ,有显著性差异 (P <0 .0 5 ) ;Ⅱ期、Ⅲ期和Ⅳ期患者血清中IL 18水平明显高于对照组 (P <0 .0 5 ) ,血清IL 18≥ 3 46pg/ml组的患者 5年生存率为 5 .3 % ,血清IL 18<3 46pg/ml的患者 5年生存率为 18.6% ;两组比较有显著性差异 (P <0 .0 5 ) ;多因素分析表明 ,血清IL 18含量是判断结肠癌患者预后的独立因素。结论 血清中IL 18含量与结肠癌患者 5年生存率有密切相关。血清中IL

蜂毒镇痛作用的昼夜变化及对外周血P物质β-内啡肽和IL-1β水平的影响

目的:探讨小鼠疼痛模型的昼夜节律和注射用蜂毒(Bee venom for injection,BVI)镇痛作用的昼夜差异及其相关机制。方法:采用热板法、辐射热甩尾法建立小鼠疼痛模型,在6个授时(Zeitgeber time,ZT)时间点(ZT2、ZT6、ZT10、ZT14、ZT18、ZT22)测量痛阈并分析其昼夜节律。将合格昆明小鼠随机分为注射用蜂毒大剂量(Bee venom for injection-High dose,BVI-H)、注射用蜂毒中剂量(Bee venom for injection-Medium dose,BVI-M)、注射用蜂毒低剂量(Bee venom for injection-low dose,BVI-L)、吗啡(Morphine,MOR)和模型(Model,MOD)组;每组再根据小鼠痛阈的昼夜节律分为两个亚组,分别在痛阈的峰值和谷值2个时间点给药。观察各组对热板法、辐射热甩尾法和扭体法疼痛模型小鼠行为学影响的动态变化;ELISA法检测血清P物质(Substances P,SP)、β-内啡肽(Beta-endorphin,β-EP)和IL-1β(interleukin-1β,IL-1β)水平。结果:小鼠疼痛模型的痛阈显示出峰值在明中期(ZT6)、谷值在暗后期(ZT22)的昼夜节律。BVI三个剂量组和MOR组均显示出明显的镇痛作用,并且BVI在热板法和扭体法模型的镇痛作用具有剂量依赖性。在热板法和辐射热法疼痛模型中,BVI于ZT22给药比ZT6给药显示出更强的镇痛作用。蜂毒对疼痛模型小鼠血清β-EP水平未显示上调作用;但可明显降低血清SP含量,且具有ZT22给药低于ZT6给药的昼夜变化(P<0.05);对扭体法和辐射热法(仅ZT22给药组)疼痛模型小鼠血清IL-1β水平显著下调,而在热板法则显示IL-1β水平明显增高。结论:小鼠的痛阈存在峰值在明中后期、谷值在暗后期的昼夜节律;BVI对小鼠多种疼痛模型均具有镇痛作用,且存在昼夜差异;BVI的镇痛作用及其昼夜变化可能与调节内源性疼痛介质有关。

Homer1a reduces inflammatory response after retinal ischemia/reperfusion injury

Elevated intraocular pressure(IOP)is one of the causes of retinal ischemia/reperfusion injury,which results in NRP3 inflammasome activation and leads to visual damage.Homerla is repo rted to play a protective role in neuroinflammation in the cerebrum.However,the effects of Homerla on NLRP3inflammasomes in retinal ischemia/reperfusion injury caused by elevated IOP remain unknown.In our study,animal models we re constructed using C57BL/6J and Homer1^(flox/-)/Homerla^(+/-)/Nestin-Cre^(+/-)mice with elevated IOP-induced retinal ischemia/repe rfusion injury.For in vitro expe riments,the oxygen-glucose deprivation/repe rfusion injury model was constructed with M uller cells.We found that Homerla ove rexpression amelio rated the decreases in retinal thickness and Muller cell viability after ischemia/reperfusion injury.Furthermore,Homerla knockdown promoted NF-κB P65^(Ser536)activation via caspase-8,NF-κB P65 nuclear translocation,NLRP3 inflammasome formation,and the production and processing of interleukin-1βand inte rleukin-18.The opposite results we re observed with Homerla ove rexpression.Finally,the combined administration of Homerla protein and JSH-23 significantly inhibited the reduction in retinal thickness in Homer1^(flox/-)Homer1a^(+/-)/Nestin-Cre^(+/-)mice and apoptosis in M uller cells after ischemia/reperfusion injury.Taken together,these studies demonstrate that Homer1a exerts protective effects on retinal tissue and M uller cells via the caspase-8/NF-KB P65/NLRP3 pathway after I/R injury.

Approach to loss of response to advanced therapies in inflammatory bowel disease

BACKGROUND Remarkable progress over the last decade has equipped clinicians with many options in the treatment of inflammatory bowel disease.Clinicians now have the unique opportunity to provide individualized treatment that can achieve and sustain remission in many patients.However,issues of primary non-response(PNR)and secondary loss of response(SLOR)to non-tumour necrosis factor inhibitor(TNFi)therapies remains a common problem.Specific issues include the choice of optimization of therapy,identifying when dose optimization will recapture response,establishing optimal dose for escalation and when to switch therapy.AIM To explores the issues of PNR and SLOR to non-TNFi therapies.METHODS This review explores the current evidence and literature to elucidate management options in cases of PNR/SLOR.It will also explore potential predictors for response following SLOR/PNR to therapies including the role of therapeutic drug monitoring(TDM).RESULTS In the setting of PNR and loss of response to alpha-beta7-integrin inhibitors and interleukin(IL)-12 and IL-23 inhibitors dose optimization is a reasonable option to capture response.For Janus kinase inhibitors dose optimization can be utilized to recapture response with loss of response.CONCLUSION The role of TDM in the setting of advanced non-TNFi therapies to identify patients who require dose optimization and as a predictor for clinical remission is not yet established and this remains an area that should be addressed in the future.

Effects of Lycium barbarum polysaccharide on cytokines in adolescents with subthreshold depression:a randomized controlled study

Strong evidence has accumulated to show a correlation between depression symptoms and inflammatory responses.Moreover,anti-inflammatory treatment has shown partial effectiveness in alleviating depression symptoms.Lycium barbarum polysaccharide(LBP),derived from Goji berries,exhibits notable antioxidative and anti-inflammatory properties.In our recent double-blinded randomized placebo-controlled trial,we found that LBP significantly reduced depressive symptoms in adolescents with subthreshold depression.It is presumed that the antidepressant effect of LBP may be associated with its influence on inflammatory cytokines.In the double-blinded randomized controlled trial,we enrolled 29 adolescents with subthreshold depression and randomly divided them into an LBP group and a placebo group.In the LBP group,adolescents were given 300 mg/d LBP.A 6-week follow up was completed by 24 adolescents,comprising 14 adolescents from the LBP group(15.36±2.06 years,3 men and 11 women)and 10 adolescents from the placebo group(14.9±1.6 years,2 men and 8 women).Our results showed that after 6 weeks of treatment,the interleukin-17A level in the LBP group was lower than that in the placebo group.Network analysis showed that LBP reduced the correlations and connectivity between inflammatory factors,which were associated with the improvement in depressive symptoms.These findings suggest that 6-week administration of LBP suppresses the immune response by reducing interleukin-17A level,thereby exerting an antidepressant effect.