Xuebijing alters tumor necrosis factor-alpha, interleukin-1beta and p38 mitogen activated protein kinase content in a rat model of cardiac arrest following cardiopulmonary resuscitation

We established a rat model of cardiac arrest by clamping the endotracheal tube of adult rats at expiration. Twenty-four hours after cardiopulmonary resuscitation, nerve cell injury and expression of tumor necrosis factor-α, interleukin-1β, and p38 mitogen activated protein kinase content were increased. Rats injected with Xuebijing, a Chinese herb compound preparation, exhibited normal cellular structure and morphology, dense neuronal cytoplasm, and decreased tumor necrosis factor-α, interleukin-1β, and p38 mitogen activated protein kinase expression at 24 hours following cardiopulmonary resuscitation. These data suggest that Xuebijing can attenuate neuronal injury induced by hypoxia and reperfusion during cardiopulmonary resuscitation.

Contribution of interleukin-1beta in neuropathic pain

炎性因子白细胞介素1β(IL-1β)参与神经病理性疼痛的中枢和周围敏化过程,此为其特征性病理变化。IL-1β是介导中枢神经系统胶质细胞与神经元相互作用的重要炎性因子,其活化受到其他炎性因子的调控,如趋化细胞因子配体2(CCL2)和基质金属蛋白酶2、9(MMP 2、9)等。本文简要概述IL-1β在中枢性和周围性神经病理性疼痛中的主要作用机制。

Interleukin-17A facilitates tumor progression via upregulating programmed death ligand-1 expression in hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal prognosis.Immunotherapy has become an important treatment strategy for HCC,as immunity is closely related to inflammation in the tumor microenvir-onment.Inflammation regulates the expression of programmed death ligand-1(PD-L1)in the immunosuppressive tumor microenvironment and affects im-munotherapy efficacy.Interleukin-17A(IL-17A)is involved in the remodeling of the tumor microenvironment and plays a protumor or antitumor role in different tumors.We hypothesized that IL-17A participates in tumor progression by affe-cting the level of immune checkpoint molecules in HCC.The upregulation of PD-L1 expression in HCC cells by IL-17A was assessed by reverse transcription PCR,western blotting,and flow cytometry.Mechanistic studies were conducted with gene knockout models and pathway inhibitors.The function of IL-17A in immune evasion was explored through coculture of T cells and HCC cells.The effects of IL-17A on the malignant biological behaviors of HCC cells were evaluated in vitro,and the antitumor effects of an IL-17A inhibitor and its synergistic effects with a PD-L1 inhibitor were studied in vivo.RESULTS IL-17A upregulated PD-L1 expression in HCC cells in a dose-dependent manner,whereas IL-17A receptor knockout or treatment with a small mothers against decapentaplegic 2 inhibitor diminished the PD-L1 expression induced by IL-17A.IL-17A enhanced the survival of HCC cells in the coculture system.IL-17A increased the viability,G2/M ratio,and migration of HCC cells and decreased the apoptotic index.Cyclin D1,VEGF,MMP9,and Bcl-1 expression increased after IL-17A treatment,whereas BAX expression decreased.The combination of IL-17A and PD-L1 inhibitors showed synergistic antitumor efficacy and increased cluster of differentiation 8+T lymphocyte infiltration in an HCC mouse model.CONCLUSION IL-17A upregulates PD-L1 expression via the IL-17A receptor/phosphorylation-small mothers against decapenta-plegic 2 signaling pathway in HCC cells.Blocking IL-17A enhances the therapeutic efficacy of PD-L1 antibodies in HCC in vivo.

Interleukin-1 receptor associated kinase 2 is a functional downstream regulator of complement factor D that controls mitochondrial fitness in diabetic cardiomyopathy

Diabetic cardiomyopathy is a disorder of the cardiac muscle that affects patients with diabetes.The exact mechanisms underlying diabetic cardiomyopathy are mostly unknown,but several factors have been implicated in the pathogenesis of the disease and its progression towards heart failure,including endothelial dysfunction,autonomic neuropathy,metabolic alterations,oxidative stress,and alterations in ion homeostasis,especially calcium transients[1].In Military Medical Research,Jiang et al.[2]sought to determine the functional role of complement factor D(Adipsin)in the pathophysiology of diabetic cardiomyopathy.

Analyze interleukin-1β,interleukin-6,and tumor necrosis factor-αlevels in dry eye and the therapeutic effect of cyclosporine A

BACKGROUND Dry eye is a common eye disease.Artificial tears supplements are widely used for the treatment of dry eyes.However,multiple adverse effects have been observed in patients receiving long-term treatment with artificial tears,which may affect the therapeutic effect.AIM To analyze the characteristics of interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-alpha(TNF-α)levels in patients with dry eye and the therapeutic effect of artificial tears combined with cyclosporine A.METHODS A total of 124 dry eye patients treated at The First People’s Hospital of Xining from April 2020 to April 2022 were selected as the observation group,while 20 healthy individuals served as the control group during the same period.Levels of inflammatory markers,including IL-1β,IL-6,and TNF-α,were analyzed.The observation group was further divided into a study group and a control group,each consisting of 62 patients.The control group received artificial tears,whereas the study group received a combination of artificial tears and cyclosporine A.Inflammatory markers,Schirmer’s test(SIT),tear break-up time(TBUT),corneal fluorescein staining(CFS),National Eye Institute Visual Function Questionnaire-25(NEI-VFQ-25)scores,and adverse events(AEs)were compared between the two groups.RESULTS The observation group exhibited significantly elevated serum levels of IL-1β,IL-6,and TNF-αin comparison to the healthy group.Following treatment,the study group demonstrated substantial reductions in IL-1β,IL-6,and TNF-αlevels relative to the control group.Moreover,after treatment,the study group experienced a marked decrease in CFS scores and significant increases in both SIT and BUT levels when compared to the control group.Additionally,significant improvements were observed in the primary symptom of dry eye and secondary symptoms such as photophobia,foreign body sensation,fatigue,red eye,and burning sensation within the study group.Furthermore,post-treatment NEI-VFQ-25 scores across all dimensions exhibited significant enhancements in the study group compared to the control group(P<0.05).It is noteworthy that significant AEs were reported in both groups throughout the treatment period.CONCLUSION Cyclosporine A combined with artificial tears is effective in treating dry eye,yielding enhanced outcomes by improving SIT and TBUT levels,reducing CFS scores,and ameliorating vision-related quality of life.

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.

Interleukin-1 beta up-regulates tissue inhibitor of matrix metalloproteinase-1 mRNA and phosphorylation of c-jun N-terminal kinase and p38 in hepatic stellate cells

AIM： To study the relationship between interleukin-lbeta （IL-1β） up-regulating tissue inhibitor of matrix metalloproteinase-1 （TIMMP-1） mRNA expression and phosphorylation of both c-jun N-terminal kinase （INK） and p38 in rat heffatic stellate cells （HSC）. METHODS： RT-PCR was performed to measure the expression of TIMMP-1 mRNA in rat HSC. Western blot was performed to measure IL-1β-induced JNK and p38 activities in rat HSC. RESULTS： TIMMP-1 mRNA expression （1.191± 0.079） was much higher after treatment with IL-1β （10 ng/mL） for 24 h than in control group （0.545±0.091） （P〈0.01）. IL-1β activated INK and p38 in a time-dependent manner. After stimulation with IL-1β for 0, 5, 15, 30, 60 and 120 min, the INK activity was 0.982±0.299, 1.501±0.720, 2.133±0.882, 3.360±0.452, 2.181±0.789, and 1.385 ± 0.368, respectively. There was a significant difference in JNK activity at 15 min （P〈 0.01）, 30 min （P〈 0.01） and 60 min （P〈0.01） in comparison to that at 0 min. The p38 activity was 1.061±0.310, 2.050±0.863, 2.380±0.573, 2.973±0.953, 2.421±0.793, and 1.755 ± 0.433 at the 6 time points （0, 5, 15, 30, 60 and 120 min） respectively. There was a significant difference in p38 activity at 5 min （P〈0.05）, 15 min （P〈0.01）, 30 min （P〈0.01） and 60 min （P〈0.01） compared to that at 0 min. TIMMP-1 mRNA expression trended to decrease in 3 groups pretreated with different concentrations of SP600125 （10 μmol/L, 1.022±0.113; 20 μmol/L, 0.869±0.070; 40 μmol/L, 0.666±0.123）. Their decreases were all significant （P〈0.05, P〈0.01, P〈0.01） in comparison to control group （without SP600125 treatment, 1.163±0.107）. In the other 3 groups pretreated with different concentrations of SB203580 （10 μmol/L, 1.507±0.099; 20 μmol/L, 1.698±0.107; 40 μmol/L, 1.857±0.054）, the expression of TIMMP-1 mRNA increased. Their levels were higher than those in the control group （without SB203580 treatment, 1.027 ± 0.061） with a significant statistical significance （P〈 0.01）. CONCLUSION： IL-1β has a direct action on hepatic fibrosis by up-regulating TIMMP-1 mRNA expression in ratessionin in rate HSC.JNK and p38 mitogen-activated protein kinases （MAPKs） are involved in IL-1β-induced TIMMP-1 gene expression, and play a distinct role in this process, indicating that p38 and .INK pathways cooperatively mediate TIMP-1 mRNA expression in rat HSC.

Effect of electroacupuncture at distal-proximal acupoint combinations on spinal interleukin-1 beta in a rat model of neuropathic pain

Objective:Pain from herniated disc is a common type of neuropathic pain.This study investigated whether electroacupuncture (EA) stimulation at distal-proximal combinations of acupoints in the rat model of neuropathic pain modulates spinal interleukin-1 beta (IL-1β) to induce acupuncture analgesia and possibly serve as a pain-relief modality for herniated disc.Methods:A rat model of neuropathic pain was established.Rats were randomly divided into normal,model,sham,EA 1,EA 2,and EA 3 groups.EA 1 rats were needled at bilateral ExB2,BL25,BL40,and BL60 acupoints.EA 2 rats Were needled at bilateral BL40 and BL60.EA 3 rats were needled at bilateral L5 Ex-B2 and BL25.EA stimulation was administered once daily over 7 days.Mechanical withdrawal threshold from noxious mechanical stimulation was measured 1 day preoperatively and at 3,5,and7 days postoperatively.After 7 days of intervention,enzyme-linked immunosorbent assay (ELISA) was used to quantify IL-1β in the spinal cord.Results:Mechanical withdrawal threshold of rats in the model group decreased at 3 days postoperatively when compared with the normal group (P < 0.01),lasting 7 days postoperatively.Mechanical withdrawal thresholds in the EA 1,EA 2,and EA 3 groups were elevated over the model group (P < 0.05;P < 0.01).No obvious differences were found between EA 1,EA 2,and EA 3 groups.ELISA demonstrated an increase in IL-1β in the spinal cord of rats in the model group compared with the normal group (P < 0.01).EA treatment attenuated the increase in spinal IL-1β in the model group.Expression of spinal IL-1β was significantly lower in EA 1,EA 2,and EA 3 groups.Conclusion:EA at distal + proximal acupoints,distal points,as well as proximal points attenuated upregulation of spinal IL-1β,alleviated the extent of neuropathic pain hypersensitivity,and promoted mechanical withdrawal threshold,resulting in EA analgesia.

Interleukin-1 Beta (IL-1<i>β</i>) in the Peripheral Blood of Dogs as a Possible Marker for the Detection of Early Stages of Inflammation

Background: Cytokines are mediators of disease. Expression levels in the blood could be of clinical relevance. Objective: Aim of this study was to show if serum levels of IL-1β could be of any clinical relevance concerning dogs. IL-1β was measured in serum samples of healthy dogs to find a reference range for healthy individuals. Measurements of IL-1β should show if this substance was a possible marker for early stages of inflammation. Therefore, a possible relation between serum levels and grades of leukocytosis was analyzed. Methods: IL-1β concentrations in the blood were assessed by the use of a human enzyme linked immunosorbent assay (ELISA). 39 dogs with different inflammatory diseases were analyzed to figure out if there was a correlation between IL-1β serum levels and the number of leukocytes in peripheral blood. The control group consisted of 16 healthy dogs. Results: about half of the samples IL-1β were detected. Most of the patients showed no detectable amounts of IL-1β. The IL-1β levels measured in the serum were stable for at least nine weeks when stored at ?20?C. The patients tested positively on IL-1β had mostly lower-grade leukocytosis compared to those who had no IL-1β in serum. All the dogs which were suffering from disease but still had no traceable IL-1β, showed a leukocytosis as a common symptom. Conclusion: This study showed that IL-1β could become an interesting marker for the detection of early stages of inflammation when leukocytosis does not yet appear in peripheral blood. Nonetheless, the possible use in diagnosis is restricted. This is due to the fact that there are only low amounts of IL-1β to be detected in the serum, even concerning patients are suffering from disease.

Lonicera japonica-induced inhibition of interleukin-1 beta thermogenesis and E-type prostaglandin receptor-3 expression in the preoptic area of rabbits

BACKGROUND： It has been shown that interleukin-1β（IL-1β） can induce fever by activating vascular endothelial cells and macrophages of the supraoptic crest to generate prostaglandin E2, which binds with receptors of the thermo-sensitive hypothalamic neurons. Lonicera japonica is one of the medicinal plants used widely in Asia for its antipyretic properties. However, these mechanisms have not yet been intensively studied. OBJECTIVE： To investigate the antipyretic effect and mechanisms of Lonicera japonica on IL-1β- induced febrile New Zealand rabbits by observing expression changes of E-type prostaglandin receptor-3 （EP3） mRNA in the preoptic anterior hypothalamus （POAH）. DESIGN： A randomized controlled study. SETTING： Electrophysiological Laboratory at the Department of Pathophysiology, Medical College of Jinan University; Department of Orthopaedics, First Hospital Affiliated to Medical College of Jinan University. MATERIALS： The experiment was performed from April to December 2005, using a total of 32 New Zealand white rabbits of both sexes, weighing 1.5 2.0 kg. All the animal experiments were performed according to the internationally accepted ethical guidelines. Lonicera japonica injection was purchased from Huanghe pharmaceutical factory of Xi＇an, China. IL-1βwas purchased from Sigma, USA. METHODS： A total of 32 rabbits were divided randomly into four groups： ① Normal saline （NS） control group;② Lonicerajaponica treatment group; ③ IL-1βtreatment group; and ④Lonicerajaponica plus IL-1βtreatment group. In the first 3 groups, the rabbits were given separate intravenous （i.v.） injections of l mL NS, l mL Lonicera japonica, and 100 ng IL-l β （dissolved in 0.9% NS without pyrogen）. In the Lonicerajaponica plus IL-1βgroup each rabbit was given i.v. injections of l mL NS and, 30 minutes later, 100 ng IL-1 β. MAIN OUTCOME MEASURES： Colonic temperature of each rabbit was measured at 0, 10, 20, 30, 40, 50, 60, and 70 minutes after injection and the maximum temperature rise （ A T） and the temperature response index after l hour （TRII） was calculated. Subsequently, in situ hybridization （ISH） was done with an ISH kit, EP3 mRNA expression in the POAH of all groups was measured （number of positive cells and average gray scale value）. RESULTS： A total of 32 rabbits were included in the result analysis, without any loss, （i） A T and TRII： there was no significant difference between the Lonicera japonica group and NS group （P 〉 0.05）. The IL-1β group was significantly greater compared to NS group （P 〈 0.01）. The Lonicera japonica plus IL-1β group was significantly less than the IL-1β group （P 〈 0.05）. ② In the NS and Lonicera japonica groups, the EP3 mRNA expression was negative （no coloration） or only weakly positive （only a few brown yellow particles in the cytoplasm cells could not be identified）. The number of positive cells and the average gray scale value were not significantly different between the two groups （P 〉 0.05）. In the IL-1β group, the number of positive cells was remarkably higher and the average gray scale value was lower than the NS group （P 〈 0.0 l）. In the Lonicera japonica plus IL-1β group, the number of positive cells was significantly less than the IL-1β group （P 〈 0.05）. However, the average gray scale value was greater than the IL-1β group （P 〈 0.05）. CONCLUSION： Lonicera japonica has obvious antipyretic effects on IL-1β-induced febrile rabbits and acts by inhibiting expression of EP3 mRNA in the POAH.

SH2-B beta upregulates the expression of interleukin-1 beta in lung and visceral primary afferent neurons in asthmatic mice

A previous study by our research group showed that nerve growth factor is involved in the onset of asthma through regulating SH2-Bβ expression in the lung and visceral primary afferent neurons of asthmatic mice. This study sought to assess the expression level of interleukin-1β in primary afferent neurons in C7-T5 spinal ganglia, spinal cord and lung in asthmatic mice after blockage of SH2-Bβ. The levels of interleukin-1β protein in primary afferent neurons in the C7-T5 spinal ganglia and lung were decreased, and interleukin-1β mRNA expression also down-regulated in the spinal cord, medulla oblongata and lung tissue after blockage of SH2-Bβ. Our findings indicate that SH2-Bβ can upregulate the expression of interleukin-1β in C7-T5 spinal ganglia, spinal cord and lung of asthmatic mice.

抗人F1-F0 ATP合成酶beta亚基单抗的制备及其抗肿瘤活性研究

目的:制备鼠抗人F1-F0ATP合成酶beta亚基(hATP5B)单抗,并对其特异性和抗肿瘤活性进行研究。方法:以原核表达人hATP5B免疫BALB/c小鼠,通过杂交瘤技术,筛选分泌抗hATP5B单抗的杂交瘤细胞株。采用Protein A亲和层析法纯化抗体腹水,SDS-PAGE检测纯化产物纯度。利用Western blot、细胞免疫荧光对其特异性进行鉴定,并通过抑制乳腺癌细胞MCF-7及其耐药株MCF-7/Adr表面ATP生成,细胞毒性实验进行抗肿瘤活性研究。结果:获得一株稳定表达抗hATP5B单抗的杂交瘤细胞株Mab3B8,Western blot和细胞免疫荧光结果表明,该抗体与乳腺癌MCF-7及其耐药细胞MCF-7/Adr细胞天然抗原结合;可明显抑制MCF-7及其耐药株MCF-7/Adr细胞膜表面ATP合成;与化疗药物多柔比星(曾用名:阿霉素)联合作用,可降低化疗药物多柔比星对肿瘤细胞的IC50。结论:成功建立了一株可特异性识别天然hATP5B的单抗,有阻断肿瘤细胞膜表面ATP合成活性并可明显增强MCF-7及其耐药株MCF-7/Adr细胞对多柔比星敏感性的作用。此项研究对膜表达F1-F0ATP合成酶功能探讨及肿瘤治疗研究都具有重要意义。

凡纳滨对虾TCP-1-Beta基因的克隆及其与耐寒性状的相关性

为研究凡纳滨对虾耐寒性状的分子机理,研究克隆了凡纳滨对虾耐寒相关基因TCP-1-Beta并对其与耐寒性状的关系进行了研究。根据电子克隆所得序列设计引物,采用RT-PCR方法克隆得到长1691 bp的凡纳滨对虾TCP-1-Beta基因序列,其中包括1608 bp的完整开放阅读框,编码535个氨基酸残基。然后,运用荧光定量PCR对TCP-1-Beta基因进行时空表达谱的分析：组织表达谱的结果显示,该基因在凡纳滨对虾肝胰腺组织中表达量最高;不同低温处理下的表达结果显示,在28℃和15℃处理下基因表达量无显著变化,13℃开始呈上调表达,11℃时表达量升高;13℃低温处理发现该基因在24h内表达量无显著变化,但36h后表达量显著升高。采用PCR-RFLP方法对216尾凡纳滨对虾TCP-1-Beta基因进行了SNP多态性检测,并将其与耐寒性状进行了关联分析。在该基因编码区第420碱基上发现G/A突变,方差分析结果表明该位点的不同基因型与耐寒力指标CDH值相关（P〈0.05）,其中GG基因型的耐寒能力比AA基因型强。

Wnt-1或Wnt/beta-catenin信号通路在恶性肿瘤中的研究进展

Wnt-1或Wnt/beta-catenin信号通路最初在鼠乳腺癌病毒诱导的乳腺癌发现的。大量研究发现,该通路异常导致人类各种肿瘤发生、发展,采用siRNA或Wnt-1抗体等手段调控该通路,显示出抗肿瘤效应。提示以Wnt-1或Wnt/beta-catenin为靶向的抗肿瘤治疗,值得进一步研究。

Cloning,Identification and Differential Expression Analysis of Full-length cDNA of Carp Interleukin-1β

[Objective] The research aimed to carry out the cloning,identification and differential expression analysis of carp interleukin-1β （IL-1β） cDNA. [Method] By using DD-RTPCR method,the differential expression cDNA fragments were gained. The cDNA library of carp peripheral blood leucocytes which was stimulated by the mitogen was screened,and the full length cDNA of carp IL-1β was cloned. Moreover,the sequence analysis and differential expression analysis were carried out. [Result] The positive clone which had a whole ORF that encoded 276 amino acids was obtained. The cluster analysis showed that the amino acid sequence of carp IL-1β and Japanese carp closely gathered as a branch,and the homoeology of amino acid sequence reached 95%. The clustering order was the carassius,zebra fish,pig,cattle,horse,human and mouse in turn. The differential expression analysis showed that the expression of IL-1β in the leucocytes significantly increased in the prior period （4 h） after the mitogen stimulated. But as the time went by （12 and 24 h）,it didn＇t increase in the same period. The total trend of expression amount presented the peak type. [Conclusion] The research laid the foundation for further studying the expression manner,function characteristic,regulation mechanism of IL-1β in vivo and its action mechanisms in the inflammatory reaction,emergency reaction and immune response.

用Beta算子逼近具有第1类间断点的函数

研究了 Beta算子关于具有第 1类不连续点函数的逼近 ,利用点态连续模 ωx(f,t)和正规算子方法 ,得到了 Beta算子对具有第 1类不连续点函数的逼近结果 ,从而推广了 Beta算子对有界变差函数的逼近 .

白细胞介素17及白细胞介素1β在成人喉乳头状瘤疾病进展中的相关性研究

目的探究白细胞介素17(interleukin-17,IL-17)及IL-1β与成人喉乳头状瘤疾病进展及人乳头状瘤病毒(human papilloma virus,HPV)感染状态的相关性。方法收集2010年1月~2020年12月首都医科大学附属北京同仁医院耳鼻咽喉头颈科手术治疗的成人喉乳头状瘤患者的组织样本,将患者分为乳头状瘤组和疾病进展组。对样本行RNA原位杂交判断HPV分型,免疫荧光检测IL-17及IL-1β表达,分析其表达的组间差异及与HPV高危亚型的相关性。结果乳头状瘤组及疾病进展组间IL-17及IL-1β免疫荧光阳性率存在显著差异,疾病进展组中IL-17及IL-1β阳性率显著升高(t=5.460,P<0.001;t=10.030,P<0.001)。HPV高危亚型与IL-17及IL-1β表达相关,HPV高危型患者中IL-17及IL-1β表达水平显著升高,其中,IL-17表达差异具有统计学意义(t=4.554,P=0.0004)。结论IL-17及IL-1β与成人喉乳头状瘤疾病进展及HPV高危型感染状态有着密切相关性,HPV高危型加剧组织局部IL-17及IL-1β聚集,造成局部免疫微环境改变,进而引发疾病进展。

子宫内膜异位症患者异位内膜组织中Ninj1、IL-1β及PGP-9.5的表达及意义

目的探讨子宫内膜异位症(endometriosis,EMT)患者的异位内膜组织中神经损伤诱导蛋白1(Ninj1)、白细胞介素-1β(IL-1β)及蛋白基因产物9.5(PGP-9.5)的表达及与痛经的关系。方法以2020年4月—2021年4月在我院行妇科术后病理检查确诊为卵巢EMT患者的异位内膜组织40例为A组,并获取其中20例患者的在位子宫内膜组织为B组,收集同期20例子宫肌瘤患者的正常子宫内膜组织作为C组。根据有无痛经将A组分为痛经亚组与非痛经亚组,每组20例。采用免疫组织化学方法检测A、B、C组内膜组织中Ninj1、IL-1β及PGP-9.5的表达,并分析其相关性;采用酶联免疫吸附试验检测A组与C组患者外周血中IL-1β的表达水平。结果A组患者外周血中IL-1β的表达水平显著高于C组(t=-4.184,P<0.05);与C组相比,A、B组内膜组织中3种蛋白阳性表达构成比均明显升高(χ^(2)=4.286~19.394,P<0.05),与B组相比,A组内膜组织中3种蛋白阳性表达构成比明显升高(χ^(2)=4.149~5.272,P<0.05)。痛经亚组内膜组织中Ninj1与PGP-9.5蛋白阳性表达构成比明显高于非痛经亚组(χ^(2)=8.533、11.905,P<0.05)。A组内膜组织中Njnj1与PGP-9.5、IL-1β的表达呈正相关(r=0.733、0.628,P<0.05)。结论Ninj1、IL-1β及PGP-9.5在异位内膜组织中阳性表达比例较高,可能参与EMT的发生与发展;痛经亚组内膜组织中Ninj1与PGP-9.5蛋白的阳性表达构成比高于非痛经亚组,可能与EMT疼痛发生机制密切相关。

吴茱萸碱通过调节核因子E2相关因子2/血红素加氧酶-1/核因子-κB信号通路对白细胞介素1β诱导的软骨细胞炎性损伤的影响

目的观察吴茱萸碱(Evo)对白细胞介素1β(IL-1β)诱导的软骨细胞炎性损伤的影响及对核因子E2相关因子2(Nrf2)/血红素加氧酶-1(HO-1)/核因子κB(NF-κB)信号通路的调节作用。方法将人软骨细胞HCCs分为对照组、模型组、Evo低剂量组、Evo高剂量组、Evo高+ML385组,对照组用DMEM培养基培养,其他组用加入50 ng/mL的IL-1β培养基培养,同时Evo低、高剂量组再加浓度分别为10、30μmol/L的Evo处理,Evo高+ML385组先用2μmol/L的Nrf2抑制剂ML385处理30 min,再用30μmol/L的Evo处理。CCK-8检测细胞增殖活力;流式细胞术检测HCCs细胞凋亡;酶联免疫吸附法检测HCCs细胞上清液中IL-6、IL-18、肿瘤坏死因子α(TNF-α)、丙二醛(MDA)、超氧化物歧化酶(SOD)水平;实时荧光定量聚合酶链式反应(qRT-PCR)法检测HCCs细胞中炎症介质环氧合酶2(COX-2)、诱导型一氧化氮合酶(iNOS)mRNA水平;Western blot法检测HCCs中Nrf2/HO-1/NF-κB通路相关蛋白表达。结果与对照组相比,模型组凋亡率、IL-6、IL-18、TNF-α、MDA水平,COX-2、iNOS mRNA表达水平,以及磷酸化NF-κB抑制蛋白α(p-IκB-α)、细胞质Nrf2、细胞核p65 NF-κB蛋白水平均升高(P<0.05),细胞存活率、SOD活性及HO-1、IκB-α、细胞核Nrf2、细胞质p65 NF-κB蛋白水平均降低(P<0.05)。与模型组相比,Evo低、高剂量组细胞凋亡率、IL-6、IL-18、TNF-α、MDA水平,COX-2、iNOS mRNA表达水平,p-IκB-α、细胞质Nrf2、细胞核p65 NF-κB蛋白水平均降低(P<0.05),细胞存活率、SOD活性及HO-1、IκB-α、细胞核Nrf2、细胞质p65 NF-κB蛋白水平均升高(P<0.05),且Evo高剂量组以上指标与Evo低剂量组组间比较差异也均有统计学意义(P<0.05)。与Evo高剂量组相比,Evo高+ML385组中Nrf2的抑制剂ML385消除了Evo高剂量对上述指标的影响。结论Evo可能通过激活Nrf2和HO-1的表达,抑制下游转录因子NF-κB的表达,改善IL-1β诱导的软骨细胞炎性损伤。