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 fac...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.展开更多
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 th...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.展开更多
Type 1 diabetes(T1D)is a chronic organ-specific autoimmune disorder characterized by a progressive loss of the insulin-secreting pancreatic beta cells,which ultimately results in insulinopenia,hyperglycemia and lifelo...Type 1 diabetes(T1D)is a chronic organ-specific autoimmune disorder characterized by a progressive loss of the insulin-secreting pancreatic beta cells,which ultimately results in insulinopenia,hyperglycemia and lifelong need for exogenous insulin therapy.In the pathophysiological landscape of T1D,T helper 17 cells(Th17 cells)and their hallmark cytokine,interleukin(IL)-17,play pivotal roles from disease onset to disease progression.In this narrative mini-review,we discuss the dynamic interplay between Th17 cells and IL-17 in the context of T1D,providing insights into the underlying immunologic mechanisms contributing to the IL-17-immunity-mediated pancreatic beta-cell destruction.Furthermore,we summarized the main animal and clinical studies that investigated Th17-and IL-17-targeted interventions as promising immunotherapies able to alter the natural history of T1D.展开更多
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 th...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.展开更多
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 ...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.展开更多
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....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.展开更多
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）...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.展开更多
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 ...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.展开更多
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 conc...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.展开更多
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 ...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.展开更多
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...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.展开更多
BACKGROUND Plantamajoside(PMS)has shown potential in mitigating cell damage caused by high glucose(HG)levels.Despite this,the precise therapeutic effects of PMS on type 2 diabetes mellitus(T2DM)and the underlying regu...BACKGROUND Plantamajoside(PMS)has shown potential in mitigating cell damage caused by high glucose(HG)levels.Despite this,the precise therapeutic effects of PMS on type 2 diabetes mellitus(T2DM)and the underlying regulatory mechanisms require further exploration.AIM To investigate PMS therapeutic effects on T2DM in mice and elucidate its mechanisms of action through in vivo and in vitro experiments.METHODS An in vitro damage model of MIN6 cells was established using HG and palmitic acid(PA).PMS's protective effect on cell damage was assessed.Next,transcriptomics was employed to examine how PMS treatment affects gene expression of MIN6 cells.Furthermore,the effect of PMS on protein processing in endoplasmic reticulum and apoptosis pathways was validated.A T2DM mouse model was used to validate the therapeutic effects and mechanisms of PMS in vivo.RESULTS PMS intervention ameliorated cell injury in HG+PA-induced MIN6 cell damage.Transcriptomic analysis revealed that protein processing in the endoplasmic reticulum and apoptosis pathways were enriched in cells treated with PMS,with significant downregulation of the gene Dnajc1.Further validation indicated that PMS significantly inhibited the expression of apoptosis-related factors(Bax,CytC)and endoplasmic reticulum stress(ERS)-related factors[ATF6,XBP1,Ddit3(CHOP),GRP78],while promoting the expression of Bcl-2 and Dnajc1.Additionally,the inhibitory effects of PMS on ERS and apoptosis were abolished upon Dnajc1 silencing.Furthermore,in vivo experiments demonstrated that PMS intervention effectively improved pancreatic damage,suppressed the expression of apoptosis-related factors(Bax,CytC),and ERS-related factors[ATF6,XBP1,Ddit3(CHOP),GRP78],while promoting the expression of Bcl-2 and Dnajc1 in a T2DM model mice.CONCLUSION PMS intervention could alleviate pancreatic tissue damage effectively.The mechanism of action involves Dnajc1 activation,which subsequently inhibits apoptosis and ERS,ameliorating damage to pancreaticβ-cells.展开更多
BACKGROUND The interleukin-17(IL-17)mediated aberrant immune-inflammatory response plays a paramount role in ulcerative colitis(UC).γδT17 cells are one of the critical sources of IL-17,but the role they play in UC r...BACKGROUND The interleukin-17(IL-17)mediated aberrant immune-inflammatory response plays a paramount role in ulcerative colitis(UC).γδT17 cells are one of the critical sources of IL-17,but the role they play in UC remains under debate.AIM To clarify the role ofγδT17 cells in patients with mild-to-moderate UC.METHODS A single-centre observational pragmatic study was conducted on patients with UC who attended the outpatient and inpatient departments of Xiyuan Hospital of the China Academy of Traditional Chinese Medicine from September 2020 to December 2022.The research population consisted of two groups of adult patients.The first group consisted of healthy volunteers with no significant abnormalities on colonoscopy,and the other group consisted of patients with mild-to-moderate ulcerative colitis.Serum samples from healthy volunteers and patients with UC were collected for the detection of relevant inflammatory factors.Moreover,five colon mucosa samples were randomly selected from each group for testing and analyses.RESULTS An increased number ofγδT17 cells and hyperactivation of the NLR family pyrin domain containing 3/IL-1βsignaling pathway were observed in colonic mucosal tissues from patients with UC.CONCLUSION Hyperactivation of the NLR family pyrin domain containing 3/IL-1βsignaling pathway promotes the activation ofγδT17 cells in colonic mucosal tissues of patients with UC.展开更多
基金a grant from the Science and Technology Department of Jilin Province,No. 200705172
文摘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.
基金Supported by the Natural Science Foundation of Gansu Province,No.21JR7RA373 and No.24JRRA295.
文摘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.
基金Supported by the European Union-NextGenerationEU,through the National Recovery and Resilience Plan of the Republic of Bulgaria,No.BG-RRP-2.004-0008.
文摘Type 1 diabetes(T1D)is a chronic organ-specific autoimmune disorder characterized by a progressive loss of the insulin-secreting pancreatic beta cells,which ultimately results in insulinopenia,hyperglycemia and lifelong need for exogenous insulin therapy.In the pathophysiological landscape of T1D,T helper 17 cells(Th17 cells)and their hallmark cytokine,interleukin(IL)-17,play pivotal roles from disease onset to disease progression.In this narrative mini-review,we discuss the dynamic interplay between Th17 cells and IL-17 in the context of T1D,providing insights into the underlying immunologic mechanisms contributing to the IL-17-immunity-mediated pancreatic beta-cell destruction.Furthermore,we summarized the main animal and clinical studies that investigated Th17-and IL-17-targeted interventions as promising immunotherapies able to alter the natural history of T1D.
基金National Institutes of Health(NIH):National Heart,Lung,and Blood Institute(NHLBI:R01-HL164772,R01-HL159062,R01-HL146691,T32-HL144456)National Institute of Diabetes and Digestive and Kidney Diseases(NIDDK:R01-DK123259,R01-DK033823)+2 种基金National Center for Advancing Translational Sciences(NCATS:UL1-TR002556-06,UM1-TR004400)(to Gaetano Santulli)Diabetes Action Research and Education Foundation(to Gaetano Santulli)Monique Weill-Caulier and Irma T.Hirschl Trusts(to Gaetano Santulli).
文摘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.
文摘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.
基金Supported by National Research Council of Thailand,No.N41A640108Mekong-Lancang Cooperation Special Fund+1 种基金The Development and Promotion of Science and Technology Talents ProjectMinistry of Education,Science,Sports,and Culture of Japan,No.22K16327 and No.22K08482.
文摘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.
文摘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.
基金This study was supported by grants from the Project of Beijing University of Chinese Medicine in China(No.JYB22 e JS022).
文摘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.
文摘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.
基金Grants from the National Natural Science Foundation of China, No. 39600061National Administration of Traditional Chinese Medicine, No.2003LHR13+3 种基金Medical Science Foundation of Guangdong Province, No. A2004327, A2006334the Natural Science Foundation of Guangdong, No. 04010443, 06105246 Administration Bureau of Traditional Chinese Medicine of Guangdong Province, No.1040074Technology Bureau of Guangzhou, No. 2007J1-C0041
文摘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.
基金grant from the Liaoning Provincial Education Bureau, No. 20060890
文摘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.
基金Yuansong Wang National Famous Traditional Chinese Medicine Expert Heritage Studio,No.4(2022).
文摘BACKGROUND Plantamajoside(PMS)has shown potential in mitigating cell damage caused by high glucose(HG)levels.Despite this,the precise therapeutic effects of PMS on type 2 diabetes mellitus(T2DM)and the underlying regulatory mechanisms require further exploration.AIM To investigate PMS therapeutic effects on T2DM in mice and elucidate its mechanisms of action through in vivo and in vitro experiments.METHODS An in vitro damage model of MIN6 cells was established using HG and palmitic acid(PA).PMS's protective effect on cell damage was assessed.Next,transcriptomics was employed to examine how PMS treatment affects gene expression of MIN6 cells.Furthermore,the effect of PMS on protein processing in endoplasmic reticulum and apoptosis pathways was validated.A T2DM mouse model was used to validate the therapeutic effects and mechanisms of PMS in vivo.RESULTS PMS intervention ameliorated cell injury in HG+PA-induced MIN6 cell damage.Transcriptomic analysis revealed that protein processing in the endoplasmic reticulum and apoptosis pathways were enriched in cells treated with PMS,with significant downregulation of the gene Dnajc1.Further validation indicated that PMS significantly inhibited the expression of apoptosis-related factors(Bax,CytC)and endoplasmic reticulum stress(ERS)-related factors[ATF6,XBP1,Ddit3(CHOP),GRP78],while promoting the expression of Bcl-2 and Dnajc1.Additionally,the inhibitory effects of PMS on ERS and apoptosis were abolished upon Dnajc1 silencing.Furthermore,in vivo experiments demonstrated that PMS intervention effectively improved pancreatic damage,suppressed the expression of apoptosis-related factors(Bax,CytC),and ERS-related factors[ATF6,XBP1,Ddit3(CHOP),GRP78],while promoting the expression of Bcl-2 and Dnajc1 in a T2DM model mice.CONCLUSION PMS intervention could alleviate pancreatic tissue damage effectively.The mechanism of action involves Dnajc1 activation,which subsequently inhibits apoptosis and ERS,ameliorating damage to pancreaticβ-cells.
基金Supported by China Academy of Chinese Medical Sciences Outstanding Young Talents(Innovative)Cultivation Project,No.ZZ17-YQ-007Special Project of the National Natural Science Foundation of China,No.82341233.
文摘BACKGROUND The interleukin-17(IL-17)mediated aberrant immune-inflammatory response plays a paramount role in ulcerative colitis(UC).γδT17 cells are one of the critical sources of IL-17,but the role they play in UC remains under debate.AIM To clarify the role ofγδT17 cells in patients with mild-to-moderate UC.METHODS A single-centre observational pragmatic study was conducted on patients with UC who attended the outpatient and inpatient departments of Xiyuan Hospital of the China Academy of Traditional Chinese Medicine from September 2020 to December 2022.The research population consisted of two groups of adult patients.The first group consisted of healthy volunteers with no significant abnormalities on colonoscopy,and the other group consisted of patients with mild-to-moderate ulcerative colitis.Serum samples from healthy volunteers and patients with UC were collected for the detection of relevant inflammatory factors.Moreover,five colon mucosa samples were randomly selected from each group for testing and analyses.RESULTS An increased number ofγδT17 cells and hyperactivation of the NLR family pyrin domain containing 3/IL-1βsignaling pathway were observed in colonic mucosal tissues from patients with UC.CONCLUSION Hyperactivation of the NLR family pyrin domain containing 3/IL-1βsignaling pathway promotes the activation ofγδT17 cells in colonic mucosal tissues of patients with UC.
