Expression and significance of CD4+T cell subtypes and their associated inflammatory factors in NE-FE-COPD patients / 重庆医学

Objective To investigate the expression of CD4+T cell subtypes and related inflammatory factors in patients with neutrophil-predominant frequent acute exacerbation chronic obstructive pulmonary disease(NE-FE-COPD).Methods COPD patients who were treated in the hospital from March 2019 to March 2021 were selected as the research objects.According to different phenotypes,they were divided into the infrequent exacerbator COPD group(IECOPD group,n=11),the eosinophilic dominant frequent acute plus severe COPD group(Eos-FE-COPD group,n=13),and the neutrophil dominant frequent exacerbator COPD group(NE-FE-COPD group,n=15).Patients with normal lung function and smoking history＞10 packs/year were the control group(CTRL group,n=9).Bronchoalveolar lavage fluid(BALF)was collected from each group,and the expression of CD4+T cell subtypes and inflammatory factors were detected by flow cytometry.The correlation between BALF and lung function and the frequency of acute exacerbation was ana-lyzed.CD4+CD28nullT cells and CD4+CD28+T cells were co-cultured with human airway epithelial cells(hAECs)and divided into co-culture group and Control group.The damage of hAECs was observed by immu-nofluorescence staining,and the mRNA and protein expression levels of ZO-1 and occludin were detected by RT-qPCR and Western blot.Results The proportion of CD4+CD28nullT cells and IL-1β level in BALF in the NE-FE-COPD group were higher than those in the CTRL group,the IE-COPD group,and the Eos-FE-COPD group,and the difference was statistically significant(P＜0.05).The proportion of CD4+CD28nullT cells and IL-1βlevel were negatively correlated with lung function(P＜0.05),and positively correlated with acute ex-acerbation frequency(P＜0.05).Compared with the Control group,hAECs tight junctions were damaged in the co-culture group,and mRNA and protein expression levels of ZO-1 and occludin decreased,with statistical significance(P＜0.05).Conclusion CD4+CD28nullT cells and IL-1β may be involved in the occurrence and de-velopment of NE-FE-COPD.

Tetrandrine attenuates IL-1β-induced injury of human articular chondrocytes in vitro / 基础医学与临床

Objective To investigate the effect of tetrandrine(Tet)on injury of primary human articular chondro-cytes induced by interleukin-1β(IL-1β).Methods Human articular chondrocytes were divided into control group,IL-1β group,hypoxia inducible factor(HIF-1α)inhibitor group[2-methoxyestradiol(2-ME2)group],Tet groups containing low,medium and high concentrations.Each group has six replicated samples.MTT assay was used to de-tect the viability of cells;cell apoptosis was detected by flow cytometry;the level of inflammatory related factors like tumor necrosis factor-α(TNF-α),matrix metalloproteinase 3(MMP-3),inducible nitric oxide synthase(iNOS),cyclooxygenase-2(COX-2)and the activity of antioxidant factors like super oxide dismutase(SOD)and glutathione peroxides(GPx)in cells were detected by ELISA;Western blot was used to detect the expression of HIF-1α and VEGF in cells.Results Compared with the control group,the apoptosis rate,level of TNF-α,MMP-3,iNOS,COX-2 and the protein expression of HIF-1α and VEGF in IL-1β group all increased,the cell survival rate and the activity of SOD and GPx significantly decreased(P＜0.05);compared with IL-1β group,the apoptosis rate,the level of TNF-α,MMP-3,iNOS,COX-2 and the protein expression of HIF-1α and VEGF in 2-ME2 group and Tet groups with low,medium,and high concentration significanthy decreased(P＜0.05).The cell survival rate and the activity of SOD and GPx significantly increased(P＜0.05).Conclusions Tetrandrine attenuates IL-1β-in-duced injury of human articular chondrocytes.

CT-guided pulsed radiofrequency combined with continuous nerve block for the treatment of refractory postherpetic neuralgia:a clinical study / 介入放射学杂志

Objective To investigate the clinical efficacy of CT-guided pulsed radiofrequency combined with continuous nerve block in the treatment of refractory postherpetic neuralgia(PHN).Methods A total of 208 patients with refractory PHN,who were admitted to the Hengshui Municipal People's Hospital of China between January 2021 and January 2023,were selected as the subjects of study.Using random number table method,the patients were divided into combination group and control group,with 104 patients in each group.The patients of control group received CT-guided pulsed radiofrequency therapy,and the patients of combination group received additional continuous nerve block therapy on the basis of the treatment of control group.The pain degree at different time point,clinical effective rate,number of analgesia remedy times,quality of sleep,and the levels of serum high mobility group box 1(HMGB1),interleukin-1 β(IL-1β)and interleukin-10(IL-10)were compared between the two groups.Results During the follow-up period,4 patients were lost in touch.Finally,103 patients were included in the combination group and 101 patients were included in the control group.The total treatment response rate in the combination group was 89.32％,which was significantly higher than 78.22％in the control group(P＜0.05).There were statistically significant differences in visual analogue scale(V AS)scores and Athens insomnia scale(AIS)scores including the time effect,inter-group effect and time-group interaction effect,between the two groups(P＜0.05).The postoperative one-week,2-week,4-week VAS scores and AIS scores in the combination group were remarkably lower than those in the control group(P＜0.05).The number of analgesia remedy times in the combination group was smaller than that in the control group,and the used dosage of tramadol in the combination group was lower than that in the control group(P＜0.05).Four weeks after treatment,the serum levels of HMGB1,IL-1β and IL-10 in the combination group were lower than those in the control group(P＜0.05).Conclusion For the treatment of refractory PHN,CT-guided pulsed radiofrequency combined with continuous nerve block can effectively alleviate neural inflammatory damage,and improve pain symptoms and sleep quality,besides,its analgesic effect and clinical efficacy are superior to CT-guided pulsed radiofrequency alone.(J Intervent Radiol,2024,33:264-268)

Correlation between the expression of miRNA-142-3p,mixed lineage kinase 3 and interleukin-1beta in nucleus pulposus and the degree of lumbar intervertebral disc degeneration / 中国组织工程研究

BACKGROUND:MicroRNA(miRNA)levels are closely related to cell apoptosis and proliferation,extracellular matrix metabolism and inflammatory response in intervertebral disc cells.However,the specific role of miR-142-3p in lumbar intervertebral disc degeneration remains unclear. OBJECTIVE:To investigate the correlation between the expression of miRNA-142-3p,mixed lineage kinase 3 and interleukin-1β in nucleus pulposus tissue and degree of human lumbar intervertebral disc degeneration. METHODS:A total of 82 patients with lumbar intervertebral disc degenerative diseases in Suzhou Ninth People's Hospital from January 2020 to March 2022 were collected as the study subjects,all of whom underwent MRI examination before operation.According to the Videman classification,the patients were divided into mild degeneration group(n=36),moderate degeneration group(n=26)and severe degeneration group(n=20).Eighty-two specimens of the nucleus pulposus were obtained.The mRNA expression of miRNA-142-3p as well as the mRNA and protein expression of mixed lineage kinase 3,interleukin-1β,type I collagen,type II collagen in nucleus pulposus tissue were detected by qPCR and western blot assay.The correlation between the degree of human lumbar intervertebral disc degeneration and the expression levels of miRNA-142-3p,mixed lineage kinase 3,and interleukin-1β was also assessed using the Spearman correlation coefficient method.Thirty adult Sprague-Dawley rats were divided into sham-operated group(executed after puncturing skin and muscle only),mild degeneration group(executed 1 week after puncturing Co7/8 segments)and severe degeneration group(executed 2 weeks after puncturing Co7/8 segments),with 10 rats in each group.After that,we detected the protein expression of mixed lineage kinase 3 and interleukin-1β as well as the gene expression of miRNA-142-3p,mixed lineage kinase 3 and interleukin-1β in the nucleus pulposus tissue. RESULTS AND CONCLUSION:In human nucleus pulposus tissue,the miRNA-142-3p expression ranked from high to low as follows:mild degeneration group>moderate degeneration group>severe degeneration group(P<0.05);the gene and protein expression of mixed lineage kinase 3 and interleukin-1β from low to high was as follows:mild degeneration group<moderate degeneration group<severe degeneration group(P<0.05);the gene and protein expression of type I collagen from low to high was as follows:mild degeneration group<moderate degeneration group<severe degeneration group(P<0.05),and the gene and protein expression of type I collagen from high to low was as follows:mild degeneration group>moderate degeneration group>severe degeneration group(P<0.05).Spearman correlation analysis showed that the degree of disc degeneration was negatively correlated with miRNA-142-3p expression(P<0.05)and positively correlated with mixed lineage kinase 3 and interleukin-1β expression(P<0.05).In rat nucleus pulposus tissue,compared with the sham-operated group,the expression of mixed lineage kinase 3 and interleukin-1β gene and protein was elevated in the mild degeneration group(P<0.05)while miRNA-142-3p expression was decreased(P<0.05);compared with the mild degeneration group,the expression of mixed lineage kinase 3 and interleukin-1β gene and protein was increased in the severe degeneration group(P<0.05)while miRNA-142-3p expression was decreased(P<0.05).To conclude,the degree of human lumbar intervertebral disc degeneration is negatively correlated with miRNA-142-3p expression and positively correlated with mixed lineage kinase 3 and interleukin-1β expression in nucleus pulposus tissue.

Sinomenine effectively inhibits interleukin-1beta-induced apoptosis in nucleus pulposus cells / 中国组织工程研究

BACKGROUND:Intervertebral disc degeneration is the basis of spinal degenerative diseases;however,there is no effective treatment. OBJECTIVE:To investigate whether sinomenine can inhibit interleukin-1β-induced apoptosis in nucleus pulposus cells and its molecular mechanism. METHODS:Rat nucleus pulposus cells were cultured in vitro by trypsin combined with type II collagenase digestion,and the cell growth curve was plotted.An appropriate sinomenine concentration was determined using the cell counting kit-8 kit.Nucleus pulposus cells were divided into control group,sinomenine group,interleukin-1β group,sinomenine+interleukin-1β group,zinc protoporphyrin group,zinc protoporphyrin+sinomenine group,zinc protoporphyrin+interleukin-1β group,and sinomenine+zinc protoporphyrin+interleukin-1β group.Proliferative activity,reactive oxygen species content,apoptosis rate,and heme oxygenase-1 expression in nucleus pulposus cells were detected. RESULTS AND CONCLUSION:The rat nucleus pulposus cells cultured in vitro were polygonal,triangular,and short wedge-shaped,and the cell growth showed an"S"curve.The cells grew slowly in the first 3 days of culture,rapidly in 4-6 days,and slowly again in 7-8 days.The cells then entered the"platform stage"where the number of cells no longer increased.The proliferative activity of myeloid cells showed no significant changes when the concentration of sinomenine was≤80 μmol/L(P>0.05).Interleukin-1β significantly reduced the proliferative activity of nucleus pulposus cells,increased the content of reactive oxygen species and led to apoptosis(P<0.01).Sinomenine intervention not only promoted heme oxygenase-1 expression(P<0.05)but also inhibited interleukin-1β-induced decrease in proliferative activity and increase in reactive oxygen species content and apoptosis rate in nucleus pulposus cells(P<0.05).These effects could be reversed by zinc protoporphyrin(P<0.01).

Evaluation of rat osteoarthritis chondrocyte models induced by interleukin-1beta / 中国组织工程研究

BACKGROUND:Establishing a chondrocyte model of osteoarthritis is of great significance for further explaining the pathological process of osteoarthritis and evaluating and screening the therapeutic drugs of osteoarthritis. OBJECTIVE:To evaluate the effect of interleukin-1β to induce osteoarthritis models in rat chondrocyte models,thereby providing a reference for further exploration of drug treatment of osteoarthritis. METHODS:Chondrocytes were isolated from the hip cartilage of 3-week-old Sprague-Dawley rats by mechanical shearing and enzymatic digestion,and then identified.Chondrocytes were randomly divided into three groups:control group,5 ng/mL interleukin-1β-induced group,10 ng/mL interleukin-1β-induced group,with induction times of 24 and 48 hours.Chondrocyte proliferation activity was detected by MTT.Real-Time PCR was used to detect the expression of type Ⅱ collagen,Aggrecan,sex-determining region Y-box protein 9(Sox9),matrix metalloproteinase 13,and a disintegrin and metaloproteinase with thrombospondin-like motifs-5(Adamts5)mRNA.Western blot was used to detect the expression of type Ⅱ collagen,Sox9,matrix metalloproteinase 13 and Adamts5. RESULTS AND CONCLUSION:Primary rat chondrocytes were successfully isolated and cultured.Induction of chondrocytes by interleukin-1β at 10 ng/mL for 24 hours could significantly reduce cell proliferation and viability(P＜0.05),while the 5 ng/mL interleukin-1β-induced group required 48 hours of induction to cause a significant decrease in cell proliferation and viability.Real-Time PCR results showed that compared with the control group,5 or 10 ng/mL interleukin-1β induction for 24 and 48 hours significantly reduced the expression levels of type Ⅱ collagen,Aggrecan,Sox9 mRNAs(P＜0.05)and increased the expression levels of matrix metalloproteinase 13 and Adamts5 mRNAs(P＜0.05).Compared with the 10 ng/mL interleukin-1β-induced group,5 ng/mL interleukin-1β induction significantly increased the mRNA expression of matrix metalloproteinase 13 and Adamts5 in chondrocytes after 48 hours of induction(P＜0.05).Western blot results showed that compared with the control group,10 ng/mL interleukin-1β induction for 24 hours and 5 ng/mL interleukin-1β induction for 48 hours significantly decreased the protein expression of type Ⅱ collagen and Sox9 in chondrocytes(P＜0.05),and significantly increased the protein expression of matrix metalloproteinase 13 and Adamts5(P＜0.05).To conclude,compared with 5 ng/mL interleukin-1β,10 ng/mL interleukin-1β may have more obvious effects on chondrocytes for 24 hours,while 5 and 10 ng/mL interleukin-1β have similar effects after 48 hours of intervention.

Prediction and validation of potential targets for the glucagon-like peptide-1 receptor agonist in the treatment of Alzheimer's disease / 中国组织工程研究

BACKGROUND:In the process of exploring the mechanism of Alzheimer's disease,the important role of bioinformatics for common target screening has been revealed,enabling the use of its screening results as a basis for exploring the therapeutic effects of drugs on the disease. OBJECTIVE:To predict the targets of liraglutide,a glucagon-like peptide-1 receptor agonist,in the treatment of Alzheimer's disease by bioinformatics and molecular biology. METHODS:DisGeNET database and SEA database were used to obtain the common genes of Alzheimer's disease and liraglutide.GO/KEGG enrichment analysis of common targets was conducted using DAVID online database.Protein-protein interaction networks were constructed using STRING database.The optimal dosage of liraglutide was determined using cell counting kit-8 assay.Expression of key proteins was analyzed using immunofluorescence and immunoblotting techniques.The mouse hippocampal neuron HT22 cell line was used for ex vivo experiments,and the cells were randomly divided into three groups:HT22 group,HT22+Aβ group,and HT22+Aβ+Lir group.No special treatment was done in the HT22 group,while Aβ1-42 was used to intervene in the HT22 cell line for 24 hours to construct an Aβ injury cell model in the HT22+Aβ group.In additional to modeling,liraglutide was added to the HT22+Aβ+Lir group for 12 hours. RESULTS AND CONCLUSION:A total of 3 333 genes associated with Alzheimer's disease were screened from DisGeNET database.Then 147 potential targets of liraglutide were obtained from SEA database.Finally,64 common targets of Alzheimer's disease and Liraglutide were determined using R packets.GO/KEGG analysis of common targets using DAVID online database suggested that common targets were mainly enriched in the following biological processes:neuroactive ligand-receptor interaction,renin-angiotensin system,bladder cancer,endopeptidase activity,peptide receptor activity,G protein-coupled peptide receptor activity,and transport vesicles.The obtained 64 common target proteins were imported into SRTING online database for protein-protein interaction network construction,and the top three genes,matrix metalloproteinases 2,9 and interleukin 1β,were obtained.The activity of cultured cells was detected by the cell counting kit-8 kit.Liraglutide at 100 nmol/L was the optimal concentration for antagonizing Aβ1-42.In the western blot and immunofluorescence assays,the expression of matrix metalloproteinases 2,9 and interleukin 1β was significantly increased in the HT22+Aβ group compared with the HT22 group(P＜0.05)but significantly decreased in the HT22+Aβ+Lir group compared with the HT22+Aβ group(P＜0.05).To conclude,the above bioinformatics data and secondary validation of differential genes in the GEO database suggest that both matrix metalloproteinases 2,9 and interleukin 1β could be potential targets of liraglutide in the treatment of Alzheimer's disease.

NLRP3 inflammasome and inflammatory factor levels predict early infection after flap repair of diabetic foot ulcers / 中国组织工程研究

BACKGROUND:Studies have shown that nucleotide binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome,interleukin-18,and interleukin-1β levels can induce an inflammatory cascade response to release inflammatory factors,affect metabolic stress,and damage endothelial cells involved in the development and progression of diabetic foot ulcers,which can provide a reference for early infections. OBJECTIVE:To investigate the predictive effect of peripheral blood mononuclear cell NLRP3 inflammasome,interleukin-18 and interleukin-1β levels on early infection after flap repair of diabetic foot ulcers. METHODS:A total of 147 patients with diabetic foot ulcers were selected and divided into infection group and non-infection group according to whether they were infected within 1 week after operation.Logistic regression was used to analyze the relationship between NLRP3 inflammasome,interleukin-18 and interleukin-1β levels in peripheral blood mononuclear cells and early postoperative infections,and to evaluate their predictive values. RESULTS AND CONCLUSION:In 147 patients with diabetic foot ulcers,35 cases(23.81%)were infected within 1 week after operation,and 47 strains of pathogenic bacteria were isolated,including 25 strains of Gram-positive bacteria(53.19%)and 22 strains of Gram-negative bacteria(46.81%).Univariate analysis showed that Wagner grade,presence of comorbid diabetic nephropathy,operation time,peripheral blood NLRP3 mRNA,Caspase-1 mRNA,ASC mRNA,interleukin-18 and interleukin-1β levels were risk factors for early postoperative infections(all P＜0.05).Multivariate analysis suggested that Wagner grade,NLRP3 mRNA,Caspase-1 mRNA,ASC mRNA,high interleukin-18,interleukin-1β were independent risk factors(all P＜0.05).Receiver operator characteristic curve results showed that the area under the receiver operator characteristic curve of NLRP3 mRNA,Caspase-1 mRNA,ASC mRNA,interleukin-18 and interleukin-1β for early postoperative infections in patients with diabetic foot ulcers was 0.823,0.705,0.676,0.811 and 0.853,respectively,and the area under the curve of combined predictive efficacy was 0.915.To conclude,patients with diabetic foot ulcers are mainly affected by Gram-positive bacteria,and the levels of NLRP3 inflammasome,interleukin-18 and interleukin-1β in peripheral blood mononuclear cells are independent risk factors for early postoperative infections.The combined prediction efficacy of these indicators is better and deserves further in-depth study.

Mechanism by which interleukin-1beta regulates the expression of Semaphorin 3A to induce intervertebral disc degeneration / 中国组织工程研究

BACKGROUND:Semaphone 3A(Sema3A)is an important neurovascular growth inhibitor.It is not clear how Sema3A is involved in the pathogenesis of discogenic low back pain.Exploring the potential mechanism of Sema3A in intervertebral disc degeneration can provide a new target and theoretical basis for the prevention and treatment of discogenic low back pain. OBJECTIVE:To explore the mechanism of interleukin-1β inhibiting the expression of Sema3A by activating the nuclear factor-κB signaling pathway to induce intervertebral disc degeneration in rats. METHODS:RT-qPCR was used to detect the expression of Sema3A mRNA in normal and degenerative human nucleus pulposus tissues.Nucleus pulposus cells of Sprague-Dawley rats were isolated,cultured,and passaged to the 3rd generation.Then,passage 3 cells were divided into three groups:the blank control group was routinely cultured for 48 hours,the degeneration group was intervened with 10 ng/mL interleukin 1β for 48 hours,and the degeneration+inhibitor group was treated by 5 μmol/L nuclear factor-κB signaling pathway-specific inhibitor BAY11-7082 for 1 hour,followed by interleukin-1β for 48 hours.At the end of the intervention,cell viability was detected by cell counting kit-8,cell apoptosis was detected by Annexin V/FITC staining,mRNA expression of cellular matrix,vascular and neural markers and Sema3A was detected by RT-qPCR,and protein expression of marker proteins,p65 and p-p65 was detected by western blot. RESULTS AND CONCLUSION:RT-qPCR assay showed that the expression of Sema3A mRNA was lower in degenerative human nucleus pulposus tissue than in normal human nucleus pulposus tissue(P＜0.05).Compared with the blank control group,the nucleus pulposus cell viability decreased and the apoptotic rate increased in the degeneration group(P＜0.05);compared with the degeneration group,the nucleus pulposus cell viability increased and the apoptotic rate decreased in the degeneration + inhibitor group(P＜0.05).Compared with the blank control group,mRNA expression of type Ⅱ collagen,polyproteoglycan,and Sema3A was decreased in the degeneration group(P＜0.05),while mRNA expression of CD31 and neurofilament 200 was increased(P＜0.05).Compared with the degeneration group,mRNA expression of type Ⅱ collagen,polyproteoglycan,and Sema3A was elevated in the degeneration+inhibitor group(P＜0.05)and mRNA expression of CD31 and neurofilament 200 decreased(P＜0.05).Compared with the blank control group,the protein expression of type Ⅱ collagen,polyproteoglycan,and Sema3A was decreased in the degeneration group(P＜0.05),and the protein expression of CD31,neurofilament protein 200,p65,and p-p65 was elevated(P＜0.05);compared with the degeneration group,the protein expression of type Ⅱ collagen,polyproteoglycan,and Sema3A was elevated in the degeneration+inhibitor group(P＜0.05),and protein expression of CD31,neurofilament 200,p65,and p-p65 was decreased(P＜0.05).To conclude,interleukin-1β does inhibit the expression of Sema3A by activating the nuclear factor-κB signaling pathway,which can also increase the degradation of extracellular matrix,promote the innervation and angiogenesis in degenerative intervertebral disc,and may be one of potential factors that contribute to intervertebral disc degeneration and discogenic low back pain.

Medical ozone alleviates pain in temporomandibular joint osteoarthritis / 中国组织工程研究

BACKGROUND:Temporomandibular joint osteoarthritis can cause severe pain,which significantly affects the patient's quality of life and psychological health.Studies have found that medical ozone can effectively alleviate pain due to temporomandibular joint osteoarthritis,but its analgesic effect and mechanism are still unclear. OBJECTIVE:To explore the effects of medical ozone on pain relief in temporomandibular joint osteoarthritis and the potential mechanisms. METHODS:Twenty-four Sprague-Dawley rats were randomly divided into four groups(n=6 per group):control group,model group,air group,and medical ozone group.A sodium iodate-induced rat model of temporomandibular joint osteoarthritis was established in all groups except for the control group.After 1 week of modeling,rats in the air group and medical ozone group were injected with clean air and medical ozone,respectively,in the temporomandibular joint.The injection frequency for the air group and medical ozone group was once a week for three times in total.The von Frey mechanized pain measurement technique was used to assess the mechanical pain threshold of the temporomandibular joint in rats before and 28 days after modeling.ELISA was utilized to detect interleukin-1β in both serum and temporomandibular joint fluid at 28 days after modeling.Histopathologic changes of the temporomandibular joint were evaluated through hematoxylin-eosin staining.Additionally,the expression levels of hypoxia-inducible factor 1α and cyclooxygenase 2 in the temporomandibular joint were analyzed using immunohistochemistry. RESULTS AND CONCLUSION:Compared with the control group,the mechanical pain thresholds of the temporomandibular joint in the model group were decreased at 1,3,7,14,21,and 28 days after modeling(P<0.01);and compared with the model and air groups,the mechanical pain thresholds of the temporomandibular joint in the medical ozone group were increased at 28 days after modeling(P<0.01).Compared with the control group,the level of interleukin 1β in the serum and joint fluid of rats in the model group was elevated(P<0.01);compared with the model and air groups,the level of interleukin 1β in the serum and joint fluid of rats in the medical ozone group was decreased(P<0.01).Hematoxylin-eosin staining results showed derangement and degeneration of the cartilage structure in the model group and the air group,while the derangement of the cartilage structure in the medical ozone group was less than that in the model group and the air group.Immunohistochemical staining showed that the expression of hypoxia-inducible factor 1α and cyclooxygenase 2 in the temporomandibular joints of rats in the model group was elevated compared with that in the control group(P<0.01);the expression of hypoxia-inducible factor 1α and cyclooxygenase 2 in the temporomandibular joints of rats in the medical ozone group was decreased compared with that in the model group and the air group(P<0.01,P<0.05).These findings suggest that medical ozone can alleviate the pain caused by osteoarthritis of the temporomandibular joints in Sprague-Dawley rats by reducing the expression of hypoxia-inducible factor 1α,interleukin 1β,and cyclooxygenase 2.

Effects of long intergenic non-protein coding RNA 00707 on chondrocyte injury and inflammatory factor secretion in osteoarthritis / 中国组织工程研究

BACKGROUND:Long intergenic non-protein coding RNA 00707(LINC00707)and microRNA-423-5p(miR-423-5p)are both involved in the occurrence and development of osteoarthritis.Starbase predicts that LINC00707 and miR-423-5p have complementary sequences,but whether LINC00707 and miR-423-5p interact to regulate the progress of osteoarthritis still needs further research. OBJECTIVE:To investigate whether LINC00707 targets miR-423-5p to affect chondrocyte injury and inflammatory factor secretion in osteoarthritis. METHODS:Articular chondrocytes were divided into eight groups:(1)blank control group was given no treatment;(2)interleukin(IL)-1β group was cultured with 10 ng/mL IL-1β for 48 hours;(3)IL-1β+si-NC group was transfected with si-NC and then treated with 10 ng/mL IL-1β for 48 hours;(4)IL-1β+si-LINC00707 group was transfected with si-LINC00707 and then treated with 10 ng/mL IL-1β for 48 hours;(5)IL-1β+miR-NC group was transfected with miR-NC and then treated with 10 ng/mL IL-1β for 48 hours;(6)IL-1β+miR-423-5p group was transfected with miR-423-5p mimic and then treated with 10 ng/mL IL-1β for 48 hours;(7)IL-1β+si-LINC00707+anti-miR-NC group was co-transfected with si-LINC00707 and anti-miR-NC and then treated with 10 ng/mL IL-1β for 48 hours;(8)IL-1β+si-LINC00707+anti-miR-423-5p group was co-transfected with si-LINC00707 and anti-miR-423-5p and then treated with 10 ng/mL IL-1β for 48 hours.Relevant tests were performed at the end of the intervention. RESULTS AND CONCLUSION:Compared with the blank control group,the mRNA expression of LINC00707,apoptosis rate,protein expression of C-caspase3 and C-caspase9,and levels of tumor necrosis factor-α and IL-6 in articular chondrocytes were increased in the IL-1β group,while there was a decrease in miR-423-5p expression and IL-10 level(P<0.05).Compared with the IL-1β group,the mRNA expression of LINC00707,apoptosis rate,protein expression of C-caspase3 and C-caspase9,and levels of tumor necrosis factor-α and IL-6 in articular chondrocytes were decreased in the IL-1β+si-LINC00707 group,while miR-423-5p expression and IL-10 level increased(P<0.05).Compared with the IL-1β+miR-NC group,the protein expression of C-caspase3 and C-caspase9 and levels of tumor necrosis factor-α and IL-6 in articular chondrocytes were decreased in the IL-1β+miR-423-5p group,while miR-423-5p expression and IL-10 level increased(P<0.05).Compared with the IL-1β+si-LINC00707+anti-miR-NC group,apoptosis rate,protein expression of C-caspase3 and C-caspase9,and levels of tumor necrosis factor-α and IL-6 in articular chondrocytes were increased in the IL-1β+si-LINC00707+anti-miR-423-5p group,while miR-423-5p expression and IL-10 level decreased(P<0.05).To conclude,inhibiting LINC00707 by targeting miR-423-5p can reduce IL-1β-induced apoptosis and inflammation in articular chondrocytes.

Interleukin-1beta enhances migration and adhesion of mesenchymal stem cells in inflammatory environments / 中国组织工程研究

BACKGROUND:Mesenchymal stem cells possess characteristics such as rapid renewal,targeted homing,tissue repair,and immune regulation,which provide potential for the treatment of inflammatory diseases.In most inflammatory diseases,interleukin-1β is highly expressed.Both exogenous and endogenous mesenchymal stem cells unavoidably exist in an environment with high interleukin-1β concentration. OBJECTIVE:To study the interaction of interleukin-1β with mesenchymal stem cells in inflammatory environment and the mechanism of its influence on the migration and adhesion of mesenchymal stem cells to provide a theoretical basis for adjusting stem cell therapy strategies. METHODS:The first author searched for studies involving interleukin-1β enhancing migration and adhesion of mesenchymal stem cells by computer on CNKI,WanFang,VIP,PubMed,and Web of Science using search terms"interleukin-1β,mesenchymal stem cell,nuclear factor-κB,MAPK,ERK,p38,migration,adhesion"in Chinese and English.The literature tracing method was also used to search for some of the literature.Finally,65 articles were included in the review analysis. RESULTS AND CONCLUSION:(1)In the inflammatory environment,interleukin-1β can regulate the migration and adhesion ability of mesenchymal stem cells.This effect may be achieved by recruiting IRAK1 through interleukin-1RI and then activating TAK1 and IKK in turn.After IKK phosphorylation,nuclear factor-κB and ERK signaling pathways are activated or CXCR expression is upregulated through the p38 pathway to promote mesenchymal stem cell migration and adhesion.However,further standardized research needs to be carried out based on the genetic background of mesenchymal stem cells,the dose and processing time of interleukin-1β.(2)In vitro experiments using pre-stimulated mesenchymal stem cells with interleukin-1β can change the survival environment of mesenchymal stem cells and alter their secretion factors to make them develop towards a more anti-inflammatory direction.On the other hand,under the premise of producing higher levels of anti-inflammatory and pro-nutrient factors,extracted mesenchymal stem cell exosomes can exert anti-inflammatory effects.(3)It has been observed in various animal disease models that pre-stimulating mesenchymal stem cells with interleukin-1β regulates their immune regulation ability,thereby affecting the development and outcome of inflammation.However,this is limited to preclinical basic research only;further verification on efficacy and safety of stem cell therapy with interleukin-1β pre-treated mesenchymal stem cells is required in clinical settings.

Role of inflammatory factors in diabetic ulcers and prospects of traditional Chinese medicine intervention / 中国组织工程研究

BACKGROUND:Diabetic ulcers are a common complication of diabetes mellitus,which is manifested as foot ulcers complicated with infection,long treatment cycle,high disability rate and mortality rate,and brings a heavy burden to patients and social care. OBJECTIVE:To review the mechanism of action and the latest treatment progress of traditional Chinese medicine(TCM)in the treatment of diabetic ulcers,and to provide a basis for further theoretical research and clinical application. METHODS:CNKI,WanFang Database and PubMed database were searched for relevant literature using the keywords of"diabetic ulcer,medicinal herb,inflammation,interleukin-1β,interleukin-6,tumor necrosis factor,hypersensitive C-reactive protein,γ-interferon,interleukin-4,interleukin-10"in Chinese and English,respectively.The relevant literature in recent years was searched,and finally 75 articles were included for review. RESULTS AND CONCLUSION:The high glucose environment of the body will increase the level of pro-inflammatory cytokines,so that diabetic ulcer wounds are in a state of chronic inflammatory response for a long time,and difficult to heal or even not heal.TCM has summed up a lot of experience in the long-term struggle with diabetic ulcer.At present,TCM divides diabetic ulcers into four syndrome types:dampness and heat poison syndrome,blood and blood stasis obstruction pattern,heat poison injury Yin pattern,and Qi and blood deficiency syndrome,as well as representative prescriptions for treatment.According to their clinical characteristics,diabetic ulcers can be also divided into three stages:primary,middle and late stages.Different treatment methods are proposed:"clear method,""warm and clear combined use"and"maintenance method."Under the guidance of dialectical typing and staging of TCM,TCM monomers,extracts and compounds inhibit the inflammatory response and promote the healing of diabetic ulcers by down-regulating the expression of pro-inflammatory factors and/or up-regulating the expression of anti-inflammatory factors.Compared with modern medicine,TCM has significant advantages in the treatment of diabetic ulcers.There are many TCM monomers,extracts and compounds for the treatment of diabetic ulcers,such as angelica,curcumin,improved Chonghe ointment,Sanhuang blood exhaustion prescription and sore-ulcer I.formula,etc.It has been found that TCM for the treatment of diabetic ulcers is mainly heat-clearing and detoxifying,invigorating blood circulation and removing blood stasis,and amassing sores and muscle-building drugs,and the frequency of use,treatment scope and therapeutic effect of TCM compounds are obviously better than those of TCM monomers and extracts.Among them,the most commonly used are the Sanhuang blood exhaustion prescription and the sore-ulcer I as well as prescription for the treatment of damp heat toxicity syndrome and Zizhu ointment for the treatment of non-ischemic diabetic ulcers.However,there are also some shortcomings in the treatment of diabetic ulcers with TCM.First,there are few clinical syndrome studies on diabetic ulcers.Secondly,there are a wide variety of TCM monomers,extracts and compounds for the treatment of diabetic ulcers,and the relevant research is insufficiently in-depth.Finally,the research on the mechanism underlying TCM treatment of diabetic ulcers is still in the preliminary exploration stage,and the mechanism of action still needs to be further explored.In the future,it is necessary to strengthen the research on the pharmacology of TCM and the clinical syndrome of diabetic ulcers,analyze the potential targets and related signaling pathways of TCM in the treatment of diabetic ulcers,give full play to the therapeutic advantages of TCM with multiple targets,multiple pathways,multiple levels and multiple systems,and develop TCM with significant efficacy,active ingredients and clear targets.

Neferine inhibits interleukin-1beta-induced chondrocyte apoptosis / 中国组织工程研究

BACKGROUND:Apoptosis is involved in the formation of degenerative joint diseases.Therefore,anti-chondrocyte apoptosis may be an effective way to treat osteoarthritis.Neferine has a wide range of pharmacological activities including anti-inflammatory,anti-tumor and anti-apoptotic activities,and its effect on chondrocyte apoptosis is not clear. OBJECTIVE:To investigate the effect of neferine on chondrocyte apoptosis induced by interleukin-1β and elucidate its possible mechanism. METHODS:(1)The rat chondrocytes at logarithmical stage were taken and intervened in five groups.The control group was cultured routinely.The model group was routinely cultured for 24 hours after treatment with interleukin-1β for 2 hours.The low-,medium-,and high-dose groups were treated with interleukin-1β for 2 hours and then cultured with 5,10,and 20 μmol/L neferine for 24 hours,respectively.At the end of culture,cell apoptosis,chondroglycoprotein 39 and type Ⅱ collagen levels in cell supernatants,mRNA and protein expression of apoptosis-related proteins,and mRNA and protein expression of proteins related to the protein kinase R-like endoplasmic reticulum kinase(PERK)/activating transcription factor 4(ATF4)signaling pathway were detected.(2)Rat chondrocytes at logarithmic growth period were taken and divided into four groups:control group and model group were treated with the same intervention as above,drug group was treated with interleukin-1β for 2 hours and then cultured with 20 μmol/L neferine for 24 hours,and activator group was treated with interleukin-1β for 2 hours and then cultured with 20 μmol/L neferine and CCT020312,an activator of PERK/ATF4 signaling pathway,for 24 hours.At the end of culture,cell proliferation was detected by cell counting kit-8 assay,apoptosis was detected by flow cytometry,and mRNA and protein expressions of apoptosis-related proteins and PERK/ATF4 signaling pathway-related proteins were detected. RESULTS AND CONCLUSION:(1)Compared with the control group,the model group showed increased apoptosis(P<0.05),decreased proliferative activity(P<0.05),increased level of chondroglycoprotein 39(P<0.05),decreased level of type Ⅱ collagen(P<0.05),decreased mRNA and protein expression of Bcl-2 protein(P<0.05),increased mRNA and protein expression of Bax protein,increased caspase-3 mRNA expression,increased Cleaved-caspase-3 protein expression(P<0.05),increased mRNA expression of PERK,ATF4,and C/EBP homologous protein(P<0.05),and increased protein expression of p-PERK,ATF4,and C/EBP homologous protein(P<0.05).Compared with the model group,neferine reversed the above effects of interleukin-1β on chondrocytes in a concentration-dependent manner.(2)Compared with the drug group,the activator group showed increased apoptosis(P<0.05),decreased proliferative activity(P<0.05),elevated mRNA expression of caspase-3,ATF4,and C/EBP homologous protein(P<0.05),and elevated protein expression of Cleaved-caspase-3,ATF4,and C/EBP homologous protein(P<0.05).(3)To conclude,neferine inhibits interleukin-1β-induced chondrocyte apoptosis and enhances cell proliferation activity,and the mechanism of action may be related to blocking the PERK/ATF4 signaling pathway in the endoplasmic reticulum.

Up-regulation of Proinflammatory Cytokines in Rostral Ventromedial Medulla Contributes to Chronic Postsurgical Pain by Promoting 5-HT Release / 中山大学学报(医学科学版)

ObjectiveTo investigate the role of proinflammatory cytokines tumor necrosis factor alpha （TNFα） and interleukin-1β （IL-1β） in rostral ventromedial medulla （RVM） in chronic postsurgical pain （CPSP） induced by skin/muscle incision and retraction （SMIR）. MethodsSD rats were randomly divided into 5 groups： ① Sham group； ② SMIR group； ③ SMIR+TNFα/IL-1β neutralizing antibody group； ④ SMIR+TNFα/IL-1β group and ⑤ SMIR+vehicle group. 50% paw mechanical withdrawal threshold （MWT） was measured by the up-down method， immunofluroscence was used to detect the TNFα and IL-1β expression and ELISA for the 5-Hydroxytryptamine （5-HT） level. ResultsSMIR elicited persistent nociceptive sensitization， upregulated TNFα and IL-1β expression in RVM neurons and astrocytes. Microinjection of TNFα or IL-1β neutralizing antibody into RVM inhibited the development of nociceptive sensitization and decreased the level of 5-HT in both RVM and spinal dorsal horn. While microinjection of recombinant TNFα or IL-1β into RVM enhanced the development of nociceptive sensitization and increased the level of 5-HT in both RVM and spinal dorsal horn. ConclusionUp-regulation of proinflammatory cytokines in RVM may contribute to SMIR induced CPSP by promoting 5-HT release.

Toxic effects of permethrin on HMC3 microglia and its associated mechanism / 环境与职业医学

Background Permethrin is a commonly used pyrethroid insecticide and has been found to be potentially neurotoxic. Microglia are innate immune cells in the central nervous system and are involved in the development of a range of neurodegenerative diseases. Objective To observe possible toxic effects of permethrin on human microglia clone 3 (HMC3) in vitro and explore associated mechanism. Methods HMC3 were treated with 0, 10, 25, and 55 μmol·L−1 permethrin for 72 h. Cell cycle and apoptosis were measured using flow cytometry. Cyclin-dependent kinase 1 (CDK1), cyclin-dependent kinase inhibitor 1A (CDKN1A), cyclin B2 (CCNB2), cellular tumor antigen p53 (p53), factor-related apoptosis (FAS), caspase 3 (CASP3), and H2A histone family member X (H2AX) were detected by quantitative real-time PCR (qPCR). The differential genes and enrichment pathways of HMC3 after 0 and 25 μmol·L−1 permethrin treatment was analyzed by RNA sequencing. HMC3 was treated by 0, 10, 25, and 55 μmol· L−1 permethrin for 72 h. The content of nitric oxide (NO) in the supernatant was detected using Griess reagent. The secretion level of interleukin-6 (IL-6) was detected by enzyme linked immunosorbent assay (ELISA). The mRNA expression levels of mitogen-activated protein kinase (MAPK) pathway (including MAPK1, MAPK8, and MAPK14), interleukin-1β (IL-1β), IL-6, and matrix metalloproteinase (MMP) families (including MMP1, MMP2, MMP3, and MMP9) were detected by qPCR. The protein expressions of phosphorylated p38 mitogen-activated protein kinase (p-p38), phosphorylated extracellular signal-regulated kinase (p-ERK), IL-1β, IL-6, and MMP1 were detected by Western blot. Results HMC3 was arrested in G2/M phase after 0, 10, 25, and 55 μmol·L−1 permethrin treatment for 72 h, of which there was a statistically significant difference between the 55 μmol·L−1 permethrin treatment group and the control group (P<0.01), and the mRNA expression of CDKN1A was up-regulated according to the qPCR (P<0.05). There was no statistically significant difference in the proportions of apoptosis between the groups (P＞0.05). The RNA sequencing showed that the differential genes were enriched in the MAPK pathway, and the mRNA expressions of MAPK1, MAPK8, and MAPK14 were up-regulated after the permethrin treatment at 55 μmol·L−1 compared to the control group by qPCR (P<0.05). The Western blot revealed that, compared to the control group, the levels of p-p38 and p-ERK were increased after the 10 μmol·L−1 permetrin treatment (P<0.05), the p-ERK level was increased after the 25 μmol·L−1 permetrin treatment (P<0.05), and the p-p38 level was up-regulated after the 55 μmol·L−1 permetrin treatment (P<0.05). The secretion of NO in the supernatant of HMC3 increased after permetrin treatment compared to the control group (P<0.05), the mRNA and protein expressions and the secretion of IL-6 showed an upward trend, the mRNA and protein expressions of IL-1β were up-regulated (P<0.05), and the mRNA and protein expressions of MMP1 were up-regulated in the 25 and 55 μmol·L−1 permethrin groups (P<0.05). Conclusion Permethrin inhibits HMC3 cell proliferation in vitro, induces cell cycle arrest, activates MAPK pathway, and promotes the expression of inflammatory factors IL-1β and MMP1, which may be one of the mechanism of neurotoxicity induced by permethrin.

Mechanism of Qingre Lishi Huazhuo Method（Modified Simiaosan） on Chronic Gouty Arthritis of Dampness-heat Obstruction Syndrome Based on NLRP3/IL-1β Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo study the clinical efficacy of the Qingre Lishi Huazhuo method on patients with chronic gouty arthritis of dampness-heat obstruction syndrome and the effect on nucleotide-binding oligomerization domain-like receptor 3（NLRP3）/interleukin-1β （IL-1β） signaling pathway to preliminarily explore its mechanism. MethodSixty patients with chronic gouty arthritis of dampness-heat obstruction syndrome were enrolled and divided into a treatment group （30 cases） and a control group （30 cases） according to the random number table method. Thirty people were assigned to the healthy group. Patients in the control group were treated with oral Febuxostat， while those in the treatment group were treated with modified Simiaosan combined with Febuxostat. Treatment lasted four weeks. The general clinical data， traditional Chinese medicine （TCM） syndrome scores， serum uric acid （UA）， serum creatinine （SCr）， blood urea nitrogen （BUN）， fasting blood glucose （FPG）， low-density lipoprotein （LDL）， triglyceride （TG）， total cholesterol （TC）， erythrocyte sedimentation rate （ESR）， and C-reactive protein （CRP） of patients were recorded. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of IL-1β，TNF-α， and IL-6，and the levels of NLRP3，cysteinyl aspartate-specific protease-1 （Caspase-1）， and apoptosis-associated speck-like protein containing a CARD （ASC） were detected by Western blot. ResultBefore treatment， the levels of body mass index （BMI）， systolic blood pressure （SBP），diastolic blood pressure （DBP），UA，SCr，BUN，FPG，LDL，TG，and TC in both groups significantly increased （P<0.05，P<0.01），and the levels of HDL significantly decreased as compared with those in the healthy group（P<0.05）. Additionally， the levels of IL-1β， TNF-α， and IL-6 in both groups significantly increased before treatment （P<0.01）. Compared with the results before treatment， patients in the two groups had significant reductions in tube pain， joint tenderness， joint swelling，joint fever， activity disorders， body fatigue， sliminess， bitter mouth， yellow and red urine， and tongue manifestation scores （P<0.05，P<0.01）. Compared with patients in the control group after treatment， those in the treatment group had a significant decrease in joint fever， body fatigue， sliminess， bitter mouth，sticky stool，yellow and red urine， tongue manifestation score， and pulse score （P<0.05）. The total effective rate in the treatment group was 80.0% （24/30）， higher than 56.7% （17/30）in the control group（χ2=11.916，P<0.05）. Compared with the results before treatment， BMI， SBP， DBP， UA， SCr， BUN， FPG， LDL， TG， TC， ESR，CRP， IL-1β， TNF-α， IL-6 levels， and VAS score in both groups significantly decreased （P<0.05，P<0.01）. Compared with patients in the control group after treatment， those in the treatment group had decreased DBP，ESR， IL-1β levels， and VAS score （P<0.05）. Western blot results showed that before treatment， the protein expression of NLRP3， Caspase-1， and ASC in peripheral blood mononuclear cells （PBMCs） of patients in both groups were higher than those in the healthy group （P<0.01）. Compared with the results before treatment， the protein expression of NLRP3， Caspase-1， and ASC in PBMCs in patients of both groups after treatment decreased （P<0.05，P<0.01）. Compared with the control group after treatment， the treatment group showed decreased expression levels of NLRP3 and Caspase-1（P<0.05）. ConclusionThe Qingre Lishi Huazhuo method can effectively improve the clinical symptoms and reduce inflammation of chronic gouty arthritis of dampness-heat obstruction syndrome with good safety. The mechanism may be related to the inhibition of the NLRP3/IL-1β signaling pathway.

Involvement of Interleukin-1 β/Insulin-Like Growth Factor 1 in Ameliorating Effects of Electroacupuncture on Myocardial Fibrosis Induced by Essential Hypertension / 中国结合医学杂志

OBJECTIVE@#To investigate the effect of electroacupuncture (EA) at Neiguan (PC 6) on myocardial fibrosis in spontaneously hypertensive rats (SHRs), and to explore the contribution of interleukin-1 β (IL-1 β), insulin-like growth factor 1 (IGF-1), and transforming growth factor β 1 (TGF- β 1) to the effects.@*METHODS@#Nine 12-weeks-old Wistar Kyoto (WKY) male rats were employed as the normal group. Twenty-seven SHRs were equally randomized into SHR, SHR+EA, and SHR + sham groups. EA was applied at bilateral PC 6 once a day 30 min per day in 8 consecutive weeks. After 8-weeks EA treatment at PC 6, histopathologic changes of collagen type I (Col I), collagen type 1 (Col 1) and the levels of IGF-1, 1L-1 β, TGF- β 1, matrix metalloproteinase (MMP)-2 and MMP-9 were examined in myocardial tissure respectively.@*RESULTS@#After 8-weeks EA treatment at PC 6, the enhanced myocardial fibrosis in SHRs were characterized by the increased mean fluorescence intensity of Col I and Col 1 in myocardium tissue (P<0.01). All these abnormal alterations above in SHR + EA group was significantly lower compared with the SHR group (P<0.01). Meanwhile, the increased levels of IL-1 β, IGF-1, TGF-β 1 in serum or myocardial tissue of SHRs, diminished MMP 9 mRNA expression in SHRs were also markedly inhibited after 8 weeks of EA treatment (P<0.05 or P<0.01). Furthermore, the contents of IL-1 β, IGF-1, TGF-β 1 in myocardial tissue were positively correlated with the systolic blood pressure and hydroxyproline respectively (P<0.01).@*CONCLUSION@#EA at bilateral PC 6 could ameliorate cardiac fibrosis in SHRs, which might be mediated by regulation of 1L-1 β/IGF-1-TGF- β 1-MMP9 pathway.

Effects of moxibustion on serum levels of β-EP, SP and expression of IL-1β and COX-2 protein in brainstem in rats with migraine / 中国针灸

OBJECTIVE@#To observe the effects of moxibustion at "Baihui" (GV 20) and "Dazhui" (GV 14) at different time points on the serum level of β-endorphin (β-EP), substance P (SP) and expression of interleukin-1β (IL-1β) and cyclooxygenase-2 (COX-2) protein in brainstem in rats with migraine, and to explore the effect and mechanism of moxibustion in preventing and treating migraine.@*METHODS@#Forty male SD rats were randomly divided into a blank group, a model group, a prevention+treatment (PT) group and a treatment group, 10 rats in each group. Except the blank group, the rats in the remaining groups were injected with nitroglycerin subcutaneously to prepare migraine model. The rats in the PT group were treated with moxibustion 7 days before modeling (once a day) and 30 min after modeling, while the rats in the treatment group were treated with moxibustion 30 min after modeling. The "Baihui" (GV 20) and "Dazhui" (GV 14) were taken for 30 minutes each time. The behavioral scores in each group were observed before and after modeling. After intervention, ELISA method was used to detect the serum level of β-EP and SP; the immunohistochemistry method was used to detect the number of positive cells of IL-1β in brainstem; the Western blot method was used to detect the expression of COX-2 protein in brainstem.@*RESULTS@#Compared with the blank group, the behavioral scores in the model group were increased 0-30 min, 60-90 min and 90-120 min after modeling (P<0.01); compared with the model group, in the treatment group and the PT group, the behavioral scores were decreased 60-90 min and 90-120 min after modeling (P<0.01). Compared with the blank group, in the model group, the serum level of β-EP was decreased (P<0.01), while the serum level of SP, the number of positive cells of IL-1β in brainstem and the expression of COX-2 protein were increased (P<0.01). Compared with the model group, in the PT group and and the treatment group, the serum level of β-EP was increased (P<0.01), while the serum level of SP, the number of positive cells of IL-1β and the expression of COX-2 protein in brainstem were decreased (P<0.01, P<0.05). Compared with the treatment group, in the PT group, the serum level of β-EP was increased and COX-2 protein expression was decreased (P<0.05).@*CONCLUSION@#Moxibustion could effectively relieve migraine. The mechanism may be related to reduce the serum level of SP, IL-1β and COX-2 protein expression in brainstem, and increase the serum level of β-EP, and the optimal effect is observed in the PT group.

Relationship between interleukin-1β and silicosis development / 中国基层医药

Silicosis is a diffuse pulmonary fibrosis disease caused by occupational exposure to silica, which is one of the occupational diseases with high incidence in developing countries. Up to now, there is no definite drug to relieve or reverse the lung injury caused by silicosis, so it is very important to prevent, diagnose and treat pulmonary fibrosis as soon as possible. Studies have shown that a chronic inflammatory environment contributes to pulmonary fibrosis to a certain extent. Interleukin-1β is a cytokine that increases the number of inflammatory factors in the microenvironment in the immune response and plays a key role in inflammatory reaction. Therefore, the release of interleukin-1β is of great significance in the pathogenesis of silicosis. This paper aims to systematically expound the development course of silicosis, the signal pathway of interleukin-1β production, and the relationship between them.