The immunogenic involvement of miRNA-492 in mycoplasma pneumoniae infection in pediatric patients

Abstract Objective: This study aimed to evaluate the role of miRNA-492 in the progression of mycoplasma pneumoniae (MP) infection in pediatric patients. Methods: Forty-six children admitted to the present study's hospital and diagnosed with mycoplasma pneumonia were recruited as the study group from March 2018 to August 2019, and 40 healthy children were selected as the control group. Results: The expression levels of miRNA-492, TNF-α, IL-6 and IL-18 in the study group were significantly higher than those in the control group (p < 0.05). There was no significant correlation between miRNA-492 and most of the immune-correlated indicators in the study group, except for IL-6, IL-18 and HMGB1. Meanwhile, overexpression of miRNA-492 increased IL-6 secretion in PMA-activated monocytes (p < 0.01). Conclusion: The present study's results suggested that miRNA-492 might play a role in the pathogenesis of mycoplasma pneumoniae pneumonia in children by regulating the secretion of immune-inflammatory factors such as IL-6 and IL-18 in the mononuclear macrophages.

Relationship between IL-17, TNF-α, IL-10, IFN-γ, and IL-18 polymorphisms with the outcome of hepatitis B virus infection in the Turkish population

SUMMARY OBJECTIVE: Hepatitis B virus is a global threat that can lead to liver cirrhosis and hepatocellular carcinoma. For the treatment of chronic hepatitis B virus, polymorphisms might be an option for gene treatments. This study aimed to investigate the effects of IL-17, TNF-α, IL-10, IFN-γ, and IL-18 gene polymorphisms on hepatitis B virus infection in the Turkish population. METHODS: The genotypes and allele distribution of 75 patients exposed to hepatitis B virus and 50 healthy control individuals were analyzed. The real-time polymerase chain reaction method was used for identification. RESULTS: A correlation was observed between susceptibility to hepatitis B virus infection and IL-17 Exon 3/3'UTR (rs1974226) C, IL-17 Exon 3 (rs763780) A, IL-18 (-607) (rs1946518) A alleles, and IL-17 Exon 3 (rs763780) AA genotype (p=0.006, p=0.009, p=0.025, and p=0.008, respectively). Furthermore, IL-18 (-137) (rs187238) TT genotype and TNF-α-308 (rs1800629) G and A alleles, were associated with protection against hepatitis B virus infection (p=0.0351 and p=0.032, respectively). CONCLUSION: This study demonstrated that TNF-α (-308), IL-17 (Exon 3/3' UTR), IL-17 (Exon 3), and IL-18 (-607) polymorphisms are associated with hepatitis B virus infection. Therefore, these may serve as potential therapeutic targets for chronic viral hepatitis in the Turkish population.

Advances in research on IL-18 in the pathogenesis of allergic airway diseases / 西安交通大学学报(医学版)

The prevalence of allergic airway diseases has been increasing in recent years. Interleukin-18 (IL-18) plays an imperative role in allergic airway diseases by binding to IL-18Rα, thereby initiating the downstream proinflammatory pathway. IL-18 also binds to IL-18BP, thus inhibiting its binding to IL-18Rα. Therefore, further understanding of the role of IL-18 and its action mechanisms in allergic airway diseases is important for the treatment of allergic airway diseases, and for the development of IL-18-related biological agents.

Assessment of urinary interleukin-18 in the early post-burn period to predict acute kidney injury of various degrees of burn patients

Background:Early detection of acute kidney injury (AKI) in burn-injured patients can help modify the treatment to prevent progression of acute renal failure and reduce the need for renal replacement therapy. The aim of the study was to evaluateurinary interleukin-18 in the early post-burn period to predict the AKIfor the various degrees of burn patients. Methods:This prospective observational study was conducted in the department of nephrology, Dhaka medical college in collaboration with burn and plastic surgery unit of the same medical college hospital, from July 2017 to June 2018 for a period of one year. The 48 burn patients (Age>18 years) who attended in the burn unit of Dhaka medical college, Dhaka of both sexes were enrolled in this study. Data were analyzedby using SPSS 22.0. A value of p<0.05 was considered statistically significant for all tests. Results:In this study, mean age of the burn patients was 32.41�.59 years. Male female ratio was 3.36:1. Urinary IL-18 in diagnosis of AKI showed accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 93.8%, 91.7%, 94.4%, 84.6% and 97.1% respectively. AUC for urinary IL-18 at admission was 0.968 (CI, 0.921-1.000) and AUC for serum creatinine at admission was0.937 (CI, 0.871-1.000).Conclusions:According to Kappa value, AUC and sensitivity and specificity urinary IL-18 is a good biomarker in predicting of early AKI in burn patients

Interventional effect of asiaticosdide on rats exposed to silica dust / 中华劳动卫生职业病杂志

Objective: To investigate the effect of asiaticoside for fibrosis in lung tissues of rats exposed to silica and to explore its possible mechanism. Methods: 144 SD male rats were randomly divided into control group, model group, positive drug control group, asiaticoside high-dose group, medium-dose group and low-dose group, each group included 24 rats. Rats in the control group were perfused with 1.0 ml of normal saline, and the other groups were given 1.0 ml 50 mg/ml SiO(2) suspension. Gavage of herbal was given from the next day after model establishment, once a day. Rats in the positive drug control group were administration with 30 mg/kg tetrandrine and rats in the low-dose group, medium-dose group and high-dose group were given 20 mg/kg, 40 mg/kg and 60 mg/kg asiaticoside for fibrosis respectively. Rats in the control group and the model group were given 0.9% normal saline. The rats were sacrificed in on the 14th, 28th and 56th day after intragastric administration and collect the lung tissues to detect the content of hydroxyproline, TGF-β(1) and IL-18, observe the pathological changes of the lung tissues by HE and Masson staining and determine the expressions of Col-I, a-SMA, TGF-β in lung tissues by Western Blot. Results: On the 14th day, 28th day and 56th day after model establishment, the lung tissues of rats in the model group showed obvious inflammatory response and accumulation of collagen fibers, and the degree of inflammation and fibrosis increased with time. The intervention of asiaticoside could effectively inhibit the pathological changes of lung tissues. The contents of hydroxyproline, IL-18 and TGF-β1 in lung tissues of model group were higher than those in the control group (P<0.05) , while the level of hydroxyproline, IL-18 and TGF-β1 in asiaticoside groups were significantly decreased, and the difference was statistically signicant (P<0.05) . Compared with the control group, the expression levels of Col-I, TGF-β1and α-SMA in lung tissue of model group were increased (P<0.05) , while the expression level of Col-I, TGF-β1 and α-SMA were decreased after the intervention of asiaticoside, and the difference was statistically signicant (P<0.05) . Conclusion: Asiaticoside can inhibit the increase of Col-I, TGF-β1 and α-SMA content in the SiO(2)-induced lung tissues of rats, reduce the release of TGF-β1 and IL-18 inflammatory factors in lung tissue, and then inhibit the synthesis and deposition of extracellular matrix in rat lung tissue, and improve silicosis fibrosis.

In vitro regulatory effects of IL-18 on natural killer-like B cells in patients with primary hepatocellular carcinoma / 中华微生物学和免疫学杂志

Objective:To investigate the changes in peripheral blood and liver-infiltrating natural killer-like B (NKB) cells in patients with primary hepatocellular carcinoma (HCC), and to assess the influence of IL-18 on NKB cells in vitro and the underlying mechanism. Methods:Forty-three HCC patients and 21 normal controls (NC) were enrolled in the study. Peripheral blood samples were collected to isolate plasma and peripheral blood mononuclear cells (PBMC). Intrahepatic lymphocytes (IHL) were isolated from tumor tissues and para-tumor tissues obtained from 16 HCC patients who received surgery. IL-12, IL-18 and IL-18 binding protein (IL-18BP) levels in plasma were measured by enzyme linked immunosorbent assay. The percentages of CD3 -NKp46 + CD19 + NKB cells and IL-18 + NKB cells in PBMC and IHL were analyzed by flow cytometry. Changes in the percentages of NKB cells and IL-18 + NKB cells were measured after stimulating PBMC and IHL with recombinant human IL-18 (1 ng/ml and 10 ng/ml). Changes in IL-18BP levels in the culture supernatants and phosphorylated nuclear factor-κB (NF-κB) in NKB cells were also assessed. Student′s t test, one-way analysis of variance or LSD-t test was used for statistical analysis. Results:There was no significant difference in plasma IL-12 level between HCC patients and NC ( P=0.245). Compared with NC, HCC patients had decreased IL-18 level in plasma [(224.3±58.89) pg/ml vs (327.0±52.27) pg/ml, P<0.000 1], but increased IL-18BP level [(4.421±0.97) ng/ml vs (0.92±0.18) ng/ml, P<0.000 1]. The percentages of peripheral blood NKB cells and IL-18 + NKB cells were lower in HCC patients than in NC [(2.68±1.23)% vs (8.88±2.95)% and (54.42±12.60)% vs (69.74±12.65)%, both P<0.000 1]. The percentage of NKB cells in IHL was reduced in tumor tissues as compared with that in para-tumor tissues [(2.89±0.86)% vs (4.66±1.17)%, P<0.000 1]. Moreover, the percentage of IL-18 + NKB cell was also down-regulated in tumor tissues as compared with that in para-tumor tissues [(51.50±13.18)% vs (62.13±9.24)%, P=0.013]. Recombinant human IL-18 stimulation reduced the IL-18BP level in the culture supernatants ( P<0.05). IL-18 stimulation at 1 ng/ml did not affect NKB cell percentage, IL-18 + NKB cell percentage or NF-κB phosphorylation in NKB cells from PBMC or IHL ( P>0.05), while 10 ng/ml of IL-18 not only elevated NKB cell percentage and IL-18+ NKB cell percentage, but also promoted NF-κB phosphorylation in NKB cells ( P<0.01). Conclusions:In vitro stimulation with high concentration of IL-18 might promote NF-κB phosphorylation by inhibition of IL-18BP expression. This process might play a positive feedback role to induce the activation of NKB cells and IL-18 secretion.

The role of inflammatory molecules related to pyroptosis pathway in the pathogenesis of atopic dermatitis / 国际儿科学杂志

Atopic dermatitis(AD)is a common skin disease in pediatrics.It is a chronic inflammatory skin disease related to allergic diathesis that interacts with genetic and environmental factors.In about 60% of patients, the onset is before the age of one.With the deepening of research on the pathogenesis of AD, current research shows that pyroptosis-related inflammatory molecules may be involved in the occurrence and development of AD.Pyroptosis is a kind of regulated cell death accompanied by the release of inflammatory cytokines.It has been proven to play an important role in diseases such as atherosclerosis, diabetes, asthma, and inflammatory bowel disease.This article summarizes the role of inflammatory molecules related to pyroptosis pathway in the pathogenesis of atopic dermatitis, in order to deepen the understanding of the pathogenesis of atopic dermatitis and explore new therapies for it.

Clinical application of biomarkers in DCD donor kidney perfusate for predicting delayed graft function after renal transplantation / 器官移植

Objective To explore the feasibility of biomarkers in static cold storage (SCS) perfusate of donor kidney from donation after cardiac death (DCD) for predicting delayed graft function (DGF) after renal transplantation. Methods Clinical data of 64 recipients and 47 donors undergoing DCD renal transplantation were retrospectively analyzed. All recipients were divided into the DGF group (n=7) and immediate graft function (IGF) group (n=57) according to the incidence of postoperative DGF in the recipients. The levels of neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid-binding protein (L-FABP), interleukin -18(IL-18) and kidney injury molecule-1 (KIM-1) in the SCS perfusate were statistically compared between two groups, and the correlation with DGF was analyzed. The predictive value of each biomarker in the occurrence of DGF in recipients after renal transplantation was analyzed. Results The incidence of DGF in the recipients undergoing DCD renal transplantation was 11% (7/64). The NGAL level in the donor kidney perfusate of the DGF group was significantly higher than that in the IGF group (P=0.009). The NGAL level in the donor kidney perfusate was positively correlated with the incidence of DGF in recipients after renal transplantation (r=0.430, P < 0.001). The receiver operating characteristic (ROC) curve analysis showed that the increased levels of NGAL and KIM-1 in the perfusate yielded certain predictive value for DGF in recipients after renal transplantation (both P < 0.05). The area under the curve (AUC) of combined detection of NGAL and KIM-1 for predicting DGF in recipients after renal transplantation was 0.932 [95% confidence interval (CI) 0.850-1.000]. The sensitivity was calculated as 1.000 and 0.754 for the specificity (P < 0.05). Conclusions The NGAL level in the SCS perfusate of DCD donor kidney is associated with the occurrence of DGF in recipients after renal transplantation. Combined detection of NGAL and KIM-1 levels in the perfusate may accurately predict the occurrence of DGF in recipients after renal transplantation.

Effect of acupuncture on NLRP3 inflammatory corpuscle in rats with intracerebral hemorrhage / 中国针灸

OBJECTIVE@#To observe the effect of acupuncture at "Baihui" (GV 20) through "Qubin" (GB 7) on NLRP3 inflammatory corpuscle in rats with intracerebral hemorrhage (ICH), and to explore the action mechanism of acupuncture on promoting the recovery of neural function in rats with ICH.@*METHODS@#Forty SPF six-week-old male SD rats were randomly divided into a sham operation group, a model group, a non-acupoint group and an acupuncture group, 10 rats in each group. The rats in the model group, non-acupoint group and acupuncture group were intervened with autologous blood injection to prepare ICH model, while the rats in the sham operation group were only intervened with operation but not injection with autologous blood. About 3 hours after the establishment of the model, the rats in the acupuncture group were intervened with acupuncture at "Baihui" (GV 20) through "Qubin" (GB 7), once every 12 hours, for 7 days; the rats in the non-acupoint group were intervened with acupuncture at the non-acupoint [parallel to the "Baihui" (GV 20), 1 cm next to the midline] on the affected side, and other treatment was the same as the acupuncture group. At the end of the intervention, the composite nerve function score of each group was evaluated; the histomorphology of the hemorrhage penumbra was observed by HE staining; the expression of NLRP3 inflammatory corpuscle in the brain was detected by immunohistochemistry; the relative protein expression levels of NLRP3, interleukin-1β (IL-1β) and interleukin-18 (IL-18) in brain were detected by the method of Western blot.@*RESULTS@#Seven days into intervention, compared with the sham operation group, each item score and total score of composite nerve function in the model group were significantly reduced (<0.01, <0.05). There was edema and karyopyknosis in brain neuron as well as necrocytosis and inflammatory cell infiltration in the model group. Compared with the model group and the non-acupoint group, the total score of composite nerve function and the scores of symmetrical movement of limbs (LS) and proprioception of tentacles (VP) in the acupuncture group were increased (<0.01, <0.05), and the cell necrosis and inflammatory cell infiltration were relieved. Compared with the sham operation group, NLRP3 inflammatory corpuscle expression and the relative protein expression levels of NLRP3, IL-1β and IL-18 in brain tissue in the model group were increased (<0.01); compared with the model group and the non-acupoint group, NLRP3 inflammatory corpuscle expression and the relative protein expression levels of NLRP3, IL-1β and IL-18 in brain tissue in the acupuncture group were reduced (<0.01).@*CONCLUSION@#Acupuncture at "Baihui" (GV 20) through "Qubin" (GB 7) could downregulate the expression of NLRP3, IL-1β and IL-18 in the brain tissue of ICH rats, inhibit the inflammatory response, and promote the recovery of neural function.

Study on the correlation between tear inflammatory factors and symptoms in patients with dry eye / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To observe the correlation between the interleukin-1β(IL-1β)and interleukin-18(IL-18)in tears of patients with dry eye and symptoms and signs.<p>METHODS: A total of 131 patients(262 eyes)who were treated for dry eye in the ophthalmology clinic of the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine were selected from September 2018 to December 12, and the patients were divided into dry eye classification standards according to the dry eye clinical consensus in 2013 No dry eye group, mild dry eye group, moderate dry eye group, severe dry eye group. All patients were examined for dry eye symptom score, break up time(BUT), and tear secretion test Schirmer I test(SⅠt), corneal fluorescein sodium staining(FL), ELISA method to detect the expression of IL-1β and IL-18 in tears, and to analyze the correlation between dry eye inflammatory factors and symptoms and signs.<p>RESULTS: There were significant differences in the expression of dry eye symptoms, BUT, SⅠt, FL and IL-1β and IL-18 in tears(<i>P</i><0.001), inflammatory factors IL-1β, IL-18 and dry eye symptom scores. FL was positively correlated(<i>P</i><0.05)and negatively correlated with BUT and SⅠt(<i>P</i><0.05).<p>CONCLUSION:Inflammatory factors in tears of dry eye patients were correlation with dry eye symptom and signsa.

Correlation of interleukin-18 gene polymorphism with the susceptibility of condyloma acuminatum in Chinese population

ABSTRACT Host immunogenetic setting is involved in the regulation of human papillomavirus (HPV) infection and development of condyloma acuminatum (CA). We investigated the correlation of two common single nucleotide polymorphisms (SNPs) (−607C/A and −137G/C) of IL-18 with the susceptibility of CA in a large Chinese cohort. Out of 408 CA patients analyzed, 300 had HPV infection transmitted through sexual contact (SC) and 108 through non-sexual contact (NSC). In addition, 360 healthy volunteers were enrolled as controls. SNPs at positions −607C/A and −137G/C in IL-18 promoter were analyzed. Comparing CA patients to healthy controls, no dominant relevance was found between the IL-18 promoter −607 C/A or −137G/C polymorphisms and the CA disease either identified genotypically (p > 0.05) or by allelically (p > 0.05). However, the IL-18 promoter −137G/C polymorphism genotype and allele frequencies in the NSC CA group, but not between in the SC group, were significantly higher than in the controls. There was no dominant relevance between IL-18-607C/A polymorphism genotype and allele frequencies among SC, NSC CA patients, and controls. Our study demonstrates that polymorphism −137G/C in IL-18 promoter is significantly correlated with risk of CA in NSC patients.

In silico molecular docking and ADME/T analysis of plant compounds against IL17A and IL18 targets in gouty arthritis

Accumulation of urate crystals and subsequent inflammation are the major cause of pathogenesis of gout. Twopro inflammatory cytokines IL17A and IL18 are upregulated in the serum of gout patients and plays a major rolein promoting inflammation. Inhibition of these cytokines by plant phytochemicals would reduce the severity ofinflammation in gout. In the present study, in silico analysis of inhibition of IL17A and IL18 by 10 plant phytochemicalswere studied using the AutoDock 4.2 based on the principles of Lamarckian genetic algorithm. The results revealed abinding energy in the range of −6.32 kcal/mol to −3.5 kcal/mol and interacted with the amino acids in active pocketof IL17A and IL18. Among all the compounds, syringaresinol showing the least binding energy of −6.05 kcal/molwith IL17A and −6.32 kcal/mol with IL18. The control drug, allopurinol showed a binding energy of −3.32 and −3.18kcal/mol with IL17A and IL18, respectively. In addition, ADME/T properties of the compounds were also analyzed topredict their drug likeliness. This docking study can be used for developing potent inhibitors of IL17A and IL18 forthe treatment of gout.

Effect of Shenling Baizhu San on Expressions of NLPR3, NLPR6 Protein and Related Inflammatory Factors in Mice with Ulcerative Colitis / 中国实验方剂学杂志

Objective: To investigate the therapeutic effect and related mechanism of Shenling Baizhu San on 3% dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice. Method: Sixty male SPF C57BL/6 mice were randomly divided into control group, salazosulfapyridine (SASP, 0.52 g·kg-1), and low, medium and high-dose (31.2, 15.6, 7.8 g·kg-1) Shenling Baizhu San groups. Except for the control group, mice in the other groups were given distilled water containing 3% dextran sulfate sodium salt for a week to establish UC models. The drug was administered once a day for 14 days. The normal group and the model group were administered with 0.9%physiological saline at 20 mL·kg-1. The mice's body weight, fecal traits, and occult blood were observed daily, and the disease activity index (DAI) was scored. After the end of the administration, the blood was collected, mice colons were collected, weighed and measured for length, and pathological sections were prepared. Enzyme-linked immunosorbent assay (ELISA) kit was used to detect the serum levels of interleukin-18 (IL-18) and IL-1β in mice; htoxylin eosin (HE) and alixin blue/schiff periodic acid shiff(AB/PAS) staining were used to observe the pathological changes of colon tissues; Western blot was used to detect the colon tissue of mice nucleotide binding oligomerization domain-like receptor 3 (NLPR3), NLPR6 protein expression levels. Result: Compared with the normal group, the DAI score of the model group was increased (PPβ content increased (PPPβ concentration was decreased (PPPPConclusion: Shenling Baizhu San has the effect in treating DSS-induced UC mice, which may be related to the regulation of NLRP3, NLRP6 protein and related inflammatory factors, so as to reduce intestinal inflammation and alleviate intestinal mucosal damage.

Effect of Modified Erchentang on NLRP3 Inflammasome Expression in Peripheral Blood Mononuclear Cells (PBMCs) of Rats with Chronic Obstructive Pulmonary Disease / 中国实验方剂学杂志

Objective: To observe the effect of modified Erchentang on the expressions of NLRP3 inflammasome genes in peripheral blood mononuclear cells (PBMCs) and the levels of interleukin-1β(IL-1β)and interleukin-18(IL-18)and chemokine8 (CXCL8) in lung tissue of rats with chronic obstructive pulmonary disease (COPD), in order to explore the molecular mechanism of modified Erchentang against inflammation of COPD. Method: Forty SD rats were randomly divided into normal control group, model group, MCC950 (NLRP3 inhibitor) group and modified Erchentang group. The COPD model of rats was prepared by using cigarette smoke and dripping with lipopolysaccharide (LPS). During the modeling period (from the 1st to the 30th day), the MCC950 group received a single intraperitoneal injection with 60 mg · kg-1 on the first day of the experiment,and the modified Erchentang group was given intragastric administration with 10 g · kg-1, once every 2 days. From the 31st to the 45th day, the MCC950 group was intraperitoneally injected with 3 mg · kg-1, once every 2 days, the modified Erchentang group was given intragastric administration with 10 g · kg-1, twice a day, and the normal group and the model group received normal saline (NS) with 10 g · kg-1, twice a day. The levels of interleukin-1β(IL-1β), interleukin-18(IL-18) and chemokine8 (CXCL8) in rats lung tissue homogenate were detected by enzyme-linked immunosorbent assay (ELISA). The expressions of NLRP3, apoptosis-associated speck-like protein (ASC) and cysteinyl aspartate specific proteinase-1 (Caspase-1) mRNA in PBMCs were measured by Real-time fluorescence quantitative PCR (Real-time PCR). Western blot was used to detect the levels of NLRP3, ASC and Caspase-1 proteins in PBMCs. Immunohistochemical(IHC)method was used to detect the expressions of NLRP3, ASC and Caspase-1 proteins in lung tissues. Result: The expressions of NLRP3, ASC and Caspase-1 mRNA and protein were increased significantly (PPPβ and CXCL8 in lung tissue homogenate in model group were significantly higher than those in the control group. However, compared with model group, the levels of IL-18, IL-1β and CXCL8 were decreased significantly (PPConclusion: NLRP3 inflammasome is involved in the inflammatory response in COPD rats. Modified Erchentang may inhibit the inflammatory response of COPD effectively. The mechanism may be correlated with the reduction of NLRP3, ASC and Caspase-1 gene expressions, and the inhibition of the release of IL-18, IL-1β and CXCL8.

Downregulation of IL-18 Expression in the Gut by Metformin-induced Gut Microbiota Modulation

IL-18 is a crucial pro-inflammatory cytokine that mediates chronic intestinal inflammation. Metformin, an anti-diabetic drug, was reported to have ameliorative effects on inflammatory bowel disease. Recently, the mechanism of action of metformin was explained as a modulation of gut microbiota. In this study, fecal microbiota transplantation (FMT) using fecal material from metformin-treated mice was found to upregulate the expression of GLP-1 and pattern-recognition receptors TLR1 and TLR4 for the improvement in hyperglycemia caused by a high-fat diet. Further, FMT downregulated the expression of the inflammatory cytokine IL-18. Within the genera Akkermansia, Bacteroides, and Butyricimonas, which were promoted by metformin therapy, Butyricimonas was found to be consistently abundant following FMT. Our findings suggest that modulation of gut microbiota is a key factor for the anti-inflammatory effects of metformin which is used for the treatment of hyperglycemia.

Correlation between NLRP3 inflammation complex and the degree of optic nerve injury in primary glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To investigate the correlation between NLRP3 inflammation and optic nerve injury in primary open-angle glaucoma(POAG). <p>METHODS: Totally 65 POAG patients(98 eyes)in our hospital from May 2016 to May 2017 were selected, meanwhile 30 cataract patients(49 eyes)were as control group. Visual impairment was judged according to the mean defect value(MD)and divided into mild(group A), moderate(group B)and severe(group C)groups. The quality of IL-1β and IL-18 in plasma was detected by ELISA, and proportion of NLRP3, ASC and Caspase-1 positive macrophages was measured by flow cytometry. <p>RESULTS: The levels of IL-1β and IL-18 and the proportion of NLRP3, ASC and Caspase-1 positive cells in POAG group were obviously higher than those in control group(<i>P</i><0.05). The levels of IL-1β and IL-18 and the proportion of NLRP3, ASC and Caspase-1 positive cells in group C were highest in subgroups(<i>P</i><0.05). The serum levels of IL-1β and IL-18 in POAG patients were positively correlated with visual field injury(<i>r</i>=0.432, 0.765), and the proportion of positive cells of NLRP3, ASC and Caspase-1 was positively correlated with visual field injury(<i>r</i>=0.517, 0.481, 0.340). <p>CONCLUSION: Serum levels of IL-1β, IL-18 and the proportion of NLRP3, ASC and Caspase-1 positive macrophages are positively correlated with the degree of optic nerve injury in POAG patients.

Prevention of contrast-induced nephropathy by Cordyceps among patients undergoing percutaneous coronary procedures using intravenous contrast

@#<p style="text-align: justify;"><strong>OBJECTIVES:</strong> This study aimed to determine the efficacy and safety of Cordyceps in preventing occurrence of contrast-induced nephropathy (CIN) among patients undergoing CA / PCI using IV contrast compared to standard therapy.</p><p style="text-align: justify;"><strong>METHODS:</strong> We searched Medline, Embase, Cochrane database, and Google Scholars for RCTs involving the use of Cordyceps in contrast-induced nephropathy. We used the search keywords "Cordyceps" and "contrast-induced nephropathy" with the Boolean operator "AND" and filtering search results to include only randomized controlled trials and clinical trials. Three trials were found which satisfied all the inclusion criteria and none of the exclusion criteria.</p><p style="text-align: justify;"><strong>RESULTS:</strong> No patient developed clinical renal failure, adverse reactions, or side effects with the Cordyceps arm. CIN occurred in 26 out of 285 patients. The incidence of CIN was less in the Cordyceps group compared to the standard therapy group (p < 0.05, CI 0.20, 1.00).</p><p style="text-align: justify;"><strong>CONCLUSION:</strong> Cordyceps shows a trend towards prevention of CIN and a decrease in biomarkers for acute kidney injury. More studies with larger populations need to be performed to further clarify its preventive effects.</p>

Role of P2X7R/NLRP3 signaling pathway in alcoholic liver injury / 中国药理学通报

Aim To investigate the role of P2X7 recep-tor and its mediated NLRP3 inflammatory signaling pathway in alcohol-induced liver injury. Methods The acute alcoholic liver injury model was established by NIAAA method, and thirty C57BL/6 male mice were randomly divided into three groups (n =10):control group, model group, A438079 group, The three groups were processed as follows in the last week:control group and model group: given an equal dose of saline intraperitoneal injection(about 0.2 mL/only) once a day. According to the weight of the mice, A438079 group was given intraperitoneally injection by 200 μmol·kg-1of A-438079 (prepared at 7 g·L-1 of A438079,about 0.2 mL/only) once a day. And it was given a single 31.5% alcohol solution by intragas-tric administration on the last day of the morning,with the dose of 10 mL·kg-1. Nine hours later alanine aminotransferase (ALT), aspartate aminotransferase (AST),cholesterol(TCHO),triglyceride(TG) were measured by orbital blood in mice. HE staining was used to observe the pathological changes of the liver. Immunohistochemical method was applied to detect the expression of P2X7R in liver tissues. Western blot was employed to detect the levels of P2X7R, NLRP3, ASC, IL-1β and IL-18 in liver tissues. Results Compared with control group,the levels of ALT,AST, TG and TCHO in model group were significantly en-hanced, and the liver injury was obvious. Compared with model group, the levels of ALT, AST, TG and TCHO in A438079 group significantly decreased. Compared with control group, the expressions of P2X7, NLRP3, ASC, IL-1β, IL-18 in model group were significantly higher than those in control group. Compared with model group, the expression levels of P2X7, NLRP3, ASC, IL-1β and IL-18 in A438079 group significantly decreased. Conclusion Alcohol-induced liver injury may be associated with P2X7R-NLRP3 signaling pathway.

Effect of osthole on p38 MAPK signaling related pathway of rat model with inflammatory radicular pain induce by nucleus pulposus in the spinal horn / 中国药理学通报

Aim To observe the effect of epidurally application of osthole on the model of nucleus pulposusinduced inflammatory radicular pain and the expression of p38 MAPK signaling related pathway in the spinal dorsal horn of rats.Methods The model of radicular pain was generated by putting nucleus pulposus to the L5 dorsal root ganglion (DRG).50％ MWT was measured using Von Frey filaments to calculate mechanical pain threshold before and after operation.50 μL of 20 g · L-1 osthole was administered epidurally in group Ost and 50 μL of 100 mL · L-1 DMSO in group DMSO at postoperative day (POD).The expression of phosphorylated p38 (p-p38),IL-18 and IL-18R in the lumbar spinal dorsal horn was detected by Western blot.IL-18 mRNA was assessed by real-time PCR.Results The mechanical pain threshold significantly decreased after operation (P ＜ 0.05),while the expression of protein p-p38 MAPK,IL-18,IL-18R and IL-18 mRNA was significantly different.Compared with DMSO group,50％ MWT was significantly increased and accompanied with the decrease of protein p-p38,IL-18,IL-lgR and IL-18 mRNA in Ost group after drug administration (P ＜ 0.05).The correlation analysis between protein concentration of p38 MAPK and IL-18 mRNA showed that the Spearman correlation coefficient was 0.9 (P ＜ 0.05).Conclusion p-p38 and IL-18 of spinal dorsal horn participate in the rat model with inflammatory radicular pain induced by nucleus pulposus,and IL-18R plays a role in maintenance of the pain.Osthole administered epidurally in the early stage of pain could alleviate the pain for a long time,which may be related with inhibiting p38 MAPK signaling related pathways.

Expression of IL-18 in sepsis-associated thrombocytopenia and its clinical significance / 实用医学杂志

Objective To investigate the expression of IL-18 in severe sepsis and sepsis-associated throm-bocytopenia and explore its clinical significance.Methods Real-time polymerase chain reaction was applied to de-tect the expression of IL-18 miRNA in 28 samples of sepsis-associated thrombocytopenia patients and 32 samples of severe sepsis. The enzyme-linked immunosorbent assay was applied to detect the concentration of IL-18 in their plasma. Results The miRNA expression of IL-18 in the sepsis-associated thrombocytopenia group was higher than in the severe sepsis group(P=0.015).The concentration of IL-18 in the severe sepsis-associated thrombocyto-penia group were also higher than those in the severe sepsis group(P=0.034). Conclusion The expression level of IL-18 is related with the severity of thrombocytopenia in patients with sepsis and is likely to play an important role in the pathogenesis of sepsis-associated thrombocytopenia.