Inflammatory mediators and microcirculatory disturbance in acute pancreatitis

BACKGROUND: Inflammatory mediators are not only initiation factors of acute pancreatitis (AP) but also key factors causing pancreatic hemorrhage and necrosis, which damage important organs such as the heart, brain, liver, kidney and lung. Microcirculatory disturbance in AP has attracted widespread attention. In order to provide a theoretical basis for clinical therapy of AP, it is very important to explore the effect of inflammatory mediators on microcirculatory disturbance in this disease. DATA SOURCES: In this review, the impact of inflammatory mediators on microcirculatory disturbance in AP was reviewed according to the literature, especially the articles indexed in PubMed and books published in China and reports from websites. RESULTS: At present, inflammatory mediation and microcirculatory disturbance are the two major hypotheses to explain the development of AP. Although experimental studies have shown that inflammatory mediators induce or aggravate microcirculatory disturbance, the clinical application of these findings is still difficult because the inflammatory mediators are diverse and their research is not comprehensive and thorough. CONCLUSION: It is very important to explore the influence of inflammatory mediators on microcirculatory disturbance in AP.

The role of inflammatory mediators in severe acute pancreatitis and regulation of glucocorticoids

OBJECTIVE: To investigate the effect of glucocorticoids on systemic inflammatory mediator release in rats with acute pancreatitis and the outcome of dexamethasone in treatment of acute pancreatitis. METHODS: Sixty-eight Wistar rats were divided into sham, acute pancreatitis, and treatment (intravenous dexamethasone 0.5 mg/kg) groups. Experimental acute pancreatitis was induced by the injection of 5% sodium taurocholate (0.1 ml/100 mg body weight) into the pancreatic-biliary duct. The bIood samples were obtained and examined for 6-keto-PGI_1α, TXB_2 and IL-6 postoperatively at 3,6 and 12 hours, respectively. The pancreatic samples were evaluated by a blinded method. Twelve-hour survival rate was determined and compared between the groups. RESULTS: The high serum concentrations of 6-keto-PGI_1α, TXB_2 and IL-6 were noted in the rats with acute pancreatitis associated with pancreatic hemorrhage and necrosis. Their 12-hour survival rate was 42.9%. The rats in the treatment group survived with significantly reduced serum concentrations of 6-keto-PGI_1α, TXB_2 and IL-6 (P<0.05). Their pancreatic morphology was normal. CONCLUSION: Dexamethasone may reduce the serum concentration of 6-keto-PGI_1α, TXB_2, and IL-6, and the severity of acute pancreatitis while increasing the survival rate of rats with acute pancreatitis.

Nucleolin Mediates LPS-induced Expression of Inflammatory Mediators and Activation of Signaling Pathways

Summary:In this study,we investigated the effects of nucleolin on lipopolysaccharide(LPS)-induced activation of MAPK and NF-KappaB(NF-kB)signaling pathways and secretion of TNF-a,IL-1βand HMGB1 in THP-1 monocytes.Immunofluorescence assay and Western blotting were used to identify the nucleolin expression in cell membrane,cytoplasm and nucleus of THP-1 monocytes.Inactivation of nucleolin was induced by neutralizing antibody against nucleolin.THP-1 monocytes were pretreated with anti-nucleolin antibody for 1 h prior to LPS challenge.The irrelevant IgG group was used as control.Secretion of inflammatory mediators(TNF-a,IL-1β and HMGB1)and activation of MAPK and NF-kB/I-kB signaling pathways were examined to assess the effects of nucleolin on LPS-mediated inflammatory response.Nucleolin existed in cell membrane,cytoplasm and nucleus of THP-1 monocytes.Pretreatment of anti-nucleolin antibody significantly inhibited the LPS-induced secretion of TNF-a,IL-1β and HMGB1.P38,JNK,ERK and NF-κB subunit p65 inhibitors could significantly inhibit the secretion of IL-1β,TNF-a and HMGB1 induced by LPS.Moreover,the phosphorylation of p38,JNK,ERK and p65(or nuclear translocation of p65)was significantly increased after LPS challenge.In contrast,pretreatment of anti-nucleolin antibody could significantly inhibit the LPS-induced phosphorylation of p38,JNK,ERK and p65(or nuclear translocation of p65).However,the irrelevant IgG,as a negative control,had no effect on LPS-induced secretion of TNF-a and IL-Iβ and phosphorylation of p38,JNK,ERK and p65(or nuclear translocation of p65).We demonstrated that nucleolin mediated the LPS-induced activation of MAPK and NF-κB signaling pathways,and regulated the secretion of inflammatory mediators(TNF-a,IL-1β and HMGB1).

Effect of bevacizumab on the expression of fibrosis-related inflammatory mediators in ARPE-19 cells

AIM：To investigate the effect of anti-vascular epithelial growth factor（VEGF）agents on the expression of fibrosisrelated inflammatory mediators under normoxic and hypoxic conditions,and to further clarify the mechanism underlying fibrosis after anti-VEGF therapy. METHODS：Human retinal pigment epithelial（RPE）cells were incubated under normoxic and hypoxic conditions.For hypoxia treatment,CoCl_2 at 200μmol/L was added to the media. ARPE-19 cells were treated as following：1）control group：no treatment; 2）bevacizumab group：bevacizumab at 0.25 mg/mL was added to the media; 3）hypoxia group：CoCl_2 at 200 μmol/L was added to the media; 4）hypoxia＋bevacizumab group：CoCl_2 at 200 μmol/L and bevacizumab at 0.25 mg/mL were added to the media.The expression of interleukin（IL）-1β,IL-6,IL-8 and tumor necrosis factor（TNF）-α were evaluated using real-time polymerase chain reaction（RT-PCR）and enzyme-linked immunosorbent assay（ELISA）at 6,12,24 and 48 h. RESULTS：Both m RNA and protein levels of IL-1β,IL-6 and IL-8 were statistically significantly higher in the bevacizumab group than in the control group at each time point,and TNF-α gene and protein expression was only significantly higher only at 24 and 48h（P〈0.05）. Under hypoxic conditions,bevacizumab significantly increased the expression of IL-1β,IL-6,IL-8 and TNF-α at 6,12,24 and 48h（P〈0.05）. IL-1β,IL-8 and TNF-α peaked at 24 h and IL-6 peaked at 12 h after the bevacizumab treatment under both normoxic and hypoxic conditions. CONCLUSION：Treatment of ARPE-19 cells with bevacizumab can significantly increase the expression of fibrosis-related inflammatory mediators under bothnormoxic and hypoxic conditions. Inflammatory factors might be involved in the process of fibrosis after antiVEGF therapy,and the up-regulation of inflammatory factors induced by anti-VEGF drugs might promote the fibrosis process.

Comparison of early changes in ocular surface markers and tear inflammatory mediators after femtosecond lenticule extraction and FS-LASIK

AIM:To compare the short-term impacts of femtosecond lenticule extraction(FLEx)and femtosecond laser-assisted laser in situ keratomileusis(FS-LASIK)on ocular surface measures and tear inflammatory mediators.METHODS:This prospective comparative nonrandomized clinical study comprised 75 eyes(75 patients).Totally 20 male and 15 female patients(age 21.62±3.25 y)with 35 eyes underwent FLEx,and 26 male and 14 female patients(age 20.18±3.59 y)with 40 eyes underwent FS-LASIK.Central corneal sensitivity,noninvasive tear breakup time,corneal fluorescein staining,Schirmer I test,tear meniscus height,and ocular surface disease index were evaluated in all patients.Tear concentrations of nerve growth factor(NGF),interleukin-1α(IL-1α),transforming growth factor-β1(TGF-β1),tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),and matrix metalloproteinase-9(MMP-9)were assessed by multiplex antibody microarray.All measurements were performed preoperatively,and 1 d,1 wk,and 1 mo postoperatively.RESULTS:Patients who underwent FLEx exhibited a more moderate reduction in central corneal sensation and less corneal fluorescein staining than those in the FS-LASIK group 1 wk after the procedure(P<0.01).NGF was significantly higher 1 d and 1 wk after surgery in the FS-LASIK group than in the FLEx group(P<0.01).By contrast,compared to those in the FLEx group,higher postoperative values and slower recovery of tear TGF-β1,IL-1α,and TNF-αconcentrations were observed in the FS-LASIK group(P<0.01).Tear concentrations of NGF,TGF-β1,TNF-α,and IL-1αwere correlated with ocular surface changes after FLEx or FS-LASIK surgery.CONCLUSION:There is less early ocular surface disruption and a reduced inflammatory response after FLEx than after FS-LASIK.NGF,TGF-β1,TNF-α,and IL-1αmay contribute to the process of ocular surface recovery.

Interplay between nuclear factor erythroid 2-related factor 2 and inflammatory mediators in COVID-19-related liver injury

Coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2 is a global pandemic and poses a major threat to human health worldwide.In addition to respiratory symptoms,COVID-19 is usually accompanied by systemic inflammation and liver damage in moderate and severe cases.Nuclear factor erythroid 2-related factor 2(NRF2)is a transcription factor that regulates the expression of antioxidant proteins,participating in COVID-19-mediated inflammation and liver injury.Here,we show the novel reciprocal regulation between NRF2 and inflammatory mediators associated with COVID-19-related liver injury.Additionally,we describe some mechanisms and treatment strategies.

Effects of realgar on stress proteins, inflammatory mediators, and complement in brain tissue and serum of rats with inflammatory brain injury

BACKGROUND：The Chinese herbal compound realgar exerts detoxification effects as an adjuvant. It is suggested that realgar exerts detoxification via the following pathways： in the pathological state, realgar corrects the oxidative stress state by increasing stress levels, activating some endogenous protective factors and antagonizing the excessive release of inflammatory factors, as well as inhibiting complement activation. OBJECTIVE： To observe the changes in stress proteins, inflammatory mediators, and complement in the brain tissue and serum of rats with inflammatory brain injury, which have been treated with the Chinese herbal compound Angong Niuhuang, and to compare the efficacy of Angong Niuhuang with that of realgar, to verify the mechanism of action of realgar. DESIGN, TIME AND SETTING： Randomized, controlled, cytological experiment, performed in the Institute of Clinical Pharmacology, Guangzhou University of Traditional Chinese Medicine in March 2006. MATERIALS： Thirty-six healthy, male, Sprague Dawley rats received 250 U/kg Bordetella pertussis via the common carotid artery within 15 seconds to induce inflammatory brain injury. Reagents and kits were as follows： Realgar and Angong Niuhuang powder （Foshan Second Pharmaceutical Factory, China）, Bordetella pertussis diagnostic antigen （National Institute for the Control of Pharmaceutical and Biological Products, China）, heat shock protein 70 （HSP70） enzyme-labeled immunosorbent assay （ELISA） kit （Stressgen, USA）, tumor necrosis factor-α （TNF-α） ELISA kit （Biosource, USA）, nitric oxide synthase （NOS） kit, Coomassie brilliant blue protein kit （Nanjing Jiancheng Bioengineering Co.,Ltd., China）, and complements C3 and C4 （Shanghai Kehua Dongling Diagnositic Products Co.,Ltd., China）. METHODS： Thirty-six rats were randomly and evenly divided into the following six groups： normal control, model, high-, middle-, and low-dose realgar-treated, and Angong Niuhuang-treated groups. At one hour prior to establishing the model, rats in the high-, middle-, and low-dose realgar-treated groups were administered 300, 150, and 75 mg/kg realgar, respectively; while rats in the Angong Niuhuang group received 1.5 g/kg Angong Niuhuang powder; In the model group, rats were administered Bordetalla pertussis only. MAIN OUTCOME MEASURES： Two hours after the administration of Bordetalla pertussis, the HSP70 level in the brain tissue and serum levels of interleukin-1β （IL-1β）, interleukin-6 （IL-6）, and TNF-α were determined by ELISA tests, hemooxygenase-1 （HO-1） activity in the brain tissue and serum was determined by dual-wavelength spectrophotometry, NOS and inducible nitric oxide synthase （iNOS） activities in the brain tissue were measured by the Bradford assay method, and serum levels of complement C3 and C4 were determined by immunoturbidimetry. RESULTS： In the high-dose realgar and Angong Niuhuang groups, the HSP70 level in the brain tissue of rats with inflammatory brain injury was increased significantly （P 〈 0.01）. In the realgar-treated groups, HO-1 activity in the brain tissue and serum was dose-dependently enhanced with increasing realgar doses. However, no significant difference existed between the realgar groups and the model group （P 〉 0.05）. In the Angong Niuhuang group, HO-1 activity in the brain tissue and serum was increased （P 〈 0.05）. In the realgar and Angong Niuhuang groups, serum levels of IL-1β, IL-6, and TNF-α were significantly decreased; the serum IL-1β level recovered to the normal level and serum levels of IL-6 and TNF-α dose-dependently decreased in the realgar groups. NOS activity in the brain tissue was lower in the high-dose realgar group than in the model group （P 〈 0.05）. iNOS activity was significantly lower in the middle- and high-dose realgar groups than in the model group （P 〈 0.01）. NOS and iNOS activities were significantly lower in the Angong Niuhuang group than in the model group （P 〈 0.01）. The serum C3 level was significantly decreased in the middle-dose realgar and Angong Niuhuang groups （P 〈 0.01）. CONCLUSION： At certain doses, realgar is able to correct the oxidative stress state, by inducing and activating endogenous protective factors, such as HSP70, and inhibiting the excessive release of inflammatory mediators, such as IL-1β, IL-6, and TNF-α. However, it remains unclear whether realgarinhibits the activation of C3 and C4.

Fingolimod alters inflammatory mediators and vascular permeability in intracerebral hemorrhage

Intracerebral hemorrhage （ICH） leads to high rates of death and disability. The pronounced inflammatory reactions that rapidly follow ICH contribute to disease progression. Our recent clinical trial demonstrated that oral administration of an immune modulator fingolimod restrained secondary injury derived from initial hematoma, but the mechanisms remain unknown. In this study, we aim to investigate the effects of fingolimod on inflammatory mediators and vascular permeability in the clinical trial of oral fingolimod for intracerebral hemorrhage （ICH）. The results showed that fingolimod decreased the numbers of circulating CD4~ T, CD8~ T, CD19~ B, NK, and NKT cells and they recovered quickly after the drug＇ was stopped. The plasma ICAM level was decreased and IL-10 was increased by fingolimod. Interestingly, fingolimod protected vascular permeability as indicated by a decreased plasma level of MMP9 and the reduced rT1%. In conclusion, modulation of systemic inflammation by fingolimod demonstrates that it is an effective therapeutic agent for ICH. Fingolimod may prevent perihematomal edema enlargement by protecting vascular permeability.

Aerosolized STAT1 Antisense Oligodeoxynucleotides Decrease the Concentrations of Inflammatory Mediators in Bronchoalveolar Lavage Fluid in Bleomycin-Induced Rat Pulmonary Fibrosis

It has been demonstrated that alveolar macrophages （AMs） play a key role in the pathogenesis of pulmonary fibrosis by releasing a variety of cytokines and inflammatory mediators. In addition, abnormal signal transducer and activator of transcription-1 （STAT1） activation in AMs may play a pivotal role in the process of alveolitis and pulmonary fibrosis. In this study, we transfected STAT1 antisense oligodeoxynucleotide （ASON） into rats by aerosolization, and then investigated the effect of STAT1 ASON on inflammatory mediators such as TGF-β, PDGF and TNF-α in bronchoalveolar lavage fluid （BALF） from rats with bleomycln （BLM）-induced rat pulmonary fibrosis. Our results showed that STAT1 ASON by aerosolization could enter into lung tissues and AMs. STAT1 ASON could inhibit mRNA and protein expressions of STAT1 and ICAM-1 in AMs of rat with pulmonary fibrosis, and had no toxic side effect on liver and kidney. Aerosolized STAT1 ASON could ameliorate the alveolitis through inhibiting the secretion of inflammatory mediators in BLM-induced rat pulmonary fibrosis. These results suggest that aerosolized STAT1 ASON might be considered as a promising new strategy in the treatment of pulmonary fibrosis.

EFFECTS OF FILTER MEMBRANES ADSORBING INFLAMMATORY MEDIATORS IN HEMOFILTRATI ON

Objective In this study, an in vitro hemofiltration model was set up to investigate adsorptive saturati on time of different membrane under different blood flow rate (Q B)and filt rate rate(Q F). Methods Anticoagulated cattle blood (2000 mL per bag) was stimulated with 1μg·mL -1 endotoxin to induce i nflammatory mediators before hemofiltration (HF) using AN69, PS and PMMA filters in vitro. Adsorptive saturation time of membrane was observed using data br idge in different Q B and different Q F. TNF was measured by radioimmu noassays. Results Before the resistance level reached the peak value in the same group, resistance level increased significantly (P<0.01). After the peak value, there was no difference (P>05). It was suggested tha t the resistance level reached plateau at 150,120,90,120, and150 minutes in Q F of 100 mL·minute -1, 200 mL·minute -1, 300 mL·minute -1 , respectively and in Q F of 1L·hour -1, 2L·hour -1, 4L·hour -1, respectively. And with the Q B and Q F increasing, resistanc e level increased significantly (P<0.01) among different groups at the same time point in A, B, C, D and E group. Conclusion Membrane resis tance level online measured by Data Bridge can instantly reflect the degree of m embrane adsorption. Adsorptive saturation time of filter membrane in different f iltration flow rate and blood flow rate are different.

Value of inflammatory mediator profiles and procalcitonin in predicting postoperative infection in patients with hypertensive cerebral hemorrhage

BACKGROUND Hypertensive cerebral hemorrhage(HICH)is a common clinical cerebrovascular disease and one of the most serious complications of hypertension.Early warning of the occurrence of infection during treatment and timely anti-infective treatment are of great significance for the early prevention and treatment of postoperative infection in patients with HICH.Changes in the levels of inflammatory mediators,which are closely related to the occurrence and development of postoperative infection,and procalcitonin(PCT),which is a sensitive indicator for diagnosing bacterial infections,are widely used in clinical practice.AIM To explore the application value of inflammatory mediator profiles and PCT in predicting postoperative infection in patients with HICH.METHODS A total of 271 patients who underwent HICH surgery at our hospital between March 2019 and March 2021 were selected and divided into the infection(n=80)and non-infection(n=191)groups according to whether postoperative infection occurred.The postoperative infection status and etiological characteristics of the infective pathogens in the infection group were analyzed.Changes in inflammatory mediator profile indices and PCT levels were compared between the two groups,pre-and postoperatively.RESULTS A total of 109 strains of pathogenic bacteria were detected in the infection group,including 67 strains(61.47%)of gram-negative bacteria,32 strains(29.36%)of gram-positive bacteria,and 10 strains(9.17%)of fungi.The main infection site of the patients in the infection group was the respiratory system(63.75%).Preoperative interleukin(IL)-4,IL-6,IL-10,tumor necrosis factor-α,interferon-γ,and PCT levels were higher in the infection group than in the non-infection group(P<0.05),and there were no significant differences in the IL-2 Levels between the two groups(P>0.05).The inflammatory mediator profile indices and PCT levels were higher in the two groups of patients on the first postoperative day than preoperatively(P<0.05),and were higher than those in the non-infection group(P<0.05).Logistic regression analysis showed that preoperative IL-6 and PCT levels correlated with postoperative infection(P<0.05).Operating characteristic curve analysis results showed that the area under the curve(AUC)values of preoperative IL-6 and PCT levels in predicting postoperative infection in patients with HICH were 0.755 and 0.824,respectively.The AUC value of joint detection was 0.866,which was significantly higher than that of the single index(P<0.05).CONCLUSION Preoperative IL-6 and PCT levels are correlated with postoperative infection in patients with HICH.Their detection is clinically significant for early identification of patients at high risk for postoperative infection.

Extracorporeal blood purification strategies in sepsis and septic shock:An insight into recent advancements

BACKGROUND Despite various therapies to treat sepsis,it is one of the leading causes of mortality in the intensive care unit patients globally.Knowledge about the pathophysiology of sepsis has sparked interest in extracorporeal therapies(ECT)which are intended to balance the dysregulation of the immune system by removing excessive levels of inflammatory mediators.AIM To review recent data on the use of ECT in sepsis and to assess their effects on various inflammatory and clinical outcomes.METHODS In this review,an extensive English literature search was conducted from the last two decades to identify the use of ECT in sepsis.A total of 68 articles from peer-reviewed and indexed journals were selected excluding publications with only abstracts.RESULTS Results showed that ECT techniques such as high-volume hemofiltration,coupled plasma adsorption/filtration,resin or polymer adsorbers,and CytoSorb®are emerging as adjunct therapies to improve hemodynamic stability in sepsis.CytoSorb®has the most published data in regard to the use in the field of septic shock with reports on improved survival rates and lowered sequential organ failure assessment scores,lactate levels,total leucocyte count,platelet count,interleukin-IL-6,IL-10,and TNF levels.CONCLUSION Clinical acceptance of ECT in sepsis and septic shock is currently still limited due to a lack of large random clinical trials.In addition to patient-tailored therapies,future research developments with therapies targeting the cellular level of the immune response are expected.

Observation on Curative Effect of Self-made Wubeizi Decoction Combined with rhaFGF in Promoting Postoperative Wound Healing in Patients with Anal Fistula

[Objectives]To explore the curative effect of Self-made Wubeizi Decoction combined with recombinant human acidic fibroblast growth factor(rhaFGF)in promoting postoperative wound healing in patients with anal fistula.[Methods]A total of 82 patients with anal fistula who underwent anal fistula resection+use of setons in Luodian Hospital during January and March of 2020 were randomly divided into observation group and control group with 41 cases in each group.The control group was given rhaFGF external application regimen,and the observation group was treated with Self-made Wubeizi Decoction on the basis of the control group.After 3 weeks of treatment,the differences in curative effects of TCM syndromes were compared between the two groups.Besides,the changes in TCM symptom scores,inflammatory mediators[interleukin-12(IL-12),tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ)],anorectal functions[anal resting pressure(ARP),maximal systolic pressure(MSP)and maximum tolerated volume(MTV)of the anal canal],quality of life[GQOLI-74 scores]were compared.[Results]After 3 weeks of treatment,the total effective rate of the observation group was significantly higher than that of the control group(P<0.05);the levels of TCM symptom scores,IL-12,TNF-α,IFN-γ,ARP,MSP,and MTV in both groups were significantly lower than those before treatment,and these levels in the observation group was significantly lower than that in the control group at the same time(P<0.05).The GQOLI-74 scores of both groups were significantly higher than those before treatment,and the observation group was significantly higher than the control group(P<0.05).[Conclusions]The Self-made Wubeizi Decoction combined with rhaFGF therapy has a significant effect in promoting postoperative wound healing in patients with anal fistula.It can effectively inhibit the local inflammation of patients,facilitate the recovery of anorectal function and improve the quality of life,thus has high clinical application value.

Understanding the mechanisms underlying obesity in remodeling the breast tumor immune microenvironment:from the perspective of inflammation

Obesity is a well-known modifiable risk factor for breast cancer and is considered a poor prognostic factor in pre-and post-menopausal women.While the systemic effects of obesity have been extensively studied,less is known about the mechanisms underlying obesityassociated cancer risk and the local consequences of obesity.Thus,obesity-induced inflammation has become the focus of research interest.Biologically,the development of cancer involves a complex interaction with numerous components.As the tumor immune microenvironment changes due to obesity-triggered inflammation,an increase in infiltration occurs for proinflammatory cytokines and adipokines,as well as adipocytes,immune cells,and tumor cells in the expanded adipose tissue.Complicated cellular-molecular crosstalk networks change critical pathways,mediate metabolic and immune function reprogramming,and have a significant role in tumor metastasis,proliferation,resistance,angiogenesis,and tumorigenesis.This review summarizes recent research findings on how inflammatory mediators in the in situ tumor microenvironment regulate the occurrence and development of breast cancer in the context of obesity.We analyzed the heterogeneity and potential mechanisms of the breast cancer immune microenvironment from the perspective of inflammation to provide a reference for the clinical transformation of precision targeted cancer therapy.

酪酸梭菌对高尿酸血症大鼠血尿酸及炎性因子水平的影响

目的研究酪酸梭菌干预对高尿酸血症大鼠血清尿酸、脂多糖、白介素6、肿瘤坏死因子α的影响。方法将40只SD大鼠随机分为正常对照组、高尿酸模型组、苯溴马隆干预组(3 mg/kg·d)和酪酸杆菌干预组(活菌1.5×107CFU/d),每组10只。除正常对照组外各组给予酵母膏联合氧嗪酸钾灌胃制备高尿酸血症模型,各组药物及活菌每天灌胃1次,连续12周。观察各组大鼠血尿酸、脂多糖、白介素6、肿瘤坏死因子α水平变化。结果实验期间高嘌呤饮食大鼠血尿酸水平较正常对照组明显升高(P<0.01),高尿酸血症模型建立成功且稳定。高尿酸模型组大鼠血脂多糖、白介素6、肿瘤坏死因子α水平与血尿酸水平呈正相关。苯溴马隆及酪酸梭菌干预处理后大鼠血尿酸、脂多糖、白介素6、肿瘤坏死因子α水平有明显下降(P<0.01),干预时间越长,效果越佳,其中苯溴马隆降尿酸效应更为明显,酪酸梭菌下调脂多糖、白介素6、肿瘤坏死因子α等炎性因子作用更为明显(P<0.01)。结论高尿酸血症大鼠可能存在慢性炎症反应,酪酸梭菌可有效降低血尿酸水平,同时抑制炎症细胞因子的生成,维持肠道免疫稳态。

Protective effects of human umbilical cord mesenchymal stem cell vein transplantation against spinal cord ischemia/reperfusion injury in rats

BACKGROUND： The majority of studies addressing spinal cord ischemia/reperfusion injury （SCIRI） have focused on drugs, proteins, cytokines, and various surgical techniques. A recent study reports that human umbilical cord mesenchymal stem cell （hUCMSC） transplantation achieves good therapeutic effects, but the mechanisms underlying nerve protection remain poorly understood. OBJECTIVE： To observe survival of transplanted hUCMSCs in SCIRI rat models and the influence on motor function in the hind limbs, to determine interleukin-8 expression and cellular apoptosis in spinal cord tissues, and to verify the hypothesis that hUCMSC transplantation exhibits protective effects on SCIRI. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Laboratory of the Department of Orthopedics in the First Affiliated Hospital of Soochow University, China between January 2007 and December 2008. MATERIALS： hUCMSCs were harvested from umbilical cord blood of healthy pregnant women after parturition in the Obstetrical Department of the First Affiliated Hospital of Soochow University, China. Rabbit anti-human BrdU monoclonal antibody was provided by DAKO, USA. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） Kit and enzyme-linked immunosorbent assay （ELISA） Kit were purchased by Wuhan Boster, China. METHODS： A total of 72 healthy, Wistar, adult rats were randomly assigned to three groups： sham-surgery, model, and transplantation, with 24 rats in each group. SCIRI was induced in the model and transplantation groups via the abdominal aorta block method. The infrarenal abdominal aorta was not blocked in the sham-surgery group. Prior to abdominal aorta occlusion, 0.2 03 mL bromodeoxyuridine （BrdU）-Iabeled hUCMSCs suspension （cell concentration 5 × 10 3/uL） was injected through the great saphenous vein of the hind limb, and an equal volume of physiological saline was administered to the model and sham-surgery groups. MAIN OUTCOME MEASURES： Pathological observation of rat spinal cord tissues was performed by hematoxylin-eosin staining at 6, 24, and 48 hours post-surgery. Immunohistochemistry was applied to determine hUCMSCs survival in the spinal cord. The amount of cellular apoptosis and interleukin-8 expression in spinal cord tissues was assayed utilizing the TUNEL and ELISA methods, respectively. Motor function in the hind limbs was evaluated according to Jacob＇s score. RESULTS： Numerous BrdU-positive cells were observed in spinal cord tissues from the transplantation group. The number of apoptotic cells and interleukin-8 levels significantly decreased in the transplantation group （P 〈 0.05）, pathological injury was significantly ameliorated, and motor function scores significantly increased （P 〈 0.05） compared with the model group. CONCLUSION： Via vein transplantation, hUCMSCs were shown to reach and survive in the injury area. Results suggested that the transplanted hUCMSCs contributed to significantly improved pathological changes in the injured spinal cord, as well as motor function, following SCIRI. The protective mechanism correlated with inhibition of cellular apoptosis and reduced production of inflammatory mediators.

The mechanisms in treatment of acute pancreatitis by traditional Chinese medicine

As common acute abdomen, most of acute pancreatifis（AP） are self-restricted. Only a few patients may develop into worse state with local complications or organ failures, and finally neastic acute pancreatitis （NAP）. With the change of people＇s dietaries, cholelithiasis morbidity and popularization of wine in recent years, the number of AP patients has increased. Although people conducted enormous studies on pathogenesis of AP and brought forward many be valuable theories, yet the exact mechanism is still unclear by far. There are many therapies of AP which should be unexceptionally classified as operative therapy and non-operative therapy. With the increasing understanding of the disease in recent years, we found many defects of operation and good therapeutic effects of traditional Chinese medicine in AP. Traditional Chinese medicine as an auxiliary therapy has been generally paid close attention in clinical practices. Traditional Chinese medicine is a treasure-house of China. This article summarizes the main mechanisms of AP treatment by traditional Chinese medicine and the progress of laboratory studies. It aims to help people recognize the multiple-target treatment effects and conspicuous efficacy of traditional Chinese medicine and promote the popularization of traditional Chinese medicine in AP treatment.

Efficacy and Safety Study of CA330 Hemadsorption Device on IL-6 Removal in Septic Patients: Study Protocol of a Multicenter Randomized Controlled Trial

Background: Sepsis persists to be the leading cause of morbidity and mortality worldwide with the huge cost of health care resources. Besides adequate antibiotics and infectious source control, definitive therapy is still being studied. The activation of multiple pro- and anti-inflammatory mediators plays a key role in the sepsis process. The application of adsorption may help deactivate and decrease the peak elevation of these mediators in the earlier course of sepsis, when levels of endotoxins and cytokines are extremely high. However, the clinical evidence to support hemadsorption for removing endotoxins and/or pro-inflammatory mediators in sepsis remains incompetent and controversial. In this study protocol, we aimed to test the efficacy of removing cytokines and the safety of a new hemadsorption device, CA330, in septic patients. Design: This is a multicenter randomized controlled clinical trial enrolling 8 tertiary hospitals in China. A total of 144 patients will be randomly divided into the experimental group and the control group according to the ratio of 1:1. The primary endpoint is the reduction rate of IL-6 serum concentration between the initiation of the first adsorption and end with the second adsorption. Discussion: To our knowledge, this clinical trial is the first to evaluate the efficacy and safety of the CA330 hemadsorption device in sepsis patients. Our study will raise the level of evidence for the treatment of sepsis patients with hemadsorption.

Cationic antimicrobial protein of Mr 37 kDa:a multifunctional inflammatory protein

investigate the role of cationic antimicrobial protein of Mr 37?kDa (CAP37) a neutrophil derived inflammatory mediator on endothelial cell function Data sources Endothelial cells used in this study were obtained from human lung microvessels and rat aorta The latter was a kind gift of Dr Paula Grammas The mono mac 6 cell line used in this study was the generous gift of Dr H W Loms Ziegler Heitbrock Study selection and data extraction Endothelial cell proteins kinase C activity was determined by measuring calcium and phospholipid dependent phosphorylation of histone Endothelial cell migration was determined using Costar TM Transwell apparatus Cell surface expression of adhesion molecules, ICAM 1 and PECAM 1 was determined using flow cytometry RT PCR was used to amplify the CAP37 from endothelial cells treated with LPS Results We demonstrated that CAP37 which was originally identified as having potent antimicrobial activity and chemotactic activity for monocytes was capable of modulating endothelial cell functions CAP37 activated endothelial cell protein kinase C in a dose and time dependent fashion Importantly CAP37 increased the adhesive properties of the endothelium for monocytes CAP37 upregulated the well known adhesion molecules, ICAM 1 and PECAM 1 in a dose and time dependent manner In addition, CAP37 promoted endothelial cell migration Further investigations indicated that CAP37 was induced in endothelial cells in response to pro inflammatory cytokines such as tumor necrosis factor α and interleukin 1α as well as inflammatory mediators such as lipopolysaccharide Unstimulated endothelial cells did not constitutively express CAP37 The cDNA sequence of endothelial CAP37 was determined and found to be highly homologous to the sequence obtained for neutrophil derived CAP37 Conclusions Our studies strongly suggest that CAP37 plays a pivotal role in monocyte endothelial interactions and the transmigration of monocytes from the vasculature into extravascular

Inflammation-associated ectopic mineralization

Ectopic mineralization refers to the deposition of mineralized complexes in the extracellular matrix of soft tissues.Calcific aortic valve disease,vascular calcification,gallstones,kidney stones,and abnormal mineralization in arthritis are common examples of ectopic mineralization.They are debilitating diseases and exhibit excess mortality,disability,and morbidity,which impose on patients with limited social or financial resources.Recent recognition that inflammation plays an important role in ectopic mineralization has attracted the attention of scientists from different research fields.In the present review,we summarize the origin of inflammation in ectopic mineralization and different channels whereby inflammation drives the initiation and progression of ectopic mineralization.The current knowledge of inflammatory milieu in pathological mineralization is reviewed,including how immune cells,pro-inflammatory mediators,and osteogenic signaling pathways induce the osteogenic transition of connective tissue cells,providing nucleating sites and assembly of aberrant minerals.Advances in the understanding of the underlying mechanisms involved in inflammatory-mediated ectopic mineralization enable novel strategies to be developed that may lead to the resolution of these enervating conditions.