Traumatic spinal cord injury result in considerable and lasting functional impairments,triggering complex inflammatory and pathological events.Spinal cord scars,often metaphorically referred to as“fire barriers,”aim...Traumatic spinal cord injury result in considerable and lasting functional impairments,triggering complex inflammatory and pathological events.Spinal cord scars,often metaphorically referred to as“fire barriers,”aim to control the spread of neuroinflammation during the acute phase but later hinder axon regeneration in later stages.Recent studies have enhanced our understanding of immunomodulation,revealing that injury-associated inflammation involves various cell types and molecules with positive and negative effects.This review employs bibliometric analysis to examine the literature on inflammatory mediators in spinal cord injury,highlighting recent research and providing a comprehensive overview of the current state of research and the latest advances in studies on neuroinflammation related to spinal cord injury.We summarize the immune and inflammatory responses at different stages of spinal cord injury,offering crucial insights for future research.Additionally,we review repair strategies based on inflammatory mediators for the injured spinal cord.Finally,this review discusses the current status and future directions of translational research focused on immune-targeting strategies,including pharmaceuticals,biomedical engineering,and gene therapy.The development of a combined,precise,and multitemporal strategy for the repair of injured spinal cords represents a promising direction for future research.展开更多
[Objectives]To observe the clinical effect of the lotus needle cupping therapy for removing blood stasis in Zhuang medicine in treating PHNand its influence on inflammatory factors.[Methods]96 patients with PHN were r...[Objectives]To observe the clinical effect of the lotus needle cupping therapy for removing blood stasis in Zhuang medicine in treating PHNand its influence on inflammatory factors.[Methods]96 patients with PHN were randomly divided into three groups:lotus nee-dle cupping therapy group,TCM surrounding acupuncture group and gabapentin group.Venous blood and acupoint blood were collected at 0,21 and 42 d of treatment,and the expression levels of 5-HT,SP and CGRPinflammatory mediators were detected before and after treatment.The changes of VAS scores before,during and after treatment and the clinical efficacy were observed.[Results]The total effective rate of the lotus needle cupping group was 87.50%,which was better than that of the TCM acupuncture group(81.25%)and the gabapentin group(62.50%);after treatment,the VAS scores and the expression of inflammatory mediators in the three groups of patients were lower than those before treatment,and the decrease was more significant in the treatment group(P<0.05).[Conclusions]The lotus needle cupping therapy for removing blood stasis in Zhuang medicine is effective in treating PHN,and its mechanism is to reduce the release of inflammatory media-tors,reduce hyperalgesia,relieve pain and improve the quality of life of patients.展开更多
AIM: To investigate the influence of high dose of dexamethasone on inflammatory mediators and apoptosis of rats with severe acute pancreatitis (SAP). METHODS: SAP rats were randomly assigned to the model group and tre...AIM: To investigate the influence of high dose of dexamethasone on inflammatory mediators and apoptosis of rats with severe acute pancreatitis (SAP). METHODS: SAP rats were randomly assigned to the model group and treatment group while the normal rats were assigned to the sham operation group. The mortality,ascite volumes,ascites/body weight ratio and pancreas pathological changes of all rats were observed at 3,6 and 12 h after operation. Their contents of amylase and endotoxin in plasma and contents of tumor necrosis factor (TNF-α),phospholipase A2 (PLA2) and IL-6 in serum were also determined. The microarray sections of their pancreatic tissues were prepared,terminal transferase dUTP nick end labeling (TUNEL) staining was performed and apoptotic indexes were calculated. RESULTS: There was no marked difference between treatment group and model group in survival. The contents of amylase and endotoxin in plasma and contents of TNF-α,PLA2 and IL-6 in serum,ascite volumes,ascites/body weight ratio and pancreas pathological scores were all lower in treatment group than in model group to different extents at different time points P < 0.05,58.3 (26.4) ng/L vs 77.535 (42.157) ng/L in TNF-α content,8.00 (2.00) points vs 9.00 (2.00) points in pathological score of pancreas respectively; P < 0.01,0.042 (0.018) EU/mL vs 0.056 (0.0195) EU/mL in endotoxin content,7791 (1863) U/L vs 9195 (1298) U/L in plasma amylase content,1.53 (0.79) vs 2.38 (1.10) in ascites/body weight ratio,8.00 (1.00) points vs 11.00 (1.50) points in pathological score of pancreas; P < 0.001,3.36 (1.56) ng/L vs 5.65 (1.08) ng/L in IL-6 content,4.50 (2.00) vs 7.20 (2.00),4.20 (1.60) vs 6.40 (2.30),3.40 (2.70) vs 7.90 (1.70) in ascite volumes,respectively. The apoptotic indexes of pancreas head and pancreas tail were all higher in treatment group than in model group at 6 h P < 0.01,0.00 (2.00)% vs 0.00 (0.00)%,0.20 (1.80) vs 0.00 (0.00) in apoptosis indexes,respectively. CONCLUSION: The mechanism of dexamethasone treatment in acute pancreatitis is related to its inhibition of inflammatory mediator generation and induction of pancreatic acinar cell apoptosis.展开更多
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, li...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.展开更多
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:Th...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.展开更多
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-eig...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.展开更多
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.Imm...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).展开更多
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 mecha...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.展开更多
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 tha...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.展开更多
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 usual...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.展开更多
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...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.展开更多
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 transdu...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.展开更多
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 Ant...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.展开更多
Introduction When the body is infected,pathogenic microorganisms and their toxins can enter the blood circulation and grow and proliferate in the blood,producing more toxins.These toxins and pathogens activate the bod...Introduction When the body is infected,pathogenic microorganisms and their toxins can enter the blood circulation and grow and proliferate in the blood,producing more toxins.These toxins and pathogens activate the body's immune system,leading to the release of a varieties of cytokines and inflammatory mediators,resulting in systemic inflammatory response syndrome[1].展开更多
Neuroinflammation is an inflammatory response in the central nervous system associated with various neurological conditions.The inflammatory process is typically treated with non-steroidal and steroidal anti-inflammat...Neuroinflammation is an inflammatory response in the central nervous system associated with various neurological conditions.The inflammatory process is typically treated with non-steroidal and steroidal anti-inflammatory drugs,which have a range of serious adverse effects.As an alternative,naturally derived molecules such as quercetin and its derivatives show promising anti-inflammatory properties and beneficial effects on various physiological functions.Our objective was to synthesize the evidence on the anti-inflammatory effect of quercetin and its derivatives in in vivo models,in the face of neuroinflammatory insults induced by lipopolysaccharide,through a systematic review and meta-analysis.A search of the preclinical literature was conducted across four databases(Pub Med,Web of Science,Scielo,and Google Scholar).Studies were selected based on inclusion and exclusion criteria,assessed for methodological quality using CAMARADES,and risk of bias using the SYRCLE tool,and data were extracted from the studies.The quantitative assessment of quercetin effects on the expression of pro-inflammatory cytokines and microgliosis was performed through a meta-analysis.A total of 384 potentially relevant articles were identified,of which 11 studies were included in the analysis.The methodological quality was assessed,resulting in an average score of 5.8/10,and the overall risk of bias analysis revealed a lack of methodological clarity in most studies.Furthermore,through the meta-analysis,it was observed that treatment with quercetin statistically reduces pro-inflammatory cytokines,such as tumor necrosis factor alpha,interleukin 6,interleukin 1β(n=89;SMD=–2.00;95%CI:–3.29 to–0.71),and microgliosis(n=33;SMD=–2.56;95%CI:–4.07 to–1.10).In terms of underlying mechanisms,quercetin and its derivatives exhibit antioxidant and anti-apoptotic properties,possibly through the nuclear factor erythroid 2-related factor 2(Nrf2)/HO-1 pathways,increasing the expression of antioxidant enzymes and reducing reactive species,and modulating the caspase pathway,increasing levels of anti-apoptotic proteins and decreasing proapoptotic proteins.Quercetin and its derivatives exhibit highly pleiotropic actions that simultaneously contribute to preventing neuroinflammation.However,despite promising results in animal models,future directions should focus on well-designed clinical studies to assess the safety,bioavailability,and efficacy of quercetin and its derivatives in humans.Additionally,standardization of methods and dosages in studies is crucial to ensure consistency of findings and optimize their application in clinical settings.展开更多
Glucocorticoids are widely utilized for treating various immune and inflammation-related diseases,prompting significant interest in their potential application for COVID-19 treatment.This study explored the efficacy a...Glucocorticoids are widely utilized for treating various immune and inflammation-related diseases,prompting significant interest in their potential application for COVID-19 treatment.This study explored the efficacy and safety of dexamethasone(DEX)and methylprednisolone(MP)in treating severe COVID-19.A cohort of 94 adult patients,aged 18 years and older,with severe COVID-19 was recruited.They received intravenous MP(40-80 mg/d)or DEX(5-10 mg/d)for 7-10 d.The primary objective was to assess the effects of these treatments on mortality rates.Additionally,the study aimed to compare the impact of these medications on various parameters,including the oxygenation index,inflammatory index,fungal infections,and hyperglycemia,serving as secondary endpoints.The findings revealed no fatalities in either group.However,there was one case of pulmonary fibrosis and Aspergillus fumigatus infection in the DEX group,and two cases of Aspergillus infection in the MP group.Although the differences were not statistically significant(P>0.05),the MP group showed a faster improvement in blood oxygen saturation compared to the DEX group,with a median time of 5 d vs 7 d.No statistically significant difference was observed between the two groups regarding improvement in C-reactive protein levels(P>0.05).Notably,DEX was associated with a higher incidence of hyperglycemia compared to MP(P<0.05).Both DEX and MP significantly reduced mortality rates among patients with severe COVID-19 and improved blood oxygen saturation and inflammatory markers.However,MP exhibited a more rapid onset of efficacy and fewer adverse reactions.展开更多
The subcutaneous air pouch model has been used extensively to study the pathophysiology of inflammatory conditions such as joint diseases and the potential efficacy of pharmacological treatments in vivo.Delivery of ai...The subcutaneous air pouch model has been used extensively to study the pathophysiology of inflammatory conditions such as joint diseases and the potential efficacy of pharmacological treatments in vivo.Delivery of air between the subcutaneous and dermal layer of the intra-scapular zone of the rodent generates an environment analogous to the synovial joint space.Introduction of monosodium urate crystals or calcium pyrophosphate crystals into the air space produces a sterile acute inflammatory response mimicking clinical gout and pseudogout,respectively.The inflammatory response can be quantitatively and robustly evaluated by measuring leukocyte infiltration,inflammatory cytokine production,eicosanoid release,complement activation and reactive oxygen species generation.Despite the utility of this model,great variation exists within the literature regarding the design,sampling time points,and endpoints measured.This systematic review summarizes the current literature on the subcutaneous air pouch model studying monosodium urate or calcium pyrophosphate crystals and provides recommendations for standardizing and improving the reliability and validity of this model.Standardizing the experimental approach would improve inter-study comparability,increase the internal validity of studies and reproducibility of results,and ultimately improve the understanding of gout and pseudogout and accelerate the discovery of new pharmacological therapies.展开更多
AIM： To assess whether a correlation exists between oxidative DNA damage occurring in chronic HCV-related hepatitis and expression levels of pro-inflammatory cytokines, TGF-α and c-myc. METHODS： The series included...AIM： To assess whether a correlation exists between oxidative DNA damage occurring in chronic HCV-related hepatitis and expression levels of pro-inflammatory cytokines, TGF-α and c-myc. METHODS： The series included 37 patients with chronic active HCV-related hepatitis and 11 with HCV-related compensated cirrhosis. Eight-hydroxydeoxyguanosine in liver biopsies was quantified using an electrochemical detector. The mRNA expression of TNF-α, IL-1β, TGF-α and c-myc in liver specimens was detected by semiquantitative comparaUve RT-PCR. RESULTS： TNF-α levels were significantly higher in hepatitis patients than in cirrhosis patients （P=0.05）. IL-1β was higher in cirrhosis patients （P=0.05）. A sig- nificant correlation was found between TNF-α and staging （P= 0.05） and between IL-1β levels and grading （P=0.04）. c-myc showed a significantly higher expression in cirrhosis patients （P=0.001）. Eight-hydroxydeoxyguanosine levels were significantly higher in cirrhosis patients （P=0.05） and in HCV genotype 1 （P=0.03）. Considering all patients, 8-hydroxydeoxyguanosine levels were found to be correlated with genotype （P=0.04） and grading （P=0.007）. Also multiple logistic regression analysis demonstrated a significant correlation among the number of DNA adducts, TNF-α expression and HCV genotype （P= 0.02）. CONCLUSION： In chronic HCV-related liver damage, oxidative DNA damage correlates with HCV genotype, grading and TNF-α levels. As HCV-related liver damage progresses, TNF-α levels drop while IL-1β and c-myc levels increase, which may be relevant to liver carcinogenesis.展开更多
Sepsis is an infection induced systemic inflammatory response syndrome and is a major cause of morbidity as well as mortality in intensive care units. A growing body of evidence suggests that the activation of a proin...Sepsis is an infection induced systemic inflammatory response syndrome and is a major cause of morbidity as well as mortality in intensive care units. A growing body of evidence suggests that the activation of a proinflammatory cascade is responsible for the development of immune dysfunction, susceptibility to severe sepsis and septic shock. The present theories of sepsis as a dysregulated inflammatory response and immune function, as manifested by excessive release of inflammatory mediators such as high mobility group box 1 protein （HMGB1）, are supported by increasing studies employing animal models and clinical observations of sepsis. HMGB1, originally described as a DNA-binding protein and released passively by necrotic cells and actively by macrophages/monocytes, has been discovered to be one of essential cytokines that mediates the response to infection, injury and inflammation. A growing number of studies still focus on the inflammation-regulatory function and its contribution to infectious and inflammatory disorders, recent data suggest that HMGB1 formation can also markedly influence the host cell-mediated immunity, including T lymphocytes and macrophages. Here we review emerging evidence that support extracellular HMGB1 as a late mediator of septic complications, and discuss the therapeutic potential of several HMGBl-targeting agents in experimental sepsis. In addition, with the development of traditional Chinese medicine in recent years, it has been proven that traditional Chinese herbal materials and their extracts have remarkable effective in treating severe sepsis. In this review, we therefore provide some new concepts of HMGBl-targeted Chinese herbal therapies in sepsis.展开更多
Thais luteostoma has been utilized as a crude drug whose shell and soft tissue have been widely used for the treatment of heat syndrome in China for thousands of years. The present study was designed to investigate th...Thais luteostoma has been utilized as a crude drug whose shell and soft tissue have been widely used for the treatment of heat syndrome in China for thousands of years. The present study was designed to investigate the antipyretic and anti-inflammatory activities of T. luteostoma. T. luteostoma was divided into shell （TLSH） and soft tissue （TLST） samples in the present study. The rat model of yeast-induced fever was used to investigate their antipyretic effects; and the rat model of hind paw edema induced by carrageenan was utilized to study their anti-inflammatory activities, and at the same time, the concentration variations of the central neurotransmitter [prostaglandin E2 （PGE2） and cyclic adenosine monophosphate （cAMP）], inflammatory mediators [tumor necrosis factor （TNFα）, interleukin-1β （IL-1）, interleukin-2 （IL-2） and interleukin-6 （IL-6）] and ion （Na^＋ and Ca^2＋） were also tested. The results showed that TLSH and TLST extracts significantly inhibited yeast-induced pyrexia in rats （P 〈 0.05）, and exhibited more lasting effects as compared to aspirin, and TLSH had the better antipyretic activity than TLST, and that TLSH and TLST could significantly prevent against carrageenan induced paw edema in rats （P 〈 0.05）; and markedly reduced levels of PGE2, cAMP, TNFα, IL-1β, IL-2, IL-6, and Na^＋/Ca^2＋. In fever model, TLST could significantly reduce the levels of PGE2 （P 〈 0.01） in rats＇ homogenate and TNF a （P 〈 0.05）, IL-113 （P 〈 0.01） in the plasma than TLSH, whereas TLSH could reduce the content of IL-2 （P 〈 0.01） and IL-6 （P 〈 0.01） in plasma and increase the content of Ca2＋ （P 〈 0.01） in plasma and homogenate more significantly than TLST. In conclusion, T. luteostoma extract has antipyretie and anti-inflammatory activities, which may be mediated through the suppression of production of PGE2, cAMP, Na^＋/Ca^2＋ , TNF a, IL-1β, IL-2, and IL-6.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82272470 (to GN),82072439 (to GN),81930070 (to SF)the Tianjin Health Key Discipline Special Project,No.TJWJ2022XK011 (to GN)+2 种基金the Outstanding Youth Foundation of Tianjin Medical University General Hospital,No.22ZYYJQ01 (to GN)Tianjin Key Medical Disciplines,No.TJYXZDXK-027A (to SF)National Key Research and Development Program-Stem Cells and Transformation Research,No.2019YFA0112100 (to SF)
文摘Traumatic spinal cord injury result in considerable and lasting functional impairments,triggering complex inflammatory and pathological events.Spinal cord scars,often metaphorically referred to as“fire barriers,”aim to control the spread of neuroinflammation during the acute phase but later hinder axon regeneration in later stages.Recent studies have enhanced our understanding of immunomodulation,revealing that injury-associated inflammation involves various cell types and molecules with positive and negative effects.This review employs bibliometric analysis to examine the literature on inflammatory mediators in spinal cord injury,highlighting recent research and providing a comprehensive overview of the current state of research and the latest advances in studies on neuroinflammation related to spinal cord injury.We summarize the immune and inflammatory responses at different stages of spinal cord injury,offering crucial insights for future research.Additionally,we review repair strategies based on inflammatory mediators for the injured spinal cord.Finally,this review discusses the current status and future directions of translational research focused on immune-targeting strategies,including pharmaceuticals,biomedical engineering,and gene therapy.The development of a combined,precise,and multitemporal strategy for the repair of injured spinal cords represents a promising direction for future research.
基金Supported by Guangxi Natural Science Foundation(2018GXNSFAA050141)Basic AbilityImprovement Project for Young and Middle-aged Teachers in Guangxi Zhuang Autonomous Region(2019KY0336)Guangxi Famous Tradi-tional Chinese Medicine Inheritance Studio-Qin Zujie[GuiZhongYiYaoKeJiao-Fa(2021)No.6].
文摘[Objectives]To observe the clinical effect of the lotus needle cupping therapy for removing blood stasis in Zhuang medicine in treating PHNand its influence on inflammatory factors.[Methods]96 patients with PHN were randomly divided into three groups:lotus nee-dle cupping therapy group,TCM surrounding acupuncture group and gabapentin group.Venous blood and acupoint blood were collected at 0,21 and 42 d of treatment,and the expression levels of 5-HT,SP and CGRPinflammatory mediators were detected before and after treatment.The changes of VAS scores before,during and after treatment and the clinical efficacy were observed.[Results]The total effective rate of the lotus needle cupping group was 87.50%,which was better than that of the TCM acupuncture group(81.25%)and the gabapentin group(62.50%);after treatment,the VAS scores and the expression of inflammatory mediators in the three groups of patients were lower than those before treatment,and the decrease was more significant in the treatment group(P<0.05).[Conclusions]The lotus needle cupping therapy for removing blood stasis in Zhuang medicine is effective in treating PHN,and its mechanism is to reduce the release of inflammatory media-tors,reduce hyperalgesia,relieve pain and improve the quality of life of patients.
基金Supported by Grants for Traditional Chinese Medicine Science of Zhejiang Province,and Medical Science and Technology of Zhejiang Province and Hangzhou
文摘AIM: To investigate the influence of high dose of dexamethasone on inflammatory mediators and apoptosis of rats with severe acute pancreatitis (SAP). METHODS: SAP rats were randomly assigned to the model group and treatment group while the normal rats were assigned to the sham operation group. The mortality,ascite volumes,ascites/body weight ratio and pancreas pathological changes of all rats were observed at 3,6 and 12 h after operation. Their contents of amylase and endotoxin in plasma and contents of tumor necrosis factor (TNF-α),phospholipase A2 (PLA2) and IL-6 in serum were also determined. The microarray sections of their pancreatic tissues were prepared,terminal transferase dUTP nick end labeling (TUNEL) staining was performed and apoptotic indexes were calculated. RESULTS: There was no marked difference between treatment group and model group in survival. The contents of amylase and endotoxin in plasma and contents of TNF-α,PLA2 and IL-6 in serum,ascite volumes,ascites/body weight ratio and pancreas pathological scores were all lower in treatment group than in model group to different extents at different time points P < 0.05,58.3 (26.4) ng/L vs 77.535 (42.157) ng/L in TNF-α content,8.00 (2.00) points vs 9.00 (2.00) points in pathological score of pancreas respectively; P < 0.01,0.042 (0.018) EU/mL vs 0.056 (0.0195) EU/mL in endotoxin content,7791 (1863) U/L vs 9195 (1298) U/L in plasma amylase content,1.53 (0.79) vs 2.38 (1.10) in ascites/body weight ratio,8.00 (1.00) points vs 11.00 (1.50) points in pathological score of pancreas; P < 0.001,3.36 (1.56) ng/L vs 5.65 (1.08) ng/L in IL-6 content,4.50 (2.00) vs 7.20 (2.00),4.20 (1.60) vs 6.40 (2.30),3.40 (2.70) vs 7.90 (1.70) in ascite volumes,respectively. The apoptotic indexes of pancreas head and pancreas tail were all higher in treatment group than in model group at 6 h P < 0.01,0.00 (2.00)% vs 0.00 (0.00)%,0.20 (1.80) vs 0.00 (0.00) in apoptosis indexes,respectively. CONCLUSION: The mechanism of dexamethasone treatment in acute pancreatitis is related to its inhibition of inflammatory mediator generation and induction of pancreatic acinar cell apoptosis.
基金supported by grants from the Technological Foundation Project of Traditional Chinese Medical Science of Zhejiang Province(No.2003C130No.2004C142)the Foundation Project for Medical Science and Technology of Zhejiang Province(No.2003B134).
文摘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.
基金Supported by the National Natural Science Foundation of China(No.81870681)Key Program of the Department of Science and Technology of Hainan Province(No.ZDYF2020151)+1 种基金Huaxia Translational Medicine Fund For Young Scholars(No.2017-D-001)Medical Science and Technology Research Foundation of Guangdong Province(No.A2020406)。
文摘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.
文摘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.
基金This work was supported by grants from Bureau of Science and Technology of Changsha,China(No.Kq 1701007)Hunan Natural Science Foundation,China(No.2018JJ6127).
文摘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).
基金Supported by Shandong Provincial Natural Science Foundation,China(No.ZR2014HM029)
文摘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.
基金supported by the National Basic Research Development Program of China (2013CB966900)the National Natural Science Foundation of China (81241144, 81371372)the National Key Clinical Specialty Construction Program of China
文摘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.
基金Supported by National Natural Science Foundation of China,No.82070632.
文摘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.
基金the National Natural Science Foundation of China, No. 30672637
文摘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.
基金This work was supported by a grant from the National Natural Science Foundation of China （No. 30570814 to Xianming Fan）.
文摘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.
文摘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.
基金supported by the Sichuan Science and Technology Program(2022NSFSC1936)Doctoral Scientific Research Start-up Foundation of China West Normal University(412984).
文摘Introduction When the body is infected,pathogenic microorganisms and their toxins can enter the blood circulation and grow and proliferate in the blood,producing more toxins.These toxins and pathogens activate the body's immune system,leading to the release of a varieties of cytokines and inflammatory mediators,resulting in systemic inflammatory response syndrome[1].
基金supported by the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior-Brasil(CAPES)[Finance Code 001](to MGS)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico(CNPq)fellowship[research grants 309840/2022-8]。
文摘Neuroinflammation is an inflammatory response in the central nervous system associated with various neurological conditions.The inflammatory process is typically treated with non-steroidal and steroidal anti-inflammatory drugs,which have a range of serious adverse effects.As an alternative,naturally derived molecules such as quercetin and its derivatives show promising anti-inflammatory properties and beneficial effects on various physiological functions.Our objective was to synthesize the evidence on the anti-inflammatory effect of quercetin and its derivatives in in vivo models,in the face of neuroinflammatory insults induced by lipopolysaccharide,through a systematic review and meta-analysis.A search of the preclinical literature was conducted across four databases(Pub Med,Web of Science,Scielo,and Google Scholar).Studies were selected based on inclusion and exclusion criteria,assessed for methodological quality using CAMARADES,and risk of bias using the SYRCLE tool,and data were extracted from the studies.The quantitative assessment of quercetin effects on the expression of pro-inflammatory cytokines and microgliosis was performed through a meta-analysis.A total of 384 potentially relevant articles were identified,of which 11 studies were included in the analysis.The methodological quality was assessed,resulting in an average score of 5.8/10,and the overall risk of bias analysis revealed a lack of methodological clarity in most studies.Furthermore,through the meta-analysis,it was observed that treatment with quercetin statistically reduces pro-inflammatory cytokines,such as tumor necrosis factor alpha,interleukin 6,interleukin 1β(n=89;SMD=–2.00;95%CI:–3.29 to–0.71),and microgliosis(n=33;SMD=–2.56;95%CI:–4.07 to–1.10).In terms of underlying mechanisms,quercetin and its derivatives exhibit antioxidant and anti-apoptotic properties,possibly through the nuclear factor erythroid 2-related factor 2(Nrf2)/HO-1 pathways,increasing the expression of antioxidant enzymes and reducing reactive species,and modulating the caspase pathway,increasing levels of anti-apoptotic proteins and decreasing proapoptotic proteins.Quercetin and its derivatives exhibit highly pleiotropic actions that simultaneously contribute to preventing neuroinflammation.However,despite promising results in animal models,future directions should focus on well-designed clinical studies to assess the safety,bioavailability,and efficacy of quercetin and its derivatives in humans.Additionally,standardization of methods and dosages in studies is crucial to ensure consistency of findings and optimize their application in clinical settings.
基金Cultivation fund in Second Hospital of Shandong University(Grant No.2023YP11).
文摘Glucocorticoids are widely utilized for treating various immune and inflammation-related diseases,prompting significant interest in their potential application for COVID-19 treatment.This study explored the efficacy and safety of dexamethasone(DEX)and methylprednisolone(MP)in treating severe COVID-19.A cohort of 94 adult patients,aged 18 years and older,with severe COVID-19 was recruited.They received intravenous MP(40-80 mg/d)or DEX(5-10 mg/d)for 7-10 d.The primary objective was to assess the effects of these treatments on mortality rates.Additionally,the study aimed to compare the impact of these medications on various parameters,including the oxygenation index,inflammatory index,fungal infections,and hyperglycemia,serving as secondary endpoints.The findings revealed no fatalities in either group.However,there was one case of pulmonary fibrosis and Aspergillus fumigatus infection in the DEX group,and two cases of Aspergillus infection in the MP group.Although the differences were not statistically significant(P>0.05),the MP group showed a faster improvement in blood oxygen saturation compared to the DEX group,with a median time of 5 d vs 7 d.No statistically significant difference was observed between the two groups regarding improvement in C-reactive protein levels(P>0.05).Notably,DEX was associated with a higher incidence of hyperglycemia compared to MP(P<0.05).Both DEX and MP significantly reduced mortality rates among patients with severe COVID-19 and improved blood oxygen saturation and inflammatory markers.However,MP exhibited a more rapid onset of efficacy and fewer adverse reactions.
文摘The subcutaneous air pouch model has been used extensively to study the pathophysiology of inflammatory conditions such as joint diseases and the potential efficacy of pharmacological treatments in vivo.Delivery of air between the subcutaneous and dermal layer of the intra-scapular zone of the rodent generates an environment analogous to the synovial joint space.Introduction of monosodium urate crystals or calcium pyrophosphate crystals into the air space produces a sterile acute inflammatory response mimicking clinical gout and pseudogout,respectively.The inflammatory response can be quantitatively and robustly evaluated by measuring leukocyte infiltration,inflammatory cytokine production,eicosanoid release,complement activation and reactive oxygen species generation.Despite the utility of this model,great variation exists within the literature regarding the design,sampling time points,and endpoints measured.This systematic review summarizes the current literature on the subcutaneous air pouch model studying monosodium urate or calcium pyrophosphate crystals and provides recommendations for standardizing and improving the reliability and validity of this model.Standardizing the experimental approach would improve inter-study comparability,increase the internal validity of studies and reproducibility of results,and ultimately improve the understanding of gout and pseudogout and accelerate the discovery of new pharmacological therapies.
基金Supported by PRIN grants from the Italian Ministry of Science and Technology, No. 2003063143-006
文摘AIM： To assess whether a correlation exists between oxidative DNA damage occurring in chronic HCV-related hepatitis and expression levels of pro-inflammatory cytokines, TGF-α and c-myc. METHODS： The series included 37 patients with chronic active HCV-related hepatitis and 11 with HCV-related compensated cirrhosis. Eight-hydroxydeoxyguanosine in liver biopsies was quantified using an electrochemical detector. The mRNA expression of TNF-α, IL-1β, TGF-α and c-myc in liver specimens was detected by semiquantitative comparaUve RT-PCR. RESULTS： TNF-α levels were significantly higher in hepatitis patients than in cirrhosis patients （P=0.05）. IL-1β was higher in cirrhosis patients （P=0.05）. A sig- nificant correlation was found between TNF-α and staging （P= 0.05） and between IL-1β levels and grading （P=0.04）. c-myc showed a significantly higher expression in cirrhosis patients （P=0.001）. Eight-hydroxydeoxyguanosine levels were significantly higher in cirrhosis patients （P=0.05） and in HCV genotype 1 （P=0.03）. Considering all patients, 8-hydroxydeoxyguanosine levels were found to be correlated with genotype （P=0.04） and grading （P=0.007）. Also multiple logistic regression analysis demonstrated a significant correlation among the number of DNA adducts, TNF-α expression and HCV genotype （P= 0.02）. CONCLUSION： In chronic HCV-related liver damage, oxidative DNA damage correlates with HCV genotype, grading and TNF-α levels. As HCV-related liver damage progresses, TNF-α levels drop while IL-1β and c-myc levels increase, which may be relevant to liver carcinogenesis.
文摘Sepsis is an infection induced systemic inflammatory response syndrome and is a major cause of morbidity as well as mortality in intensive care units. A growing body of evidence suggests that the activation of a proinflammatory cascade is responsible for the development of immune dysfunction, susceptibility to severe sepsis and septic shock. The present theories of sepsis as a dysregulated inflammatory response and immune function, as manifested by excessive release of inflammatory mediators such as high mobility group box 1 protein （HMGB1）, are supported by increasing studies employing animal models and clinical observations of sepsis. HMGB1, originally described as a DNA-binding protein and released passively by necrotic cells and actively by macrophages/monocytes, has been discovered to be one of essential cytokines that mediates the response to infection, injury and inflammation. A growing number of studies still focus on the inflammation-regulatory function and its contribution to infectious and inflammatory disorders, recent data suggest that HMGB1 formation can also markedly influence the host cell-mediated immunity, including T lymphocytes and macrophages. Here we review emerging evidence that support extracellular HMGB1 as a late mediator of septic complications, and discuss the therapeutic potential of several HMGBl-targeting agents in experimental sepsis. In addition, with the development of traditional Chinese medicine in recent years, it has been proven that traditional Chinese herbal materials and their extracts have remarkable effective in treating severe sepsis. In this review, we therefore provide some new concepts of HMGBl-targeted Chinese herbal therapies in sepsis.
基金supported by Marine Industry Research Special Funds for Public Welfare Projects(201205024–1)The Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(ysxk-2010)
文摘Thais luteostoma has been utilized as a crude drug whose shell and soft tissue have been widely used for the treatment of heat syndrome in China for thousands of years. The present study was designed to investigate the antipyretic and anti-inflammatory activities of T. luteostoma. T. luteostoma was divided into shell （TLSH） and soft tissue （TLST） samples in the present study. The rat model of yeast-induced fever was used to investigate their antipyretic effects; and the rat model of hind paw edema induced by carrageenan was utilized to study their anti-inflammatory activities, and at the same time, the concentration variations of the central neurotransmitter [prostaglandin E2 （PGE2） and cyclic adenosine monophosphate （cAMP）], inflammatory mediators [tumor necrosis factor （TNFα）, interleukin-1β （IL-1）, interleukin-2 （IL-2） and interleukin-6 （IL-6）] and ion （Na^＋ and Ca^2＋） were also tested. The results showed that TLSH and TLST extracts significantly inhibited yeast-induced pyrexia in rats （P 〈 0.05）, and exhibited more lasting effects as compared to aspirin, and TLSH had the better antipyretic activity than TLST, and that TLSH and TLST could significantly prevent against carrageenan induced paw edema in rats （P 〈 0.05）; and markedly reduced levels of PGE2, cAMP, TNFα, IL-1β, IL-2, IL-6, and Na^＋/Ca^2＋. In fever model, TLST could significantly reduce the levels of PGE2 （P 〈 0.01） in rats＇ homogenate and TNF a （P 〈 0.05）, IL-113 （P 〈 0.01） in the plasma than TLSH, whereas TLSH could reduce the content of IL-2 （P 〈 0.01） and IL-6 （P 〈 0.01） in plasma and increase the content of Ca2＋ （P 〈 0.01） in plasma and homogenate more significantly than TLST. In conclusion, T. luteostoma extract has antipyretie and anti-inflammatory activities, which may be mediated through the suppression of production of PGE2, cAMP, Na^＋/Ca^2＋ , TNF a, IL-1β, IL-2, and IL-6.
