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 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
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 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...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.展开更多
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 extr...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.展开更多
[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.[...[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.展开更多
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 ...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.展开更多
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 c...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, 0.2-0.3 mL bromodeoxyuridine (BrdU)-labeled hUCMSCs suspension (cell concentration 5 × 103/μL) 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.展开更多
<strong>Background:</strong> 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 con...<strong>Background:</strong> 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. <strong>Design:</strong> 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. <strong>Discussion:</strong> 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.展开更多
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 ...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展开更多
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 mineraliz...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.展开更多
Epilepsy is a chronic neurological disorder that has an extensive impact on a patient’s life.Accumulating evidence has suggested that inflammation participates in the progression of spontaneous and recurrent seizures...Epilepsy is a chronic neurological disorder that has an extensive impact on a patient’s life.Accumulating evidence has suggested that inflammation participates in the progression of spontaneous and recurrent seizures.Proconvulsant incidences can stimulate immune cells,augment the release of pro-inflammatory cytokines,elicit neuronal excitation as well as blood-brain barrier(BBB)dysfunction,and finally trigger the generation or recurrence of seizures.Understanding the pathogenic roles of inflammatory mediators,including inflammatory cytokines,cells,and BBB,in epileptogenesis will be beneficial for the treatment of epilepsy.In this systematic review,we performed a literature search on the PubMed database using the following keywords:“epilepsy”or“seizures”or“epileptogenesis”,and“immunity”or“inflammation”or“neuroinflammation”or“damage-associated molecular patterns”or“cytokines”or“chemokines”or“adhesion molecules”or“microglia”or“astrocyte”or“blood-brain barrier”.We summarized the classic inflammatory mediators and their pathogenic effects in the pathogenesis of epilepsy,based on the most recent findings from both human and animal model studies.展开更多
Coronavirus disease 19(COVID-19)is placing a major burden on healthcare,economy and social systems world-wide owing to its fast spread and unacceptably high death toll.The unprecedented research effort has established...Coronavirus disease 19(COVID-19)is placing a major burden on healthcare,economy and social systems world-wide owing to its fast spread and unacceptably high death toll.The unprecedented research effort has established the role of a deregulated immune response to the severe acute respiratory syndrome coronavirus 2,resulting in systemic inflammation.After that,the immunomodulatory approach has been placed in the top list of the re-search agenda for COVID-19.Corticosteroids have been used for more than 70 years to modulate the immune response in a broad variety of diseases.These drugs have been shown to prevent and attenuate inflammation both in tissues and in circulation via non-genomic and genomic effects.At the bedside,numerous observational cohorts have been published in the past months and have been inconclusive.Randomized controlled trials with subsequent high quality meta-analyses have provided moderate to strong certainty for an increased chance of survival and relief from life supportive therapy with corticosteroids given at a dose of 6 mg per day dexametha-sone or equivalent doses of hydrocortisone or methylprednisolone.The corticotherapy was not associated with an increased risk of bacterial infection or of delayed viral clearance.In daily practice,physicians may be encouraged to use corticosteroids when managing patients with COVID-19 requiring oxygen supplementation.展开更多
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 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.
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.
文摘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.
文摘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.
基金Supported by Hospital-level Program of Luodian Hospital in Baoshan District of Shanghai(21-A-8)District-level Program of Scientific and Technological Commission of Baoshan District of Shanghai(2023-E-39)+1 种基金District-level Program of Key Discipline Construction in Baoshan District of Shanghai[BSZK-2023-BZ03(02)]Baoshan District Health Commission Excellent Youth(Yucai)Program(BSWSYC-2023-13)。
文摘[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.
基金supported by grants from the National Natural Science Foundation of China(Grant No.82203786)the Natural Science Foundation of Liaoning Province of China(Grant No.2022-YGJC-68)Chinese Young Breast Experts Research project(Grant No.CYBER-2021-A02).
文摘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.
文摘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, 0.2-0.3 mL bromodeoxyuridine (BrdU)-labeled hUCMSCs suspension (cell concentration 5 × 103/μL) 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.
文摘<strong>Background:</strong> 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. <strong>Design:</strong> 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. <strong>Discussion:</strong> 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.
基金supported in part by an Established Investigata Grant from the American Heart Association and Public Health Service Grant AI28018 from the Natianal Institute of Allergy and Infectious Diseases
文摘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
基金grants 81870805 from the National Natural Science Foundation of China,grant 2020TD-033 from the Shaanxi Key Scientific and Technological Innovation Team and by the Youth Innovation Team of Shaanxi Universities.
文摘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.
基金the National Natural Science Foundation of China(81471326).
文摘Epilepsy is a chronic neurological disorder that has an extensive impact on a patient’s life.Accumulating evidence has suggested that inflammation participates in the progression of spontaneous and recurrent seizures.Proconvulsant incidences can stimulate immune cells,augment the release of pro-inflammatory cytokines,elicit neuronal excitation as well as blood-brain barrier(BBB)dysfunction,and finally trigger the generation or recurrence of seizures.Understanding the pathogenic roles of inflammatory mediators,including inflammatory cytokines,cells,and BBB,in epileptogenesis will be beneficial for the treatment of epilepsy.In this systematic review,we performed a literature search on the PubMed database using the following keywords:“epilepsy”or“seizures”or“epileptogenesis”,and“immunity”or“inflammation”or“neuroinflammation”or“damage-associated molecular patterns”or“cytokines”or“chemokines”or“adhesion molecules”or“microglia”or“astrocyte”or“blood-brain barrier”.We summarized the classic inflammatory mediators and their pathogenic effects in the pathogenesis of epilepsy,based on the most recent findings from both human and animal model studies.
文摘Coronavirus disease 19(COVID-19)is placing a major burden on healthcare,economy and social systems world-wide owing to its fast spread and unacceptably high death toll.The unprecedented research effort has established the role of a deregulated immune response to the severe acute respiratory syndrome coronavirus 2,resulting in systemic inflammation.After that,the immunomodulatory approach has been placed in the top list of the re-search agenda for COVID-19.Corticosteroids have been used for more than 70 years to modulate the immune response in a broad variety of diseases.These drugs have been shown to prevent and attenuate inflammation both in tissues and in circulation via non-genomic and genomic effects.At the bedside,numerous observational cohorts have been published in the past months and have been inconclusive.Randomized controlled trials with subsequent high quality meta-analyses have provided moderate to strong certainty for an increased chance of survival and relief from life supportive therapy with corticosteroids given at a dose of 6 mg per day dexametha-sone or equivalent doses of hydrocortisone or methylprednisolone.The corticotherapy was not associated with an increased risk of bacterial infection or of delayed viral clearance.In daily practice,physicians may be encouraged to use corticosteroids when managing patients with COVID-19 requiring oxygen supplementation.
