This study aimed to investigate the anti-inflammatory properties and underlying molecular mechanisms of 2,4',5'-trihydroxyl-5,2'-dibromo diphenylmethanone(LM49)using a carrageenan-induced paw edema model i...This study aimed to investigate the anti-inflammatory properties and underlying molecular mechanisms of 2,4',5'-trihydroxyl-5,2'-dibromo diphenylmethanone(LM49)using a carrageenan-induced paw edema model in mice,which serves as a well-established model for acute inflammation.Mice were randomly assigned into six groups,and acute inflammation was induced by injecting 1%carrageenan solution into the paw.To elucidate the anti-inflammatory effects and mechanisms of LM49,a comprehensive approach was employed,including pathology,transcriptomics,flow cytometry,RT-qPCR,Western blotting analysis,and molecular docking analysis.The results demonstrated that LM49 exerted a significant protective effect by reducing paw edema and lowering serum levels of pro-inflammatory cytokines IL-1βand TNF-a,while concurrently elevating anti-inflammatory cytokine IL-10 levels.Transcriptomic analysis identified 453 differentially expressed genes in the LM49-treated group.KEGG and GO enrichment analyses indicated that LM49 suppressed the NF-kB signaling pathway and modulated several other immuneinflammatory pathways.Molecular docking studies identified eight key targets of LM49 within the NF-kB signaling pathway.Furthermore,Western blotting analysis confirmed that LM49 inhibited the phosphorylation of p65 and IB-αand downregulated the expression of MYD88 and TLR4 in mouse paw tissues.These findings provided a foundational understanding of the anti-inflammatory effects and molecular mechanisms of LM49,paving the way for further in-depth studies in this field.展开更多
Acute lung injury(ALI)/acute respiratory distress syndrome(ARDS)is a severe clinical disorder characterized by widespread inflammation,diffuse alveolar damage,and pulmonary edema,often leading to respiratory failure a...Acute lung injury(ALI)/acute respiratory distress syndrome(ARDS)is a severe clinical disorder characterized by widespread inflammation,diffuse alveolar damage,and pulmonary edema,often leading to respiratory failure and death.Despite significant advances in clinical care,ALI/ARDS remains the leading cause of death among intensive care unit patients.Sepsis is the primary risk factor for the development of ALI/ARDS,as excessive inflammatory responses contribute to organ injury and high mortality in critically ill patients.展开更多
Inflammatory bowel diseases(IBD), which comprise Crohn's disease and ulcerative colitis, are chronic intestinal disorders with an increased prevalence and incidence over the last decade in many different regions o...Inflammatory bowel diseases(IBD), which comprise Crohn's disease and ulcerative colitis, are chronic intestinal disorders with an increased prevalence and incidence over the last decade in many different regions over the world. The etiology of IBD is still not well defined, but evidence suggest that it results from per-turbation of the homeostasis between the intestinal microbiota and the mucosal immune system, with the involvement of both genetic and environmental factors. Genome wide association studies, which involve large-scale genome-wide screening of potential polymorphism, have identified several mutations associated with IBD. Among them, Card9, a gene encoding an adapter molecule involved in innate immune response to fungi(via type C-lectin sensing) through the activation of IL-22 signaling pathway, has been identified as one IBD susceptible genes. Dietary compounds, which represent a source of energy and metabolites for gut bacteria, are also appreciated to be important actors in the etiology of IBD, for example by altering gut microbiota composition and by regulating the generation of short chain fatty acids. A noteworthy study published in the June 2016 issue of Nature Medicine by Lamas and colleagues investigates the interaction between Card9 and the gut microbiota in the generation of the microbiota-derived tryptophan metabolite. This study highlights the role of tryptophan in dampening intestinal inflammation in susceptible hosts.展开更多
Hypothalamic neuropeptides named hypocretin/orexins which were identified in 1998 regulate critical functions such as wakefulness in the central nervous system.These past 20 years had revealed that orexins/receptors s...Hypothalamic neuropeptides named hypocretin/orexins which were identified in 1998 regulate critical functions such as wakefulness in the central nervous system.These past 20 years had revealed that orexins/receptors system was also present in the peripheral nervous system where they participated to the regulation of multiple functions including blood pressure regulation,intestinal motility,hormone secretion,lipolyze and reproduction functions.Associated to these peripheral functions,it was found that orexins and their receptors were involved in various diseases such as acute/chronic inflammation,metabolic syndrome and cancers.The present review suggests that orexins or the orexin neural circuitry represent potential therapeutic targets for the treatment of multiple pathologies related to inflammation including intestinal bowel disease,multiple sclerosis and septic shock,obesity and digestive cancers.展开更多
CD93 and GAIP-interacting protein, C termius （GIPC） have been shown to interactively alter phagocytic processes of immune cells. CD93 and GIPC expression and localization during cen-tral nervous system inflammation ...CD93 and GAIP-interacting protein, C termius （GIPC） have been shown to interactively alter phagocytic processes of immune cells. CD93 and GIPC expression and localization during cen-tral nervous system inflammation have not yet been reported. In this study, we established a rat model of brain inlfammation by lipopolysaccharide injection to the lateral ventricle. In the brain of rats with inlfammation, western blots showed increased CD93 expression that decreased over time. GIPC expression was unaltered. Immunohistochemistry demonstrated extensive distribution of CD93 expression mainly in cell membranes in the cerebral cortex. After lipopoly-saccharide stimulation, CD93 expression increased and then reduced, with distinct staining in the cytoplasm and nucleus. Double immunolfuorescence staining in cerebral cortex of normal rats showed that CD93 and GIPC widely expressed in resting microglia and neurons. CD93 was mainly expressed in microglial and neuronal cell membranes, while GIPC was expressed in both cell membrane and cytoplasm. In the cerebral cortex at 9 hours after model establishment, CD93-immunoreactive signal diminished in microglial membrane, with cytoplasmic transloca-tion and aggregation detected. GIPC localization was unaltered in neurons and microglia. These results are the ifrst to demonstrate CD93 participation in pathophysiological processes of central nervous system inlfammation.展开更多
Background:Alterations in ambient temperature have been associated with multiple detrimental effects on broilers such as intestinal barrier disruption and dysbiosis resulting in systemic inflammation.Inflammation and ...Background:Alterations in ambient temperature have been associated with multiple detrimental effects on broilers such as intestinal barrier disruption and dysbiosis resulting in systemic inflammation.Inflammation and 25-hydroxycholecalciferol(25-OH-D_(3))have shown to play a negative and positive role,respectively,in the regulation of bone mass.Hence the potential of 25-OH-D_(3)in alleviating heat induced bone alterations and its mechanisms was studied.Results:Heat stress(HS)directly induced a decrease in tibia material properties and bone mass,as demonstrated by lower mineral content,and HS caused a notable increase in intestinal permeability.Treatment with dietary 25-OH-D_(3)reversed the HS-induced bone loss and barrier leak.Broilers suffering from HS exhibited dysbiosis and increased expression of inflammatory cytokines in the ileum and bone marrow,as well as increased osteoclast number and activity.The changes were prevented by dietary 25-OH-D_(3)administration.Specifically,dietary 25-OH-D_(3)addition decreased abundance of B-and T-cells in blood,and the expression of inflammatory cytokines,especially TNF-α,in both the ileum and bone marrow,but did not alter the diversity and population or composition of major bacterial phyla.With regard to bone remodeling,dietary 25-OH-D_(3)supplementation was linked to a decrease in serum C-terminal cross-linked telopeptide of type I collagen reflecting bone resorption and a concomitant decrement in osteoclast-specific marker genes expression(e.g.cathepsin K),whereas it did not apparently change serum bone formation markers during HS.Conclusions:These data underscore the damage of HS to intestinal integrity and bone health,as well as that dietary 25-OH-D_(3)supplementation was identified as a potential therapy for preventing these adverse effects.展开更多
Microglial cells are the key innate immune cells in the brain and they are crucial in maintaining brain parenchyma homeostasis.Under physiological conditions,microglial cells assume a ramified morphology with a small ...Microglial cells are the key innate immune cells in the brain and they are crucial in maintaining brain parenchyma homeostasis.Under physiological conditions,microglial cells assume a ramified morphology with a small cell body and an extensive network of fine processes,which secrete neurotrophic factors and patrol the surroundings in search for pathogens and eliminate cellular debris via phagocytosis.Microglial cells express a repertoire of pattern recognition receptors(PRRs)that enable them to detect diverse danger-associated molecular patterns(DAMPs)released from damaged cells or cells under stress,or pathogen-associated molecular patterns generated by pathogens during infection.展开更多
10,11-Dehydrocurvularin(DCV)is a natural-product macrolide that has been shown to exert anti-inflammatory activity.However,the underlying mechanism of its anti-inflammatory activity remains poorly understood.Aberrant ...10,11-Dehydrocurvularin(DCV)is a natural-product macrolide that has been shown to exert anti-inflammatory activity.However,the underlying mechanism of its anti-inflammatory activity remains poorly understood.Aberrant activation of the NLRP3 inflammasome is involved in diverse inflammation-related diseases,which should be controlled.The results showed that DCV specifically inhibited the activation of the NLRP3 inflammasome in association with reduced IL-1βsecretion and caspase-1 activation,without effect on the NLRC4 and AIM2 inflammasomes.Furthermore,DCV disturbed the interaction between NEK7 and NLRP3,resulting in the inhibition of NLRP3 inflammasome activation.The C=C double bond of DCV was required for the NLRP3 inflammasome inhibition induced by DCV.Importantly,DCV ameliorated inflammation in vivo through inhibiting the NLRP3 inflammasome.Taken together,our study reveals a novel mechanism by which DCV suppresses inflammation,which indicates the potential role of DCV in NLRP3 inflammasome-driven inflammatory disorders.展开更多
Ulcerative colitis (UC) has reactive oxygen species (ROS) and immunologic pathways implicated in its pathogenesis. The search for new therapeutic protocols in managing UC is tailored in suppressing or preventing these...Ulcerative colitis (UC) has reactive oxygen species (ROS) and immunologic pathways implicated in its pathogenesis. The search for new therapeutic protocols in managing UC is tailored in suppressing or preventing these pathways. The influence of trivalent chromium (Cr3+), an essential mineral on experimental colitis was investigated. Mice were grouped into 3;group 1 (control) received clean drinking water while groups 2 and 3 received 10 and 100 ppm Cr3+ respectively for 12 weeks through drinking water. After Cr3+ administration, 5 animals per group were sacrificed on day 0. Thereafter, experimental colitis was induced intra-rectally using acetic acid (4%, 0.3mL) and 5 mice per group were subsequently sacrificed on days 3, 7 and 14. Blood and colonic tissues were obtained and processed appropriately. Blood Cr3+ level, haematological variables, gross and microscopic colitis scores, colonic myeloperoxidase (MPO), Superoxide Dismutase (SOD) and malondialdehyde (MDA) levels were determined using standard methods. Colon cytokine mRNA genes were quantified using real-time PCR. There was a significant decrease in colon gross and histology scores on days 3 and 7 in chromium treated compared with control. The MPO and MDA in chromium groups reduced significantly compared with control while SOD activities increased significantly in Cr3+ groups compared with control. Total RNA increased in chromium groups compared with control on day 3 post-colitis. There was up-regulation of IL-10, down-regulation of TNF-α and IFN-λ in chromium administered groups compared with control. Chromium enhanced healing of colitis by suppression of ROS, inflammation and promotion of antioxidant activities.展开更多
Microglial cells are the key immunocompetent cells in the central nervous system (CNS) and play a crucial role in CNS health and disease (Paolicelli et al.,2022).Under the homeostatic conditions,microglial cells assum...Microglial cells are the key immunocompetent cells in the central nervous system (CNS) and play a crucial role in CNS health and disease (Paolicelli et al.,2022).Under the homeostatic conditions,microglial cells assume diverse and dynamic states,depending upon interactions with neighboring cells and structures in local contextual settings,continuously patrol brain parenchyma utilizing their highly mobile fine processes,phagocytize protein aggregates,unwanted synapses and cells to maintain CNS health,and secrete neurotrophic factors to support neuronal function (Colonna and Butovsky,2017;Paolicelli et al.,2022).展开更多
Multiple factors are involved in the etiology of cardiovascular disease(CVD). Pathological changes occur in a variety of cell types long before symptoms become apparent and diagnosis is made. Dysregulation of physiolo...Multiple factors are involved in the etiology of cardiovascular disease(CVD). Pathological changes occur in a variety of cell types long before symptoms become apparent and diagnosis is made. Dysregulation of physiological functions are associated with the activation of immune cells,leading to local and finally systemic inflammation that is characterized by production of high levels of reactive oxygen species(ROS). Patients suffering from inflammatory diseases often present with diminished levels of antioxidants either due to insufficient dietary intake or,and even more likely,due to increased demand in situations of overwhelming ROS production by activated immune effector cells like macrophages. Antioxidants are suggested to beneficially interfere with diseases-related oxidative stress,however the interplay of endogenous and exogenous antioxidants with the overall redox system is complex. Moreover,molecular mechanisms underlying oxidative stress in CVD are not fully elucidated. Metabolic dybalances are suggested to play a major role in disease onset and progression. Several central signalingpathways involved in the regulation of immunological,metabolic and endothelial function are regulated in a redox-sensitive manner. During cellular immune response,interferon γ-dependent pathways are activated such as tryptophan breakdown by the enzyme indoleamine 2,3-dioxygenase(IDO) in monocyte-derived macrophages,fibroblasts,endothelial and epithelial cells. Neopterin,a marker of oxidative stress and immune activation is produced by GTP-cyclohydrolase Ⅰ in macrophages and dendritic cells. Nitric oxide synthase(NOS) is induced in several cell types to generate nitric oxide(NO). NO,despite its low reactivity,is a potent antioxidant involved in the regulation of the vasomotor tone and of immunomodulatory signaling pathways. NO inhibits the expression and function of IDO. Function of NOS requires the cofactor tetrahydrobiopterin(BH4),which is produced in humans primarily by fibroblasts and endothelial cells. Highly toxic peroxynitrite(ONOO-) is formed solely in the presence of superoxide anion(O2-). Neopterin and kynurenine to tryptophan ratio(Kyn/Trp),as an estimate of IDO enzyme activity,are robust markers of immune activation in vitro and in vivo. Both these diagnostic parameters are able to predict cardiovascular and overall mortality in patients at risk. Likewise,a significant association exists between increase of neopterin concentrations and Kyn/Trp ratio values and the lowering of plasma levels of vitamin-C,-E and-B. Vitamin-B deficiency is usually accompanied by increased plasma homoycsteine. Additional determination of NO metabolites,BH4 and plasma antioxidants in patients with CVD and related clinical settings can be helpful to improve the understanding of redox-regulation in health and disease and might provide a rationale for potential antioxidant therapies in CVD.展开更多
Alcoholic liver disease(ALD)is a growing global health concern,and its early pathogenesis includes steatosis and steatohepatitis.Inhibiting lipid accumulation and inflammation is a crucial step in relieving ALD.Eviden...Alcoholic liver disease(ALD)is a growing global health concern,and its early pathogenesis includes steatosis and steatohepatitis.Inhibiting lipid accumulation and inflammation is a crucial step in relieving ALD.Evidence shows that puerarin(Pue),an isoflavone isolated from Pueraria lobata,exerts cardio-protective,neuroprotective,anti-inflammatory,antioxidant activities.However,the therapeutic potential of Pue on ALD remains unknown.In the study,both the NIAAA model and ethanol(EtOH)-induced AML-12 cell were used to explore the protective effect of Pue on alcoholic liver injury in vivo and in vitro and related mechanism.The results showed that Pue(100 mg·kg^(−1))attenuated EtOH-induced liver injury and inhibited the levels of SREBP-1c,TNF-α,IL-6 and IL-1β,compared with silymarin(Sil,100 mg·kg^(−1)).In vitro results were consistent with in vivo results.Mechanistically,Pue might suppress liver lipid accumulation and inflammation by regulating MMP8.In conclusion,Pue might be a promising clinical candidate for ALD treatment.展开更多
Objective:To investigate the anti-inflammatory effects of the total flavonoids from Saussurea involucrata on lipopolysaccharides(LPS)-stimulated murine RAW264.7 macrophages and explore its underlying mechanism of acti...Objective:To investigate the anti-inflammatory effects of the total flavonoids from Saussurea involucrata on lipopolysaccharides(LPS)-stimulated murine RAW264.7 macrophages and explore its underlying mechanism of action.Methods:Total flavonoids from Saussurea involucrata were extracted using chromatographic column method.Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay.The production of nitric oxide was detected by Griess assay and the release of cytokines(IL-10 and TNF-α)and chemokines(MCP-1,MIP-1α,and CCL5/RANTES)was determined by ELISA to evaluate the anti-inflammatory activity of total flavonoids from Saussurea involucrata.Moreover,nuclear translocation of p65,c-Jun,and IRF3 was detected by immunofluorescence microscopy and Western blotting analysis was performed to determine the expression of related proteins.Results:Total flavonoids extracted from Saussurea involucrata were 751.5 mg/g and the content of rutin was 506.5 mg/g.The production of inflammatory mediators including nitric oxide,cytokines,and chemokines was effectively inhibited by total flavonoids from Saussurea involucrata.Meanwhile,total flavonoids also suppressed the nuclear translocation of p65,c-Jun,and IRF3 in LPS-stimulated RAW264.7 cells.The LPS-induced expression of iNOS and COX-2 was remarkably reduced by treatment with total flavonoids from Saussurea involucrata.Moreover,total flavonoids decreased the expression levels of p-IKKα/β,p-TBK1,p-p38,p-ERK,p-JNK,p-p65,p-c-Jun,and p-IRF3 in LPS-exposed RAW264.7 macrophages.Conclusions:Total flavonoids from Saussurea involucrata potentially inhibit the secretion of pro-inflammatory mediators,which may be related to inhibition of p65,c-Jun,and IRF3 signaling pathways in LPS-stimulated RAW264.7 cells.展开更多
Inflammatory bowel disease(IBD)is a chronic inflammatory disorder of the gastrointestinal tract,which increases the incidence of colorectal cancer(CRC).In the pathophysiology of IBD,ubiquitination/deubiquitination pla...Inflammatory bowel disease(IBD)is a chronic inflammatory disorder of the gastrointestinal tract,which increases the incidence of colorectal cancer(CRC).In the pathophysiology of IBD,ubiquitination/deubiquitination plays a critical regulatory function.Josephin domain containing 2(JOSD2),a deubiquitinating enzyme,controls cell proliferation and carcinogenesis.However,its role in IBD remains unknown.Colitis mice model developed by dextran sodium sulfate(DSS)or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages.JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation.DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation.Mechanistically,JOSD2 binds to the C-terminal of inosine-5′-monophosphate dehydrogenase 2(IMPDH2)and preferentially cleaves K63-linked polyubiquitin chains at the K134 site,suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B(NF-κB)and inflammation in macrophages.It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane(AOM)/DSS-induced CRC,and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice.These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2,suggesting that targeting JOSD2 is a potential strategy for treating IBD.展开更多
Chronic liver disease represents a significant global health burden.Regardless of etiology,its pathogenesis is driven by persistent liver inflammation,which can lead to fibrosis,cirrhosis,and an increased risk of canc...Chronic liver disease represents a significant global health burden.Regardless of etiology,its pathogenesis is driven by persistent liver inflammation,which can lead to fibrosis,cirrhosis,and an increased risk of cancer development.Myeloid cells,including neutrophils,eosinophils,monocytes,macrophages,and dendritic cells,play diverse and critical roles in hepatic immunity and the maintenance of tissue homeostasis but are also involved in liver injury,disease progression,and resolution.With the emergence of high-resolution omics technologies and in vivo fate-mapping models,our understanding of myeloid cell ontogeny and functional heterogeneity has been significantly refined.In this review,we discuss current insights into the myeloid cell landscape in nonviral chronic liver inflammatory conditions and summarize the roles of myeloid cell subsets in disease pathogenesis.展开更多
Joint is often regarded as a sensitive indicator of systemic inflammation,capable of responding to various pathological states ranging from local infections to systemic inflammatory diseases.We are all familiar with t...Joint is often regarded as a sensitive indicator of systemic inflammation,capable of responding to various pathological states ranging from local infections to systemic inflammatory diseases.We are all familiar with the phenomenon that the joint pain(arthralgia)caused by joint inflammation(arthritis)usually happens when the body has inffammation in other distant unrelated organs such as lupus1.展开更多
Abdominal aortic aneurysm(AAA)is strongly correlated with obesity,partially due to the abnormal expansion of abdominal perivascular adipose tissue(PVAT).Cell death-inducing DNA fragmentation factor-like effector C(CID...Abdominal aortic aneurysm(AAA)is strongly correlated with obesity,partially due to the abnormal expansion of abdominal perivascular adipose tissue(PVAT).Cell death-inducing DNA fragmentation factor-like effector C(CIDEC),also known as fat-specific protein 27(FSP27)in rodents,is specifically expressed in adipose tissue where it mediates lipid droplet fusion and adipose tissue expansion.Whether and how CIDEC/FSP27 plays a role in AAA pathology remains elusive.Here,we show that FSP27 exacerbates obesity and angiotensinⅡ(AngⅡ)-induced AAA progression.FSP27 deficiency in mice inhibited high-fat diet-induced PVAT expansion and inflammation.Both global and adipose tissue-specific FSP27 ablation significantly decreased obesity-related AAA incidence.Deficiency of FSP27 in adipocytes abrogated matrix metalloproteinase-12(MMP12)expression in aortic tissues.Infiltrated macrophages,which partially colocalize with MMP12,were significantly decreased in the FSP27-deficient aorta.Mechanistically,knockdown of Fsp27 in 3T3-L1 adipocytes inhibited C-C motif chemokine ligand 2(CCL2)expression and secretion through a c-Jun N-terminal kinase(JNK)-dependent pathway,thereby leading to reduced induction of macrophage migration,while Cidec overexpression rescued this effect.Overall,our study demonstrates that CIDEC/FSP27 in adipose tissue contributes to obesity-related AAA formation,at least in part,by enhancing PVAT inflammation and macrophage infiltration,thus shedding light on its significance as a key regulator in the context of obesity-related AAA.展开更多
Andrographolide from traditional Chinese herbal medicines previously showed it possesses a strong anti- inflammatory activity. In present study, we investigated whether Andrographolide could inhibit allergen-induced a...Andrographolide from traditional Chinese herbal medicines previously showed it possesses a strong anti- inflammatory activity. In present study, we investigated whether Andrographolide could inhibit allergen-induced airway inflammation and airways hyper-responsiveness and explored the mechanism of Andrographolide on allergen-induced airway inflammation and airways hyper-responsiveness. After sensitized and challenged by ovalbumin, the BALB/c mice were administered intraperitoneally with Andrographolide. Hyper-responsiveness was recorded. The lung tissues were assessed by histological examinations. NF-κB in lung was determined by immunofluorescence staining and Western blotting. Treatment of mice with Androqrapholide displayed lower Penh in response to asthma group mice. After treatment with Andrographolide, the extent of inflammation and cellular infiltration in the airway were reduced. Andrographolide interrupted NF-κB to express in cell nucleus. The level of NF-κB expression was inhibited by Andrographolide. The data indicate that Andrographolide from traditional Chinese herbal medicines could inhibit extensive infiltration of inflammatory cells in lung and decrease airway hyperreactivity. Andrographolide could inhibit NF-κB expression in lung and suppress NF-κB expressed in the nucleus of airway epithelial cells.展开更多
The role of IL-17 in many inflammatory and autoimmune diseases is now well established,with three currently registered anti-IL-17-targeted therapies.This story has taken place over a period of 20 years and led to the ...The role of IL-17 in many inflammatory and autoimmune diseases is now well established,with three currently registered anti-IL-17-targeted therapies.This story has taken place over a period of 20 years and led to the demonstration that a T cell product could regulate,and often amplify,the inflammatory response.The first results described the contribution of IL-17 to local features in arthritis.Then,understanding was extended to its systemic effects,with a focus on cardiovascular aspects.This review provides a historical perspective of these discoveries focused on arthritis,which started in 1995,followed 10 years later by the description of Th17 cells.Today,IL-17 inhibitors for three chronic inflammatory diseases have been registered.More options are now being tested in ongoing and future clinical trials.Inhibitors of IL-17 family members and Th17 cells ranging from antibodies to small molecules are under active development.The identification of patients with IL-17-driven disease is a key target for the improved selection of patients expected to have a strongly positive response.展开更多
Dear Editor,Acute lung injury(ALI)is a significant contributor to the development of acute respiratory distress syndrome(ARDS),which is a severe clinical condition associated with high morbidity and mortality.1 It is ...Dear Editor,Acute lung injury(ALI)is a significant contributor to the development of acute respiratory distress syndrome(ARDS),which is a severe clinical condition associated with high morbidity and mortality.1 It is increasingly evident that preserving mitochondrial health in alveolar epithelial cells holds great therapeutic potential for ARDS.2 Mitophagy,a cellular process aimed at maintaining mitochondrial health,plays a critical role in this regard.3 Therefore,gaining a comprehensive understanding of the factors that regulate mitophagy in alveolar epithelial cells during ALI could greatly inform the development of future therapeutic approaches for ARDS.展开更多
基金The National Natural Science Foundation of China(Grant No.82003770)the National Science and Technology Major Project of China(Grant No.2018ZX09711001-001-017)the Key Research and Development Plan of Shanxi Province(Grant No.202102130501005)。
文摘This study aimed to investigate the anti-inflammatory properties and underlying molecular mechanisms of 2,4',5'-trihydroxyl-5,2'-dibromo diphenylmethanone(LM49)using a carrageenan-induced paw edema model in mice,which serves as a well-established model for acute inflammation.Mice were randomly assigned into six groups,and acute inflammation was induced by injecting 1%carrageenan solution into the paw.To elucidate the anti-inflammatory effects and mechanisms of LM49,a comprehensive approach was employed,including pathology,transcriptomics,flow cytometry,RT-qPCR,Western blotting analysis,and molecular docking analysis.The results demonstrated that LM49 exerted a significant protective effect by reducing paw edema and lowering serum levels of pro-inflammatory cytokines IL-1βand TNF-a,while concurrently elevating anti-inflammatory cytokine IL-10 levels.Transcriptomic analysis identified 453 differentially expressed genes in the LM49-treated group.KEGG and GO enrichment analyses indicated that LM49 suppressed the NF-kB signaling pathway and modulated several other immuneinflammatory pathways.Molecular docking studies identified eight key targets of LM49 within the NF-kB signaling pathway.Furthermore,Western blotting analysis confirmed that LM49 inhibited the phosphorylation of p65 and IB-αand downregulated the expression of MYD88 and TLR4 in mouse paw tissues.These findings provided a foundational understanding of the anti-inflammatory effects and molecular mechanisms of LM49,paving the way for further in-depth studies in this field.
基金supported by National Natural Science Foundation of China(82471792,82270004,81870061,82202382,31770945)Beijing Municipal Natural Science Foundation(7242135)Zhejiang Provincial Natural Science Foundation(LY20H010003).
文摘Acute lung injury(ALI)/acute respiratory distress syndrome(ARDS)is a severe clinical disorder characterized by widespread inflammation,diffuse alveolar damage,and pulmonary edema,often leading to respiratory failure and death.Despite significant advances in clinical care,ALI/ARDS remains the leading cause of death among intensive care unit patients.Sepsis is the primary risk factor for the development of ALI/ARDS,as excessive inflammatory responses contribute to organ injury and high mortality in critically ill patients.
基金Supported by National Institutes of Health(NIH),Nos.DK099071 and DK083890the Career Development Award from the Crohn’s and Colitis Foundation of America(CCFA)
文摘Inflammatory bowel diseases(IBD), which comprise Crohn's disease and ulcerative colitis, are chronic intestinal disorders with an increased prevalence and incidence over the last decade in many different regions over the world. The etiology of IBD is still not well defined, but evidence suggest that it results from per-turbation of the homeostasis between the intestinal microbiota and the mucosal immune system, with the involvement of both genetic and environmental factors. Genome wide association studies, which involve large-scale genome-wide screening of potential polymorphism, have identified several mutations associated with IBD. Among them, Card9, a gene encoding an adapter molecule involved in innate immune response to fungi(via type C-lectin sensing) through the activation of IL-22 signaling pathway, has been identified as one IBD susceptible genes. Dietary compounds, which represent a source of energy and metabolites for gut bacteria, are also appreciated to be important actors in the etiology of IBD, for example by altering gut microbiota composition and by regulating the generation of short chain fatty acids. A noteworthy study published in the June 2016 issue of Nature Medicine by Lamas and colleagues investigates the interaction between Card9 and the gut microbiota in the generation of the microbiota-derived tryptophan metabolite. This study highlights the role of tryptophan in dampening intestinal inflammation in susceptible hosts.
基金INSERM U1149/The Inflammation Research Center,Inserm Transfert,The Institut National du Cancer,No.2013-213Ligue Nationale Contre le Cancer,No.R16020HH,GB/MA/CD/EP-12062and AgroParisTech(INRAE and UniversitéParis-Saclay).
文摘Hypothalamic neuropeptides named hypocretin/orexins which were identified in 1998 regulate critical functions such as wakefulness in the central nervous system.These past 20 years had revealed that orexins/receptors system was also present in the peripheral nervous system where they participated to the regulation of multiple functions including blood pressure regulation,intestinal motility,hormone secretion,lipolyze and reproduction functions.Associated to these peripheral functions,it was found that orexins and their receptors were involved in various diseases such as acute/chronic inflammation,metabolic syndrome and cancers.The present review suggests that orexins or the orexin neural circuitry represent potential therapeutic targets for the treatment of multiple pathologies related to inflammation including intestinal bowel disease,multiple sclerosis and septic shock,obesity and digestive cancers.
基金supported by the National Natural Science Foundation of China,No.31170766the Nantong Municipal Social Undertakings Technological Innovation and Demonstration Project Foundation,No.HS2012032the Natural Science Pre-research Project Foundation of Nantong University in 2012,No.12ZY020
文摘CD93 and GAIP-interacting protein, C termius （GIPC） have been shown to interactively alter phagocytic processes of immune cells. CD93 and GIPC expression and localization during cen-tral nervous system inflammation have not yet been reported. In this study, we established a rat model of brain inlfammation by lipopolysaccharide injection to the lateral ventricle. In the brain of rats with inlfammation, western blots showed increased CD93 expression that decreased over time. GIPC expression was unaltered. Immunohistochemistry demonstrated extensive distribution of CD93 expression mainly in cell membranes in the cerebral cortex. After lipopoly-saccharide stimulation, CD93 expression increased and then reduced, with distinct staining in the cytoplasm and nucleus. Double immunolfuorescence staining in cerebral cortex of normal rats showed that CD93 and GIPC widely expressed in resting microglia and neurons. CD93 was mainly expressed in microglial and neuronal cell membranes, while GIPC was expressed in both cell membrane and cytoplasm. In the cerebral cortex at 9 hours after model establishment, CD93-immunoreactive signal diminished in microglial membrane, with cytoplasmic transloca-tion and aggregation detected. GIPC localization was unaltered in neurons and microglia. These results are the ifrst to demonstrate CD93 participation in pathophysiological processes of central nervous system inlfammation.
基金This work was supported by the China Scholarship Council(CSC,[2019]110)The support by DSM Nutritional Products(Basel,Switzerland)for the analysis of vitamin D3 and metabolites is well appreciatedThe Ghent University Special Research Fund is acknowledged for the financial support to the UGCT Centre of Expertise(BOF.EXP.2017.0007).
文摘Background:Alterations in ambient temperature have been associated with multiple detrimental effects on broilers such as intestinal barrier disruption and dysbiosis resulting in systemic inflammation.Inflammation and 25-hydroxycholecalciferol(25-OH-D_(3))have shown to play a negative and positive role,respectively,in the regulation of bone mass.Hence the potential of 25-OH-D_(3)in alleviating heat induced bone alterations and its mechanisms was studied.Results:Heat stress(HS)directly induced a decrease in tibia material properties and bone mass,as demonstrated by lower mineral content,and HS caused a notable increase in intestinal permeability.Treatment with dietary 25-OH-D_(3)reversed the HS-induced bone loss and barrier leak.Broilers suffering from HS exhibited dysbiosis and increased expression of inflammatory cytokines in the ileum and bone marrow,as well as increased osteoclast number and activity.The changes were prevented by dietary 25-OH-D_(3)administration.Specifically,dietary 25-OH-D_(3)addition decreased abundance of B-and T-cells in blood,and the expression of inflammatory cytokines,especially TNF-α,in both the ileum and bone marrow,but did not alter the diversity and population or composition of major bacterial phyla.With regard to bone remodeling,dietary 25-OH-D_(3)supplementation was linked to a decrease in serum C-terminal cross-linked telopeptide of type I collagen reflecting bone resorption and a concomitant decrement in osteoclast-specific marker genes expression(e.g.cathepsin K),whereas it did not apparently change serum bone formation markers during HS.Conclusions:These data underscore the damage of HS to intestinal integrity and bone health,as well as that dietary 25-OH-D_(3)supplementation was identified as a potential therapy for preventing these adverse effects.
基金supported in part by grants from the Disciplinary Group of Psychology and Neuroscience Xinxiang Medical University(2016PN-KFKT-06)a visiting professorship from University of Tours(to LHJ)
文摘Microglial cells are the key innate immune cells in the brain and they are crucial in maintaining brain parenchyma homeostasis.Under physiological conditions,microglial cells assume a ramified morphology with a small cell body and an extensive network of fine processes,which secrete neurotrophic factors and patrol the surroundings in search for pathogens and eliminate cellular debris via phagocytosis.Microglial cells express a repertoire of pattern recognition receptors(PRRs)that enable them to detect diverse danger-associated molecular patterns(DAMPs)released from damaged cells or cells under stress,or pathogen-associated molecular patterns generated by pathogens during infection.
基金the National Natural Science Foundation of China(No.81902852)China Postdoctoral Science Foundation(No.2020M670220)+2 种基金the Natural Science Foundation of Hubei Province of China(No.2022CFB481)the Natural Science Foundation of Hubei Provincial Department of Education(No.T2022021)Wudang Local Chinese Medicine Research of Hubei University of Medicine(No.WDCM2020004).
文摘10,11-Dehydrocurvularin(DCV)is a natural-product macrolide that has been shown to exert anti-inflammatory activity.However,the underlying mechanism of its anti-inflammatory activity remains poorly understood.Aberrant activation of the NLRP3 inflammasome is involved in diverse inflammation-related diseases,which should be controlled.The results showed that DCV specifically inhibited the activation of the NLRP3 inflammasome in association with reduced IL-1βsecretion and caspase-1 activation,without effect on the NLRC4 and AIM2 inflammasomes.Furthermore,DCV disturbed the interaction between NEK7 and NLRP3,resulting in the inhibition of NLRP3 inflammasome activation.The C=C double bond of DCV was required for the NLRP3 inflammasome inhibition induced by DCV.Importantly,DCV ameliorated inflammation in vivo through inhibiting the NLRP3 inflammasome.Taken together,our study reveals a novel mechanism by which DCV suppresses inflammation,which indicates the potential role of DCV in NLRP3 inflammasome-driven inflammatory disorders.
文摘Ulcerative colitis (UC) has reactive oxygen species (ROS) and immunologic pathways implicated in its pathogenesis. The search for new therapeutic protocols in managing UC is tailored in suppressing or preventing these pathways. The influence of trivalent chromium (Cr3+), an essential mineral on experimental colitis was investigated. Mice were grouped into 3;group 1 (control) received clean drinking water while groups 2 and 3 received 10 and 100 ppm Cr3+ respectively for 12 weeks through drinking water. After Cr3+ administration, 5 animals per group were sacrificed on day 0. Thereafter, experimental colitis was induced intra-rectally using acetic acid (4%, 0.3mL) and 5 mice per group were subsequently sacrificed on days 3, 7 and 14. Blood and colonic tissues were obtained and processed appropriately. Blood Cr3+ level, haematological variables, gross and microscopic colitis scores, colonic myeloperoxidase (MPO), Superoxide Dismutase (SOD) and malondialdehyde (MDA) levels were determined using standard methods. Colon cytokine mRNA genes were quantified using real-time PCR. There was a significant decrease in colon gross and histology scores on days 3 and 7 in chromium treated compared with control. The MPO and MDA in chromium groups reduced significantly compared with control while SOD activities increased significantly in Cr3+ groups compared with control. Total RNA increased in chromium groups compared with control on day 3 post-colitis. There was up-regulation of IL-10, down-regulation of TNF-α and IFN-λ in chromium administered groups compared with control. Chromium enhanced healing of colitis by suppression of ROS, inflammation and promotion of antioxidant activities.
基金A PhD Studentship from University of Leeds (to PM)Start-Up Fund from Xinxiang Medical University (to LHJ)。
文摘Microglial cells are the key immunocompetent cells in the central nervous system (CNS) and play a crucial role in CNS health and disease (Paolicelli et al.,2022).Under the homeostatic conditions,microglial cells assume diverse and dynamic states,depending upon interactions with neighboring cells and structures in local contextual settings,continuously patrol brain parenchyma utilizing their highly mobile fine processes,phagocytize protein aggregates,unwanted synapses and cells to maintain CNS health,and secrete neurotrophic factors to support neuronal function (Colonna and Butovsky,2017;Paolicelli et al.,2022).
文摘Multiple factors are involved in the etiology of cardiovascular disease(CVD). Pathological changes occur in a variety of cell types long before symptoms become apparent and diagnosis is made. Dysregulation of physiological functions are associated with the activation of immune cells,leading to local and finally systemic inflammation that is characterized by production of high levels of reactive oxygen species(ROS). Patients suffering from inflammatory diseases often present with diminished levels of antioxidants either due to insufficient dietary intake or,and even more likely,due to increased demand in situations of overwhelming ROS production by activated immune effector cells like macrophages. Antioxidants are suggested to beneficially interfere with diseases-related oxidative stress,however the interplay of endogenous and exogenous antioxidants with the overall redox system is complex. Moreover,molecular mechanisms underlying oxidative stress in CVD are not fully elucidated. Metabolic dybalances are suggested to play a major role in disease onset and progression. Several central signalingpathways involved in the regulation of immunological,metabolic and endothelial function are regulated in a redox-sensitive manner. During cellular immune response,interferon γ-dependent pathways are activated such as tryptophan breakdown by the enzyme indoleamine 2,3-dioxygenase(IDO) in monocyte-derived macrophages,fibroblasts,endothelial and epithelial cells. Neopterin,a marker of oxidative stress and immune activation is produced by GTP-cyclohydrolase Ⅰ in macrophages and dendritic cells. Nitric oxide synthase(NOS) is induced in several cell types to generate nitric oxide(NO). NO,despite its low reactivity,is a potent antioxidant involved in the regulation of the vasomotor tone and of immunomodulatory signaling pathways. NO inhibits the expression and function of IDO. Function of NOS requires the cofactor tetrahydrobiopterin(BH4),which is produced in humans primarily by fibroblasts and endothelial cells. Highly toxic peroxynitrite(ONOO-) is formed solely in the presence of superoxide anion(O2-). Neopterin and kynurenine to tryptophan ratio(Kyn/Trp),as an estimate of IDO enzyme activity,are robust markers of immune activation in vitro and in vivo. Both these diagnostic parameters are able to predict cardiovascular and overall mortality in patients at risk. Likewise,a significant association exists between increase of neopterin concentrations and Kyn/Trp ratio values and the lowering of plasma levels of vitamin-C,-E and-B. Vitamin-B deficiency is usually accompanied by increased plasma homoycsteine. Additional determination of NO metabolites,BH4 and plasma antioxidants in patients with CVD and related clinical settings can be helpful to improve the understanding of redox-regulation in health and disease and might provide a rationale for potential antioxidant therapies in CVD.
基金the National Natural Science Foundation of China(No.31900285)the Natural Science FoundationofAnhuiProvince(Nos.2108085QH309and 2208085MH203)Anhui Medical University"Three Complete Education"Comprehensive Reform Pilot Project(No.2021xsqyr05)。
文摘Alcoholic liver disease(ALD)is a growing global health concern,and its early pathogenesis includes steatosis and steatohepatitis.Inhibiting lipid accumulation and inflammation is a crucial step in relieving ALD.Evidence shows that puerarin(Pue),an isoflavone isolated from Pueraria lobata,exerts cardio-protective,neuroprotective,anti-inflammatory,antioxidant activities.However,the therapeutic potential of Pue on ALD remains unknown.In the study,both the NIAAA model and ethanol(EtOH)-induced AML-12 cell were used to explore the protective effect of Pue on alcoholic liver injury in vivo and in vitro and related mechanism.The results showed that Pue(100 mg·kg^(−1))attenuated EtOH-induced liver injury and inhibited the levels of SREBP-1c,TNF-α,IL-6 and IL-1β,compared with silymarin(Sil,100 mg·kg^(−1)).In vitro results were consistent with in vivo results.Mechanistically,Pue might suppress liver lipid accumulation and inflammation by regulating MMP8.In conclusion,Pue might be a promising clinical candidate for ALD treatment.
基金This work was supported by the National Natural Science Foundation of China(Grant Number 81803793 and 82003957)the Young Scientist Program by Beijing University of Chinese Medicine,and the Fundamental Research Funds for the Central Universities(Grant Number 2018-JYBZZ-XJSJJ008).
文摘Objective:To investigate the anti-inflammatory effects of the total flavonoids from Saussurea involucrata on lipopolysaccharides(LPS)-stimulated murine RAW264.7 macrophages and explore its underlying mechanism of action.Methods:Total flavonoids from Saussurea involucrata were extracted using chromatographic column method.Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay.The production of nitric oxide was detected by Griess assay and the release of cytokines(IL-10 and TNF-α)and chemokines(MCP-1,MIP-1α,and CCL5/RANTES)was determined by ELISA to evaluate the anti-inflammatory activity of total flavonoids from Saussurea involucrata.Moreover,nuclear translocation of p65,c-Jun,and IRF3 was detected by immunofluorescence microscopy and Western blotting analysis was performed to determine the expression of related proteins.Results:Total flavonoids extracted from Saussurea involucrata were 751.5 mg/g and the content of rutin was 506.5 mg/g.The production of inflammatory mediators including nitric oxide,cytokines,and chemokines was effectively inhibited by total flavonoids from Saussurea involucrata.Meanwhile,total flavonoids also suppressed the nuclear translocation of p65,c-Jun,and IRF3 in LPS-stimulated RAW264.7 cells.The LPS-induced expression of iNOS and COX-2 was remarkably reduced by treatment with total flavonoids from Saussurea involucrata.Moreover,total flavonoids decreased the expression levels of p-IKKα/β,p-TBK1,p-p38,p-ERK,p-JNK,p-p65,p-c-Jun,and p-IRF3 in LPS-exposed RAW264.7 macrophages.Conclusions:Total flavonoids from Saussurea involucrata potentially inhibit the secretion of pro-inflammatory mediators,which may be related to inhibition of p65,c-Jun,and IRF3 signaling pathways in LPS-stimulated RAW264.7 cells.
基金supported by the National Natural Science Foundation of China(82300589 to Xin Liu,82004042 to Mincong Huang,and 82370244 to Yi Wang)the Zhejiang Provincial Key Scientific Project(2021C03041 to Guang Liang,China).
文摘Inflammatory bowel disease(IBD)is a chronic inflammatory disorder of the gastrointestinal tract,which increases the incidence of colorectal cancer(CRC).In the pathophysiology of IBD,ubiquitination/deubiquitination plays a critical regulatory function.Josephin domain containing 2(JOSD2),a deubiquitinating enzyme,controls cell proliferation and carcinogenesis.However,its role in IBD remains unknown.Colitis mice model developed by dextran sodium sulfate(DSS)or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages.JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation.DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation.Mechanistically,JOSD2 binds to the C-terminal of inosine-5′-monophosphate dehydrogenase 2(IMPDH2)and preferentially cleaves K63-linked polyubiquitin chains at the K134 site,suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B(NF-κB)and inflammation in macrophages.It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane(AOM)/DSS-induced CRC,and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice.These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2,suggesting that targeting JOSD2 is a potential strategy for treating IBD.
基金PR is supported by a UKRI Medical Research Council Senior Clinical Fellowship(MR/W015919/1)ET is supported by a UKRI Medical Research Council New Investigator Research Grant(MR/X009904/1).
文摘Chronic liver disease represents a significant global health burden.Regardless of etiology,its pathogenesis is driven by persistent liver inflammation,which can lead to fibrosis,cirrhosis,and an increased risk of cancer development.Myeloid cells,including neutrophils,eosinophils,monocytes,macrophages,and dendritic cells,play diverse and critical roles in hepatic immunity and the maintenance of tissue homeostasis but are also involved in liver injury,disease progression,and resolution.With the emergence of high-resolution omics technologies and in vivo fate-mapping models,our understanding of myeloid cell ontogeny and functional heterogeneity has been significantly refined.In this review,we discuss current insights into the myeloid cell landscape in nonviral chronic liver inflammatory conditions and summarize the roles of myeloid cell subsets in disease pathogenesis.
基金supported by the National Key Research and Development Plan(2022YFC3500202,China)the National Natural Science Foundation of China(No.U24A20794).
文摘Joint is often regarded as a sensitive indicator of systemic inflammation,capable of responding to various pathological states ranging from local infections to systemic inflammatory diseases.We are all familiar with the phenomenon that the joint pain(arthralgia)caused by joint inflammation(arthritis)usually happens when the body has inffammation in other distant unrelated organs such as lupus1.
基金supported by the National Natural Science Foundation of China(32271334,32100945,and 81871228)the National Key R&D Program of China(2018YFA0506900 and 2018YFA0800301)+3 种基金Shanghai Basic Research Field Project“Science and Technology Innovation Action Plan”(21JC1400400)the Lingang Laboratory(LG-QS-202204-06)the High-Level Medicine Foundation of Shanghai Government(to P.L.)Shanghai Municipal Science and Technology Major Project(2017SHZDZX01).
文摘Abdominal aortic aneurysm(AAA)is strongly correlated with obesity,partially due to the abnormal expansion of abdominal perivascular adipose tissue(PVAT).Cell death-inducing DNA fragmentation factor-like effector C(CIDEC),also known as fat-specific protein 27(FSP27)in rodents,is specifically expressed in adipose tissue where it mediates lipid droplet fusion and adipose tissue expansion.Whether and how CIDEC/FSP27 plays a role in AAA pathology remains elusive.Here,we show that FSP27 exacerbates obesity and angiotensinⅡ(AngⅡ)-induced AAA progression.FSP27 deficiency in mice inhibited high-fat diet-induced PVAT expansion and inflammation.Both global and adipose tissue-specific FSP27 ablation significantly decreased obesity-related AAA incidence.Deficiency of FSP27 in adipocytes abrogated matrix metalloproteinase-12(MMP12)expression in aortic tissues.Infiltrated macrophages,which partially colocalize with MMP12,were significantly decreased in the FSP27-deficient aorta.Mechanistically,knockdown of Fsp27 in 3T3-L1 adipocytes inhibited C-C motif chemokine ligand 2(CCL2)expression and secretion through a c-Jun N-terminal kinase(JNK)-dependent pathway,thereby leading to reduced induction of macrophage migration,while Cidec overexpression rescued this effect.Overall,our study demonstrates that CIDEC/FSP27 in adipose tissue contributes to obesity-related AAA formation,at least in part,by enhancing PVAT inflammation and macrophage infiltration,thus shedding light on its significance as a key regulator in the context of obesity-related AAA.
文摘Andrographolide from traditional Chinese herbal medicines previously showed it possesses a strong anti- inflammatory activity. In present study, we investigated whether Andrographolide could inhibit allergen-induced airway inflammation and airways hyper-responsiveness and explored the mechanism of Andrographolide on allergen-induced airway inflammation and airways hyper-responsiveness. After sensitized and challenged by ovalbumin, the BALB/c mice were administered intraperitoneally with Andrographolide. Hyper-responsiveness was recorded. The lung tissues were assessed by histological examinations. NF-κB in lung was determined by immunofluorescence staining and Western blotting. Treatment of mice with Androqrapholide displayed lower Penh in response to asthma group mice. After treatment with Andrographolide, the extent of inflammation and cellular infiltration in the airway were reduced. Andrographolide interrupted NF-κB to express in cell nucleus. The level of NF-κB expression was inhibited by Andrographolide. The data indicate that Andrographolide from traditional Chinese herbal medicines could inhibit extensive infiltration of inflammatory cells in lung and decrease airway hyperreactivity. Andrographolide could inhibit NF-κB expression in lung and suppress NF-κB expressed in the nucleus of airway epithelial cells.
文摘The role of IL-17 in many inflammatory and autoimmune diseases is now well established,with three currently registered anti-IL-17-targeted therapies.This story has taken place over a period of 20 years and led to the demonstration that a T cell product could regulate,and often amplify,the inflammatory response.The first results described the contribution of IL-17 to local features in arthritis.Then,understanding was extended to its systemic effects,with a focus on cardiovascular aspects.This review provides a historical perspective of these discoveries focused on arthritis,which started in 1995,followed 10 years later by the description of Th17 cells.Today,IL-17 inhibitors for three chronic inflammatory diseases have been registered.More options are now being tested in ongoing and future clinical trials.Inhibitors of IL-17 family members and Th17 cells ranging from antibodies to small molecules are under active development.The identification of patients with IL-17-driven disease is a key target for the improved selection of patients expected to have a strongly positive response.
基金This research was supported by the National Key Research and Development Program of China(No.2021YFF0702000-F.L.)the National Natural Science Foundation of China(Nos.81770072-F.L.,32070764-F.L.,82170001-X.T.,and 81800087-X.T.)West China Hospital(No.ZYJC21023-H.W.).The authors gratefully acknowledge support from Jeffrey.A.Whitsett(Cincinnati Children’s Hospital)for reviewing the manuscript,and Yang He(West China Hospital)for providing a confocal microscope.
文摘Dear Editor,Acute lung injury(ALI)is a significant contributor to the development of acute respiratory distress syndrome(ARDS),which is a severe clinical condition associated with high morbidity and mortality.1 It is increasingly evident that preserving mitochondrial health in alveolar epithelial cells holds great therapeutic potential for ARDS.2 Mitophagy,a cellular process aimed at maintaining mitochondrial health,plays a critical role in this regard.3 Therefore,gaining a comprehensive understanding of the factors that regulate mitophagy in alveolar epithelial cells during ALI could greatly inform the development of future therapeutic approaches for ARDS.
