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Background and Aims: Short-chain fatty acids (SCFAs), key metabolites produced by gut microbiota, have neuroprotective effects in neurodegenerative diseases by modulating immune responses. However, their role in human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) remains largely unexplored., Methods: We recruited HAND patients, HIV Control, and healthy controls (HC). Plasma SCFAs and SCFA-producing gut microbiota were quantified via gas chromatography-mass spectrometry and fecal metagenomic analysis. Inflammatory cytokine levels were measured using liquid chromatography. Receiver operating characteristic (ROC) curves were generated to evaluate the predictive accuracy of SCFAs for HAND., Results: Plasma SCFAs were significantly reduced in HAND patients, correlating with a decrease in SCFA-producing gut bacteria, such as Prevotella and its related species. Reduced SCFAs were positively correlated with pro-inflammatory cytokines and cognitive impairment, while being negatively correlated with anti-inflammatory cytokines. ROC curve analysis demonstrated that several SCFAs exhibited strong predictive accuracy for HAND status., Conclusions: SCFAs may influence cognitive function by modulating inflammatory responses, and identifies plasma SCFAs as potential biomarkers and therapeutic targets for HAND. Further investigation is needed to delineate the mechanisms that SCFAs influence HAND pathology., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the Beijing Youan hospital’s ethics committee (JYKL 2023–057), and all participants provided signed informed consent. Consent for publication: All authors have read and agreed with the submission of the manuscript to Lipids in Health and Disease. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Previous studies that explored the prognostic and clinical value of the systemic immune-inflammation index (SII) in biliary tract cancer (BTC) had inconsistent results. We conducted this meta-analysis to evaluate the prognostic and clinicopathological role of the SII in biliary tract cancer. Combined analysis demonstrated that high SII levels had worse overall survival (HR = 1.92, 95% CI: 1.66-2.21, p < 0.001) than those with low SII levels. And an elevated SII was associated with lymph node metastasis (OR = 1.44, 95% CI = 1.18-1.76; p < 0.001), TNM stage (OR = 1.49, 95% CI = 1.05-2.13; p = 0.028), and vascular invasion (OR = 1.49, 95% CI = 1.05-2.13; p = 0.028). Conversely, no significant association between a high SII and sex or tumor differentiation was found. Our findings demonstrate that high SII levels were correlated with unfavorable survival outcomes among patients with BTC and that they were also correlated with some higher malignancy features of BTC., Competing Interests: The authors declared that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xiulan Peng et al.)

Phenotypic polarization of macrophages is regulated by a milieu of cues in the local tissue microenvironment. Currently, little is known about how the intrinsic regulators modulate proinflammatory (M1) versus prohealing (M2) macrophages activation. Here, it is observed that insulin-like growth factor 2 messenger RNA (mRNA)-binding protein 2 (IGF2BP2)-deleted macrophages exhibit enhanced M1 phenotype and promote dextran sulfate sodium induced colitis development. However, the IGF2BP2 -/- macrophages are refractory to interleukin-4 (IL-4) induced activation and alleviate cockroach extract induced pulmonary allergic inflammation. Molecular studies indicate that IGF2BP2 switches M1 macrophages to M2 activation by targeting tuberous sclerosis 1 via an N6-methyladenosine (m 6 A)-dependent manner. Additionally, it is also shown a signal transducer and activators of transcription 6 (STAT6)-high mobility group AT-hook 2-IGF2BP2-peroxisome proliferator activated receptor- γ axis involves in M2 macrophages differentiation. These findings highlight a key role of IGF2BP2 in regulation of macrophages activation and imply a potential therapeutic target of macrophages in the inflammatory diseases., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Objective: Coronavirus disease 2019 (COVID-19) is a considerable global public health threat. This study sought to investigate whether blood glucose (BG) levels or comorbid diabetes are associated with inflammatory status and disease severity in patients with COVID-19., Methods: In this retrospective cohort study, the clinical and biochemical characteristics of COVID-19 patients with or without diabetes were compared. The relationship among severity of COVID-19, inflammatory status, and diabetes or hyperglycemia was analyzed. The severity of COVID-19 in all patients was determined according to the diagnostic and treatment guidelines issued by the Chinese National Health Committee (7th edition)., Results: Four hundred and sixty-one patients were enrolled in our study, and 71.58% of patients with diabetes and 13.03% of patients without diabetes had hyperglycemia. Compared with patients without diabetes ( n = 366), patients with diabetes ( n = 95) had a higher leucocyte count, neutrophil count, neutrophil to lymphocyte ratio (NLR), and erythrocyte sedimentation rate (ESR). There was no association between severity of COVID-19 and known diabetes adjusted for age, sex, body mass index (BMI), known hypertension, and coronary heart disease. The leucocyte count, NLR, and C-reactive protein (CRP) level increased with increasing BG level. Hyperglycemia was an independent predictor of critical (OR 4.00, 95% CI 1.72-9.30) or severe (OR 3.55, 95% CI 1.47-8.58) COVID-19, and of increased inflammatory levels (high leucocyte count (OR 4.26, 95% CI 1.65-10.97), NLR (OR 2.76, 95% CI 1.24-6.10), and CRP level (OR 2.49, 95% CI 1.19-5.23)), after adjustment for age, sex, BMI, severity of illness, and known diabetes., Conclusion: Hyperglycemia was positively correlated with higher inflammation levels and more severe illness, and it is a risk factor for the increased severity of COVID-19. The initial measurement of plasma glucose levels after hospitalization may help identify a subset of patients who are predisposed to a worse clinical course., Competing Interests: No authors declare any conflicts of interest., (Copyright © 2021 Wen Zhang et al.)

The mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) are specific ER domains that contact the mitochondria and function to facilitate communication between ER and mitochondria. Disruption of contact between the mitochondria and ER is associated with a variety of pathophysiological conditions including neurodegenerative diseases. Considering the many cellular functions of MAMs, we hypothesized that MAMs play an important role in regulating microRNA (miRNA) activity linked to its unique location between mitochondria and ER. Here we present new findings from human and rat brains indicating that the MAMs are subcellular sites enriched for specific miRNAs. We employed subcellular fractionation and TaqMan® RT-qPCR miRNA analysis to quantify miRNA levels in subcellular fractions isolated from male rat brains and six human brain samples. We found that MAMs contain a substantial number of miRNAs and the profile differs significantly from that of cytosolic, mitochondria, or ER. Interestingly, MAMs are particularly enriched in inflammatory-responsive miRNAs, including miR-146a, miR-142-3p, and miR-142-5p in both human and rat brains; miR-223 MAM enrichment was observed only in human brain samples. Further, mitochondrial uncoupling or traumatic brain injury in male rats resulted in the alteration of inflammatory miRNA enrichment in the isolated subcellular fractions. These observations demonstrate that miRNAs are distributed differentially in organelles and may re-distribute between organelles and the cytosol in response to cellular stress and metabolic demands.

Recent studies suggested that prolyl hydroxylase 2 (PHD2) functions as an important regulator in vascular inflammation and Streptococcus pneumonia infection. However, whether PHD2 contributed to tumor progression prompted by intratumoral inflammation remains elusive. In this study, the effects of PHD2 in colon cancer were evaluated, and the underlying molecular mechanisms were investigated. The results showed that overexpressing PHD2 exerted proliferative and migratory inhibition in colon cancer cells. The expression of cell cycle and epithelial-mesenchymal transition (EMT)-associated proteins were changed: CyclinD1, CDK4, N-cadherin, and Vimentin were down-regulated, while E-cadherin was up-regulated in PHD2-overexpressing colon cancer cells. Moreover, in colon cancer xenograft mice, PHD2 overexpression suppressed tumor growth accompanied by decreased Ki67 expression. Importantly, we further demonstrated that overexpressing PHD2 attenuated inflammation in colon cancer xenograft mice through weakening accumulation of myeloid-derived suppressor cells (MDSCs) and M2-like tumor-associated macrophages (TAMs), as well as secretions of pro-inflammatory cytokines including G-CSF, TNF-α, IL-6, IL-8, IL-1β, and IL-4. Mechanistically, PHD2 overexpression obviously suppressed NF-κB activity through decreasing phosphorylated IκB-α while increasing cytoplasmic NF-κB p65 levels in colon cancer. Our findings support the anti-cancer and anti-inflammatory roles of PHD2 and offer a preclinical proof of tumor progression regulated by cancer cells and inflammation., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Quercetin, a natural flavonol existing in many food resources, has been reported to be an effective antimicrobial and anti-inflammatory agent for restricting the inflammation in periodontitis. In this study, we aimed to investigate the anti-inflammatory effects of quercetin on Porphyromonas gingivalis ( P. gingivalis ) lipopolysaccharide- (LPS-) stimulated human gingival fibroblasts (HGFs). HGFs were pretreated with quercetin prior to LPS stimulation. Cell viability was evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. The levels of inflammatory cytokines, including interleukin-1 β (IL-1 β ), interleukin-6 (IL-6), and tumor necrosis factor- α (TNF- α ), along with chemokine interleukin-8 (IL-8), were determined by enzyme-linked immunosorbent assay (ELISA). The mRNA levels of IL-1 β , IL-6, IL-8, TNF- α , I κ B α , p65 subunit of nuclear factor-kappa B (NF- κ B), peroxisome proliferator-activated receptor- γ (PPAR- γ ), liver X receptor α (LXR α ), and Toll-like receptor 4 (TLR4) were measured by real-time quantitative PCR (RT-qPCR). The protein levels of I κ B α , p-I κ B α , p65, p-p65, PPAR- γ , LXR α , and TLR4 were characterized by Western blotting. Our results demonstrated that quercetin inhibited the LPS-induced production of IL-1 β , IL-6, IL-8, and TNF- α in a dose-dependent manner. It also suppressed LPS-induced NF- κ B activation mediated by TLR4. Moreover, the anti-inflammatory effects of quercetin were reversed by the PPAR- γ antagonist of GW9662. In conclusion, these results suggested that quercetin attenuated the production of IL-1 β , IL-6, IL-8, and TNF- α in P. gingivalis LPS-treated HGFs by activating PPAR- γ which subsequently suppressed the activation of NF- κ B., Competing Interests: The authors declare no conflicts of interest.

Tim-3 is expressed on monocytes/macrophages and is involved in the regulation of inflammatory responses. The aim of this study was to determine the effect of Tim-3 on inflammatory response triggered by peripheral monocytes from patients with chronic hepatitis B (CHB). Tim-3 expression on peripheral monocytes and frequency of Th17 cells in peripheral blood mononuclear cells (PBMCs) derived from CHB patients were detected. Followed by lipopolysaccharides (LPS) activation of circulating monocytes from CHB patients, expression of inflammatory cytokines including TNF-α，IL-1β and IL-6 were examined in the presence and absence of Galectin-9 which is the ligand for Tim-3. Subsequently, after purified CD4+T cells were cocultured with LPS-activated monocytes from CHB patients in the presence of anti-Tim-3 antibody, percentage of Th17 cells and production of IL-17 were measured. Tim-3 expression was significantly upregulated and closely correlated to the frequency of Th17 cells in patients with CHB. Expression of TNF-α，IL-1β and IL-6 increased significantly in monocytes stimulated with LPS and Galectin-9, compared to LPS stimulation alone. LPS-activated monocytes from CHB patients could drive differentiation of memory CD4+T cells to Th17 cells. However, under the blockade of Tim-3 signalling by anti-Tim-3 antibody, percentage of Th17 cells and production of IL-17 decreased significantly. Our results demonstrate that upregulated expression of Tim-3 on circulating monocytes accelerates inflammatory response by promoting production of inflammatory cytokines and Th17 responses in CHB., (© 2019 The Foundation for the Scandinavian Journal of Immunology.)

This study investigated the protective effect and underlying mechanism of action of umbelliferone (Umb) against lipopolysaccharide (LPS)-induced acute lung injury (ALI). An intragastric Umb injection prior to the administration of LPS dramatically decreased the wet/dry lung weight ratio, attenuated inflammatory cell infiltration in lung tissue, and reduced the LPS-induced production of inflammatory cytokines, including monocyte chemotactic protein-1(MCP-1), interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and IL-1β, in broncheoalveolar lavage fluid (BALF). In addition, Umb resulted in significant anti-oxidative effects as shown by decreased myeloperoxidase (MPO) and malondialdehyde (MDA) activity and increased superoxide dismutase (SOD) activity compared with the LPS group. Finally, the inhibitory effects of Umb on the expression of toll-like receptor 4 (TLR4)/myeloid differentiation protein 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway proteins were also measured. Our results clearly indicated that Umb exerted significant protective effects on LPS-induced ALI by inhibiting the activation of the TLR4/MyD88/NF-κB pathway.

Coenzyme Q10 (Co-Q10) is extraordinarily popular and has been used in abundant interventions as an antioxidant reagent that participates in numerous oxidation reactions. According to substantial evidence previously reported, interleukin-1β (IL-1β) is deemed to be one of the chief orchestrator molecules in the degeneration of intervertebral disc (IVD). However, it is unknown whether Co-Q10 is able to protect against IVD degeneration. In the current study, mouse-derived IVDs as well as primary human nucleus pulposus (NP) cells were isolated and cultured. NP cells were stimulated with IL-1β, with or without selective addition of Co-Q10 to investigate the therapeutic effect of Co-Q10 on IVD degeneration. Levels of IL-1β-induced inflammatory biomarkers including TNF-α, COX-2, IL-6 and iNOS were reduced by Co-Q10, which was possibly associated with inhibition of NF-κB signaling activation. Furthermore, Co-Q10 maintained the production of anabolic biomarkers in NP cells such as collagen 2, aggrecan and Sox-9 and altered the enhanced catabolism induced by IL-1β. Moreover, the therapeutic role of Co-Q10 in sustaining IVD tissue-enhanced anabolism is potentially dependent on activation of the Akt signaling pathway. In summary, Co-Q10 may potentially represent an available molecular target that may shed light on approaches to the prevention and treatment of IVD degeneration in the future., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Rheumatoid arthritis (RA) is a multifactorial autoimmune disease, characterized by inflammation of synovial joints. Carnosic acid (CA) is a phenolic diterpene isolated from Rosmarinus officinailis, playing a central role in cytoprotective responses to oxidative stress and inflammation response. Our study aimed to investigate the effects of CA on RA progression in diabetic animals. Carnosic acid (CA) was used to treat collagen-induced arthritis (CIA)-induced db/db mice. Blood glucose, oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were investigated to explore insulin resistance. CA significantly down-regulated fasting blood glucose, glucose level in OGTT and ITT, ameliorated CIA-induced bone loss, and reduced pro-inflammatory cytokines and reactive oxygen species (ROS) in db/db mice with arthritis induced by CIA. In vitro, CA suppressed Receptor Activator for Nuclear Factor-κ B Ligand (RANKL)- and Macrophage colony-stimulating factor (M-CSF)-induced osteoclastogenesis. The osteoclastic specific markers were inhibited by CA. Signal transduction studies showed that CA significantly decreased the expression of molecules contributing to ROS and increased anti-oxidants. Additionally, CA inactivated the RANKL- and M-CSF-induced p38 mitogen activated protein kinases (MAPK), inhibited NF-κB phosphorylation, causing pro-inflammatory cytokines down-regulation. Together, CA ameliorated osteoclast formation and CIA-induced bone loss in db/db mice through inflammation suppression by regulating ROS-dependent p38 pathway., (Copyright © 2017. Published by Elsevier Inc.)

The systematic application of antiangiogenic therapy remains an issue of concern, mainly due to the hypoxic and inflammatory changes in the tumor microenvironment elicited by antiangiogenic therapy. Versican, a 'bridge' connecting inflammation with tumor progression as well as playing a central role in the generation of an inflammatory tumor microenvironment is a promising candidate for the intervention of inflammatory changes in the tumor microenvironment elicited by antiangiogenic therapy. To examine this hypothesis, a short-hairpin RNA targeting versican (shVCAN) was designed and shVCAN stable-transfected B16F1 and Lewis lung carcinoma (LLC) cell lines were established. Simultaneously, the established B16F1 and LLC tumor models were used to investigate the effect of versican silencing on the tumor burden of mice. The results showed that, versican silencing exerted an inhibitory effect on the proliferative and migratory ability of B16F1 cells, but did not affect LLC cells. Endostatin exhibited modest inhibition of tumor growth in tumor-bearing mice. Versican silencing alone effectively suppressed orthotopic tumor growth and significantly prolonged survival time of mice more effectively when combined with endostatin. Endostatin elicited inflammatory and immunosuppressive changes in the tumor microenvironment, including an accumulation of myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs) and inflammatory cytokines. In addition, NF-κB and HIF-1α were overexpressed in the tumor. Versican silencing improved the antitumor efficacy of endostatin by alleviating its induced changes in the tumor microenvironment. Thus, versican silencing in the tumor microenvironment offers a promising approach to reverse the tumor refractoriness to antiangiogenic therapies.

Inflammation can cause endoplasmic reticulum (ER) stress and therefore activates the unfolded protein response (UPR). ER stress and the consequent UPR have the potential to activate NF-κB. However, the factors mediating the crosstalk between ER stress and the NF-κB pathway remain unclear. Here, we determined that ER stress inducible protein Mesencephalic Astrocyte-derived Neurotrophic Factor (MANF) was up-regulated in autoimmune diseases and inflammatory disease models. Inflammation caused MANF to relocalize to the nuclei. MANF interacted with the DNA binding domain of p65 through its C-terminal SAP-like domain in the nuclei under the condition of inflammation or ER stress. MANF consequently inhibited p65-mediated transcriptional activation by interfering with the binding of p65 to its target genes promoters. Consistently, MANF suppressed the expressions of NF-κB-dependent target genes and the proliferation of inflammatory synoviocytes. These findings suggest that MANF may be a negative regulator of inflammation and mediate the crosstalk between the NF-κB pathway and ER stress.

The circadian clock regulates many physiological parameters involving immune response to infectious agents, which is mediated by activation of the transcription factor NF-κB. Thus, understanding the NF-κB dynamics regulated by circadian clocks will help in developing better therapeutics. To this end, we proposed a detailed model in the present work on the basis of understanding inflammatory response under control from circadian clocks. Our results show that the frequencies and amplitudes of the NF-κB oscillation are dependent on the strength and modes of coupling to circadian clock. This circadian control of NF-κB pathway can therefore serve as a useful mechanism in keeping the system in check and controlling inflammatory response induced by infection and other agents. The results are consistent with earlier experimental findings., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Aims: The NLRP3 inflammasome is a cytoplasmic multiprotein complex of the innate immune system that regulates the cleavage of interleukin-1β and interleukin-18 precursors. It can detect a wide range of danger signals and trigger a series of immune-inflammatory reactions. There were plenty of studies indicating that activation of the immune system played pivotal roles in depression. However, the underlying mechanisms of immune-depression interactions remained elusive and there was no report about the involvement of inflammasome activation in depression., Methods: We established an acute depression mouse model with lipopolysaccharide to explore the involvement of inflammasome activation in depression., Results: The lipopolysaccharide-treated mice displayed depressive-like behaviors and pro-inflammatory cytokine interleukin-1β protein and mRNA levels significantly increased. The NLRP3 inflammasome mRNA expression level also significantly elevated in depressed mice brain. Pretreatment with the NLRP3 inflammasome inhibitor Ac-YVAD-CMK significantly abrogated the depressive-like behaviors induced by lipopolysaccharide., Conclusion: These data suggest for the first time that the NLRP3 inflammasome is involved in lipopolysaccharide-induced mice depressive-like behaviors. The NLRP3 inflammasome may be a central mediator between immune activation and depression, which raises the possibility that it may be a more specific target for the depression treatments in the near future., (© 2013 John Wiley & Sons Ltd.)

Objective: The purpose of this study was to explore the correlation between inflammatory indicators and blood lipids and to further provide a theoretical basis for the diagnosis and treatment of clinical polycystic ovary syndrome (PCOS). Methods: Whole-blood cell counts and hormone and blood lipid levels were measured in 110 patients with PCOS and 126 healthy women. The differences in the above levels and the correlation between inflammation and blood lipid levels in the two groups were determined, and classified according to BMI. Differences in inflammatory indices were also analyzed. The independent risk factors for PCOS were analyzed by binary logistic regression. Results: The PCOS group had greater BMI and greater body weight than the control group. The inflammatory indicators WBC, neutrophil, lymphocyte, monocyte counts and the NLR were significantly higher than those of the control group. It had higher testosterone (TSTO), triglyceride (TG) and total cholesterol (TC) levels. Correlation analysis showed that leukocyte and neutrophil counts were positively correlated with TSTO and TG levels and negatively correlated with HDL. In the BMI ≥ 24 and BMI < 24 groups, WBC was higher in PCOS patients than in healthy controls. Logistic regression showed that TSTO, TG and FSH were independent risk factors for PCOS. Conclusion: Inflammatory markers are correlated with blood lipids in PCOS. During the treatment of PCOS, blood lipids and serum inflammatory factors should be monitored. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) and its complications are a leading cause of death worldwide. Endothelial dysfunction plays a crucial role in the initiation and progression of CVD, serving as a pivotal factor in the pathogenesis of cardiovascular, metabolic, and other related diseases. The regulation of endothelial dysfunction is influenced by various risk factors and intricate signaling pathways, which vary depending on the specific disease context. Despite numerous research efforts aimed at elucidating the mechanisms underlying endothelial dysfunction, the precise molecular pathways involved remain incompletely understood. This review elucidates recent research findings on the pathophysiological mechanisms involved in endothelial dysfunction, including nitric oxide availability, oxidative stress, and inflammation‐mediated pathways. We also discuss the impact of endothelial dysfunction on various pathological conditions, including atherosclerosis, heart failure, diabetes, hypertension, chronic kidney disease, and neurodegenerative diseases. Furthermore, we summarize the traditional and novel potential biomarkers of endothelial dysfunction as well as pharmacological and nonpharmacological therapeutic strategies for endothelial protection and treatment for CVD and related complications. Consequently, this review is to improve understanding of emerging biomarkers and therapeutic approaches aimed at reducing the risk of developing CVD and associated complications, as well as mitigating endothelial dysfunction. [ABSTRACT FROM AUTHOR]

IntroductionAutoimmune hepatitis (AIH) is a chronic progressive hepatic inflammatory disease, characterized by elevated transaminase levels, inflammatory liver histology, and intrahepatic lymphocyte activation (Zachou et al. 2013). With the advances in [...], Autoimmune hepatitis (AIH) is a chronic progressive autoimmune disease characterized by hepatic inflammation. This study aimed to investigate the effect of antagomir-155 on concanavalin A (ConA)-induced AIH, and its possible mechanisms. According to the results, the expression of miR-155 was raised in liver tissues after 48 h exposure to ConA Treatment with antagomir-155 attenuated ConA-induced liver injury in mice by reducing serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels. In addition, antagomir-155 significantly alleviated the differentiation of Treg/Th17 cells in the livers of AIH mice, and suppressed Th17-cells-mediated production of pro-inflammatory cytokines IL-17A, IL-23, but not Treg-cells-mediated production of anti-inflammatory cytokine IL-10. Finally, the beneficial effect of antagomir-155 on ConA-induced AIH was abolished by administration of recombinant IL-17A. Our data demonstrated that antagomir-155 treatment could prevent AIH via regulating the differentiation of Treg and Th17 cells, suggesting that microRNA-155 may be an intriguing therapeutic target of AIH.Key words: autoimmune hepatitis, microRNA-155, Treg, Th17.L'hepatite auto-immune (HAI) est une maladie auto-immune evolutive chronique caracterisee par une inflammation du foie. Ces travaux visaient a etudier l'effet de l'antagomir-155 sur l'HAI provoquee par la concanavaline A (ConA), ainsi que ses modes d'action eventuels. D'apres les resultats, l'expression du miR-155 augmentait dans les tissus hepatiques apres une exposition de 48 h a la ConA. L'administration d'antagomir-155 permettait d'attenuer les lesions hepatiques provoquees par la ConA chez la souris en faisant diminuer l'alanine aminotransferase, l'asparate aminotransferase et la phosphatase alcaline dans le serum. De plus, l'antagomir-155 entramait une attenuation notable de la differenciation des cellules Treg/Th17 dans le foie des souris atteintes d'HAI, ainsi qu'une inhibition de la production mediee par les cellules Th17 des cytokines pro- inflammatoires IL-17A et IL-23, mais pas de la production mediee par les cellules Treg de la cytokine anti-inflammatoire IL-10. Enfin, l'effet benefique de l'antagomir-155 sur l'HAI provoquee par la ConA etait aboli apres l'administration d'IL-17A recombinante. Nos donnees ont montre que l'administration d'antagomir-155 pourrait prevenir l'HAI par l'intermediaire de la regulation de la differenciation des cellules Treg et Th17, ce qui laisse entendre que le microRNA-155 pourrait etre une cible therapeutique interessante dans l'HAI. [Traduit par la Redaction]Mots-cles: hepatite auto-immune, microRNA-155, Treg, Th17.

Artemisia japonica Thunb. has been used as a traditional Chinese medicine and a vegetable for thousands of years in China. However, there are few reports on the chemical composition and biological activity of its leaves. Thus, this study aimed to evaluate the chemical composition, antioxidant and anti-inflammatory effects of water extracts of A. japonica leaves and their underlying mechanisms. A total of 48 compounds were identified in the water extract using UPLC-QTOF-MS2 analysis, with phenolic acids, particularly chlorogenic acid compounds, being the predominant components. The ethyl acetate fraction (EAF) contained most of the total phenolic content (385.4217 mg GAE/g) and displayed superior antioxidant capacity with the IC50DPPH•, IC50ABTS•+, and OD0.5reducing power at 10.987 μg/mL, 43.630 μg/mL and 26.883 μg/mL, respectively. Furthermore, EAF demonstrated potent antioxidant and anti-inflammatory effects in LPS-induced RAW264.7 cells by upregulating the Nrf2/HO-1 signal pathway. These findings highlight that A. japonica leaves possess remarkable abilities to mitigate inflammation and oxidative stress, suggesting their potential utilization as medicinal agents and food additives for promoting human health. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the protective effects and mechanisms of myricetin on acute liver failure in mice induced by lipopolysaccharide (LPS)/D-galactosamine (D-Gal). Our results showed myricetin (25, 50 and 100 mg/kg) pretreatment significantly improved the pathological changes of liver tissues, decreased serum ALT and AST (p < 0.001) induced by LPS/D-GalN. Moreover, MDA and MPO levels were reduced (p < 0.001), CAT and SOD activities were increased (p < 0.001) with myricetin (50 and 100 mg/kg) pretreatment. Likewise, inflammatory cytokines TNF-α and IL-6 mRNA in liver tissues were markedly decreased (p < 0.001) by myricetin. Besides, Nrf2 protein expression was drastically elevated (p < 0.001) by myricetin (25, 50 and 100 mg/kg). All these findings imply that myricetin may protect against acute liver failure by suppressing inflammation and regulating oxidative stress via Nrf2 signaling, and that it may be a possible strategy to avoid liver damage. [ABSTRACT FROM AUTHOR]

Excessive release of cytokines such as IL-1β and other inflammatory mediators synthesized and secreted by macrophages is the fundamental link of uncontrolled inflammatory response in sepsis. 17β-Estradiol (E2) plays anti-inflammatory and vascular protective effects by regulating leukocyte infiltration and the expression of chemokines or cytokines induced by injury. However, the role of E2 in the inflammatory response of macrophages in sepsis and its mechanism are still not fully understood. In the present study, we show that E2 alleviates vascular inflammation in sepsis mice induced by cecal ligation puncture (CLP). E2 significantly decreases RAW 264.7 cell inflammation response by downregulating the expression of NLRP3. Furthermore, we found that miR-29a-5p was significantly downregulated in LPS-treated macrophages. Treating RAW 264.7 cells with E2 markedly upregulated the miR-29a-5p expression level. More importantly, we demonstrated that miR-29a-5p repressed NLRP3 expression by directly targeting its 3 ′ -UTR. Loss- and gain-of-function experiments revealed that transfection of the miR-29a-5p mimic abrogates LPS-induced macrophage inflammation. Moreover, depletion of miR-29a-5p by its inhibitor largely promotes LPS-induced macrophage inflammation. In summary, miR-29a-5p upregulation induced by E2 alleviated RAW 264.7 cell inflammation response by aggravating miR-29a-5p repression of NLRP3 expression. E2 exerts significant anti-inflammatory efficacy in macrophages by regulating the miR-29a-5p/NLRP3 axis. Targeting miR-29a-5p may be a novel therapeutic strategy to suppress sepsis-induced vascular inflammation. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine whether vitamin D supplementation and maintaining vitamin D sufficiency are associated with changes in inflammatory and metabolic biomarkers in patients with knee osteoarthritis (OA) and vitamin D deficiency. A total of 413 participants with symptomatic knee OA and vitamin D deficiency were enrolled in a randomised, placebo-controlled trial and received 1·25 mg vitamin D3 or placebo monthly for 24 months across two sites. In this post hoc analysis, 200 participants from one site (ninety-four from the placebo group and 106 from the vitamin D group; mean age 63·1 (sd 7·3) years, 53·3 % women) were randomly selected for measurement of serum levels of inflammatory and metabolic biomarkers at baseline and 24 months using immunoassays. In addition, participants were classified into two groups according to serum 25-hydroxyvitamin D (25(OH)D) levels at months 3 and 24: (1) not consistently sufficient (25(OH)D≤50 nmol/l at either month 3 or 24, n 61), and (2) consistently sufficient (25(OH)D>50 nmol/l at both months 3 and 24, n 139). Compared with placebo, vitamin D supplementation had no significant effect on change in serum high-sensitive C-reactive protein, IL-6, IL-8, IL-10, leptin, adiponectin, resistin, adipsin and apelin. Being consistently vitamin D sufficient over 2 years was also not associated with changes in these biomarkers compared with not being consistently sufficient. Vitamin D supplementation and maintaining vitamin D sufficiency did not alter serum levels of inflammatory and metabolic biomarkers over 2 years in knee OA patients who were vitamin D insufficient, suggesting that they may not affect systemic inflammation in knee OA patients. [ABSTRACT FROM AUTHOR]

Acute liver injury is a severe clinical syndrome with markedly high mortality and poor prognosis. An accumulating body of evidence has demonstrated that epigenetic mechanisms have essential roles in the pathogenesis of acute liver injury. Lysine-specific demethylase 1 (LSD1) belongs to the amine oxidase superfamily of flavin adenine dinucleotide (FAD)-dependent enzymes, specifically demethylates H3 lysine 4. In the study, we investigated the effects and mechanisms of LSD1 in lipopolysaccharide (LPS)/D-Galactosamine (D-Gal)-induced acute liver injury in mice. Western blot analysis showed that LSD1 phosphorylation and di-methylated histone H3 on lysine 4 (H3K4me2) protein expression were significantly increased after LPS/D-Gal treatment (2.3 and 2.4 times higher than control respectively). GSK-LSD1 2HCl is an irreversible and selective LSD1 inhibitor. Pre-treatment with LSD1 inhibitor alleviated LPS/D-Gal-induced liver damage, decreased serum levels of alanine transaminase and aspartate aminotransferase in mice. Moreover, the LSD1 phosphorylation level in low, medium, and high LSD1 inhibitor groups was lower by a factor of 1.6, 1.9, and 2.0 from the LPS/D-Gal group, respectively. Mechanistically, LSD1 inhibitor further inhibited NF-κB signaling cascades and subsequently inhibited the production of pro-inflammatory cytokine TNF-α, IL-6, and IL-1β induced by LPS/D-Gal in liver tissues. Furthermore, LSD1 inhibitor upregulated the protein expression of Nrf2/HO-1 signaling pathways, and the activities of related antioxidant enzymes were enhanced. Collectively, our data demonstrated that LSD1 inhibitor protected against the LPS/D-Gal-induced acute liver injury via inhibiting inflammation and oxidative stress, and targeting the epigenetic marker may be a potent therapeutic strategy for acute liver injury. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a major cause of death and disability. However, the molecular events contributing to the pathogenesis are not well understood. Mitochondria serve as the powerhouse of cells, respond to cellular demands and stressors, and play an essential role in cell signaling, differentiation, and survival. There is clear evidence of compromised mitochondrial function following TBI; however, the underlying mechanisms and consequences are not clear. MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression post-transcriptionally, and function as important mediators of neuronal development, synaptic plasticity, and neurodegeneration. Several miRNAs show altered expression following TBI; however, the relevance of mitochondria in these pathways is unknown. Here, we present evidence supporting the association of miRNA with hippocampal mitochondria, as well as changes in mitochondria-associated miRNA expression following a controlled cortical impact (CCI) injury in rats. Specifically, we found that the miRNA processing proteins Argonaute (AGO) and Dicer are present in mitochondria fractions from uninjured rat hippocampus, and immunoprecipitation of AGO associated miRNA from mitochondria suggests the presence of functional RNA-induced silencing complexes. Interestingly, RT-qPCR miRNA array studies revealed that a subset of miRNA is enriched in mitochondria relative to cytoplasm. At 12 h following CCI, several miRNAs are significantly altered in hippocampal mitochondria and cytoplasm. In addition, levels of miR-155 and miR-223, both of which play a role in inflammatory processes, are significantly elevated in both cytoplasm and mitochondria. We propose that mitochondria-associated miRNAs may play an important role in regulating the response to TBI. [ABSTRACT FROM AUTHOR]

Background Emerging evidence indicates that the interaction between glucocorticoid receptor α ( GRα) and nuclear factor κB ( NF-κB) is a key pathogenetic cross talk in the autoimmune and inflammatory disorders. The objective of this study was to determine the GRα expression in patients with oral lichen planus ( OLP) and investigate its correlation with NF-κB in OLP. Methods We compared the expression of GRα and NF-κB in oral biopsy specimens from patients with OLP ( n = 32) against normal controls ( n = 12) and investigated the correlation between the expression of GRα and NF-κB in OLP. Results Immunohistochemistry showed that GRα mainly expressed in the cytoplasm of keratinocytes of basal and spinosum layer of OLP. Both real-time quantitative PCR and Western blots revealed that the mRNA and protein expression levels of GRα were decreased compared with normal controls (both P < 0.001). Conversely, those levels of nuclear factor-kappa B (NF-κB) were increased compared with normal controls (both P < 0.001). Importantly, a significant inverse correlation between the GRα and NF-κB was found ( P < 0.05). Conclusions Our findings demonstrated that low expression of GRα in OLP correlates with activation of NF-κB, which indicates that the cross talk between GRα and NF-κB in OLP may become a new therapeutic target and represent a new approach to explore the pathogenesis of OLP. [ABSTRACT FROM AUTHOR]

Background: Peptidoglycan (PGN) is a component of cell wall in Gram-positive bacteria that stimulates inflammatory responses through Toll-like receptor 2 (TLR2). The carboxyl terminus of constitutive heat shock cognate 70 (HSC70)-interacting protein (CHIP, also known as Stub1) is a U-box-type E3 ubiquitin ligase, which plays an important role in protein quality control and inflammation through ubquitin-mediated proteasomal degradation. However, it is unclear whether TLR2 agonist PGN regulates the expression and activation of CHIP. Methods/Results: In this study, we showed that PGN significantly up-regulated the expression of CHIP in both mRNA and protein levels in RAW264.7 cells in a time-dependant manner, and the expression of CHIP induced by PGN was abolished in TLR2 knockout macrophages. No significant change in CHIP was observed after lipopolysaccharide (LPS, TLR4 agonist) and cytosine-phosphorous-guanine oligonucleotide (CpG ODN, TLR9 agonist) treatment. Moreover, PGN markedly induced the expression and activity of CHIP in macrophages, whereas this effect was attenuated by SP600125, a selective inhibitor of JNK. Conclusion: Our study for the first time demonstrates that TLR2 activation enhances the expression and activity of CHIP through JNK signaling pathway. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Low molecular weight heparin (LMWH) exhibits anti-inflammatory properties, but its effect on inflammation in colitis remains unclear. This study aimed to evaluate the therapeutic effects of LMWH on dextran sulfate sodium (DSS)-induced colitis in mice, in which acute colitis progresses to chronic colitis, and to explore the potential mechanism involved in this process. C57BL/6 mice were randomly divided into control, DSS, and DSS plus LMWH groups (n = 18). Disease activity was scored by a disease activity index (DAI). Histological changes were evaluated by hematoxylin and eosin (HE) staining. The mRNA levels of syndecan-1, interleukin (IL)-1β, and IL-10 were determined by quantitative reverse transcription polymerase chain reaction. Protein expression of syndecan-1 was detected by immunohistochemistry. The serum syndecan-1 level was examined by a dot immunobinding assay. LMWH ameliorated the disease activity of colitis induced by DSS administration in mice. Colon destruction with the appearance of crypt damage, goblet cell loss, and a larger ulcer was found on day 12 after DSS administration, which was greatly relieved by the treatment of LMWH. LMWH upregulated syndecan-1 expression in the intestinal mucosa and reduced the serum syndecan-1 level on days 12 and 20 after DSS administration (P<0.05 vs. DSS group). In addition, LMWH significantly decreased the expression of both IL-1β and IL-10 mRNA on days 12 and 20 (P<0.05 vs. DSS group). LMWH has therapeutic effects on colitis by downregulating inflammatory cytokines and inhibiting syndecan-1 shedding in the intestinal mucosa. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate whether norepinephrine (NE) could regulate macrophage production of tumor necrosis factor alpha (TNF-α) by influencing the phosphorylation of mitogen-activated protein kinases (MAPKs). Primary macrophages from male BALB/c mice were applied to explore the mechanism by which NE influences the the secretion of TNF-α when macrophages were activated by lipopolysaccharides (LPS). We found that NE could increase crophage production of TNF-α when macrophages were activated by LPS, and this effect could be inhibited by α adrenergic antagonist phentolamine. Also, NE could increase the phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinases (ERK), and p38, through α receptor. Furthermore, JNK inhibitor SP600125, ERK inhibitor U0126, and p38 inhibitor SB203580 could all partially counteract NE's effect on the phosphorylation of MAPKs, as well as TNF-α production by macrophages. This study revealed that as macrophages were activated by LPS, NE promoted the secretion of inflammatory factors by increasing the phosphorylation of MAPKs through an α receptor-dependent pathway. Our results provide the evidence of a relationship between stress and diseases, as well as the mechanism by which stress induces or affects the inflammation-related diseases. [ABSTRACT FROM AUTHOR]

PM 2.5 exposure is an emerging environmental concern and severe health insult closely related to psychological conditions such as anxiety and depression in adolescence. Adolescence is a critical period for neural system development characterized by continuous brain maturation, especially in the prefrontal cortex. The etiology of these adolescent conditions may derive from fetal origin, probably attributed to the adverse effects induced by intrauterine environmental exposure. Anxiety- and depression-like behavior can be induced by gestational exposure to PM 2.5 in mice offspring which act as a useful model system. Recent studies show that B-vitamin may alleviate PM 2.5 -induced hippocampal neuroinflammation- and function-related spatial memory impairment in adolescent mice offspring. However, cortical damage and related neurobehavioral defects induced by gestational PM 2.5 exposure, as well as the potential reversibility by interventions in mice offspring require to be elucidated. Here, we aimed to investigate whether B-vitamin would protect mice offspring from the adverse effects derived from gestational exposure to urban PM 2.5 on cortical areas to which anxiety and depression are closely related. Pregnant mice were divided into three groups: control group (treated with PBS alone), model group (treated with both PM 2.5 and PBS), and intervention group (treated with both PM 2.5 and B-vitamin), respectively. The mice offspring were then applied to comprehensive neurobehavioral, ultrastructural, biochemical, and molecular biological analyses. Interestingly, we observed that gestational PM 2.5 exposure led to neurobehavioral defects including anxiety- and depression-like behavior. In addition, neuroinflammation, oxidative damage, increased apoptosis, and caspase-1-mediated inflammasome activation in the prefrontal cortex were observed. Notably, both behavioral and molecular changes could be significantly alleviated by B-vitamin treatment. In summary, our results suggest that the anxiety- and depression-like behavior induced by gestational PM 2.5 exposure in mice offspring can be ameliorated by B-vitamin supplementation, probably through the suppression of apoptosis, oxidative damage, neuroinflammation, and caspase-1-mediated inflammasome activation. Image 1 • PM 2.5 induces apoptosis, oxidative damage, and inflammation in prefrontal cortex. • PM 2.5 induces caspase-1-mediated inflammasome activation in prefrontal cortex. • B-vitamin alleviates PM 2.5 exposure induced anxiety- and depression-like behavior. • B-vitamin alleviates PM 2.5 exposure induced neuroinflammation. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases, mainly caused by atherosclerosis, are the leading causes of morbidity and mortality worldwide. Despite the discrepancies in clinical manifestations between different abnormalities, atherosclerosis shares similar pathophysiological processes, such as mitochondrial dysfunction. Cardiolipin (CL) is a conserved mitochondria-specific lipid that contributes to the cristae structure of the inner mitochondrial membrane (IMM). Alterations in the CL, including oxidative modification, reduced quantity, and abnormal localization, contribute to the onset and progression of atherosclerosis. In this review, we summarize the knowledge that CL is involved in the pathogenesis of atherosclerosis. On the one hand, CL and its oxidative modification promote the progression of atherosclerosis via several mechanisms, including oxidative stress, apoptosis, and inflammation in response to stress. On the other hand, CL externalizes to the outer mitochondrial membrane (OMM) and acts as the pivotal "eat-me" signal in mitophagy, removing dysfunctional mitochondria and safeguarding against the progression of atherosclerosis. Given the imbalance between proatherogenic and antiatherogenic effects, we provide our understanding of the roles of the CL and its oxidative modification in atherosclerotic cardiovascular diseases, in addition to potential therapeutic strategies aimed at restoring the CL. Briefly, CL is far more than a structural IMM lipid; broader significances of the evolutionarily conserved lipid need to be explored. [Display omitted] [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease with few treatment options and poor prognosis. Emodin, extracted from Chinese rhubarb, was found to be able to alleviate bleomycin (BLM)-induced pulmonary fibrosis, yet the underlying mechanism remains largely unknown. This study aimed to further investigate the effects of emodin on the inflammation and fibrosis of BLM-induced pulmonary fibrosis and the mechanism involved in rats. Our results showed that emodin improved pulmonary function, reduced weight loss and prevented death in BLM-treated rats. Emodin significantly relieved lung edema and fibrotic changes, decreased collagen deposition, and suppressed the infiltration of myofibroblasts [characterized by expression of α-smooth muscle actin (α-SMA)] and inflammatory cells (mainly macrophages and lymphocytes). Moreover, emodin reduced levels of TNF-α, IL-6, TGF-β1 and heat shock protein (HSP)-47 in the lungs of BLM-treated rats. In vitro , emodin profoundly inhibited TGF-β1-induced α-SMA, collagen IV and fibronectin expression in human embryo lung fibroblasts (HELFs). Emodin also inhibited TGF-β1-induced Smad2/3 and STAT3 activation, indicating that Smad2/3 and STAT3 inactivation mediates emodin-induced effects on TGF-β1-induced myofibroblast differentiation. These results suggest that emodin can exert its anti-fibrotic effect via suppression of TGF-β1 signaling and subsequently inhibition of inflammation, HSP-47 expression, myofibroblast differentiation and extracellular matrix (ECM) deposition. [ABSTRACT FROM AUTHOR]

Pathological vascular remodeling and cell proliferation play vital roles in many proliferative vascular diseases. Estrogen can protect the cardiovascular system, but its exact molecular mechanism is unknown. Here we report that 17β-estradiol (E2) suppressed vascular smooth muscle cells (VSMCs) proliferation and inflammation. qRT-PCR and Western blot demonstrated that E2 decreased NF-κB p50 expression and reduced VSMCs proliferation and inflammation. Mechanistically, a dual luciferase reporter assay and chromatin immunoprecipitation suggested that KLF5 promoted NF-κB p50 expression by binding to the NF-κB p50 promoter, whereas E2 reduced the effect of KLF5 binding to the NF-κB p50 promoter and inhibited NF-κB p50 expression. Furthermore, a coimmunoprecipitation assay and immunofluorescence staining showed that the interaction between KLF5 and ERα increased in VSMCs treated with E2, which in turn decreased NF-κB p50 expression levels. Altogether, we reveal that E2 inhibits VSMCs proliferation and inflammation by reducing NF-κB expression induced by an increased interaction between KLF5 and ERα. These data provide further insights into how E2 inhibits vascular proliferation and inflammation. • 17β-estradiol (E2) inhibits VSMCs proliferation and inflammation in vivo and in vitro. • E2 inhibits NF-κB p50 expression and reduced proliferation and inflammation of VSMCs and vascular intimal. • E2 reduces NF-κB p50 expression via KLF5 regulating NF-κB p50 promoter. • The interaction between ERα and KLF5 increases in the presence of E2, then decreases NF-κB p50 expression. [ABSTRACT FROM AUTHOR]

We compared the assessment of active synovitis in knee osteoarthritis (OA) by utilising superb microvascular imaging (SMI) and conventional power Doppler (cPD) techniques, and then correlated each technique with paients' symptoms, radiographic features and magnetic resonance imaging (MRI)-detected synovitis. A subgroup of participants with symptomatic knee OA underwent dynamic ultrasound assessment for semi-quantitative scores for SMI and cPD in the suprapatellar, medial and lateral parapatellar knee recesses. Knee pain and other symptoms were evaluated with the knee injury and osteoarthritis outcome score (KOOS). OA severity was assessed using the Kellgren and Lawrence grade (KLG) on radiograph and effusion-synovitis and Hoffa's synovitis score of MRI osteoarthritis knee score on non-contrast-enhanced MRI sequences. The χ2 test and κ statistics were conducted to compare detectability of SMI and cPD for low-grade inflammation, and the Spearman's correlation and Fisher's r to z transformation were conducted to compare correlations of both techniques with symptoms and imaging severity. A total of 89 participants were included in the analyses. SMI increased the detection rate by 25.5% for grade 0 cPD, by 35.4% for grade 1 cPD and by 9% for grade 2 cPD. SMI showed significant correlations with KOOS symptoms, KLG, MRI effusion-synovitis and Hoffa's synovitis scores (r = -0.24 [-0.45, -0.01]; r = 0.31 [0.10, 0.50]; r = 0.49 [0.33, 0.63]; and r = 0.54 [0.37, 0.68]). The cPD was significantly correlated with KOOS pain, other symptoms, MRI effusion-synovitis and Hoffa's synovitis (r = -0.23 [-0.44, -0.01]; r = -0.29 [-0.49, -0.06]; r = 0.46 [0.28, 61], r = 0.46 [0.25, 0.63]). However, no significant differences were detected in their extent of correlations. SMI can detect low-grade inflammation implicated in OA disease better than cPD and reveal a significant correlation with symptoms, radiographic features and MRI synovitis. The added clinical value of SMI over cPD is still not clear. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • RhIL-1Ra reduces the expression of IL-1β in I/R regions of the myocardium. • RhIL-1Ra increases myocardium viability after I/R injury. • RhIL-1Ra improves cardiac function following I/R injury. Abstract The interleukin-1 (IL-1) signaling pathway plays a vital role in multiple mechanisms associated with myocardial ischemia–reperfusion (I/R) injury, including inflammation and apoptosis. An IL-1 receptor antagonist (IL-1Ra) can block IL-1 by competitive binding to the IL-1 receptor type I (IL-1RI) and thus may provide a cardioprotective effect. In the present investigation, we determined whether exogenous administration of recombinant human IL-1Ra (rhIL-1Ra) provides a protective role against myocardial I/R injury. Sprague-Dawley rats underwent surgical coronary artery ligation (or sham operation) by occlusion of the left anterior descending artery (LAD) for 30 min followed by reperfusion. After 30 min of reperfusion, a 2 mg/kg dose of rhIL-1Ra was injected subcutaneously. This was followed up with once daily injections for seven days. Echocardiography revealed that ejection fraction (EF) values were significantly greater in the rhIL-1Ra-treated animals. RhIL-1Ra was found to reduce the severity of myocardial injury and increase the viability of the cardiac tissue. There was found to be less IL-1β expression in rhIL-1Ra-treated animals than in controls. These results provide compelling data to suggest administration of IL-1Ra could have a significant cardioprotective effect against myocardial I/R injury and thus IL-1Ra could emerge as a potential clinical drug for the treatment of myocardial I/R injury. [ABSTRACT FROM AUTHOR]