scholarly journals Galectin-9 Regulates Monosodium Urate Crystal-Induced Gouty Inflammation Through the Modulation of Treg/Th17 Ratio

2021 ◽  
Vol 12 ◽  
Author(s):  
Adel Abo Mansour ◽  
Federica Raucci ◽  
Anella Saviano ◽  
Samantha Tull ◽  
Francesco Maione ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Molecular Mechanisms ◽  
Gouty Arthritis ◽  
Joint Inflammation ◽  
Monosodium Urate ◽  
T Helper 17 ◽  
Inflammatory Monocytes ◽  
Urate Crystal

Gout is caused by depositing monosodium urate (MSU) crystals within the articular area. The infiltration of neutrophils and monocytes drives the initial inflammatory response followed by lymphocytes. Interestingly, emerging evidence supports the view that in situ imbalance of T helper 17 cells (Th17)/regulatory T cells (Treg) impacts the subsequent damage to target tissues. Galectin-9 (Gal-9) is a modulator of innate and adaptive immunity with both pro- and anti-inflammatory functions, dependent upon its expression and cellular location. However, the specific cellular and molecular mechanisms by which Gal-9 modulates the inflammatory response in the onset and progression of gouty arthritis has yet to be elucidated. In this study, we sought to comprehensively characterise the functional role of exogenous Gal-9 in an in vivo model of MSU crystal-induced gouty inflammation by monitoring in situ neutrophils, monocytes and Th17/Treg recruited phenotypes and related cyto-chemokines profile. Treatment with Gal-9 revealed a dose-dependent reduction in joint inflammation scores, knee joint oedema and expression of different pro-inflammatory cyto-chemokines. Furthermore, flow cytometry analysis highlighted a significant modulation of infiltrating inflammatory monocytes (CD11b+/CD115+/LY6-Chi) and Th17 (CD4+/IL-17+)/Treg (CD4+/CD25+/FOXP-3+) cells following Gal-9 treatment. Collectively the results presented in this study indicate that the administration of Gal-9 could provide a new therapeutic strategy for preventing tissue damage in gouty arthritic inflammation and, possibly, in other inflammatory-based diseases.

scholarly journals LC-MS Analysis of Serum for the Metabolomic Investigation of the Effects of Pulchinenoside b4 Administration in Monosodium Urate Crystal-Induced Gouty Arthritis Rat Model

Molecules ◽  
2019 ◽  
Vol 24 (17) ◽  
pp. 3161
Author(s):  
Shang Lyu ◽  
Ruowen Ding ◽  
Peng Liu ◽  
Hui OuYang ◽  
Yulin Feng ◽  
...  
Keyword(s):  
Rat Model ◽  
Clinical Symptoms ◽  
Biological Activities ◽  
Gouty Arthritis ◽  
Joint Inflammation ◽  
Ultra Performance Liquid Chromatography ◽  
Monosodium Urate ◽  
Wide Range ◽  
Urate Crystal ◽  
Anti Inflammatory

Gouty arthritis (GA) is commonly caused by deposition of monosodium urate (MSU) crystals within the joint capsule, bursa, cartilage, bone, or other periarticular tissues after chronic hyperuricemia. Clinically, GA is characterized by acute episodes of joint inflammation, which is most frequently encountered in the major joints, and also has a significant impact on quality of life. Pulchinenoside b4(P-b4) has a wide range of biological activities, including antitumor, anti-inflammatory, antiviral and immunomodulatory activities. Currently, the anti-GA activity and metabolomic profiles after being treated by P-b4 have not been reported. In this paper, for the first time, we have performed a non-targeted metabolomics analysis of serum obtained from an MSU crystal-induced GA rat model intervened by P-b4, using ultra-performance liquid chromatography coupled to quadrupole time-of-flight tandem mass spectrometry. In this study, the main pharmacodynamics of different dosing methods and dosages of P-b4 was firstly investigated. Results have shown that P-b4 possesses high anti-inflammatory activity. These results demonstrated changes in serum metabolites with 32 potential biomarkers. Arachidonic acid, sphingolipid, and glycerophospholipid metabolism are considered to be the most relevant metabolic pathway with P-b4 treatment effect in this study. Moreover, the changes of metabolites and the self-extinction of model effects within 24 h reveals important information for GA diagnostic criteria: The regression of clinical symptoms or the decline of some biochemical indicators cannot be regarded as the end point of GA treatment. Furthermore, our research group plans to conduct further metabolomics research on the clinical course of GA.

In situ forming chitosan hydrogels: Preliminary evaluation of the in vivo inflammatory response

2017 ◽  
Vol 75 ◽  
pp. 279-285 ◽  
Author(s):  
Maria José Moura ◽  
João Brochado ◽  
Maria Helena Gil ◽  
Maria Margarida Figueiredo
Keyword(s):  
Inflammatory Response ◽  
Preliminary Evaluation ◽  
In Situ Forming ◽  
Chitosan Hydrogels

scholarly journals Cichoric Acid Ameliorates Monosodium Urate-Induced Inflammatory Response by Reducing NLRP3 Inflammasome Activation via Inhibition of NF-kB Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Qi Wang ◽  
Bingfeng Lin ◽  
Zhifeng Li ◽  
Jie Su ◽  
Yulin Feng
Keyword(s):  
Inflammatory Response ◽  
Signaling Pathway ◽  
Nlrp3 Inflammasome ◽  
Gouty Arthritis ◽  
Inflammasome Activation ◽  
Cichoric Acid ◽  
Monosodium Urate ◽  
Protein Levels ◽  
Nlrp3 Inflammasome Activation ◽  
Tnf Α

Gouty arthritis is characterized by the deposition of monosodium urate (MSU) within synovial joints and tissues due to increased urate concentrations. Here, we elucidated the role of the natural compound cichoric acid (CA) on the MSU crystal-stimulated inflammatory response. The THP-1-derived macrophages (THP-Ms) were pretreated with CA and then stimulated with MSU suspensions. The protein levels of p65 and IκBα, the activation of the NF-κB signaling pathway by measuring the expression of its downstream inflammatory cytokines, and the activity of NLRP3 inflammasome were measured by western blotting and ELISA. CA treatment markedly inhibited the degradation of IκBα and the activation of NF-κB signaling pathway and reduced the levels of its downstream inflammatory genes such as IL-1β, TNF-α, COX-2, and PGE2 in the MSU-stimulated THP-M cells. Therefore, we infer that CA effectively alleviated MSU-induced inflammation by suppressing the degradation of IκBα, thereby reducing the activation of the NF-κB signaling pathway and the NLRP3 inflammasome. These results suggest that CA could be a novel therapeutic strategy in averting acute episodes of gout.

scholarly journals circHMGCS1–016 reshapes immune environment by sponging miR-1236-3p to regulate CD73 and GAL-8 expression in intrahepatic cholangiocarcinoma

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Ya-Ping Xu ◽  
Ze-Ning Dong ◽  
Si-Wei Wang ◽  
Yi-Min Zheng ◽  
Chi Zhang ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Intrahepatic Cholangiocarcinoma ◽  
Molecular Mechanisms ◽  
Prognostic Significance ◽  
Luciferase Reporter ◽  
Mouse Tumor ◽  
Rna Seq ◽  
Potential Biomarker

Abstract Background Accumulating evidence indicates that circRNAs may serve as essential regulators in the progression of several human cancers, but the function and mechanism of circRNAs in intrahepatic cholangiocarcinoma (ICC) are largely unknown. Methods RNA-seq was used to assess differentially expressed circRNAs between 4 ICC and peritumor tissues. Quantitative RT-PCR and in situ hybridization were used to determine the circHMGCS1–016 expression in ICC tissues. The function and mechanism of circHMGCS1–016 were further identified via in vivo experiments. The clinical characteristics and prognostic significance of circHMGCS1–016 were analyzed by a retrospective study. The functions of circHMGCS1–016 were assessed via modifying circRNA expression in ICC cells. Moreover, the molecular mechanisms of circHMGCS1–016 in ICC cells were explored by circRNA precipitation, miRNA immunoprecipitation, SILAC and luciferase reporter assays. Results We identified that compared with peritumor tissues, ICC tissues expressed hsa_circ_0008621 (circHMGCS1–016) high by RNA-seq, which was further identified by qRT-PCR and in situ hybridization. Moreover, the expression of circHMGCS1–016 was revealed to be associated with survival and recurrence of ICC patients. By regulating circHMGCS1–016 expression, we found that elevated circHMGCS1–016 promoted ICC development both in vitro and in vivo. By SILAC and circRNA-pull down, we demonstrated that circHMGCS1–016 induced ICC cell invasion and reshaped the tumor immune microenvironment via the miR-1236-3p/CD73 and GAL-8 axis. In ICC tissues, we uncovered that a high level of circHMGCS1–016 was positively associated with CD73 and GAL-8 expression and negatively related to the CD8+ T cells infiltration, which was further validated by establishing a humanized mouse tumor model. Importantly, we displayed that ICC patients with high levels of circHMGCS1–016 in tumor tissues benefited less from anti-PD1 treatment compared to those with low levels of circHMGCS1–016. Conclusions CircHMGCS1–016 is a forceful contributor in ICC development and immune tolerance via miR-1236-3p/CD73 and GAL-8 axis. CircHMGCS1–016 can be explored as a new potential biomarker and therapeutic target for PD1-resistant ICC.

scholarly journals Deregulated immune cell recruitment orchestrated by FOXM1 impairs human diabetic wound healing

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Andrew P. Sawaya ◽  
Rivka C. Stone ◽  
Stephen R. Brooks ◽  
Irena Pastar ◽  
Ivan Jozic ◽  
...  
Keyword(s):  
Wound Healing ◽  
Inflammatory Response ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Diabetic Mouse ◽  
Transcriptional Networks ◽  
Life Threatening ◽  
Diabetic Wound Healing ◽  
Diabetic Wounds

Abstract Diabetic foot ulcers (DFUs) are a life-threatening disease that often result in lower limb amputations and a shortened lifespan. However, molecular mechanisms contributing to the pathogenesis of DFUs remain poorly understood. We use next-generation sequencing to generate a human dataset of pathogenic DFUs to compare to transcriptional profiles of human skin and oral acute wounds, oral as a model of “ideal” adult tissue repair due to accelerated closure without scarring. Here we identify major transcriptional networks deregulated in DFUs that result in decreased neutrophils and macrophages recruitment and overall poorly controlled inflammatory response. Transcription factors FOXM1 and STAT3, which function to activate and promote survival of immune cells, are inhibited in DFUs. Moreover, inhibition of FOXM1 in diabetic mouse models (STZ-induced and db/db) results in delayed wound healing and decreased neutrophil and macrophage recruitment in diabetic wounds in vivo. Our data underscore the role of a perturbed, ineffective inflammatory response as a major contributor to the pathogenesis of DFUs, which is facilitated by FOXM1-mediated deregulation of recruitment of neutrophils and macrophages, revealing a potential therapeutic strategy.

scholarly journals Aloin Preconditioning Attenuates Hepatic Ischemia/Reperfusion Injury via Inhibiting TLR4/MyD88/NF-κB Signal Pathway In Vivo and In Vitro

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Yichao Du ◽  
Baolin Qian ◽  
Lin Gao ◽  
Peng Tan ◽  
Hao Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Response ◽  
Liver Tissue ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion ◽  
Primary Hepatocytes ◽  
Hepatic Ischemia ◽  
Hepatic Ischemia Reperfusion

Background. Aloin exerts considerable protective effects in various disease models, and its effect on hepatic ischemia-reperfusion (HIR) injury remains unknown. This research is aimed at conducting an in-depth investigation of the antioxidant, anti-inflammatory, and antiapoptosis effects of aloin in HIR injury and explain the underlying molecular mechanisms. Methods. In vivo, different concentrations of aloin were intraperitoneally injected 1 h before the establishment of the HIR model in male mice. The hepatic function, pathological status, oxidative stress, and inflammatory and apoptosis markers were measured. In vitro, aloin (AL, C21H22O9) or lipopolysaccharide (LPS) was added to a culture of mouse primary hepatocytes before it underwent hypoxia/reoxygenation (H/R), and the apoptosis in the mouse primary hepatocytes was analyzed. Results. We found that 20 mg/kg was the optimum concentration of aloin for mitigating I/R-induced liver tissue damage, characterized by decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Aloin pretreatment substantially suppressed the generation of hepatic malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), and IL-6 and enhanced the hepatic superoxide dismutase (SOD) activities as well as glutathione (GSH) and IL-10 levels in the liver tissue of I/R mice; this indicated that aloin ameliorated I/R-induced liver damage by reducing the oxidative stress and inflammatory response. Moreover, aloin inhibited hepatocyte apoptosis and inflammatory response that was caused by the upregulated expression of Bcl-2, the downregulated expression of cleaved caspase3(C-caspase3), Bax, Toll-like receptor 4 (TLR4), FADD, MyD88, TRAF6, phosphorylated IKKα/β (p-IKKα/β), and phosphorylated nuclear factor κB p65 (p-NF-κB p65).

Anti-inflammatory effects of traditional mixed extract of medicinal herbs (MEMH) on monosodium urate crystal-induced gouty arthritis

2017 ◽  
Vol 15 (8) ◽  
pp. 561-575 ◽  
Author(s):  
Ju-Suk Nam ◽  
Supriya Jagga ◽  
Ashish Ranjan Sharma ◽  
Joon-Hee Lee ◽  
Jong Bong Park ◽  
...  
Keyword(s):  
Gouty Arthritis ◽  
Medicinal Herbs ◽  
Monosodium Urate ◽  
Urate Crystal ◽  
Anti Inflammatory

scholarly journals In situ Synthesized Monosodium Urate Crystal Enhances Endometrium Decidualization via Sterile Inflammation During Pregnancy

2021 ◽  
Vol 9 ◽  
Author(s):  
Yu-Yuan Zhu ◽  
Yao Wu ◽  
Si-Ting Chen ◽  
Jin-Wen Kang ◽  
Ji-Min Pan ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Early Stage ◽  
Sterile Inflammation ◽  
Monosodium Urate ◽  
Endometrial Stromal Cells ◽  
Elective Abortion ◽  
Urate Crystal ◽  
High Level

High level of uric acid (UA) is the major origin of gout, and is highly associated with various pregnant complications, such as preeclampsia and gestational diabetes. However, UA’s level and role in the very early stage of pregnancy has not been uncovered. This study aims to investigate the relevance of serum UA and decidualization, an essential process for the establishment and maintenance of pregnancy in women and mice during the early stage of pregnancy. In this study, we first proved that expression level of UA synthase xanthine dehydrogenase (XDH) is highly increased along with decidualization of endometrial stromal cells in both in vitro and in vivo models. Furthermore, serum and endometrial levels of UA are higher in mice with decidualized uterin horn and in vitro decidualized stromal cells. The existence of monosodium urate (MSU) crystal was also confirmed by immunostaining. Next, the roles of MSU on decidualization were explored by both in vitro and in vivo models. Our data shows MSU crystal but not UA enhances the decidualization response of endometrial stromal cells, via the upregulation of inflammatory genes such Ptgs2 and Il11. inhibiting of Cox-2 activity abolishes MSU crystal induced higher expression of decidualization marker Prl8a2. At last, in women, we observed enriched expression of XDH in decidua compare to non-decidualized endometrium, the serum level of UA is significantly increased in women in very early stage of pregnancy, and drop down after elective abortion. In summary, we observed an increased serum UA level in the early stage of women’s pregnancy, and proved that the increased level of UA results from the expressed XDH in decidualizing endometrium of both human and mouse, leading to the formation of MSU crystal. MSU crystal can enhance the decidualization response via inflammatory pathways. Our study has uncovered the association between UA, MSU, and decidualization during the early stage of pregnancy.

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