scholarly journals MCC950, the NLRP3 Inhibitor, Protects against Cartilage Degradation in a Mouse Model of Osteoarthritis

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Bowei Ni ◽  
Wenbin Pei ◽  
Yunkun Qu ◽  
Rui Zhang ◽  
Xiangyu Chu ◽  
...  
Keyword(s):  
Cartilage Degeneration ◽  
Bioinformatic Analysis ◽  
Cartilage Degradation ◽  
Protective Role ◽  
In Vivo Experiments ◽  
P16 Ink4a ◽  
Anti Inflammatory ◽  
Matrix Degrading Enzymes

Osteoarthritis (OA), characterized by chronic systemic low-level inflammation and cartilage degeneration, is a type of arthritis closely associated with aging. Inflammation and aging play a pivotal role in the occurrence and progression of OA. NLRP3 inflammasome is involved in many inflammatory and aging diseases, and NLRP3 inhibitor MCC950 has anti-inflammatory and antisenescence effects on some diseases such as Alzheimer’s disease. In the present study, we found that NLRP3 protein was upregulated in human and mouse OA cartilage. Moreover, NLRP3 and Caspase1 expression induced by IL-1β in chondrocytes was blocked by MCC950. In addition, MCC950 inhibited the expression of inflammatory mediators, matrix-degrading enzymes, senescence marker protein P16 (INK4A), and β-galactosidase, as well as excessive production of ROS. Meanwhile, MCC950 promoted autophagy-related protein expression and autophagy flux under the inflammatory condition. However, autophagy inhibitor 3-MA reversed anti-inflammatory and anticatabolic effects of MCC950. In in vivo experiments, intra-articular administration of MCC950 further showed its protective effect on cartilage degeneration. Bioinformatic analysis and in vitro experimental results revealed that MCC950 might play a protective role in cartilage by regulating Nrf2/HO-1/NQO1, PI3k/Akt/mTOR, P38/MAPK, and JNK/MAPK pathways. In conclusion, our work demonstrated that NLRP3 inhibitor MCC950 might serve as a promising strategy for OA treatment.

scholarly journals Biocompatible N-acetyl-nanoconstruct alleviates lipopolysaccharide-induced acute lung injury in vivo

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Seongchan Kim ◽  
Shin Young Kim ◽  
Seung Joon Rho ◽  
Seung Hoon Kim ◽  
So Hyang Song ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Intratracheal Instillation ◽  
Sprague Dawley ◽  
In Vivo Experiments ◽  
Anti Inflammatory

AbstractOxidative stress plays important roles in inflammatory responses during acute lung injury (ALI). Recently, nanoconstruct (Nano)-based drug-delivery systems have shown promise in many models of inflammation. In this study, we evaluated the anti-inflammatory effects of N-acetylcysteine (NAC) loaded in a biocompatible Nano using a rat model of ALI. We synthesized a Nano with a good NAC-releasing capacity using porous silica Nano, which was used to produce Nano/NAC complexes. For in vivo experiments, Sprague–Dawley rats were intraperitoneally administered NAC or Nano/NAC 30 min after intratracheal instillation of lipopolysaccharide. After 6 h, bronchoalveolar lavage fluids and lung tissues were collected. The anti-oxidative effect of the Nano/NAC complex was confirmed by demonstrating reduced levels of reactive oxygen species after treatment with the Nano/NAC in vitro. In vivo experiments also showed that the Nano/NAC treatment may protect against LPS‐induced ALI thorough anti‐oxidative and anti‐inflammatory effects, which may be attributed to the inactivation of the NF‐κB and MAPK pathways. In addition, the effects of Nano/NAC treatment were shown to be superior to those of NAC alone. We suggest the therapeutic potential of Nano/NAC treatment as an anti‐inflammatory agent against ALI. Furthermore, our study can provide basic data for developing nanotechnology-based pharmacotherapeutics for ALI.

scholarly journals Comparative Study Regarding the Properties of Methylene Blue and Proflavine and Their Optimal Concentrations for In Vitro and In Vivo Applications

Diagnostics ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 223 ◽  
Author(s):  
Maria-Eliza Nedu ◽  
Mihaela Tertis ◽  
Cecilia Cristea ◽  
Alexandru Valentin Georgescu
Keyword(s):  
Methylene Blue ◽  
Fluorescent Dyes ◽  
Tissue Level ◽  
In Vivo Studies ◽  
Cell Nuclei ◽  
In Vivo Experiments ◽  
Bacteriostatic Agent ◽  
Anti Inflammatory

Methylene blue and proflavine are fluorescent dyes used to stain nucleic acid from the molecular level to the tissue level. Already clinically used for sentinel node mapping, detection of neuroendocrine tumors, methemoglobinemia, septic shock, ifosfamide-induced encephalopathy, and photodynamic inactivation of RNA viruses, the antimicrobial, anti-inflammatory, and antioxidant effect of methylene blue has been demonstrated in different in vitro and in vivo studies. Proflavine was used as a disinfectant and bacteriostatic agent against many gram-positive bacteria, as well as a urinary antiseptic involved in highlighting cell nuclei. At the tissue level, the anti-inflammatory effects of methylene blue protect against pulmonary, renal, cardiac, pancreatic, ischemic-reperfusion lesions, and fevers. First used for their antiseptic and antiviral activity, respectively, methylene blue and proflavine turned out to be excellent dyes for diagnostic and treatment purposes. In vitro and in vivo studies demonstrated that both dyes are efficient as perfusion and tissue tracers and permitted to evaluate the minimal efficient concentration in different species, as well as their pharmacokinetics and toxicity. This review aims to identify the optimal concentrations of methylene blue and proflavine that can be used for in vivo experiments to highlight the vascularization of the skin in the case of a perforasome (both as a tissue tracer and in vascular mapping), as well as their effects on tissues. This review is intended to be a comparative and critical presentation of the possible applications of methylene blue (MB) and proflavine (PRO) in the surgical field, and the relevant biomedical findings from specialized literature to date are discussed as well.

Gigantol Alleviates IL-1β-Induced Inflammation and Catabolism in Mouse Osteoarthritis via PI3K/Akt/NF-κB Pathways In Vivo and In Vitro

2021 ◽  
Author(s):  
Gaosheng Zhu ◽  
Keze Miao ◽  
Mingwei Dong ◽  
Jie Cai ◽  
Zhihao Shen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Therapeutic Option ◽  
Interleukin 1 ◽  
Cartilage Degradation ◽  
Research Society ◽  
Necrosis Factor Alpha ◽  
Persistent Inflammation ◽  
Anti Inflammatory

Abstract Osteoarthritis (OA), a prevalent disabling disease, is characterized by irreversible cartilage degradation and persistent inflammation. The etiology as well as pathogenesis of OA are not completely unclear and need further investigation. Gigantol, is a bibenzyl derivative extracted from Dendrobium plants and has been found exhibit multiple effects such as anti-inflammatory effects. Nevertheless, the biological function of gigantol on osteoarthritis (OA) is still uncertain. This study aimed at examining the anti-inflammatory effects and latent mechanisms of gigantol in IL-1β-mediated OA progression. In vitro, we identified that gigantol treatment suppressed tumor necrosis factor-alpha (TNF-α), nitric oxide (NO), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS) and interleukin-6 (IL-6) in interleukin-1 beta (IL-1β) mediated mouse OA chondrocytes. Gigantol was also shown to dose dependently downregulate the metalloproteinase 13 (MMP13) as well as thrombospondin motifs 5 (ADAMTS5) levels. Moreover, IL-1β-mediated AKT and PI3K phosphorylation as well as NF-κB activation were inhibited by gigantol. Meanwhile, in vivo, we detected that gigantol treatment inhibited degradation of the cartilage degradation and lowered the Osteoarthritis Research Society International scores (OARSI) in OA mouse. Therefore, gigantol is a promising therapeutic option for OA.

PPARγ Regulates the Anti-Inflammatory Effects of Carbon Monoxide on Macrophages: A Gene Profiling Study.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3445-3445
Author(s):  
Martin Bilban ◽  
Sherrie L. Otterbein ◽  
Emeka Ifedigbo ◽  
Keiji Enjyoji ◽  
Anny Usheva ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
Inflammatory Response ◽  
Acute Phase Proteins ◽  
Expression Patterns ◽  
Endotoxic Shock ◽  
Gene Profiling ◽  
In Vivo Experiments ◽  
Anti Inflammatory

Abstract Carbon monoxide (CO) at low concentrations has generated recent interest due to its ability to modulate the inflammatory response associated with chronic graft rejection, vascular injury and septic shock. Both in vivo and in vitro CO can inhibit the expression of pro-inflammatory genes such as TNFα in macrophages while simultaneously increasing the expression of the anti-inflammatory cytokine IL-10. The mechanisms by which this occurs are still unclear. To better understand the mechanisms underlying the effects of CO, we employed the Affymetrix GeneChip technology to evaluate the time-dependent expression patterns of >12,000 genes in macrophages stimulated with bacterial endotoxin (LPS) in the presence or absence of a low concentration of CO previously demonstrated to evoke an anti-inflammatory response. We were particularly interested whether CO would, by itself, modulate in a specific manner the expression of proteins that might explain the anti-inflammatory effects observed following subsequent administration of endotoxin. RAW 264.7 murine macrophages were grown to 75% confluency and then exposed to CO (250 ppm) for 3 hr prior to administration of LPS (10 ng/ml). At 0, 15, 30, 60, 120 and 240 min thereafter, total RNA was isolated by standard methods and the RNA was then labeled and hybridized to U74Av2 GeneChips. Of >12,000 genes assessed, 116 of 270 that were LPS-responsive were affected by CO treatment. CO inhibited the majority of LPS-induced pro-inflammatory cytokines and acute phase proteins including expression of early growth response-1 (Egr-1), a transcription factor that serves as a central intermediary regulating many genes. Egr-1 was nearly completely inhibited by CO as was Egr-1-dependent expression of tissue factor (TF) and PAI-1. Treatment of cells with CO alone led to a rapid early increase in PPARγ, the expression of which was essential for the anti-inflammatory effects of CO. Inhibition of PPARγ using the selective chemical inhibitor GW9662 reversed the CO inhibitory effects on LPS-induced Egr-1 and TF expression. Correlative in vivo experiments in mice showed that CO pre-treatment blocked endotoxin-induced Egr-1 expression and decreased markers of lung inflammmation the effects of which were also lost with inhibition of PPARγ. Our analyses of gene expression patterns has led to the first molecular understanding of how treatment with CO, in this case by inducing PPARγ, blocks the pro-inflammatory response. These experiments provide novel insights into the mechanisms and pathophysiology of endotoxic shock and identify cellular targets by which CO mediates these cytoprotective effects.

scholarly journals The Anti-Inflammatory Activity of HMGB1 A Box Is Enhanced When Fused with C-Terminal Acidic Tail

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Wei Gong ◽  
Yingru Zheng ◽  
Fan Chao ◽  
Yuan Li ◽  
Zhizhen Xu ◽  
...  
Keyword(s):  
Fusion Proteins ◽  
Inflammatory Diseases ◽  
Inflammatory Activity ◽  
In Vivo Experiments ◽  
Specific Antagonist ◽  
Proinflammatory Activity ◽  
Anti Inflammatory ◽  
Inflammatory Effect

HMGB1, composed of the A box, B box, and C tail domains, is a critical proinflammatory cytokine involved in diverse inflammatory diseases. The B box mediates proinflammatory activity, while the A box alone acts as a specific antagonist of HMGB1. The C tail contributes to the spatial structure of A box and regulates HMGB1 DNA binding specificity. It is unknown whether the C tail can enhance the anti-inflammatory effect of A box. In this study, we generated fusion proteins consisting of the A box and C tail, in which the B box was deleted and the A box and C tail were linked either directly or by the flexible linker sequence(Gly4Ser)3. In vitro and in vivo experiments showed that the two fusion proteins had a higher anti-inflammatory activity compared to the A box alone. This suggests that the fused C tail enhances the anti-inflammatory effect of the A box.

scholarly journals Study of Osteoarthritis Treatment with Anti-Inflammatory Drugs: Cyclooxygenase-2 Inhibitor and Steroids

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Hongsik Cho ◽  
Andrew Walker ◽  
Jeb Williams ◽  
Karen A. Hasty
Keyword(s):  
Gene Expression ◽  
Type Ii Collagen ◽  
Cartilage Degradation ◽  
Cyclooxygenase 2 ◽  
Cox Inhibitor ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory

Patients with osteoarthritis (OA), a condition characterized by cartilage degradation, are often treated with steroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and cyclooxygenase-2 (COX-2) selective NSAIDs. Due to their inhibition of the inflammatory cascade, the drugs affect the balance of matrix metalloproteinases (MMPs) and inflammatory cytokines, resulting in preservation of extracellular matrix (ECM). To compare the effects of these treatments on chondrocyte metabolism, TNF-αwas incubated with cultured chondrocytes to mimic a proinflammatory environment with increasing production of MMP-1 and prostaglandin E2 (PGE2). The chondrocytes were then treated with either a steroid (prednisone), a nonspecific COX inhibitor NSAID (piroxicam), or a COX-2 selective NSAID (celecoxib). Both prednisone and celecoxib decreased MMP-1 and PGE-2 production while the nonspecific piroxicam decreased only the latter. Both prednisone and celecoxib decreased gene expression of MMP-1 and increased expression of aggrecan. Increased gene expression of type II collagen was also noted with celecoxib. The nonspecific piroxicam did not show these effects. The efficacy of celecoxibin vivowas investigated using a posttraumatic OA (PTOA) mouse model.In vivo, celecoxib increases aggrecan synthesis and suppresses MMP-1. In conclusion, this study demonstrates that celecoxib and steroids exert similar effects on MMP-1 and PGE2 productionin vitroand that celecoxib may demonstrate beneficial effects on anabolic metabolismin vivo.

Potential Anti-inflammatory Sesquiterpene Lactones from Eupatorium lindleyanum

Planta Medica ◽  
2017 ◽  
Vol 84 (02) ◽  
pp. 123-128 ◽  
Author(s):  
Fang Wang ◽  
Huanhuan Zhong ◽  
Shiqi Fang ◽  
Yunfeng Zheng ◽  
Cunyu Li ◽  
...  
Keyword(s):  
Sesquiterpene Lactones ◽  
Folk Medicine ◽  
2D Nmr ◽  
In Vitro Assays ◽  
Raw 264.7 Cells ◽  
Therapeutic Effects ◽  
In Vivo Experiments ◽  
Anti Inflammatory

Abstract Eupatorium lindleyanum has traditionally been used as folk medicine in Asian countries for its therapeutic effects on tracheitis and tonsillitis. Investigation of the anti-inflammatory active constituents from E. lindleyanum led to the isolation of two novel sesquiterpene lactones, named eupalinolide L (1) and eupalinolide M (2), and seven known sesquiterpene lactones (3–9). The structures and configurations of the new compounds were determined on the basis of spectroscopic analysis, especially 2D NMR techniques. In vivo experiments showed that the sesquiterpenes fraction significantly reduced mouse ear edema induced by xylene (18.6%, p < 0.05). In in vitro assays, compounds 1–9 showed excellent anti-inflammatory activities, as they lowered TNF-α and IL-6 levels in lipopolysaccharide-stimulated murine macrophage RAW 264.7 cells (p < 0.001). The above results suggest that the sesquiterpene lactones from E. lindleyanum can be developed as novel potential natural anti-inflammatory agents.

scholarly journals The role of the angiotensins in the pathogenesis of inflammatory joint disease

2021 ◽  
Vol 93 (5) ◽  
pp. 635-639
Author(s):  
Andrei V. Gordeev ◽  
Elena A. Galushko ◽  
Natalia M. Savushkina
Keyword(s):  
Cardiovascular System ◽  
The Body ◽  
Joint Disease ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
In Vivo Experiments ◽  
Anti Inflammatory

The significant humoral effect of the renin-angiotensin-aldosterone system on the regulation of the cardiovascular system and blood pressure has long been widely known. However, the identification and interpretation of new components of renin-angiotensin-aldosterone system in recent years can significantly expand the range of its potential effects on the body. The anti-inflammatory effect of drugs that block angiotensin II and its receptors, including in rheumatic diseases, can become practically significant for General therapists by their effect on reducing the concentration of inflammatory mediators and angiogenesis processes. The organoprotective and anti-inflammatory potentials of drugs that reduce the production of at demonstrated in vitro and in vivo experiments allow us to consider them as first-line angiotropic agents in patients with rheumatoid arthritis, especially in the presence of pathology of the cardiovascular system and kidneys.

Evidence for the anti-inflammatory activity of Bupleurum marginatum (Apiaceae) extracts using in vitro and in vivo experiments supported by virtual screening

2018 ◽  
Vol 70 (7) ◽  
pp. 952-963 ◽  
Author(s):  
Mohamed L. Ashour ◽  
Fadia S. Youssef ◽  
Haidy A. Gad ◽  
Mahmoud Z. El-Readi ◽  
Amel Bouzabata ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Inflammatory Activity ◽  
In Vivo Experiments ◽  
Anti Inflammatory

scholarly journals Early activation of the cardiac CX3CL1/CX3CR1 axis delays β-adrenergic-induced heart failure

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
M. Flamant ◽  
N. Mougenot ◽  
E. Balse ◽  
L. Le Fèvre ◽  
F. Atassi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Protective Role ◽  
Cardiomyocyte Hypertrophy ◽  
Adrenergic Stimulation ◽  
Intramyocardial Injection ◽  
In Vivo Experiments ◽  
Concentric Hypertrophy

AbstractWe recently highlighted a novel potential protective paracrine role of cardiac myeloid CD11b/c cells improving resistance of adult hypertrophied cardiomyocytes to oxidative stress and potentially delaying evolution towards heart failure (HF) in response to early β-adrenergic stimulation. Here we characterized macrophages (Mφ) in hearts early infused with isoproterenol as compared to control and failing hearts and evaluated the role of upregulated CX3CL1 in cardiac remodeling. Flow cytometry, immunohistology and Mφ-depletion experiments evidenced a transient increase in Mφ number in isoproterenol-infused hearts, proportional to early concentric hypertrophy (ECH) remodeling and limiting HF. Combining transcriptomic and secretomic approaches we characterized Mφ-enriched CD45+ cells from ECH hearts as CX3CL1- and TNFα-secreting cells. In-vivo experiments, using intramyocardial injection in ECH hearts of either Cx3cl1 or Cx3cr1 siRNA, or Cx3cr1−/− knockout mice, identified the CX3CL1/CX3CR1 axis as a protective pathway delaying transition to HF. In-vitro results showed that CX3CL1 not only enhanced ECH Mφ proliferation and expansion but also supported adult cardiomyocyte hypertrophy via a synergistic action with TNFα. Our data underscore the in-vivo transient protective role of the CX3CL1/CX3CR1 axis in ECH remodeling and suggest the participation of CX3CL1-secreting Mφ and their crosstalk with CX3CR1-expressing cardiomyocytes to delay HF.

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