Experimental evidence of heparanase, Hsp70 and NF-κB gene expression on the response of anti-inflammatory drugs in TNBS-induced colonic inflammation

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat tendinopathy, but evidence for this treatment is lacking, and little is known regarding effects of NSAIDs on human tendinopathic tendon. This study investigated the effects of NSAID treatment (ibuprofen) on human tendinopathic tendon, with changes in gene expression as the primary outcome, and tendon pain, function, and blood flow as secondary outcomes. Twenty-six adults (16 men, 10 women), diagnosed with chronic Achilles tendinopathy, were randomized to 1-wk treatment with ibuprofen (600 mg ×3/day) ( n = 13) or placebo ( n = 13) (double-blinded). Ibuprofen content in blood, visual analog scale score for tendon pain at rest and activity, Victorian Institute of Sports Assessment-Achilles (VISA-A) scores for tendon function, tendon thickness (with ultrasonography), and color Doppler were measured before and 1 h after treatment. After the last posttreatment test, a full-width tendon biopsy was taken from the affected area. Real-time-RT-PCR was used to assess expression of collagen I, collagen III, transforming growth factor (TGF-β) isoforms, cyclooxygenase-2 (COX-2), angiopoietin-like 4 (ANGPTL4), and cyclic AMP-dependent transcription factor (ATF3) in tendon tissue. Expression of collagens and TGF-β isoforms showed relatively low variation and was unaffected by ibuprofen treatment. Further, no changes were seen in tendon thickness or VISA-A score. The placebo treatment reduced the color Doppler (in tendon plus surrounding tissue) compared with the ibuprofen group and also increased the perception of pain at rest. In conclusion, there was no indication that short-term ibuprofen treatment affects gene expression in human chronic tendinopathic tendon or leads to any clear changes in tendon pain or function. NEW & NOTEWORTHY Nonsteroidal anti-inflammatory drugs are widely used in the treatment of tendinopathy, but little is known of the effects of these drugs on tendon tissue. We find that 1 wk of ibuprofen treatment has no effect on gene expression of collagen and related growth factors in adult human tendinopathic tendon in vivo (in spite of relatively low levels of variation in gene expression), suggesting that tendinopathic cells are not responsive to ibuprofen.

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Nonsteroidal Anti-inflammatory Drugs Modulate Gene Expression of Inflammatory Mediators in Oral Squamous Cell Carcinoma

Anticancer Research ◽

10.21873/anticanres.13356 ◽

2019 ◽

Vol 39 (5) ◽

pp. 2385-2394

Author(s):

DANIELLA MORAES ANTUNES ◽

MARIA FERNANDA SETÚBAL DESTRO RODRIGUES ◽

DOUGLAS MAGNO GUIMARÃES ◽

CARINA MAGALHÃES ESTEVES DUARTE ◽

LUCYENE MIGUITA ◽

...

Keyword(s):

Gene Expression ◽

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Inflammatory Mediators ◽

Inflammatory Drugs ◽

Anti Inflammatory

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Systemic Antibiotic and Nonsteroidal Anti-Inflammatory Drug Treatment Decreases the Level of Endogenous Angiogenic Vascular Endothelial Growth Factor in Inflamed Human Periapical Tissues

Applied Sciences ◽

10.3390/app11114976 ◽

2021 ◽

Vol 11 (11) ◽

pp. 4976

Author(s):

Aleksandra Palatyńska-Ulatowska ◽

Marta Michalska ◽

Anna Drelich ◽

Aleksandra Sałagacka-Kubiak ◽

Ewa Balcerczak ◽

...

Keyword(s):

Gene Expression ◽

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Control Group ◽

Vascular Endothelial ◽

Rt Pcr ◽

Tissue Samples ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

Endothelial Growth Factor

Vascular endothelial growth factor (VEGF)-induced angiogenesis contributes to inflammatory bone resorption in humans. Widely documented antagonists to resorption include antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs). The purpose of this study was to investigate the effect of these drugs on proangiogenic VEGF levels in periradicular lesions. Periapical tissue biopsies were obtained from 42 patients with chronic periapical periodontitis. VEGF levels were measured using a commercial ELISA kit in patients divided into groups according to treatment: no drugs (control group, n = 25), NSAIDs (n = 7), antibiotics (n = 5), and NSAIDs and antibiotics (n = 5). Reverse transcriptase (RT) reaction was performed in all the samples under analysis. Presence of VEGFA and VEGFB gene expression was assessed using reverse-transcription-polymerase chain reaction (RT-PCR). ELISA analysis indicated that average VEGF levels in tissue samples of patients treated with NSAIDs (6.097 ± 1.930 ng/mL), antibiotics (5.661 ± 2.395 ng/mL), and NSAIDs and antibiotics (7.142 ± 2.601 ng/mL) were significantly lower than in samples of control patients (10.432 ± 4.257 ng/mL, ANOVA p = 0.008). The RT-PCR did not reveal VEGFA gene expression in any of the 42 samples. VEGFB gene expression was found in 26 of 42 samples (69.1%). The use of NSAIDs or antibiotics in patients with exacerbated chronic periodontitis decreases VEGF levels in periapical tissues. Pharmacotherapy may minimize the effects of VEGF on apical periodontitis progression in that way.

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Exploratory genome-wide interaction analysis of non-steroidal anti-inflammatory drugs and predicted gene expression on colorectal cancer risk

Cancer Epidemiology Biomarkers & Prevention ◽

10.1158/1055-9965.epi-19-1018 ◽

2020 ◽

pp. cebp.1018.2019

Author(s):

Xiaoliang Wang ◽

Yu-Ru Su ◽

Paneen S Petersen ◽

Stephanie Bien ◽

Stephanie L Schmit ◽

...

Keyword(s):

Gene Expression ◽

Colorectal Cancer ◽

Cancer Risk ◽

Interaction Analysis ◽

Colorectal Cancer Risk ◽

Genome Wide ◽

Inflammatory Drugs ◽

Anti Inflammatory

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

BioMed Research International ◽

10.1155/2015/595273 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 25

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.

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Gene Expression Profile of Coronary Artery Cells Treated With Nonsteroidal Anti-inflammatory Drugs Reveals Off-target Effects

Journal of Cardiovascular Pharmacology ◽

10.1097/fjc.0b013e31824ba6b5 ◽

2012 ◽

Vol 59 (6) ◽

pp. 487-499 ◽

Cited By ~ 13

Author(s):

Sanjeewani T. Palayoor ◽

Molykutty J-Aryankalayil ◽

Adeola Y. Makinde ◽

David Cerna ◽

Michael T. Falduto ◽

...

Keyword(s):

Gene Expression ◽

Coronary Artery ◽

Gene Expression Profile ◽

Expression Profile ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

Target Effects

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Identification of Genes and Pathways of Nonsteroidal Anti-inflammatory Drugs acting on Synovia from Women with Knee Osteoarthritis by Bioinformatics Analysis

10.21203/rs.3.rs-407139/v1 ◽

2021 ◽

Author(s):

Chao Zhao ◽

Han Wang ◽

Conglei Dong ◽

Huijun Kang ◽

Fei Wang

Keyword(s):

Gene Expression ◽

Knee Osteoarthritis ◽

Bioinformatics Analysis ◽

Gene Expression Omnibus ◽

Control Group ◽

Ppi Network ◽

Kegg Pathways ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

R Programming

Abstract Objective: Through the bioinformatics analysis, to identify the genes and pathways of nonsteroidal anti-inflammatory drugs(NSARDs) acting on synovia from women with knee osteoarthritis (KOA), and to provide reference for clinical application. Methods: We downloaded the gene microarray datasets with the accession number of GSE55457 and GSE55584 from the Gene Expression Omnibus (GEO; https://www.ncbi.nlm.nih.gov/geo/) database, including 5 untreated KOA patients, 9 NSARDs treated KOA patients and 2 patients without KOA The samples in the untreated KOA group and the NSARDs treated KOA group were used for main analysis. The samples in the untreated KOA group and the normal control group were used for cooperative analysis. Then we performed robust multi-array (RMA) normalization with affy R programming package. After that, differential expression genes (DEGs) in main analysis and cooperative analysis were identified based on limma package separately. Screening the common DEGs from main analysis and cooperative analysis. Enriched gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of DEGs were obtained through the Database for Annotation, Visualization and Integrated Discovery (DAVID). What's more, protein-protein interaction (PPI) network was constructed, and we identified modules of PPI network through Cytoscape to screen valuable targets. The value of gene expression fold change (FC) ≥1.4 or ≤1/1.4, and P <0.05 were used as the screening conditions. P <0.05 and Associated genes count>5 were used as the screening conditions.Results: There were 338 DEGs in main analysis. Among them, 211 genes were up-regulated and 127 genes were down-regulated. There were 7005 DEGs in cooperative analysis. Among them, 6952 genes were up-regulated and 53 genes were down-regulated. A total of 129 common DEGs were identified between main analysis and cooperative analysis. There are 2 biological processes, 3 cell components and 2 molecular functions for the enrichment of differentially expressed genes.Conclusion: NSARDs may play a certain role in synovia from women with KOA by regulating the mRNA expressions of il-6, TNFRSF11A and CSF1R, which may become one of the indicators for monitoring the efficacy of NSAIDs.

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