ArticleInflammopharmacology2021
Methotrexate and theaflavin-3, 3'-digallate synergistically restore the balance between apoptosis and autophagy in synovial fibroblast of RA: an ex vivo approach with cultured human RA FLS.
Article in Inflammopharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 18 citations in OpenAlex.
- Fibroblast-like Synoviocytes as Therapeutic Targets in Rheumatoid Arthritis: Current Evidence on DMARD-Mediated Modulation.Biomedicines · 2026Review
- Therapeutic effects of Melittin acupoint injection on rheumatoid arthritis through autophagy activation and PI3K/AKT/mTOR pathway inhibition.Quantitative imaging in medicine and surgery · 2026Article
- Parthenolide ameliorates glucocorticoid-induced inhibition of osteogenic differentiation and osteoporosis by activating ERK signaling pathway.Journal of orthopaedic surgery and research · 2025Article
- Infliximab Ameliorates Methotrexate-Induced Nephrotoxicity in Experimental Rat Model: Impact on Oxidative Stress, Mitochondrial Biogenesis, Apoptotic and Autophagic Machineries.Cell biochemistry and biophysics · 2023Article
- Bioinformatic identification and validation of autophagy-related genes in rheumatoid arthritis.Clinical rheumatology · 2023Article
- Can pyroptosis be a new target in rheumatoid arthritis treatment?Frontiers in immunology · 2023Review
- Global trends in research of fibroblasts associated with rheumatoid diseases in the 21st century: A bibliometric analysis.Frontiers in immunology · 2023Article
- PINK1/Parkin-Mediated Mitochondrial Autophagy Participates in HJournal of inflammation research · 2023Article
- The elucidation of the anti-inflammatory mechanism of EMO in rheumatoid arthritis through an integrative approach combining bioinformatics and experimental verification.Frontiers in pharmacology · 2023Article
- Targeting fibroblast-like synoviocytes in rheumatoid arthritis.Current opinion in pharmacology · 2022Review
- Insights on attenuating autophagy cellular and molecular pathways versus methotrexate-induced toxicity via liposomal turmeric therapy.Journal, genetic engineering & biotechnology · 2022Article
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundImbalance between apoptosis and autophagy in fibroblast-like synoviocytes (FLS) is one of the pathogenic mechanisms responsible for their abnormal proliferation in rheumatoid arthritis (RA). Methotrexate (MTX) demonstrated limited efficacy in amending this imbalance in fluid-derived (fd)-FLS. The active compound of black tea Theaflavin 3,3'-digallate (TF3) may be effective in restoring apoptosis-autophagy imbalance in (fd)-FLS. The combined effect of MTX + TF3 upon the same is yet to be elucidated.
objectiveTo evaluate the effect of MTX + TF3 on fd-FLS to induce apoptosis and inhibit autophagy through Endoplasmic Reticulum (ER) stress-mediated pathways.
methodsFLS from synovial fluid of 11 RA and 10 osteoarthritis patients were cultured after treatment with MTX/TF3 or a combination of MTX (125 nM) and TF3(10 µM) and the following parameters were evaluated. C-reactive protein, cytokines (TNF-α, IL-6), angiogenic markers were quantified by ELISA. fd-FLS viability was determined by MTT assay and apoptosis by flow cytometry. ER stress markers were estimated by RT-PCR (IRE1A, spliced-XBP-1) and immunoblotting (Grp78, Hsp70, CHOP, HIF-1α). Immunoblot studies were done to evaluate apoptotic (Bcl-2, Bax, Caspases) and autophagic (Beclin1, LC3b, p62) proteins.
resultsMTX (IC
conclusionDisruption in homeostasis between apoptosis and autophagy in fd-FLS might be an underlying phenomenon in the progression of pathophysiology in RA. Co-administration of MTX + TF3 successfully restored the homeostasis by inducing apoptosis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.