Pharmacomicrobiology of Methotrexate in Rheumatoid Arthritis: Gut Microbiome as Predictor of Therapeutic Response DOI Creative Commons
Huanhuan Yan, Rui Su,

Hongwei Xue

и другие.

Frontiers in Immunology, Год журнала: 2021, Номер 12

Опубликована: Дек. 16, 2021

Rheumatoid arthritis (RA) is a disabling autoimmune disease with invasive as the main manifestation and synovitis basic pathological change, which can cause progressive destruction of articular cartilage bone, ultimately leading to joint deformity loss function. Since its introduction in 1980s widespread use treatment RA, low-dose methotrexate (MTX) therapy has dramatically changed course outcome RA treatment. The clinical this drug will be more rational better understanding pharmacology, anti-inflammatory mechanisms action adverse reaction about it. At present, current status newly diagnosed that MTX initiated first regardless patients’ suitability. But up 50% patients could not reach adequate efficacy or have severe events. Prior initiation, prognostic tool for response lacking, thought most important situation. A growing body studies shown differences microbial metagenomes (including bacterial strains, genes, enzymes, proteins and/or metabolites) gastrointestinal tract may at least partially determine their bioavailability subsequent MTX. Based on this, some researchers established random forest model predict whether different (with gut microbiome) would respond Of course, MTX, turn, alters microbiome dose-dependent manner. interaction between drugs microorganisms called pharmacomicrobiology. Then, concept precision medicine been raised. In view, we summarize characteristics highlight aiming find optimal according individual discuss application prospect medicine.

Язык: Английский

Comorbidities and extra-articular manifestations in difficult-to-treat rheumatoid arthritis: different sides of the same coin? DOI Open Access
Mrinalini Dey,

György M. Nagy,

Elena Nikiphorou

и другие.

Lara D. Veeken, Год журнала: 2022, Номер 62(5), С. 1773 - 1779

Опубликована: Окт. 6, 2022

Despite the improvement in treatment for people with RA, ∼30% of patients remain symptomatic presence optimized medical therapy, described as having 'difficult-to-treat' (D2T) RA. The average patient RA has 1.6 other clinical conditions, which accumulate over time. Comorbidities are increasingly recognized key contributors to D2T disease, and themselves perpetuated by state. In this review, we discuss commonest comorbidities context We propose need a paradigm shift research agenda comorbidities-including consider manage these prior development disease not an afterthought.

Язык: Английский

Процитировано

31
Revisiting p38 Mitogen-Activated Protein Kinases (MAPK) in Inflammatory Arthritis: A Narrative of the Emergence of MAPK-Activated Protein Kinase Inhibitors (MK2i) DOI Creative Commons
Payal Ganguly, Tom Macleod, Chi Huey Wong

и другие.

Pharmaceuticals, Год журнала: 2023, Номер 16(9), С. 1286 - 1286

Опубликована: Сен. 12, 2023

The p38 mitogen-activated protein kinase (p38-MAPK) is a crucial signaling pathway closely involved in several physiological and cellular functions, including cell cycle, apoptosis, gene expression, responses to stress stimuli. It also plays central role inflammation immunity. Owing disparate p38-MAPK it has thus far formed an elusive drug target with failed clinical trials inflammatory diseases due challenges hepatotoxicity, cardiac toxicity, lack of efficacy, tachyphylaxis, which brief initial improvement rapid disease rebound. To overcome these limitations, downstream antagonism the MAPK-activated (MAPKAPK, known as MK2) blockade demonstrated potential abrogate without prior recognized toxicities. Such MK2 inhibition (MK2i) associated robust suppression key pro-inflammatory cytokines, TNFα IL-6 others experimental systems vitro. Considering this recent evidence regarding MK2i arthritis, we revisit discuss literature encompassing inhibitors focus on pathway. We then highlight how novel strategies, although encouraging pre-clinical arena, may either show for efficacy or emergent human data from different settings.

Язык: Английский

Процитировано

21
Anti‐Acidification and Immune Regulation by Nano‐Ceria‐Loaded Mg–Al Layered Double Hydroxide for Rheumatoid Arthritis Therapy DOI Creative Commons
Hao Fu, Yuedong Guo,

Wenming Fang

и другие.

Advanced Science, Год журнала: 2023, Номер 11(6)

Опубликована: Дек. 8, 2023

Abstract Rheumatoid arthritis (RA) is a chronic autoimmune disease featuring an abnormal immune microenvironment and resultant accumulation of hydrogen ions (H + ) produced by activated osteoclasts (OCs). Currently, clinic RA therapy can hardly achieve sustained or efficient therapeutic outcomes due to the failures in generating sufficient modulation manipulating H that deteriorates bone damage. Herein, highly effective modulatory nanocatalytic platform, nanoceria‐loaded magnesium aluminum layered double hydroxide (LDH‐CeO 2 ), proposed for enhanced based on acid neutralization metal ion inherent bioactivity. Specifically, mild alkaline LDH initiates significant M2 repolarization macrophages triggered elevated antioxidation effect CeO via neutralizing excessive microenvironment, thus resulting recruitment regulatory T cell (Treg) suppressions helper 17 (Th 17) plasma cells. Moreover, osteogenic activity stimulated Mg released from LDH, thereby promoting damaged healing. The encouraging adjuvant‐induced model mice demonstrate high feasibility such concept, which provides novel modality bone‐repairing effects inorganic material.

Язык: Английский

Процитировано

18
Itaconate reduces proliferation and migration of fibroblast-like synoviocytes and ameliorates arthritis models DOI

Maria Tada,

Yuki Kudo, Michihito Kono

и другие.

Clinical Immunology, Год журнала: 2024, Номер 264, С. 110255 - 110255

Опубликована: Май 18, 2024

Язык: Английский

Процитировано

7
Pharmacomicrobiology of Methotrexate in Rheumatoid Arthritis: Gut Microbiome as Predictor of Therapeutic Response DOI Creative Commons
Huanhuan Yan, Rui Su,

Hongwei Xue

и другие.

Frontiers in Immunology, Год журнала: 2021, Номер 12

Опубликована: Дек. 16, 2021

Rheumatoid arthritis (RA) is a disabling autoimmune disease with invasive as the main manifestation and synovitis basic pathological change, which can cause progressive destruction of articular cartilage bone, ultimately leading to joint deformity loss function. Since its introduction in 1980s widespread use treatment RA, low-dose methotrexate (MTX) therapy has dramatically changed course outcome RA treatment. The clinical this drug will be more rational better understanding pharmacology, anti-inflammatory mechanisms action adverse reaction about it. At present, current status newly diagnosed that MTX initiated first regardless patients’ suitability. But up 50% patients could not reach adequate efficacy or have severe events. Prior initiation, prognostic tool for response lacking, thought most important situation. A growing body studies shown differences microbial metagenomes (including bacterial strains, genes, enzymes, proteins and/or metabolites) gastrointestinal tract may at least partially determine their bioavailability subsequent MTX. Based on this, some researchers established random forest model predict whether different (with gut microbiome) would respond Of course, MTX, turn, alters microbiome dose-dependent manner. interaction between drugs microorganisms called pharmacomicrobiology. Then, concept precision medicine been raised. In view, we summarize characteristics highlight aiming find optimal according individual discuss application prospect medicine.

Язык: Английский

Процитировано

35