Promising Therapeutic Targets for Treatment of Rheumatoid Arthritis

Frontiers in Immunology, Год журнала: 2021, Номер 12

Опубликована: Июль 9, 2021

Rheumatoid arthritis (RA) is a systemic poly-articular chronic autoimmune joint disease that mainly damages the hands and feet, which affects 0.5% to 1.0% of population worldwide. With sustained development disease-modifying antirheumatic drugs (DMARDs), significant success has been achieved for preventing relieving activity in RA patients. Unfortunately, some patients still show limited response DMARDs, puts forward new requirements special targets novel therapies. Understanding pathogenetic roles various molecules could facilitate discovery potential therapeutic approaches. In this review, both existing emerging targets, including proteins, small molecular metabolites, epigenetic regulators related RA, are discussed, with focus on mechanisms result inflammation blocking modulators RA.

Язык: Английский

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Recent Advances in Understanding the Pathogenesis of Rheumatoid Arthritis: New Treatment Strategies

Cells, Год журнала: 2021, Номер 10(11), С. 3017 - 3017

Опубликована: Ноя. 4, 2021

Rheumatoid arthritis (RA) is considered a chronic systemic, multi-factorial, inflammatory, and progressive autoimmune disease affecting many people worldwide. While patients show very individual courses of disease, with RA focusing on the musculoskeletal system, joints are often severely affected, leading to local inflammation, cartilage destruction, bone erosion. To prevent joint damage physical disability as one symptoms RA, early diagnosis critical. Auto-antibodies play pivotal clinical role in systemic RA. As biomarkers, they could help make more efficient diagnosis, prognosis, treatment decision. Besides auto-antibodies, several other factors involved progression such epigenetic alterations, post-translational modifications, glycosylation, autophagy, T-cells. Understanding interplay between these would contribute deeper insight into causes, mechanisms, progression, disease. In this review, latest research findings discussed better understand pathogenesis, finally, strategies for therapy presented, including both conventional approaches new methods that have been developed recent years or currently under investigation.

Язык: Английский

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Glycine increased ferroptosis via SAM-mediated GPX4 promoter methylation in rheumatoid arthritis

Lara D. Veeken, Год журнала: 2022, Номер 61(11), С. 4521 - 4534

Опубликована: Фев. 3, 2022

Abstract Objective Over-proliferation of synovium is a key event invasive pannus formation and cartilage damage in the progression RA disease. At same time, ferroptosis may play pivotal role maintaining balance proliferation death synovium. In this study, we firstly evaluated level fibroblast-like synoviocytes (FLS) then explored glycine ferroptosis. Methods Ferroptosis was FLS. The therapeutic effect on by clinical histopathological score cytokine CIA mouse model. influence mitochondrial morphology observation membrane potential assay Methylase expression detected to explore mechanism behind glutathione peroxidase 4 (GPX4) methylation. Results Compared with healthy controls, decreased FLS, decrease Acyl Coenzyme A Synthetase Long Chain (ACSL4) an increase Ferritin heavy chain 1 (FTH1), GPX4 cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11). Although both oxidation antioxidation levels lipids were higher FLS than slightly oxidation. RNA-seq verification showed that regulated pathway through S-adenosylmethionine (SAM) concentration FTH1 promoting SAM-mediated promoter methylation reducing Conclusions summary, confirmed decline enhanced via ferritin decrease.

Язык: Английский

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Epigenome-wide meta-analysis of DNA methylation differences in prefrontal cortex implicates the immune processes in Alzheimer’s disease

Nature Communications, Год журнала: 2020, Номер 11(1)

Опубликована: Ноя. 30, 2020

Abstract DNA methylation differences in Alzheimer’s disease (AD) have been reported. Here, we conducted a meta-analysis of more than 1000 prefrontal cortex brain samples to prioritize the most consistent multiple cohorts. Using uniform analysis pipeline, identified 3751 CpGs and 119 differentially methylated regions (DMRs) significantly associated with Braak stage. Our genes such as MAMSTR , AGAP2 AZU1 . The significant DMR is located on gene, which encodes cofactor that stimulates MEF2C. Notably, MEF2C cooperates another transcription factor, PU.1, central hub AD gene network. enrichment highlighted potential roles immune system polycomb repressive complex 2 pathological AD. These results may help facilitate future mechanistic biomarker discovery studies

Язык: Английский

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Pathogenesis of rheumatoid arthritis and its treatment with anti-inflammatory natural products

Molecular Biology Reports, Год журнала: 2023, Номер 50(5), С. 4687 - 4706

Опубликована: Апрель 6, 2023

Язык: Английский

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Bazi Bushen mitigates epigenetic aging and extends healthspan in naturally aging mice

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 160, С. 114384 - 114384

Опубликована: Фев. 9, 2023

Bazi Bushen (BZBS), a traditional Chinese medicine, has been proven effective in the treatment of age-related disease mouse models. However, whether its therapeutic effects are due to antiaging mechanism not yet explored. In present study, we investigated BZBS naturally aging mice by using behavioral tests, liver DNA methylome sequencing, methylation age estimation, and frailty index assessment. The analysis revealed decrease mCpG levels aged liver. tended restore age-associated decline prune pattern toward that young mice. More importantly, significantly rejuvenated mice, which was computed an upgraded clock. These results were consistent with enhanced memory muscular endurance, as well decreased score pathological changes. KEGG together aging-related database screening identified methylation-targeted pathways upon treatment, including oxidative stress, repair, MAPK signaling, inflammation. Upregulation key effectors their downstream on elevating Sod2 expression diminishing damage further investigated. Finally, vitro experiments senescent HUVECs proved direct effect extracts regulation enzymes during cellular aging. summary, our work for first time slowing suggest might have great potential extend healthspan also explored action diseases.

Язык: Английский

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Exposome: Epigenetics and autoimmune diseases

Autoimmunity Reviews, Год журнала: 2024, Номер 23(6), С. 103584 - 103584

Опубликована: Июнь 1, 2024

Systemic autoimmune diseases are complex conditions characterized by an immune system dysregulation and aberrant activation against self-antigens, leading to tissue organ damage. Even though genetic predisposition plays a role, it cannot fully explain the onset of these diseases, highlighting significant impact non-heritable influences such as environment, hormones infections. The exposome represents all those factors, ranging from chemical pollutants dietary components psychological stressors infectious agents. Epigenetics, which studies changes in gene expression without altering DNA sequence, is crucial link between development diseases. Key epigenetic mechanisms include methylation, histone modifications, non-coding RNAs. These modifications could provide potential piece puzzle understanding systemic their connection with exposome. In this work we have collected most important recent evidence linked (systemic lupus erythematosus, idiopathic inflammatory myopathies, ANCA-associated vasculitis, rheumatoid arthritis), emphasizing roles may play disease pathogenesis, diagnostic biomarkers prospective targeted therapies.

Язык: Английский

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Supplementary Treatment for Alleviating Pain and Enhancing Functional Ability in Geriatric Patients with Osteoarthritis

Healthcare, Год журнала: 2025, Номер 13(2), С. 127 - 127

Опубликована: Янв. 11, 2025

Background and Objectives: A degenerative joint disease that primarily affects elderly individuals, osteoarthritis (OA) causes pain, decreased mobility, a lower quality of life. Procaine is regarded as “veteran” medicine due to its extensive clinical use, although it remains molecule interest, researchers are uncovering new biological pharmacological effects through innovative experimental methods. This study evaluates the efficacy “procaine complex”, developed in our country, alleviating pain improving functionality individuals with knee hip. Materials Methods: We conducted an assessment longitudinal short-term involving 177 patients aged 65 older, who were randomly divided into two groups. One group received physical therapy complex” periarticular injections (n = 101), while other just 76). assessed using visual analog scale (VAS), addition functional evaluations Lequesne Index, Activities Daily Living (ADL), Instrumental ADL (IADL) scores. evaluated these CGA (complex geriatric assessment), walk test, “Up Go” Mini Mental State (MMSE) Geriatric Depression Scale (GDS) for cognitive status. analyzed all data from this PSPP v3 software. Results: The procaine complex treatment exhibited significant reduction (p < 0.001) improvement daily activities relative control group. However, there was no notable difference walking test scores 0.171). No substantial detrimental identified. did not surpass reducing depressive disorders, but both groups showed some enhancement regard. Conclusions: demonstrates approach management by integrating therapy. provides experiencing limitations secure efficacious alternative surgery, or may diminish years disability.

Язык: Английский

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IFNγ regulates ferroptosis in KFs by inhibiting the expression of SPOCD1 through DNMT3A

Cell Death Discovery, Год журнала: 2025, Номер 11(1)

Опубликована: Янв. 16, 2025

Abstract Keloid is benign skin tumor, and their curing relatively difficult due to the unclear mechanism of formation. Inducing ferroptosis keloid fibroblasts (KFs) may become a new method for treating keloid. Here, we discover interferon (IFN)γ could induce KFs through inhibiting SPOC domain-containing protein 1 (SPOCD1), serving as mode action CD8 + T cell (CTL)-mediated killing. Mechanistically, IFNγ deficiency in combination with reduced DNMT3A increase expression SPOCD1, thereby promoting KFs’ proliferation its ferroptosis. Moreover, SPOCD1 attenuates progression extracellular matrix (ECM) deposition. Reducing simultaneously can positive rate reactive oxygen species (ROS) promote mitochondrial shrinkage. Ex-vivo explant culture has also confirmed that reduction helps reduce KFs, inhibit angiogenesis scars, thus Thus, signaling paired natural CTLs. Targeting pathway potential anti-keloid approach.

Язык: Английский

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Epigenetics in autoimmune diseases: Unraveling the hidden regulators of immune dysregulation

Autoimmunity Reviews, Год журнала: 2025, Номер 24(6), С. 103784 - 103784

Опубликована: Март 3, 2025

Autoimmune diseases result from complex interactions between genetic and environmental factors. Recent advances in epigenetic research shed light on the intricate regulatory mechanisms that contribute to development progression of such conditions. The present review aims explore role modifications, including DNA methylation, histone non-coding RNAs, context autoimmune diseases. We discuss current understanding alterations associated with various disorders, their impact immune cell function, potential as innovative therapeutic targets. Additionally, we highlight main future directions field epigenetics autoimmunity.

Язык: Английский

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