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1.
Front Immunol ; 15: 1390907, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962006

RESUMO

Autoimmune diseases (AID) have emerged as prominent contributors to disability and mortality worldwide, characterized by intricate pathogenic mechanisms involving genetic, environmental, and autoimmune factors. In response to this challenge, a growing body of research in recent years has delved into genetic modifications, yielding valuable insights into AID prevention and treatment. Sirtuins (SIRTs) constitute a class of NAD-dependent histone deacetylases that orchestrate deacetylation processes, wielding significant regulatory influence over cellular metabolism, oxidative stress, immune response, apoptosis, and aging through epigenetic modifications. Resveratrol, the pioneering activator of the SIRTs family, and its derivatives have captured global scholarly interest. In the context of AID, these compounds hold promise for therapeutic intervention by modulating the SIRTs pathway, impacting immune cell functionality, suppressing the release of inflammatory mediators, and mitigating tissue damage. This review endeavors to explore the potential of resveratrol and its derivatives in AID treatment, elucidating their mechanisms of action and providing a comprehensive analysis of current research advancements and obstacles. Through a thorough examination of existing literature, our objective is to advocate for the utilization of resveratrol and its derivatives in AID treatment while offering crucial insights for the formulation of innovative therapeutic approaches.


Assuntos
Doenças Autoimunes , Resveratrol , Sirtuínas , Resveratrol/uso terapêutico , Resveratrol/farmacologia , Humanos , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/imunologia , Doenças Autoimunes/metabolismo , Animais , Sirtuínas/metabolismo
2.
Biomed Pharmacother ; 174: 116481, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38522239

RESUMO

Sirtuins (SIRTs) represent a class of nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases that exert a crucial role in cellular signal transduction and various biological processes. The mammalian sirtuins family encompasses SIRT1 to SIRT7, exhibiting therapeutic potential in counteracting cellular aging, modulating metabolism, responding to oxidative stress, inhibiting tumors, and improving cellular microenvironment. These enzymes are intricately linked to the occurrence and treatment of diverse pathological conditions, including cancer, autoimmune diseases, and cardiovascular disorders. Given the significance of histone modification in gene expression and chromatin structure, maintaining the equilibrium of the sirtuins family is imperative for disease prevention and health restoration. Mounting evidence suggests that modulators of SIRTs play a crucial role in treating various diseases and maintaining physiological balance. This review delves into the molecular structure and regulatory functions of the sirtuins family, reviews the classification and historical evolution of SIRTs modulators, offers a systematic overview of existing SIRTs modulation strategies, and elucidates the regulatory mechanisms of SIRTs modulators (agonists and inhibitors) and their clinical applications. The article concludes by summarizing the challenges encountered in SIRTs modulator research and offering insights into future research directions.


Assuntos
Sirtuínas , Sirtuínas/metabolismo , Humanos , Animais , Neoplasias/tratamento farmacológico
3.
Front Biosci (Landmark Ed) ; 29(1): 5, 2024 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-38287796

RESUMO

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease characterized by destruction of synovial joints, abnormal immune responses and chronic inflammatory manifestations, which seriously affects patients' well-being. We explored this study to ascertain the effect and mechanism of silent information regulator 6 (SIRT6) on RA. METHODS: Genes of RA patients and normal volunteers were analyzed using Gene Expression Omnibus (GEO), Kyoto-Encyclopedia of Genes and Genomes (KEGG) and Disconet databases. Serum samples of RA patients and normal subjects were collected before detection of myeloid differentiation factor-88 (MyD88)-extracellular signal-regulated kinase (ERK) pathway proteins expression with Western blot. In vitro RA fibroblast-like synoviocytes (FLS) cell model (RA-FLS) was established by treating RSC-364 with recombinant rat IL-1ß (10 ng/mL) after which SIRT6 and MyD88 adenoviruses treatment was carried out. The enzyme linked immunoassay (ELISA), real time polymerase chain reaction (RT-PCR) and Western blot were respectively used to measure inflammatory factors, related messenger ribonucleic acid (mRNA) and protein expressions. Also, we constructed RA rat model with bovine type II collagen (BIIC) and complete Freund's adjuvant, before treatment with SIRT6 and MyD88 adenoviruses. RESULTS: Low expression of SIRT6 gene were detected in RA patients. Also, levels of MyD88, ERK and phosphorylated extracellular signal-regulated protein kinase (p-ERK) protein expressions in RA patients were increased, whilst that of SIRT6 protein decreased. Compared to FLS cells in Control group, inflammatory factors levels of rats in Model batch increased significantly. SIRT6 adenovirus treatment potentially and significantly inhibited inflammation including suppression of increased inflammatory factors induced by MyD88. In comparison with FLS cells in Control group, Model batch cells' MyD88, interleukin (IL)-1ß, IL-21, IL-22, IL-6, IL-17, tumor necrosis factor-alpha (TNF-α) and monocyte chemo-attractant protein-1 (MCP-1) mRNA expressions increased but SIRT6 gene treatment could reduce mRNA expression of the aforesaid factors, even after MyD88 adenovirus treatment. Besides, overpressed SIRT6 negatively regulated levels of MyD88, ERK and p-ERK proteins expressions. SIRT6 demonstrated anti-RA effect by regulating MyD88-ERK pathway and inhibiting inflammatory response in RA rats. CONCLUSIONS: SIRT6 could potentially inhibit the inflammatory response of RA via a regulatory mechanism mainly relating to MyD88-ERK signal pathway. Thus, SIRT6 and its agonists may serve as new targets for developing drugs that can potentially treat RA.


Assuntos
Artrite Reumatoide , Sirtuínas , Humanos , Animais , Bovinos , Ratos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Fator 88 de Diferenciação Mieloide/farmacologia , Artrite Reumatoide/genética , Transdução de Sinais , Inflamação/metabolismo , RNA Mensageiro/metabolismo , Sirtuínas/genética , Sirtuínas/metabolismo , Sirtuínas/farmacologia , Fibroblastos/metabolismo , Células Cultivadas
4.
Front Immunol ; 14: 1186231, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37483618

RESUMO

In recent years, epigenetic modifications have been widely researched. As humans age, environmental and genetic factors may drive inflammation and immune responses by influencing the epigenome, which can lead to abnormal autoimmune responses in the body. Currently, an increasing number of studies have emphasized the important role of epigenetic modification in the progression of autoimmune diseases. Sirtuins (SIRTs) are class III nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylases and SIRT-mediated deacetylation is an important epigenetic alteration. The SIRT family comprises seven protein members (namely, SIRT1-7). While the catalytic core domain contains amino acid residues that have remained stable throughout the entire evolutionary process, the N- and C-terminal regions are structurally divergent and contribute to differences in subcellular localization, enzymatic activity and substrate specificity. SIRT1 and SIRT2 are localized in the nucleus and cytoplasm. SIRT3, SIRT4, and SIRT5 are mitochondrial, and SIRT6 and SIRT7 are predominantly found in the nucleus. SIRTs are key regulators of various physiological processes such as cellular differentiation, apoptosis, metabolism, ageing, immune response, oxidative stress, and mitochondrial function. We discuss the association between SIRTs and common autoimmune diseases to facilitate the development of more effective therapeutic strategies.


Assuntos
Sirtuína 3 , Sirtuínas , Humanos , Sirtuína 1/genética , Sirtuína 3/genética , Envelhecimento , Estresse Oxidativo/genética , Epigênese Genética , Sirtuínas/genética
6.
Autoimmunity ; 54(7): 398-405, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34431424

RESUMO

Considered as an autoimmune disease, rheumatoid arthritis (RA) is an chronic inflammatory disorder that causes inflammation of the joints. This study is performed with the aim to clarify the expression of phospholipase D1 (PLD1) in RA and its specific regulation role of RA as well as the underlying mechanisms. In this study, synovial tissue samples were collected from RA patients, and RA-fibroblast-like synoviocytes (FLSs) were subsequently isolated. The expression levels of PLD1 and pathway-related proteins were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blotting or immunohistochemistry (IHC). Upon shPLD1 treatment, cell viability, proliferation, migration, invasion, and the level of inflammation-related factors were measured by Cell Counting Kit-8 (CCK-8), Edu, wound healing, Transwell and enzyme-linked immunosorbent assay (ELISA). Furthermore, C-reactive protein (CRP), rheumatoid factor (RF), arthritis score and synovial tissue lesions were assessed by collecting the blood or tissues from collagen induced arthritis (CIA) model rats. Our results showed that PLD1 level was increased in RA synovial tissues. Cell viability, proliferation, migration, invasion, and the level of inflammatory factors were reduced upon PLD1 knockdown in RA-FLSs. Moreover, p-IκBα/IκBα, ß-catenin, p-IKKß/IKKß and TCF-4 were inhibited under PLD1 knockdown treatment. PLD1 knockdown alleviated the collagen-induced addition of arthritis score, CRP and RF, as well as the filling of inflammatory cells and proliferation of synovium in CIA model rat. To sum up, knockdown of PLD1 could reduce RA-FLSs metastasis as well as inflammatory response by modulating the activity of NF-κB and Wnt/ß-catenin pathways.


Assuntos
Artrite Reumatoide , Fosfolipase D/genética , Sinoviócitos , Via de Sinalização Wnt , Animais , Artrite Reumatoide/metabolismo , Proliferação de Células , Células Cultivadas , Fibroblastos/metabolismo , Humanos , Inflamação/metabolismo , NF-kappa B/metabolismo , Ratos , Sinoviócitos/metabolismo
7.
Rheumatol Int ; 38(10): 1885-1890, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30062435

RESUMO

The utility of superb microvascular imaging (SMI) for evaluating hand joint lesions in patients with rheumatoid arthritis (RA) in clinical remission is unreported. This study aimed to compare SMI and power Doppler imaging (PDI) for the evaluation of hand joint lesions in these patients. Twenty-six patients with RA in clinical remission were enrolled. A total of 572 joints (52 wrist, 260 proximal interphalangeal, and 260 metacarpophalangeal joints) were detected by SMI and PDI. A semi-quantitative scale of 0-3 was used to compare the detection of synovial blood flow signal by SMI and PDI. Inter-observer agreement for the assessment of SMI and PDI scores was measured with kappa values. In the ten healthy volunteers, SMI and PDI signals were both scored 0. In the 26 RA patients, the remission rate via PDI was 65.4% but was only 42.3% via SMI. SMI also detected microvessel flow signal in seven patients diagnosed with clinical remission via PDI. Moreover, a total of 106 blood flow signals (18.5%) were detected by SMI, while 50 blood flow signals (8.7%) were detected by PDI. Compared with PDI, SMI increased 18.0% of power flow signals from Grade 0-1 and increased 13.7% of power flow signals from Grade 1-2. One joint classified as Grade 1 by PDI was classified as Grade 0 by SMI. Inter-observer agreement for PDI and SMI semi-quantitative scoring was moderate (kappa = 0.463). SMI seems more sensitive than PDI for detecting hand joint lesions in RA in clinical remission PDI, and could aid the achievement of true remission in RA patients.


Assuntos
Artrite Reumatoide/diagnóstico por imagem , Articulação da Mão/diagnóstico por imagem , Ultrassonografia Doppler/métodos , Articulação da Mão/irrigação sanguínea , Humanos , Articulação Metacarpofalângica/irrigação sanguínea , Articulação Metacarpofalângica/diagnóstico por imagem , Microvasos , Variações Dependentes do Observador , Índice de Gravidade de Doença , Articulação do Punho/irrigação sanguínea , Articulação do Punho/diagnóstico por imagem
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