Small molecule metabolites: discovery of biomarkers and therapeutic targets

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Март 20, 2023

Metabolic abnormalities lead to the dysfunction of metabolic pathways and metabolite accumulation or deficiency which is well-recognized hallmarks diseases. Metabolite signatures that have close proximity subject's phenotypic informative dimension, are useful for predicting diagnosis prognosis diseases as well monitoring treatments. The lack early biomarkers could poor serious outcomes. Therefore, noninvasive methods with high specificity selectivity desperately needed. Small molecule metabolites-based metabolomics has become a specialized tool biomarker pathway analysis, revealing possible mechanisms human various deciphering therapeutic potentials. It help identify functional related variation delineate biochemical changes indicators pathological damage prior disease development. Recently, scientists established large number profiles reveal underlying networks target exploration in biomedicine. This review summarized analysis on potential value small-molecule candidate metabolites clinical events, may better diagnosis, prognosis, drug screening treatment. We also discuss challenges need be addressed fuel next wave breakthroughs.

Язык: Английский

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Advanced methods and novel biomarkers in autoimmune diseases ‑ a review of the recent years progress in systemic lupus erythematosus

Frontiers in Medicine, Год журнала: 2023, Номер 10

Опубликована: Июнь 23, 2023

There are several autoimmune and rheumatic diseases affecting different organs of the human body. Multiple sclerosis (MS) mainly affects brain, rheumatoid arthritis (RA) joints, Type 1 diabetes (T1D) pancreas, Sjogren’s syndrome (SS) salivary glands, while systemic lupus erythematosus (SLE) almost every organ Autoimmune characterized by production autoantibodies, activation immune cells, increased expression pro-inflammatory cytokines, type I interferons. Despite improvements in treatments diagnostic tools, time it takes for patients to be diagnosed is too long, main treatment these still non-specific anti-inflammatory drugs. Thus, there an urgent need better biomarkers, as well tailored, personalized treatment. This review focus on SLE affected this disease. We have used results from various involved with aim identify advanced methods possible biomarkers utilized diagnosis SLE, disease monitoring, response

Язык: Английский

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Neddylation is a novel therapeutic target for lupus by regulating double negative T cell homeostasis

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Янв. 15, 2024

Abstract Systemic lupus erythematosus (SLE), a severe autoimmune disorder, is characterized by systemic inflammatory response, autoantibody accumulation and damage to organs. The dysregulation of double-negative (DN) T cells considered as crucial commander during SLE. Neddylation, significant type protein post-translational modification (PTM), has been well-proved regulate cell-mediated immune response. However, the function neddylation in SLE still unknown. Here, we reported that inactivation with MLN4924, specific inhibitor NEDD8-activating enzyme E1 (NAE1), or genetic abrogation Ube2m decreased DN cell attenuated murine development. Further investigations revealed blocked Bim ubiquitination degradation maintained level cells, contributing apoptosis accumulated mice. Then double knockout (KO) lupus-prone mice ( -/- lpr ) were generated results showed loss reduced deficiency-induced reversed alleviated progression. Our findings identified promoted Bim-mediated Clinically, also found patients, proportion was raised their reduced. Moreover, compared healthy groups, patients exhibited levels elevated Cullin1 levels. Meantime, inhibition induced Bim-dependent isolated from patients. Altogether, our provide direct evidence about lupus, suggesting promising therapeutic approach for this disease.

Язык: Английский

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Metabolic dysregulation of lymphocytes in autoimmune diseases

Trends in Endocrinology and Metabolism, Год журнала: 2024, Номер 35(7), С. 624 - 637

Опубликована: Фев. 13, 2024

Язык: Английский

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Epigenetic Dysregulation in the Pathogenesis of Systemic Lupus Erythematosus

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(2), С. 1019 - 1019

Опубликована: Янв. 13, 2024

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease in which immune disorders lead to autoreactive responses and cause inflammation tissue damage. Genetic environmental factors have been shown trigger SLE. Recent evidence has also demonstrated that epigenetic contribute the pathogenesis of Epigenetic mechanisms play an important role modulating chromatin structure regulating gene transcription. Dysregulated changes can alter expression impair cellular functions cells, resulting responses. Therefore, elucidating dysregulated system crucial for understanding In this paper, we review roles

Язык: Английский

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Imbalance of Th17 cells, Treg cells and associated cytokines in patients with systemic lupus erythematosus: a meta-analysis

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Июль 17, 2024

This article aims to investigate the changes of T helper 17 (Th17) cells, regulatory (Treg) cells and their associated cytokines in patients with systemic lupus erythematosus (SLE). Multiple databases were investigated identify articles that explored Th17 Treg relevant SLE patients. A random effects model was used for calculating pooled standardized mean differences. Stata version 15.0 utilized conduct meta-analysis. The levels IL-17, IL-6, IL-21 IL-10 higher than healthy controls (HCs), but TGF-β lower. percentage lower HCs individuals older 33. Among studies had 93% or females, greater HCs. However, when proportion females less 90%. Patients nephritis active an increased a decreased cells. level related could be main reason elevated Th17/Treg ratio SLE. percentages gender, age, disease activity kidney function. Furthermore, reduced proportions may primarily result rise https://www.crd.york.ac.uk/prospero, identifier CRD42023454937.

Язык: Английский

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Molecular characterization of PANoptosis-related genes with features of immune dysregulation in systemic lupus erythematosus

Clinical Immunology, Год журнала: 2023, Номер 253, С. 109660 - 109660

Опубликована: Июнь 7, 2023

Язык: Английский

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A single-cell map of peripheral alterations after FMT treatment in patients with systemic lupus erythematosus

Journal of Autoimmunity, Год журнала: 2023, Номер 135, С. 102989 - 102989

Опубликована: Янв. 5, 2023

Язык: Английский

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m6A methyltransferase METTL3 programs CD4+ T-cell activation and effector T-cell differentiation in systemic lupus erythematosus

Molecular Medicine, Год журнала: 2023, Номер 29(1)

Опубликована: Апрель 3, 2023

Abstract Background Systemic lupus erythematosus (SLE) is an autoimmune disorder in which excessive CD4 + T-cell activation and imbalanced effector differentiation play critical roles. Recent studies have implied a potential association between posttranscriptional N6 -methyladenosine (m 6 A) modification T-cell-mediated humoral immunity. However, how this biological process contributes to not well understood. In work, we investigated the role of m A methyltransferase like 3 (METTL3) activation, differentiation, SLE pathogenesis both vitro vivo. Methods The expression METTL3 was knocked down enzyme activity inhibited using siRNA catalytic inhibitor, respectively. vivo evaluation inhibition on achieved sheep red blood cell (SRBC)-immunized mouse model chronic graft versus host disease (cGVHD) model. RNA-seq performed identify pathways gene signatures targeted by METTL3. RNA-immunoprecipitation qPCR applied confirm targets. Results defective T cells patients. varied following vitro. Pharmacological promoted influenced cells, predominantly Treg Moreover, increased antibody production aggravated lupus-like phenotype cGVHD mice. Further investigation revealed that reduced Foxp3 enhancing mRNA decay A-dependent manner, hence suppressing differentiation. Conclusion summary, our findings demonstrated required for stabilizing via maintain program. contributed participating imbalance could serve as target therapeutic intervention SLE.

Язык: Английский

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Double-Negative T (DNT) Cells in Patients with Systemic Lupus Erythematosus

Biomedicines, Год журнала: 2024, Номер 12(1), С. 166 - 166

Опубликована: Янв. 12, 2024

Double-negative T (DNT) cells are a rare and unconventional T-lymphocyte subpopulation lacking both CD4 CD8 markers. Their immunopathological roles clinical relevance have yet to be elucidated. Beyond autoimmune lymphoproliferative syndrome (ALPS), these may also play role in rheumatic disorders, including systemic lupus erythematosus (SLE); indeed, two diseases share several manifestations (including nephritis). Moreover, one of the main experimental murine models used investigate lupus, namely MRL/lpr mouse, is characterized by an expansion DNT cells, which can support production pathogenic autoantibodies and/or modulate immune response this context. However, not completely consistent with their human SLE counterpart, course. In mini review, we summarize analyze most relevant studies investigating cell population patients. Overall, based on present literature review analysis, homeostasis seems altered patients SLE. Indeed, available (which include adults children) reported increased percentage patients, especially during active phases, even though no clear correlation disease activity inflammatory parameters has been clearly established. Well-designed, standardized, longitudinal focused needed, order further elucidate actual contribution pathogenesis interactions other (also implicated SLE, such as basophils), clarify whether immunophenotypic aspects any (and, then, represent potential markers and, perspective, therapeutic targets) or just unspecific epiphenomenon autoimmunity.

Язык: Английский

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