Current Understanding and Translational Prospects of Tetrahedral Framework Nucleic Acids

JACS Au, Год журнала: 2025, Номер 5(2), С. 486 - 520

Опубликована: Фев. 10, 2025

Tetrahedral framework nucleic acids (tFNAs) represent a promising advancement in acid nanotechnology due to their unique structural properties, high biocompatibility, and multifaceted biomedical applications. Constructed through one-pot annealing method, four single-stranded DNAs self-assemble into stable, three-dimensional tetrahedral nanostructures with enhanced mechanical robustness physiological stability, resisting enzymatic degradation. Their ability permeate mammalian cells without transfection agents, coupled modifiable surfaces, positions tFNAs as versatile carriers for drug gene delivery systems. The tFNA-based platforms exhibit superior therapeutic efficacy, including antioxidative anti-inflammatory effects, alongside efficient cellular uptake tissue penetration. These features underpin role precision medicine, enabling targeted of diverse agents such synthetic compounds, peptides, acids. Additionally, demonstrate significant potential regenerative immune modulation, antibacterial strategies, oncology. By addressing challenges translational integration, stand poised accelerate the development research clinical applications, fostering novel therapies enhancing outcomes across wide spectrum diseases. This Perspective thoroughly details attributes applications critically evaluates tFNAs' potential, outlining inherent implementation exploring solutions these obstacles.

Язык: Английский

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Genetic insight into dissecting the immunophenotypes and inflammatory profiles in the pathogenesis of Sjogren syndrome

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Янв. 13, 2025

Sjogren syndrome (SS) is a chronic systemic autoimmune disease and its pathogenesis often involves the participation of numerous immune cells inflammatory factors. Despite increased researches studies recently focusing on this area, it remains to be fully elucidated. We decide incorporate genetic insight into investigation causal link between various cells, factors (SS). Our study leveraged variants multi-omics statistics extracted from genome-wide association (GWAS), University Bristol FinnGen study. performed bidirectional Mendelian randomization mediation based randomly allocated instrumental variables infer causality, followed by external validation with UK Biobank data Bayesian colocalization. demonstrated that an elevated level CD27 IgD + CD24 B cell, subset expressing both CD24, was associated higher risk SS (OR = 1.119, 95% CI: 1.061–1.179, P < 0.001), while CD3 CD45RA CD4 Treg protective factor 0.917, 95%CI: 0.877–0.959, 0.001). Results meta-analysis colocalization further supported significant results identified in primary analysis. A total 4 cytokines 7 circulating proteins exhibited potential relationships despite no result achieved after FDR correction. Finally, analysis indicated CD40L receptor levels had mediating effects (β 0.0314, 0.0004–0.0624, 0.0471) at proportion 28% (95% 0.364%-55.6%) relationship cell SS. By providing novel unveiling roles autoimmunity inflammation syndrome, our findings may potentially lead identifying new clinical biomarkers for monitoring therapeutic targets offer more effective alternatives treating condition. Therefore, provide valuable evidence future intervention targeted immunotherapy.

Язык: Английский

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Identification of Epigenetic Alteration of the IFI44L Gene in B Cells of Sjogren’s Syndrome as a Clinical Biomarker and Molecular Significance

Journal of Inflammation Research, Год журнала: 2025, Номер Volume 18, С. 2499 - 2512

Опубликована: Фев. 1, 2025

Type 1 interferon (IFN-I)-related genes play a critical role in Sjögren's syndrome (SS). However, study on its and impact peripheral blood B cells of SS is limited. This investigated gene expression epigenetic changes IFI44L, analyzing correlation with disease activity clinical indicators. Differentially expressed (DEGs) were identified from the GSE199868 dataset, while IFN-I-related collected GeneCards. Intersection analysis revealed DEGs SS. ClueGO, Kyoto Encyclopedia Genes Genomes (KEGG) enrichment, PPI network construction, hub identification conducted, validated GSE135809. Following this, we recruited 30 patients as group 11 healthy individuals control group. Clinical information samples all participants. After isolating blood, used quantitative real-time polymerase chain reaction (RT-qPCR) pyrosequencing to examine mRNA DNA methylation status IFI44L gene. Further analyses conducted conjunction 125 upregulated 16 downregulated DEGs. Among 2794 GeneCards, 26 overlapped, enriched viral genome replication IFN-I pathways. 14 identified, 7 confirmed GSE135809: ISG15, IFIT1, OASL, IFI6, RSAD2, USP18. was significantly higher (P < 0.05), lower 0.05). correlated positively ESSDAI, ESSPRI, IgG levels, negatively ESSDAI ESSPRI ROC that had high diagnostic value (AUC = 0.8515). The highlights relevance hypomethylation SS, underscoring potential biomarker for progression.

Язык: Английский

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Updating on the Dual Role of Salivary Gland Epithelial Cell (SGEC) in Sjögren’s Disease

Journal of Inflammation Research, Год журнала: 2025, Номер Volume 18, С. 3039 - 3053

Опубликована: Фев. 28, 2025

Sjögren's disease, an autoimmune inflammatory currently lacks effective treatment options. The salivary gland, a crucial exocrine organ responsible for saliva production and local immune responses on mucous membranes, is frequently impaired in individuals with disease. Restoring gland function poses significant challenge researchers. Salivary epithelial cells, recognized as pivotal components of the have been increasingly implicated key initiators inflammation exhibit innate cell-like properties. On whole, SGEC plays protective role physiological state, can also participate persistence initiating factor pathological state. In review, we explore interplay between Ca+, endoplasmic reticulum (ER), mitochondrial homeostasis imbalance cells. Additionally, provide overview current literature research advancements related to Pattern Recognition Receptors (PRRs), programmed cell death, posttranslational modification (PTM), oral microecology, etc. specifically focusing their implications Given cells onset based may potential alleviate condition by addressing response glands.

Язык: Английский

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miRNA let-7f-5p-encapsulated labial gland MSC-derived EVs ameliorate experimental Sjögren’s syndrome by suppressing Th17 cells via targeting RORC/IL-17A signaling axis

Journal of Nanobiotechnology, Год журнала: 2025, Номер 23(1)

Опубликована: Март 20, 2025

Sjögren's syndrome (SS) is an autoimmune disease primarily affecting salivary glands, with xerostomia as a distinct clinical manifestation. This also poses significantly increased risk of lymphoma, severely impacting patients' quality life. The imbalance between Th17 and Treg cells plays critical role in SS progression, driving severe immune dysregulation, chronic inflammation, escalating tissue dysfunction. However, current treatments for still remain limited, it continues to be recognized refractory disease. Therefore, the development novel effective therapeutic strategies pressing demand research. In recent years, extracellular vesicle (EV) therapy has emerged promising approach treatment, showing encouraging outcomes modulating balance alleviating symptoms. EVs carry diverse cargo, among which microRNAs (miRNAs) are highly abundant play roles. These small RNAs essential EV-mediated functions, particularly regulating gene expression microenvironment. Our research team first isolated labial gland mesenchymal stem (LGMSCs) their derived (LGMSC-EVs), offer potential advantages due origin. Then we screened identified enriched miRNA let-7f-5p key regulator through profiling analysis. To achieve better outcomes, transfected exogenous into LGMSC-EVs upregulate its expression, thereby constructing let-7f-5p-encapsulated LGMSC-EVs. modified were subsequently tested experimental mouse model evaluate potential. upregulation enhanced effects, resulting improvements such flow reduced lymphocytic infiltration. Mechanistically, suppressed by directly targeting 3'-untranslated region (3'UTR) RORC, inhibiting RORC/IL-17A signaling axis, reducing IL-17A production, restoring Th17/Treg promoting anti-inflammatory profile. Collectively, this LGMSC-EV offers target-driven treatment SS, achieving improved rebalance after modification let-7f-5p, presents new SS.

Язык: Английский

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Targeting the Neonatal Fc Receptor in Autoimmune Diseases: Pipeline and Progress

BioDrugs, Год журнала: 2025, Номер unknown

Опубликована: Март 29, 2025

Язык: Английский

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Case Report: A case of membranous nephropathy associated with primary Sjögren’s syndrome treated with telitacicept

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Апрель 11, 2025

Primary Sjögren’s syndrome (pSS) is an autoimmune disease that often affects the exocrine glands. However, pSS can also affect kidneys, most commonly involving kidney interstitium. Recent studies have demonstrated some membranous nephropathy (MN) cases are associated with syndrome. unified recommendations for selecting immunosuppressive agents treating MN currently lacking. In case reported herein, a patient experienced improvement following methylprednisolone and telitacicept treatment.

Язык: Английский

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PANoptosis in autoimmune diseases interplay between apoptosis, necrosis, and pyroptosis

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Окт. 31, 2024

PANoptosis is a newly identified inflammatory programmed cell death (PCD) that involves the interplay of apoptosis, necrosis, and pyroptosis. However, its overall biological effects cannot be attributed to any one type PCD alone. regulated by signaling cascade triggered recognition pathogen-associated molecular patterns (PAMPs) damage-associated (DAMPs) various sensors. This triggers assembly PANoptosome, which integrates key components from other pathways via adapters ultimately activates downstream execution molecules, resulting in with necrotic, apoptotic, pyroptotic features. Autoimmune diseases are characterized reduced immune tolerance self-antigens, leading abnormal responses, often accompanied systemic chronic inflammation. Consequently, PANoptosis, as unique innate immune-inflammatory pathway, has significant pathophysiological relevance inflammation autoimmunity. most previous research on focused tumors infectious diseases, leaving activation role autoimmune unclear. review briefly outlines characteristics summarizes several PANoptosome complexes, their mechanisms, components. We also explored dual potential therapeutic approaches targeting PANoptosis. Additionally, we existing evidence for explore regulatory mechanisms involved.

Язык: Английский

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Age-Associated B Cells in Autoimmune Diseases: Pathogenesis and Clinical Implications

Clinical Reviews in Allergy & Immunology, Год журнала: 2025, Номер 68(1)

Опубликована: Фев. 17, 2025

Abstract As a heterogeneous B cell subset, age-associated cells (ABCs) exhibit distinct transcription profiles, extrafollicular differentiation processes, and multiple functions in autoimmunity. TLR7 TLR9 signals, along with IFN-γ IL-21 stimulation, are both essential for ABC differentiation, which is also regulated by chemokine receptors including CXCR3 CCR2 integrins CD11b CD11c. Given their antigen uptake presentation, autoantibody proinflammatory cytokine secretion, T helper activation, ABCs display potential the prognosis, diagnosis, therapy autoimmune diseases, systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome, sclerosis, neuromyelitis optica spectrum disorders, ankylosing spondylitis. Specifically targeting inhibiting T-bet CD11c activating ARA2 represents therapeutic strategies SLE RA. Although single-cell sequencing technologies have recently revealed characteristics of ABCs, further investigations to explore validate ABC-target therapies still warranted.

Язык: Английский

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Spatial transcriptomics in autoimmune rheumatic disease: potential clinical applications and perspectives

Inflammation and Regeneration, Год журнала: 2025, Номер 45(1)

Опубликована: Фев. 20, 2025

Spatial transcriptomics is a cutting-edge technology that analyzes gene expression at the cellular level within tissues while integrating spatial location information. This concept, which combines high-plex RNA sequencing with data, emerged in early 2010s. has rapidly expanded development of technologies such as situ hybridization, sequencing, barcoding, and microdissection-based methods. Each technique offers advanced mapping resolution precise assessments single-cell level. Over past decade, use on clinical samples enabled researchers to identify expressions specific diseased foci, significantly enhancing our understanding interactions disease processes. In field rheumatology, complex elusive pathophysiology diseases rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome remains challenge for personalized treatment. provides insights into how different cell populations interact synovial tissue, kidneys, salivary glands. review summarizes current autoimmune rheumatic diseases, focusing immune distribution tissues. We also explore potential from perspective discuss possibilities translating this bedside.

Язык: Английский

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