Genetics and epigenetics of primary Sjögren syndrome: implications for future therapies

Nature Reviews Rheumatology, Год журнала: 2023, Номер 19(5), С. 288 - 306

Опубликована: Март 13, 2023

Язык: Английский

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Down-regulated miR-146a expression with increased neutrophil extracellular traps and apoptosis formation in autoimmune-mediated diffuse alveolar hemorrhage

Journal of Biomedical Science, Год журнала: 2022, Номер 29(1)

Опубликована: Авг. 26, 2022

Increasing evidences have suggested an important role of microRNAs (miRNAs) in regulating cell death processes including NETosis and apoptosis. Dysregulated expression miRNAs increased formation neutrophil extracellular traps (NETs) apoptosis participate autoimmune-mediated diffuse alveolar hemorrhage (DAH), mostly associated with pulmonary capillaritis systemic lupus erythematosus (SLE) patients. In particular, besides the inhibition apoptosis, miR-146a can control innate acquired immune responses, regulate toll-like receptor pathway through targeting TRAF6 to reduce pro-inflammatory cytokines/chemokines like IL-8, a inducer.Expression miR-146a, NETs were examined peripheral blood neutrophils (PBNs) lung tissues from SLE-associated DAH patients, pristane-induced C57BL/6 mice. To assess formation, we NETosis-related DNAs morphology crucial mediators protein arginine deiminase 4 citrullinated Histone 3. Expression its endogenous RNA SNHG16 studied HL-60 promyelocytic cells MLE-12 during processes, respectively. MiR-146a-overexpressed CRISPR-Cas13d-mediated SNHG16-silenced investigated for NETosis. analyzed Pristane-injected mice received intra-pulmonary delivery evaluate therapeutic efficacy DAH.In there down-regulated levels PMA/LPS-induced PBNs, TRAF6, high-mobility group box 1 (HMGB1), tissues. HMGB1-stimulated mouse had IL-8 expression. PMA-stimulated enhanced or showed reduced Apoptotic HMGB1 release, while miR-146a-overexpressed production. There HMGB1, Intra-pulmonary could suppress by reducing expression.Our results demonstrate firstly DAH, implicate potential delivery.

Язык: Английский

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The complex effects of miR-146a in the pathogenesis of Alzheimer’s disease

Neural Regeneration Research, Год журнала: 2024, Номер 20(5), С. 1309 - 1323

Опубликована: Июнь 3, 2024

Alzheimer’s disease is a neurodegenerative disorder characterized by cognitive dysfunction and behavioral abnormalities. Neuroinflammatory plaques formed through the extracellular deposition of amyloid-β proteins, as well neurofibrillary tangles intracellular hyperphosphorylated tau comprise two typical pathological features disease. Besides symptomatic treatment, there are no effective therapies for delaying progression. MicroRNAs (miR) small, non-coding RNAs that negatively regulate gene expression at transcriptional translational levels play important roles in multiple physiological processes. Indeed, miR-146a , NF-κB-regulated gene, has been extensively implicated development several pathways. Research demonstrated substantial dysregulation both during initial phases throughout progression this disorder. MiR-146a believed to reduce protein hyperphosphorylation TLR/IRAK1/TRAF6 pathway; however, also evidence supporting it can promote these processes many other pathways, thus exacerbating manifestations It widely reported mediates synaptic dysfunction, mitochondrial neuronal death targeting mRNAs encoding synaptic-related mitochondrial-related membrane mRNAs. Regarding impact on glial cells, exhibits differential effects. On one hand, causes widespread sustained inflammation certain while reverse polarization astrocytes microglia, alleviate neuroinflammation, oligodendrocyte progenitor cell differentiation, maintaining normal function myelin sheath exerting protective effect neurons. In review, we provide comprehensive analysis involvement pathogenesis We aim elucidate relationship between key disease, such deposition, hyperphosphorylation, death, summarize recent relevant studies have highlighted potential clinical diagnostic marker therapeutic target

Язык: Английский

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The hijacking of HBV by small extracellular vesicles inhibits M1 macrophages to facilitate immune evasion

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Авг. 27, 2024

Small extracellular vesicles (sEVs) have the ability to transfer genetic material between cells, but their role in mediating HBV infection and regulating M1 macrophages promote immune evasion remains unclear. In this study, we utilized PMA + LPS IFN-γ induce THP-1 into macrophages. We then extracted sEVs from HepG2.2.15 cell treated with these sEVs. QPCR detection revealed presence of HBV-DNA Additionally, RT-qPCR WB analysis demonstrated a significantly decreased expression TLR4, NLRP3, pro-caspase-1, caspase-1p20, IL-1β IL-18 (P < 0.05). Furthermore, results displayed high levels that miR-146a FEN-1 derived cells 0.01). RT -qPCR showed enhanced or through 0.05), while simultaneously reducing summary, our findings indicate loaded inhibit inflammatory function escape. present play crucial process.

Язык: Английский

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Extracellular Vesicles Derived From Lipopolysaccharide‐Challenged Gingival Fibroblast Reveal Distinct miRNA Expression Patterns Associated With Reduced Cancer Survival

Clinical and Experimental Dental Research, Год журнала: 2025, Номер 11(1)

Опубликована: Фев. 1, 2025

ABSTRACT Objectives Periodontitis is a prevalent inflammatory disease with established systemic implications. Extracellular vesicles (EVs) have emerged as key mediators of intercellular communication, potentially linking periodontitis to diseases. However, the molecular cargo EVs from inflamed periodontal cells remains poorly characterized. This study investigates EV human gingival fibroblasts (hGF‐hTERT) following lipopolysaccharide (LPS) stimulation and explores their potential role in cancer progression. Materials Methods were isolated LPS‐treated untreated via ultracentrifugation. Dynamic light scattering scanning electron microscopy characterized size morphology. RNA sequencing identified differentially expressed miRNAs, validated by qPCR. Functional pathway enrichment in‐silico analyses using The Cancer Genome Atlas (TCGA) performed assess EV‐associated miRNA impact on tumorigenesis. Results concentration remained unchanged after LPS stimulation. LPS‐derived exhibited 2.6‐fold increase content, three significantly upregulated miRNAs: miR‐146a‐5p, miR‐486‐5p, miR‐451a. analysis revealed involvement inflammation, immune modulation, pathways. In vitro, enhanced prostate (LnCap) cell proliferation. TCGA linked miRNAs poor prognosis. Conclusions alters fibroblast‐derived EVs, enhancing pathways associated inflammation These findings suggest mechanistic for pathogenesis, warranting further investigation into diagnostic therapeutic potential.

Язык: Английский

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Integrative miRNA-mRNA profiling uncovers mechanisms of belimumab action in systemic lupus erythematosus

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Март 14, 2025

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder driven by autoreactive B cells and characterized the production of pathogenic autoantibodies. Belimumab, an anti-BAFF monoclonal antibody, has demonstrated efficacy in reducing disease activity corticosteroid use SLE patients, although responses remain variable. B-cell activating factor (BAFF) essential for cell survival autoantibody production, positioning it as key target pathogenesis. MicroRNAs (miRNAs), critical regulators gene expression immune homeostasis, have emerging role pathophysiology. However, their regulation response to therapies, such belimumab, remains unexplored. This study investigates miRNA-mRNA interactions T cells, myeloid from patients before after belimumab treatment. A total 79 miRNAs associated with treatment 525 miRNA-gene were identified. Validation 18 responders revealed significant changes miRNA but not cells. Belimumab was found modulate development regulating genes BLNK, BANK1, MEF2C, well CD40/CD40L axis. In influenced interferon signaling inflammatory cytokines via NF-κB activation. Changes downregulation KLF13, CCL5, IL4, appear be secondary modulation. These findings provide novel insights into miRNA-mediated regulatory networks underlying belimumab's immunomodulatory effects SLE. Further research required validate these through vitro experiments better understand guiding responses.

Язык: Английский

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Biomarker Identification in Patients with Multiple Sclerosis Treated with Autologous Hematopoietic Stem Cell Transplantation

Sclerosis, Год журнала: 2025, Номер 3(2), С. 9 - 9

Опубликована: Март 29, 2025

Introduction: Approximately 80% of individuals with multiple sclerosis (MS) have a positive response to autologous hematopoietic stem cell transplantation (aHSCT). Markers that may predict the transplant outcome are necessary. The objective this work is identify markers refine selection patients who could benefit from aHSCT. Methods: We evaluated levels six biomarkers in peripheral blood MS before design study cross-sectional; were divided into two transplant-responses-at-12-months groups, responders (ΔEDSS < 0) and non-responders > 0). Pre-transplant samples used assess different markers. Results: Thirty-four enrolled: fourteen twenty Among biomarkers, significant difference was only detected miR-146a levels, increased values non-responder group. Conclusions: biomarker miR146a be useful evaluate aHSCT MS.

Язык: Английский

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Cytokine storm in the pathophysiology of COVID-19: Possible functional disturbances of miRNAs

International Immunopharmacology, Год журнала: 2021, Номер 101, С. 108172 - 108172

Опубликована: Сен. 21, 2021

Язык: Английский

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CNP-miR146a improves outcomes in a two-hit acute- and ventilator-induced lung injury model

Nanomedicine Nanotechnology Biology and Medicine, Год журнала: 2023, Номер 50, С. 102679 - 102679

Опубликована: Апрель 26, 2023

Язык: Английский

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MicroRNAs in autoimmune thyroid diseases and their role as biomarkers

Best Practice & Research Clinical Endocrinology & Metabolism, Год журнала: 2023, Номер 37(2), С. 101741 - 101741

Опубликована: Фев. 8, 2023

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the posttranscriptional level. They emerging as potential biomarkers and therapeutic targets for several diseases including autoimmune thyroid (AITD). control a wide range of biological phenomena, immune activation, apoptosis, differentiation development, proliferation metabolism. This function makes miRNAs attractive disease biomarker candidates or even agents. Because their stability reproducibility circulating have been an interesting area research in many diseases, studies describing role response progressively developed. The mechanisms underlying AITD remain elusive. pathogenesis is characterized by multifactorial interplay based on synergy between susceptibility genes environmental stimulation, together with epigenetic modulation. Understanding regulatory could lead to identify pathways, diagnostic this disease. Herein we update our present knowledge microRNAs discuss importance possible prognostic most prevalent AITDs: Hashimoto's thyroiditis (HT), Graves' (GD) Ophthalmopathy (GO). review provides overview state art pathological roles well novel miRNA-based approaches AITD.

Язык: Английский

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