Quantitative assessment of interstitial lung disease in Sjögren’s syndrome

PLoS ONE, Год журнала: 2019, Номер 14(11), С. e0224772 - e0224772

Опубликована: Ноя. 8, 2019

Interstitial lung disease (ILD) is a frequent manifestation of Sjögren's syndrome (SS), an autoimmune salivary and lacrimal glands, affects approximately 20% patients. No clinical or serological features appear to be useful predict its presence, severity progression, chest high-resolution computed tomography (CT) remains the gold standard for diagnosis. Semiquantitative CT (SQCT) based on visual assessment (Goh Taouli scoring) can estimate ILD extent, although it burdened by relevant intra- interobserver variability. Quantitative (QCT) promising alternative modality assess severity.To determine whether QCT identify extensive limited in patients with SS ILD.This multi-center, cross-sectional retrospective study enrolled scan. SQCT was carried out blinded centralized manner calculate both Goh scores. An operator-independent analysis all scans open-source software platform Horos used evaluate indices. Patients were classified according extent differences index distribution investigated non-parametric tests.From total 102 consecutive SS, prevalence 35.3% (36/102). There statistically significant difference between without groups (p<0.001). Moreover, SS-ILD >20% (by score) had different from those Finally, indices showed moderate-to-good correlation scores (from 0.44 0.65; p<0.001).QCT discriminate lesser greater disease.

Язык: Английский

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Management of Sjögren's Syndrome: Present Issues and Future Perspectives

Frontiers in Medicine, Год журнала: 2021, Номер 8

Опубликована: Июнь 7, 2021

In view of the new possibilities for treatment primary Sjögren's syndrome (pSS) given by availability biotechnological agents targeting various molecular and cellular actors pathological process disease, classification criteria aimed at selecting patients to be enrolled in therapeutic trials, validated outcome measures used as response these therapies, have been developed last decades. Unfortunately, trials so far completed with treatments yielded unsatisfactory or only partially positive results. The main issues that evoked justify poor results attempts are: (i) extreme variability disease phenotypes which are dependent on different underlying patterns biological mechanisms, (ii) fact has a long indolent course, most might already irreversible clinical features. advances research biomarkers can better distinguish diagnose an earlier phase also discussed.

Язык: Английский

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C1q/tumor necrosis factor‐related protein‐6 attenuates TNF‐α‐induced apoptosis in salivary acinar cells via AMPK/SIRT1‐modulated miR‐34a‐5p expression

Journal of Cellular Physiology, Год журнала: 2021, Номер 236(8), С. 5785 - 5800

Опубликована: Янв. 5, 2021

Abstract C1q/tumor necrosis factor‐related protein‐6 (CTRP6) is a newly identified adipokine involved in diverse biological processes. However, its role salivary glands remains unknown. Here, we demonstrated that CTRP6 was mainly distributed the nuclei, apicolateral membranes, and cytoplasm of human submandibular (SMGs), serous cells parotid glands, ducts membranes rats mice. inhibited apoptosis rate reversed increased levels cleaved caspase 3, 8, 9, cytochrome C decreased Bcl‐2 expression induced by tumor factor (TNF)‐α both SMG‐C6 cultured SMG tissues. Microarray analysis 43 differentially expressed microRNAs (miRNAs) SMGs nonobese diabetic miR‐34a‐5p selected due to upregulation TNF‐α, which abolished CTRP6. The inhibitor promoted whereas mimic suppressed effects on TNF‐α‐induced apoptosis. AMP‐activated protein kinase (AMPK) phosphorylation SIRT1 downregulation cells. AraA, an AMPK inhibitor, alterations SIRT1, miR‐34a‐5p, Bcl‐2, 3 vitro ex vivo, activating AICAR decrease increase TNF‐α. Inhibition EX527 changes apoptosis‐related proteins. Our findings indicate are novel sites for synthesis secretion. protects acinar against via AMPK/SIRT1‐modulated expression.

Язык: Английский

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Serum microRNA Levels in Diabetes Mellitus

Diagnostics, Год журнала: 2021, Номер 11(2), С. 284 - 284

Опубликована: Фев. 11, 2021

The aim of our study is to evaluate the serum circulating levels some miRNA, such as hsa-let-7b-5p, hsa-let-7a-5p, hsa-miR-320b, hsa-miR-23a-3p, hsa-miR-27a-3p, hsa-miR-15a-5p, and hsa-miR-495-3, in diabetic patients without retinopathy (DR), with DR, and, healthy subjects order find reliable reproducible biomarkers for DR. A total 45 underwent sampling miRNAs evaluation a complete ophthalmologic examination, including microperimetry widefield swept source optical coherence tomography angiography (OCTA). Total RNA was isolated from using miRNeasy Serum/Plasma Kit. Serum miRNA expression were significantly different three groups. In detail, hsa-miR-15a-5p reduced both DR (p = 0.027). hsa-miR-495-3p lower 0.049). Hsa-miR-23a-3p 0.013). Significant associations anatomical/perfusion parameters functional observed We evidence damage progression that are evidently early diabetes considered have strong potential novel biomarker detection suffering could represent noninvasive target therapies block disease at stages.

Язык: Английский

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Role of ncRNAs in the Pathogenesis of Sjögren’s Syndrome

Biomedicines, Год журнала: 2024, Номер 12(7), С. 1540 - 1540

Опубликована: Июль 11, 2024

Sjögren’s syndrome is a multisystemic autoimmune disease that mainly affects the exocrine glands, causing dryness of eyes and mouth as principal symptoms. Non-coding RNAs (ncRNAs), once regarded genomic “junk”, are now appreciated important molecular regulators gene expression, not least in other diseases. Here we review research into causative roles microRNAs (miRNAs), long non-coding (lncRNAs), circular (circRNAs) on immunological responses, inflammation, salivary gland epithelial cell function patients. These ncRNAs represent promising new therapeutic targets for treating possibly biomarkers early diagnosis.

Язык: Английский

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Non-coding RNAs – A primer for the laboratory scientist

British Journal of Biomedical Science, Год журнала: 2019, Номер 76(4), С. 157 - 165

Опубликована: Окт. 2, 2019

Advances in molecular genetics have identified several species of RNA that fail to translate – hence the non-coding RNAs. The two major groups within this class nucleic acids are microRNAs (miRNA) and long RNAs (lncRNA). There is growing body evidence supporting view these molecules regulatory effect on both DNA RNA. objective brief review explain genetic molecules, summarize their potential as mediators disease, highlight value diagnostic markers tools disease management.

Язык: Английский

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Small RNA Expression Profiling Reveals hsa-miR-181d-5p Downregulation Associated With TNF-α Overexpression in Sjögren’s Syndrome Patients

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Апрель 1, 2022

MicroRNAs (miRNAs) are small non-coding RNAs (sRNA), that alter gene expression by binding to target messenger (mRNAs) and repressing translation. Dysregulated miRNA has been implicated in the pathogenesis of autoimmune diseases such as Sjögren’s syndrome (SS). The aim this study was characterize global profile sRNAs labial salivary glands (LSG) from SS-patients validate potential candidates glandular inflammation. LSG 21 9 sicca controls were analyzed. A next generation sequencing (NGS)-based sRNA profiling approach employed identify direct targets whereby differentially expressed miRNAs predicted using bioinformatics tools. levels validated TaqMan mRNA determined quantitative real-time PCR. We also performed vitro assays recombinant TNF-α. NGS shows ~30% miRNAs. In comparison with samples controls, four found low focus score (LFS) 18 high (HFS). most significant changes identified hsa-miR-181d-5p downregulation confirmed analysis. Levels TNF-α mRNA, a hsa-miR-181d-5p, significantly increased negatively correlated presence. Moreover, positive correlations between transcript levels, score, ESSDAI, autoantibody detected. Furthermore, stimulation decreased . Downregulation could contribute pro-inflammatory environment deregulation its Further dissection pathophysiological mechanisms underlying hsa-miR-181d-5p-mediated action inflammatory conditions be useful evaluate benefits increasing for restoration gland epithelial cell architecture function.

Язык: Английский

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Distinct microRNA expression profiles in saliva and salivary gland tissue differentiate patients with primary Sjögren's syndrome from non‐Sjögren's sicca patients

Journal of Oral Pathology and Medicine, Год журнала: 2020, Номер 49(10), С. 1044 - 1052

Опубликована: Авг. 16, 2020

Abstract Objectives Increasing evidence suggests that aberrant expression of microRNAs (miRNAs) is involved in the pathogenesis primary Sjögren's syndrome (pSS). The aim was thus to characterize miRNA profile saliva, salivary gland tissue, and plasma from patients with pSS compare findings those having Sjögren‐like disease (non‐pSS). In addition, correlate levels clinicopathological features pSS. Methods real‐time quantitative polymerase chain reaction performed on plasma, tissue samples 24 16 non‐pSS 384‐well plates. T test used for comparison profiles, followed by Benjamini‐Hochberg correction. discriminatory power miRNAs evaluated receiver‐operating characteristic curves, Pearson/Spearman correlation analyses. Results 14 were significantly differentially expressed between non‐pSS, including downregulation miR‐17 family pSS, miR‐29a‐3p upregulated. Plasma did not differ two groups, although tended be downregulated. combination miR‐17‐5p let‐7i‐5p saliva yielded an area under curve 97% (CI 92%‐100%). Several correlated one another flow rates histopathology. Conclusion Our indicate may enable discriminate patients. However, further validation larger cohorts needed as well functional analyses interest.

Язык: Английский

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MicroRNAs in Ocular Infection

Microorganisms, Год журнала: 2019, Номер 7(9), С. 359 - 359

Опубликована: Сен. 17, 2019

MicroRNAs (miRNAs) are small, non-coding, regulatory RNA molecules and constitute a newly recognized, important layer of gene-expression regulation at post-transcriptional levels. miRNAs quantitatively fine tune the expression their downstream genes in cell type- developmental stage-specific fashion. have been proven to play roles normal development function as well pathogenesis diseases all tissues organ systems. emerged new therapeutic targets biomarkers for treatment diagnosis various diseases. Although miRNA research ocular infection remains its early stages, handful pioneering studies provided insight into parasitic, fungal, bacterial, viral infections. Here, we review current status several major infectious We predict that field will greatly expand with discovery novel miRNA-involved molecular mechanisms inform therapies identify diagnostic biomarkers.

Язык: Английский

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MicroRNA-130a Contributes to Type-2 Classical DC-activation in Sjögren's Syndrome by Targeting Mitogen- and Stress-Activated Protein Kinase-1

Frontiers in Immunology, Год журнала: 2019, Номер 10

Опубликована: Июнь 20, 2019

Objectives: Considering the critical role of microRNAs (miRNAs) in regulation cell activation, we investigated their circulating type-2 conventional dendritic cells (cDC2s) patients with primary Sjögren's syndrome (pSS) compared to healthy controls (HC). Methods: CD1c-expressing cDC2s were isolated from peripheral blood. A discovery cohort (15 pSS, 6 HC) was used screen expression 758 miRNAs and a replication 11 confirm differential 18 identified targets. Novel targets for two replicated by SILAC HEK-293T validated cDC2s. Differences cytokine production between pSS HC evaluated intracellular flow-cytometry. cultured presence MSK1-inhibitors investigate effect on production. Results: Expression miR-130a miR-708 significantly decreased both cohorts, downregulated upon stimulation via endosomal TLRs. Upstream mediator MSK1 as novel target overexpression reduced showed higher an increased fraction IL-12 TNF-α-producing cells. MSK1-inhibition cDC2 activation IL-12, TNF-α, IL-6. Conclusions: The seems reflect activation. MSK1, which regulates pro-inflammatory production, provide proof-of-concept therapeutic avenue impede activity pSS.

Язык: Английский

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