Long Non-Coding RNAs in Sjögren's Disease.

Sjögren's disease (SjD) is a heterogeneous autoimmune disease characterized by severe dryness of mucosal surfaces, particularly the mouth and eyes; fatigue; and chronic pain. Chronic inflammation of the salivary and lacrimal glands, auto-antibody formation, and extra-glandular manifestations occur in subsets of patients with SjD. An aberrant expression of long, non-coding RNAs (lncRNAs) has been described in many autoimmune diseases, including SjD. Here, we review the current literature on lncRNAs in SjD and their role in regulating X chromosome inactivation, immune modulatory functions, and their potential as biomarkers.

Radioproteomics stratifies molecular response to antifibrotic treatment in pulmonary fibrosis.

Antifibrotic therapy with nintedanib is the clinical mainstay in the treatment of progressive fibrosing interstitial lung disease (ILD). High-dimensional medical image analysis, known as radiomics, provides quantitative insights into organ-scale pathophysiology, generating digital disease fingerprints. Here, we performed an integrative analysis of radiomic and proteomic profiles (radioproteomics) to assess whether changes in radiomic signatures can stratify the degree of antifibrotic response to nintedanib in (experimental) fibrosing ILD. Unsupervised clustering of delta radiomic profiles revealed 2 distinct imaging phenotypes in mice treated with nintedanib, contrary to conventional densitometry readouts, which showed a more uniform response. Integrative analysis of delta radiomics and proteomics demonstrated that these phenotypes reflected different treatment response states, as further evidenced on transcriptional and cellular levels. Importantly, radioproteomics signatures paralleled disease- and drug-related biological pathway activity with high specificity, including extracellular matrix (ECM) remodeling, cell cycle activity, wound healing, and metabolic activity. Evaluation of the preclinical molecular response-defining features, particularly those linked to ECM remodeling, in a cohort of nintedanib-treated fibrosing patients with ILD, accurately stratified patients based on their extent of lung function decline. In conclusion, delta radiomics has great potential to serve as a noninvasive and readily accessible surrogate of molecular response phenotypes in fibrosing ILD. This could pave the way for personalized treatment strategies and improved patient outcomes.

BRD3 Regulates the Inflammatory and Stress Response in Rheumatoid Arthritis Synovial Fibroblasts.

BACKGROUND: Individual functions of members of the bromodomain (BRD) and extra-terminal (BET) protein family underlying the anti-inflammatory effects of BET inhibitors in rheumatoid arthritis (RA) are incompletely understood. Here, we aimed to analyze the regulatory functions of BRD3, an understudied member of the BET protein family, in RA synovial fibroblasts (FLS). METHODS: BRD3 was silenced in FLS prior to stimulation with TNF. Alternatively, FLS were treated with I-BET. Transcriptomes were analyzed by RNA sequencing (RNAseq), followed by pathway enrichment analysis. We confirmed results for selective target genes by real-time PCR, ELISA, and Western blotting. RESULTS: BRD3 regulates the expression of several cytokines and chemokines in FLS, and positively correlates with inflammatory scores in the RA synovium. In addition, RNAseq pointed to a profound role of BRD3 in regulating FLS proliferation, metabolic adaption, and response to stress, including oxidative stress, and autophagy. CONCLUSIONS: BRD3 acts as an upstream regulatory factor that integrates the response to inflammatory stimuli and stress conditions in FLS and executes many functions of BET proteins that have previously been identified using pan-BET inhibitors.