Resveratrol attenuates inflammation and fibrosis in rheumatoid arthritis-associated interstitial lung disease via the AKT/TMEM175 pathway.

Background And Purpose: Interstitial lung disease (ILD) represents a significant complication of rheumatoid arthritis (RA) that lacks effective treatment options. This study aimed to investigate the intrinsic mechanism by which resveratrol attenuates rheumatoid arthritis complicated with interstitial lung disease through the AKT/TMEM175 pathway.

Methods: We established an arthritis model by combining chicken type II collagen and complete Freund's adjuvant.

Long Non-coding RNA SNHG7 Suppresses Inflammation and Apoptosis of Chondrocytes Through Inactivating of p38 MAPK Signaling Pathway in Osteoarthritis.

This study aims to explore the molecular mechanism of LncRNA SNHG7 in Osteoarthritis (OA). Cartilage tissues of OA patients or patients with trauma or amputation were collected. Compared to normal cartilage tissues, SNHG7 was downregulated while miR-324-3p was upregulated in cartilage tissues of OA patients.

Targeting Bcl-xL is a potential therapeutic strategy for extranodal NK/T cell lymphoma.

Extranodal natural killer/T cell lymphoma, nasal type (ENKTL) is an aggressive lymphoid malignancy with a poor prognosis and lacks standard treatment. Targeted therapies are urgently needed. Here we systematically investigated the druggable mechanisms through chemogenomic screening and identified that Bcl-xL-specific BH3 mimetics effectively induced ENKTL cell apoptosis.

The regulatory role and mechanism of lncTUG1 on cartilage apoptosis and inflammation in osteoarthritis.

Background: Long-stranded non-coding RNA TUG1 is lowly expressed in osteoarthritic chondrocytes. This study aimed to elucidate the role of TUG1 in osteoarthritic cartilage damage and the underlying mechanisms.

Methods: Combined database analysis, using primary chondrocytes as well as the C28/I2 cell line, was performed by qRT-PCR, Western blotting, and immunofluorescence to determine the expression of TUG1, miR-144-3p, DUSP1, and other target proteins.

PINK1/Parkin-Mediated Mitochondrial Autophagy Participates in HO-Induced Abnormal Proliferation of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis.

Introduction: To explore the role of PINK1/Parkin-mediated mitochondrial autophagy in HO-induced abnormal proliferation of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS).

Methods: Firstly, we isolated fibroblast like synoviocytes (RA-FLS) from RA patients. HO-induced oxidative stress, and NAC (a ROS inhibitor) or FCCP (a mitochondrial autophagy activator) treatment inhibited ROS level or activate mitochondrial autophagy in RA-FLS.

Resveratrol Ameliorates Fibrosis in Rheumatoid Arthritis-Associated Interstitial Lung Disease via the Autophagy-Lysosome Pathway.

Interstitial lung disease associated with rheumatoid arthritis (RA-ILD) can lead to interstitial fibrosis and even lung failure as a complication of rheumatoid arthritis (RA), and there is currently no effective treatment and related basic research. Studies have found that resveratrol (Res) can improve the progression of RA by regulating autophagy, and increasing evidence supports the connection between autophagy and common interstitial lung disease (ILD). We explored changes in autophagy levels in fibrotic lungs in RA-ILD and found that the level of autophagy is enhanced in the early stage but inhibited in the late stage.

Discovery and characterization of novel potent BCR-ABL degraders by conjugating allosteric inhibitor.

The oncogenic fusion protein BCR-ABL is the driving force of leukemogenesis in chronic myeloid leukemia (CML). Despite the great advance in CML treatment through the application of tyrosine kinase inhibitors (TKIs) against BCR-ABL, disease recurrence after TKI discontinuation and clinical resistance mainly due to BCR-ABL mutations continue to be an issue. Herein we report our efforts to synthesize a novel series of CRBN-recruiting proteolysis-targeting chimeras (PROTACs) targeting BCR-ABL based on the allosteric inhibitor asciminib.

The role of resveratrol on rheumatoid arthritis: From bench to bedside.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by symmetrical polyarthritis as its main clinical manifestation. Uncontrolled RA eventually leads to joint deformities and loss of function. Currently, the pathogenesis of RA remains under discussion, and RA treatment is still at the bottleneck stage.

Discovery of novel BCR-ABL PROTACs based on the cereblon E3 ligase design, synthesis, and biological evaluation.

Protein degradation is a promising strategy for drug development. Proteolysis-targeting chimeras (PROTACs) hijacking the E3 ligase cereblon (CRBN) exhibit enormous potential and universal degradation performance due to the small molecular weight of CRBN ligands. In this study, the CRBN-recruiting PROTACs were explored on the degradation of oncogenic fusion protein BCR-ABL, which drives the pathogenesis of chronic myeloid leukemia (CML).

Discovery of SIAIS178 as an Effective BCR-ABL Degrader by Recruiting Von Hippel-Lindau (VHL) E3 Ubiquitin Ligase.

The oncogenic fusion protein BCR-ABL is the driving force of leukemogenesis in chronic myeloid leukemia (CML). Despite great progress for CML treatment through application of tyrosine kinase inhibitors (TKIs) against BCR-ABL, long-term drug administration and clinical resistance continue to be an issue. Herein, we described the design, synthesis, and evaluation of novel proteolysis-targeting chimeric (PROTAC) small molecules targeting BCR-ABL which connect dasatinib and VHL E3 ubiquitin ligase ligand by extensive optimization of linkers.