Lysine succinylation analysis reveals the effect of on synovial fibroblasts in rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is an autoimmune disease with complex etiology, and its pathological mechanism remains unclear. Our aim was to explore the effect of protein succinylation on RA by silencing , sequencing succinylated proteins, and analyzing the sequencing results to identify potential biomarkers. We wanted to gain a clearer understanding of RA pathogenesis, quantitative assessment of succinylated proteins in Fibroblast-like synoviocytes (FLS) from RA patients using liquid chromatography- tandem mass spectrometry and enrichment analysis investigated using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG).

Evaluation of F-FAPI-04 Imaging in Assessing the Therapeutic Response of Rheumatoid Arthritis.

Purpose: Fibroblast activating protein (FAP) is highly expressed in the synovial tissues of rheumatoid arthritis (RA) patients. The aim of this study was to determine the feasibility of PET imaging with an Al[F] F-NOTA-labeled FAP inhibitor 04(F-FAPI-04) for the evaluation of arthritic progression and therapeutic response in experimental arthritis.

Methods: Fibroblast-like synoviocytes (FLSs) were obtained from patients with RA or osteoarthritis (OA), and the relationship between F-FAPI-04 uptake and the inflammatory activity of RA FLSs was investigated.

Telotristat Etiprate alleviates rheumatoid arthritis by targeting LGALS3 and affecting MAPK signaling.

Rheumatoid arthritis (RA) is one of the most widespread chronic immune-mediated inflammatory diseases characterized by continuous erosion of bone and cartilage by synovial hyperplasia. Telotristat Etiprate is an inhibitor of tryptophan hydroxylase, a rate-limiting enzyme in the biosynthesis of serotonin. Telotristat Etiprate can be used in the treatment of carcinoid syndrome.

ATF6α contributes to rheumatoid arthritis by inducing inflammatory cytokine production and apoptosis resistance.

Objective: The contribution of activating transcription factor 6α (ATF6α) in rheumatoid arthritis (RA) pathogenesis, especially on fibroblast-like synoviocytes (FLSs), has been suggested by its sensitivity to inflammatory stimulus. However, the exact role and therapeutic potential of ATF6α in RA remains to be fully elucidated.

Methods: ATF6α expression was determined in joint tissues and FLS, and gain-of-function and loss-of-function analyses were applied to evaluate the biological roles of ATF6α in RA FLSs.

Modulates Leaf Rolling by Regulating Accumulation of MicroRNAs Related to Leaf Development in Rice.

As an important agronomic trait in rice (), moderate leaf rolling helps to maintain the erectness of leaves and minimize shadowing between leaves, leading to improved photosynthetic efficiency and grain yield. However, the molecular mechanisms underlying rice leaf rolling still need to be elucidated. Here, we isolated a rice mutant, , showing adaxially rolled leaf phenotype due to decreased number and size of bulliform cells.

PET imaging to assess fibroblast activation protein inhibitor biodistribution: A training program adapted to pharmacology education.

In the process of pharmacology education, practical teaching is an important complement to theoretical teaching. These activities include the use of experimental animals to obtain certain pharmacological parameters or to help students understand certain classical concepts. However, the growing interest in laboratory animal welfare, the rapid development of pharmacology research and the challenges of cultivating innovative pharmacy talent create a need for innovative and flexible in vitro experiments for teaching purposes.

Renal Abscess Caused by Crizotinib: A Rare Case Report.

Crizotinib is a tyrosine kinase inhibitor that has been found to be effective in the treatment of c-ros oncogene 1-positive non-small cell lung cancer. Although this targeted agent for treating cancer has shown superiority to standard chemotherapy in some ways, this drug has adverse effects, such as the development of renal abscesses. Some associated renal damage may disappear with crizotinib withdrawal.

Investigation into the correlation between humanistic care ability and emotional intelligence of hospital staff.

Background: There are different degrees of flaws in the knowledge structure of humanistic medicine of medical staff. The level of emotional intelligence of medical staff affects their career development as well as their relationship with patients. Currently, the research on humanistic care ability (HCA) and emotional intelligence of medical staff in China and other countries is rare.

Preclinical evaluation and pilot clinical study of [F]AlF-NOTA-FAPI-04 for PET imaging of rheumatoid arthritis.

Purpose: Fibroblast-like synoviocytes (FLSs) are key effector cells in the inflamed joints of patients with rheumatoid arthritis (RA). Previous studies have suggested that fibroblast activation protein (FAP) is highly expressed in RA-derived FLSs and is a specific marker of activated RA FLSs. In this study, we developed aluminum-[F]-labeled 1,4,7-triazacyclononane-N,N',N″-triacetic acid-conjugated FAP inhibitor 04 ([F]AlF-NOTA-FAPI-04) to image RA-FLSs in vitro and arthritic joints in collagen-induced arthritis (CIA) mice and RA patients.

Euphorbia factor L3 ameliorates rheumatoid arthritis by suppressing the inflammatory response by targeting Rac family small GTPase 1.

Euphorbia factor L3 (EFL3) is extracted from and is known for its anti-inflammatory properties. This study focused on the potential anti-inflammatory and therapeutic effects of EFL3 on rheumatoid arthritis (RA) using fibroblast-like synoviocytes (FLSs) and arthritis animal models. Functional analysis showed that EFL3 could ameliorate the inflammatory phenotype of FLSs derived from RA patients, as evidenced by the decreases in cell viability, migration, invasion and cytokine production.

ATF6α promotes prostate cancer progression by enhancing PLA2G4A-mediated arachidonic acid metabolism and protecting tumor cells against ferroptosis.

Background: Despite the clinical success of androgen receptor (AR)-targeted therapies, prostate cancer (PCa) inevitably progresses to castration-resistant prostate cancer (CRPC). Transcription factor 6 α (ATF6α), an effector of the unfolded protein response (UPR) that modulates the cellular response to endoplasmic reticulum (ER) stress, has been linked to tumor development, metastasis, and relapse. However, the role of ATF6α in CRPC remains unclear.

Azithromycin alleviates the severity of rheumatoid arthritis by targeting the unfolded protein response component of glucose-regulated protein 78 (GRP78).

Background And Purpose: Azithromycin is a macrolide antibiotic with anti-inflammatory properties. We aim to substantiate the treatment potential of azithromycin in rheumatoid arthritis.

Experimental Approach: Gene expression profiles were collected by RNA sequencing and the effects of azithromycin were assessed by in vitro and in vivo assays on the effects of azithromycin-mediated blockade of glucose-regulated protein 78 (GRP78).

IL13Rα1 prevents a castration resistant phenotype of prostate cancer by targeting hexokinase 2 for ubiquitin-mediated degradation.

Objective: Androgen deprivation therapy (ADT) is still the principal treatment option for prostate cancer (PCa). In addition to reactivation of androgen receptor signaling, the resistance of PCa to apoptosis during ADT also contributes to castration resistant PCa (CRPC). A previous study reported that gene transfer of IL-13Rα2 into PCa cells sensitized the cells to the IL-13R-targeted cytotoxin IL13Rα1, leading to apoptosis.

Immunopathogenic mechanisms of rheumatoid arthritis and the use of anti-inflammatory drugs.

Rheumatoid arthritis (RA) is a chronic, progressive autoimmune disease characterized by synovitis and symmetrical joint destruction. RA has become one of the key diseases endangering human health, but its etiology is not clear. Therefore, identifying the immunopathogenic mechanisms of RA and developing therapeutic drugs to treat autoimmune diseases have always been difficult.

The E2F transcription factor 2: What do we know?

E2F transcription factor 2 (E2F2) is a member of the E2F family of transcription factors. The classical view is that some E2Fs act as "activators" and others "inhibitors" of cell cycle gene expression. However, the so-called "activator" E2F2 is particularly enigmatic, with seemingly contradictory roles in the cell cycle, proliferation, apoptosis, inflammation, and cell migration and invasion.

ChIP-sequencing analysis of E2F transcription factor 2 reveals its role in various biological processes of rheumatoid arthritis synovial fibroblasts.

The development and progression of rheumatoid arthritis (RA) are complex and the pathogenesis of this disease is not fully understood. E2F transcription factor 2 (E2F2) affects the development and progression of many diseases. To identify the mechanisms underlying the role of E2F2 in RA, chromatin immunoprecipitation was performed followed by sequencing (ChIP-seq) using the E2F2 antibody.

Microbial community in Chinese traditional fermented acid rice soup (rice-acid) and its correlations with key organic acids and volatile compounds.

Rice-acid is a unique Chinese traditional fermented acid rice soup and its microbial community plays an important role in the formation of flavour compounds. In the study, rice-acid products from high-temperature and low-temperature fermentation methods were selected to analyze the microbial community, organic acids, and volatile flavour compounds (VFCs). The main bacterial and fungal phyla in Chinese traditional fermented rice-acid were determined to be Firmicutes and Ascomycota, including 62 bacterial genera and 57 fungal genera.

IL13Rα1 protects against rheumatoid arthritis by combating the apoptotic resistance of fibroblast-like synoviocytes.

Background: Endoplasmic reticulum (ER) stress is closely related with the pathological progression of rheumatoid arthritis (RA), and fibroblast-like synoviocytes (FLSs) are known as its resistance against ER stress-induced apoptosis. Studies on overcoming such resistance would provide a novel treatment strategy for RA in a clinical setting.

Methods: IL13Rα1 expression was assessed in the synovial tissue by RT-qPCR, immunohistology, and Western blot.

TXNDC5 protects synovial fibroblasts of rheumatoid arthritis from the detrimental effects of endoplasmic reticulum stress.

TXNDC5 is an endoplasmic reticulum (ER)-resident chaperone that protects the endothelium from secondary effects of ER stress. Previous studies by the current authors identified TXNDC5 as a key pathological factor in promoting the inflammatory phenotype of fibroblast-like synoviocytes (FLSs) from rheumatoid arthritis (RA). However, its activity in RA FLSs under ER stress remains unclear.

A lil3 chlp double mutant with exclusive accumulation of geranylgeranyl chlorophyll displays a lethal phenotype in rice.

Background: Phytyl residues are the common side chains of chlorophyll (Chl) and tocopherols. Geranylgeranyl reductase (GGR), which is encoded by CHLP gene, is responsible for phytyl biosynthesis. The light-harvesting like protein LIL3 was suggested to be required for stability of GGR and protochlorophyllide oxidoreductase in Arabidopsis.

CD109 regulates the inflammatory response and is required for the pathogenesis of rheumatoid arthritis.

Objective: The aim of this study was to investigate the role of CD109 in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs) and to evaluate its potential as a therapeutic target.

Methods: CD109 expression was examined in synovial tissues and FLSs from RA patients and collagen-induced arthritis (CIA) model mice. CD109-deficient mice were developed to evaluate the severity of CIA.

Inhibition of hexokinases holds potential as treatment strategy for rheumatoid arthritis.

Introduction: Abnormal glycolytic metabolism contributes to joint inflammation and destruction in rheumatoid arthritis (RA). We examine the expression and function of hexokinases in RA and evaluate the potential of their specific inhibitor for clinical treatment.

Methods: Detection of HKs was assessed in synovial tissue by immunohistology and Western blot.

E2F2 directly regulates the STAT1 and PI3K/AKT/NF-κB pathways to exacerbate the inflammatory phenotype in rheumatoid arthritis synovial fibroblasts and mouse embryonic fibroblasts.

Background: Expression of E2F transcription factor 2 (E2F2), a transcription factor related to the cell cycle, is abnormally high in rheumatoid arthritis synovial fibroblasts (RASFs). Deregulated expression of E2F2 leads to abnormal production of proinflammatory cytokines, such as interleukin (IL)-1α, IL-1β, and tumor necrosis factor (TNF)-α in RASFs. However, the underlying mechanism by which E2F2 regulates expression of IL-1α, IL-1β, and TNF-α has not been fully elucidated.