Macrophage-derived mir-100-5p orchestrates synovial proliferation and inflammation in rheumatoid arthritis through mTOR signaling.

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by synovial inflammation, causing substantial disability and reducing life quality. While macrophages are widely appreciated as a master regulator in the inflammatory response of RA, the precise mechanisms underlying the regulation of proliferation and inflammation in RA-derived fibroblast-like synoviocytes (RA-FLS) remain elusive. Here, we provide extensive evidence to demonstrate that macrophage contributes to RA microenvironment remodeling by extracellular vesicles (sEVs) and downstream miR-100-5p/ mammalian target of rapamycin (mTOR) axis.

Repurposed drug agomelatine is therapeutic against collagen-induced arthritis via iNOS targeting.

Background: The most promising biologics tumor necrosis factor α (TNFα) inhibitors are effective in treating rheumatoid arthritis (RA) in only 50-70 % of the cases; thus, new drugs targeting TNFα-mediated inflammation are required.

Methods: Firstly, the drugs that could inhibit FLS proliferation and TNFα induced inflammatory cytokine production were screened. Secondly, treatment effects of the identified drugs were screened in collagen-induced arthritis (CIA) mouse model.

Hypouricemia as a novel predictor of mortality in anti-MDA5 positive dermatomyositis patients with ILD: A retrospective cohort study.

Objective: Anti-melanoma differentiation-associated gene 5 antibody positive dermatomyositis (MDA5+ DM) is a unique subtype of idiopathic inflammatory myopathy (IIM) that is associated with rapidly progressive interstitial lung disease (RPILD) and high mortality. This retrospective study aimed to identify predictors of mortality and discover novel easily detectable indicators.

Methods: We retrospectively reviewed 183 MDA5+ DM-ILD patients who were from West China Hospital of Sichuan University myositis cohort, the largest single-center cohort of southwest China, from January 2016 to October 2021.

Deficiency of inflammation-sensing protein neuropilin-2 in myeloid-derived macrophages exacerbates colitis via NF-κB activation.

Neuropilin-2 (NRP2) is a multifunctional protein engaged in the regulation of angiogenesis, lymphangiogenesis, axon guidance, and tumor metastasis, but its function in colitis remains unclear. Here, we found that NRP2 was an inflammation-sensing protein rapidly and dramatically induced in myeloid cells, especially in macrophages, under inflammatory contexts. NRP2 deficiency in myeloid cells exacerbated dextran sulfate sodium salt-induced experimental colitis by promoting polarization of M1 macrophages and colon injury.

[YKL-40 Promotes the Expression of Inflammatory Factors in Type Ⅱ Alveolar Epithelial Cell Model of A549 Cell Line].

Objective: YKL-40, also known as chitinase-3-like-1 (CHI3L1), is a human cartilage glycoprotein-39, with its N-terminus consisting of tyrosine (Y), lysine (K), and leucine (L), hence the name YKL-40. In this study, we explored whether YKL-40 could promote the expression of inflammatory factors in type Ⅱ alveolar epithelial cells.

Methods: A549 cells were cultured with interleukin (IL)-1β (20 ng/mL), IL-6 (20 ng/mL), tumor necrosis factor-alpha (TNF-α) (20 ng/mL), and interferon-gamma (IFN-γ) (20 ng/mL).

Comprehensive transcriptomic analysis and machine learning reveal unique gene expression profiles in patients with immune-mediated necrotizing myopathy.

Background: Immune-mediated necrotizing myopathy (IMNM) is an autoimmune myopathy characterized by severe proximal weakness and muscle fiber necrosis, yet its pathogenesis remains unclear. So far, there are few bioinformatics studies on underlying pathogenic genes and infiltrating immune cell profiles of IMNM. Therefore, we aimed to characterize differentially expressed genes (DEGs) and infiltrating cells in IMNM muscle biopsy specimens, which may be useful for elucidating the pathogenesis of IMNM.

Fexofenadine protects against lipopolysaccharide-induced acute lung injury by targeting cytosolic phospholipase A2.

Objective: Acute lung injury (ALI) causes acute respiratory distress syndrome, with a high mortality rate of 40%, with currently available pharmacological treatments. Cytosolic phospholipase A2 (cPLA2) plays a critical role in the lipopolysaccharide (LPS)-induced pathology of ALI. This study assessed the therapeutic effects of fexofenadine (FFD), an on-market small-molecule drug that can target cPLA2 in LPS-induced ALI.

Apelin-mediated deamidation of HMGA1 promotes tumorigenesis by enhancing SREBP1 activity and lipid synthesis.

Enhanced fatty acid synthesis provides proliferation and survival advantages for tumor cells. Apelin is an adipokine, which serves as a ligand of G protein-coupled receptors that promote tumor growth in malignant cancers. Here, we confirmed that apelin increased sterol regulatory element-binding protein 1 (SREBP1) activity and induced the expression of glutamine amidotransferase for deamidating high-mobility group A 1 (HMGA1) to promote fatty acid synthesis and proliferation of lung cancer cells.

Stat5 CD4 T cells elicit anti-melanoma effect by CD4 T cell remolding and Notch1 activation.

Signal transducers and activators of transcription 5 (Stat5) is known to engage in regulating the differentiation and effector function of various subsets of T helper cells. However, how Stat5 regulates the antitumor activity of tumor-infiltrating CD4 T cells is largely unknown. Here, we showed that mice with specific deletion of Stat5 in CD4 T cells were less susceptible to developing subcutaneous and lung metastatic B16 melanoma with CD4 tumor-infiltrating lymphocytes (TILs) remolding.

miR-15a-5p inhibits metastasis and lipid metabolism by suppressing histone acetylation in lung cancer.

Metabolic reprogramme was a key characteristic of malignant tumors. Increased evidences indicated that besides Warburg effect (abnormal glucose metabolism), abnormal lipid metabolism played more and more important in progression and metastasis of malignant tumors. MiR-15a-5p could inhibit development of lung cancer, while its regulating mechanism, especially the role in lipid metabolism still remained unclear.

Apelin enhances biological functions in lung cancer A549 cells by downregulating exosomal miR-15a-5p.

Apelin acts as a tumor promoter in multiple malignant tumors; however, its regulatory mechanism remains unclear. Previous studies have indicated that exosomes are pivotal to mediating tumor progression and metastasis. This study examined whether apelin enhances proliferation and invasion ability of lung cancer cells via exosomal microRNA (miRNA).

BAI1 acts as a tumor suppressor in lung cancer A549 cells by inducing metabolic reprogramming via the SCD1/HMGCR module.

Brain-specific angiogenesis inhibitor 1 (BAI1) is an important tumor suppressor in multiple cancers. However, the mechanisms behind its anti-tumor activity, particularly the relationship between BAI1 and metabolic aberrant of a tumor, remained unveiled. This study aimed to investigate whether BAI1 could inhibit biological functions in lung cancer A549 cells and the critical regulating molecules that induce metabolic reprogramming.

FRK plays an oncogenic role in non-small cell lung cancer by enhancing the stemness phenotype via induction of metabolic reprogramming.

The role of Fyn-related kinase (FRK) in malignant tumors remains controversial. Our study investigated the function of FRK in lung cancer. Immunohistochemistry staining and generating a knockout of FRK by CRISPR/Cas9 in H1299 (FRK-KO-H1299) cells were strategies used to explore the role of FRK.

A retrospective study on intensity-modulated radiation therapy combined with chemotherapy after D2 radical surgery for gastric carcinoma.

In order to investigate the clinical value of different chemotherapies, the efficacy of intensity-modulated radiation therapy with concurrent chemotherapy following D2 radical surgery for gastric carcinoma was evaluated in this study. A total of 102 patients who underwent D2 radical surgery for gastric carcinoma followed by concurrent chemoradiotherapy (CRT) between January, 2008 and March, 2012, were selected. The 5/7 field intensity-modulated radiation therapy was used, with a planning target volume dose of 45 Gy in 25 fractions over 5 weeks.