Altered expression of ET-1 and HMGB1 together with higher MMP-9 activity in serum-derived exosomes of chronic lymphocytic leukemia.

of serum response factor in hepatocellular carcinoma: An association with matrix metalloproteinase

LncRNA TTN-AS1 targets miR-520d-5p to regulate the function of synovial fibroblasts and influences the progression of osteoarthritis.

BACKGROUND Synovial inflammation is involved in all stages of osteoarthritis (OA) and is a key factor in promoting the occurrence and development of OA. AIM To investigate the effects of lncRNA TTN-AS1 on human synovial fibroblasts. MATERIALS AND METHODS RT-qPCR was employed to detect the expression of the long non-coding RNA TTN-AS1, miR-520d-5p, ADAMTS5, vascular endothelial growth factor (VEGF) and matrix metallopeptidase 13 (MMP13). The Enzyme-Linked Immunosorbent Assay (ELISA) method was employed to detect interleukin-6 (IL-6) and interleukin-8 (IL-8) in cell supernatants. The proliferation and apoptosis of cells were detected by the Cell Counting Kit-8 (CCK-8) method and flow cytometry, respectively. Interactions between genes were demonstrated using dual luciferase assays and Pearson correlation analysis. RESULTS In the OA synovial tissue and cell model, lncRNA TTN-AS1 and ADAMTS5 were upregulated, while miR-520d-5p was downregulated. Following TNF-α and IL-1β treatment, IL-6 and IL-8 levels significantly increased in FLSs-OA. In terms of cellular function, inhibiting lncRNA TTN-AS1 could promote expression of SOD and GSH in FLSs-OA cells, while also decreasing the expression of MDA, VEGF and MMP13. Furthermore, inhibiting lncRNA TTN-AS1 could inhibit the proliferation of FLSs-OA cells and enhance their apoptosis. However, inhibiting miR-520d-5p could reverse the cellular effects produced by inhibiting lncRNA TTN-AS1 on FLSs-OA cells. In terms of mechanism, Negative regulatory relationships existed between lncRNA TTN-AS1 and miR-520d-5p, as well as between miR-520d-5p and ADAMTS5. CONCLUSION LncRNA TTN-AS1 regulated the functions of FLSs-OA cells induced by TNF-α and IL-1β, such as oxidative stress, angiogenesis, cell proliferation and apoptosis, as well as cartilage matrix degradation, through the miR-520d-5p, and ADAMTS5 may be the target gene for its functional effects.

Regulation of Extracellular HMGB-1 Alarmin Levels by CIGB-300 Anticancer Peptide In Vitro and In Vivo

Data reveal for the first time that CIGB-300 treatment is able to induce extracellular HMGB-1 release in vitro and in vivo which could be indicative of ICD induction in some kinds of tumors; furthermore, the induction of extracellular HMGB-1 alarmin as a putative CIGB-300 response biomarker merits further investigation.

Infliximab treatment affects the serum expression of matrix metalloproteinases MMP-2 and MMP-9 in Crohn's disease via the NLRP3 pathway, mediated by extracellular vesicle-derived RAGE

Background Infliximab is an effective biologic agent for Crohn’s disease (CD), but its precise mechanisms on matrix metalloproteinases (MMPs) and related pathways remain incompletely understood. This study aimed to investigate the effects of infliximab on serum MMP-2 and MMP-9 expression and to explore the mediating role of the NLRP3 inflammasome pathway via extracellular vesicle (EV)-derived RAGE. Methods A prospective cohort study was conducted at Beijing Chaoyang Hospital, Capital Medical University. Sixty-eight patients with active CD receiving infliximab therapy and 30 healthy controls were enrolled. Serum MMP-2 and MMP-9 levels, EV-derived RAGE expression, and NLRP3-related markers (IL-1β, IL-18, NLRP3, caspase-1) were measured at baseline and after treatment (weeks 6 and 30). In vitro experiments using patient-derived EVs on THP-1 macrophages and primary monocytes were performed to validate the mechanistic axis. Results Infliximab treatment significantly decreased serum MMP-9 and increased MMP-2 levels (P < 0.001). It also suppressed NLRP3 inflammasome activation and reduced EV-derived RAGE expression. EV-RAGE levels positively correlated with MMP-9 and NLRP3 activity. In vitro, pre-treatment EVs induced MMP-9 and IL-1β production in a RAGE- and NLRP3-dependent manner, while post-treatment EVs showed attenuated effects. Clinical responders exhibited more pronounced modulation of this axis. Conclusions Infliximab modulates the balance of MMP- 2 and MMP-9 in CD patients, at least partly through inhibition of the EV-derived RAGE/NLRP3 inflammasome pathway. Targeting this axis may provide new therapeutic strategies and biomarkers for personalized treatment in Crohn’s disease.

Matrix metalloproteinase-7 Induces Cellular Senescence By Activation Of p21 In Hyperglycemia

 Background: Matrix metalloproteinase-7 (MMP7) belongs to a major enzyme group of proteinases involved in extracellular matrix degradation and in controlling several biological processes such as cell division, apoptosis, and the development of Diabetes mellitus (DM) and its complications. High glucose can elicit a damaging DNA response, which ultimately leads to p21-dependent senescence. This study aimed to detect the effects of elevated glucose on increased expression levels of MMP7 and p21 in human sample, and to identify the correlation between expression levels of MMP7 and p21.   Materials and methods:  The influence of high glucose on serum levels of MMP7 and p21 was evaluated in 90 subjects, divided into two groups (diabetic patients, and healthy control). The key indicators of the male and female participants, in each  group, were evaluated based on fasting blood sugar (FBS) and glycosylated hemoglobin (HbA1c). Finally the correlation among all study variables was established. Results: Expression levels of MMP7 and p21 were significantly higher in participants with diabetes and HbA1c, as compared to the healthy controls. A positive correlation was established between MMP7 and p21 within the study group. Conclusions: The elevated blood glucose enhanced the expression of MMP7 and p21 in diabetic patients, highlighting potential influence on disease progression. The positive correlation between MMP7 and p21 offers new insight into the role of MMP7 in promoting cellular apoptosis in diabetes.

Study on the Expression of MiR-642b-3p in Spontaneous Intracerebral Hemorrhage and Its Regulatory Mechanism on Endothelial Cell Injury