Role of Long Intergenic Nonprotein-Coding RNA 00511 in Nod-Like Receptor Protein Pyrin Domain 3-Induced Chondrocyte Pyroptosis via the MicroRNA-9-5p/FUT1 Axis.

This study aimed to determine the function of LINC00511 in Nod-Like Receptor Pyrin Domain 3 inflammasome-mediated chondrocyte pyroptosis via the regulation of miR-9-5p and FUT 1. Chondrocyte inflammatory injury was induced by treating chondrocytes with LPS. Afterwards, the levels of IL-1ß and IL-18, the expression of NLRP3, ASC, Caspase-1, and GSDMD, cell viability, and LDH activity in chondrocytes were assessed. LINC00511 expression in LPS-treated chondrocytes was detected, and LINC00511 was subsequently silenced to analyse its role in chondrocyte pyroptosis. The subcellular localization of LINC00511 was predicted and verified. Furthermore, the binding relationships between LINC00511 and miR-9-5p and between miR-9-5p and FUT1 were validated. LINC00511 regulated NLRP3 inflammasome-mediated chondrocyte pyroptosis through the miR-9-5p/FUT1 axis. LPS-treated ATDC5 cells exhibited elevated levels of inflammatory injury; increased levels of NLRP3, ASC, Caspase-1, and GSDMD; reduced cell viability; increased LDH activity; and increased LINC00511 expression, while LINC00511 silencing inhibited the NLRP3 inflammasome to restrict LPS-induced chondrocyte pyroptosis. Next, LINC00511 sponged miR-9-5p, which targeted FUT1. Silencing LINC00511 suppressed FUT1 by upregulating miR-9-5p. Additionally, downregulation of miR-9-5p or overexpression of FUT1 neutralized the suppressive effect of LINC00511 knockdown on LPS-induced chondrocyte pyroptosis. Silencing LINC00511 inhibited the NLRP3 inflammasome to quench Caspase-1-dependent chondrocyte pyroptosis in OA by promoting miR-9-5p and downregulating FUT1.

The role of short-chain fatty acids in inflammatory skin diseases.

Short-chain fatty acids (SCFAs) are metabolites of gut microbes that can modulate the host inflammatory response, and contribute to health and homeostasis. Since the introduction of the gut-skin axis concept, the link between SCFAs and inflammatory skin diseases has attracted considerable attention. In this review, we have summarized the literature on the role of SCFAs in skin inflammation, and the correlation between SCFAs and inflammatory skin diseases, especially atopic dermatitis, urticaria, and psoriasis. Studies show that SCFAs are signaling factors in the gut-skin axis and can alleviate skin inflammation. The information presented in this review provides new insights into the molecular mechanisms driving gut-skin axis regulation, along with possible pathways that can be targeted for the treatment and prevention of inflammatory skin diseases.

Strategies to Modulate the Redifferentiation of Chondrocytes.

Because of the low self-healing capacity of articular cartilage, cartilage injuries and degenerations triggered by various diseases are almost irreversible. Previous studies have suggested that human chondrocytes cultured in vitro tend to dedifferentiate during the cell-amplification phase and lose the physiological properties and functions of the cartilage itself, which is currently a critical limitation in the cultivation of cartilage for tissue engineering. Recently, numerous studies have focused on the modulation of chondrocyte redifferentiation. Researchers discovered the effect of various conditions (extracellular environment, cell sources, growth factors and redifferentiation inducers, and gene silencing and overexpression) on the redifferentiation of chondrocytes during the in vitro expansion of cells, and obtained cartilage tissue cultured in vitro that exhibited physiological characteristics and functions that were similar to those of human cartilage tissue. Encouragingly, several studies reported positive results regarding the modulation of the redifferentiation of chondrocytes in specific conditions. Here, the various factors and conditions that modulate the redifferentiation of chondrocytes, as well as their limitations and potential applications and challenges are reviewed. We expect to inspire research in the field of cartilage repair toward the future treatment of arthropathy.

MEK1/2 Inhibitor (GDC0623) Promotes Osteogenic Differentiation of Primary Osteoblasts Inhibited by IL-1ß through the MEK-Erk1/2 and Jak/Stat3 Pathways.

OBJECTIVE: We evaluated the effects and mechanisms of GDC0623 on osteogenic differentiation of osteoblasts induced by IL-1ß. Methodology. Osteoblasts were treated with 20 ng/ml IL-1ß and 0.1 µM GDC0623. Cell proliferation levels were evaluated by the cell counting kit 8 (CCK8), EdU assay, and western blotting [proliferating cell nuclear antigen (PCNA) and Cyclin D1]. Osteoblasts were cultured in an osteogenic induction medium for 1-3 weeks after which their differentiations were assessed by alkaline phosphatase (ALP) staining, Alizarin Red staining, calcium concentration, immunocytochemistry staining, real-time quantitative PCR (RT-qPCR), and immunofluorescence staining. The osteogenesis-associated mechanisms were further evaluated by western blotting using appropriate antibodies. RESULTS: Relative to the control group, IL-1ß induced the rapid proliferation of osteoblasts and suppressed their osteogenic differentiations by upregulating the activities of MEK-Erk1/2 as well as Jak-Stat3 pathways and by elevating MMP13 and MMP9 levels. However, blocking of the MEK-Erk1/2 signaling pathway by GDC0623 treatment reversed these effects. CONCLUSION: Inhibition of Jak-Stat3 pathway by C188-9 downregulated the expression levels of MMP9 and MMP13, activated MEK-Erk1/2 pathway, and inhibited osteogenic differentiation.

Acupuncture of fascia points to relieve hand spasm after stroke: a study protocol for a multicenter randomized controlled trial.

BACKGROUND: The loss of functional ability of patients after stroke is mostly caused by dysfunction of the upper limbs, especially the hands. Hand functional exercise is the premise of alleviating hand dysfunction, and the relief of hand spasm is the basis of timely and effective hand functional exercise. Previous clinical observation have shown that fascial-point needling can effectively alleviate hand spasm immediately after stroke, but further evidence from large-sample studies is needed. The overall objective of this trial is to further evaluate the clinical efficacy of fascial-point acupuncture on hand spasm after stroke. METHODS/DESIGN: This multicenter randomized controlled trial will compare the efficacy of fascial-point acupuncture versus sham acupuncture and routine rehabilitation therapy in stroke patients with hand spasm. Patients will be randomized to undergo either the fascial-point acupuncture, the sham acupuncture or the control (routine rehabilitation therapy). We will recruit 210 stroke inpatients who meet the trial criteria and observe the remission of hand spasm and improvement of limb function after 4 weeks of intervention. The first evaluation indices are the remission of hand spasm and the duration of spasm remission. The second evaluation indices are the hand function of the affected limbs and the activities of daily living. When the accumulative total number of cases included reaches 120, a mid-term analysis will be conducted to determine any evidence that experimental intervention does have an advantage. DISCUSSION: Our aim is to evaluate the efficacy of fascial-point acupuncture in relieving hand spasm after stroke. The results should provide more evidence for the clinical application of this therapy in the future. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR), ID: ChiCTR1900022379. Registered on 9 April 2019.