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Aims: To explore the effect and mechanism of gastrodin (GAS) on human umbilical vein endothelial cells (HUVECs) apoptosis induced by oxidative stress and its function in wound healing. Main methods: HUVECs were incubated with tert-butyl hydroperoxide (TBHP) to induce endothelial cell dysfunction and GAS was used as a protector. Cell viability was detected by Counting Kit-8 (CCK-8). HUVECs apoptosis was evaluated by TUNEL assay and western blotting for cleaved caspase3 (C-caspase3) and other apoptosis-related proteins. Transwell migration assay, tube formation assay, and cell-matrix adhesion assay were performed to evaluated cell function of HUVECs. Transfection with nuclear factor-erythroid 2-related factor 2 (Nrf2) small interfering ribonucleic acid and western blotting for Nrf2, HO-1, and apoptosis-related proteins were performed to prove that Nrf2/HO-1 pathway is involved in the protective effects of GAS. The skin wound model of rat was used to assess the protective effects of GAS in vivo. Key Findings: The results show that treating HUVECs with GAS attenuated TBHP-induced apoptosis and cellular dysfunction, including cellular tube formation, migration, and adhesion. Mechanistically, we found that GAS protects HUVECs from TBHP-induced cellular apoptosis by activating the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway. An in vivo study illustrated that the oral administration of GAS enhances vascularization in regenerated tissue and facilitates wound healing. Significance: The findings of this study demonstrated that GAS may serve as a potential agent that accelerates wound healing.

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The inflammatory environment and excessive chondrocyte apoptosis have been demonstrated to play crucial roles in the onset of osteoarthritis (OA). Hydrogen sulfide (H 2 S), a gaseous signalling molecule, exerts an inhibitory effect on inflammation and apoptosis in several degenerative diseases. However, the protective effect of H 2 S against OA has not been fully clarified, and its underlying mechanism should be examined further. In the current study, the role of endogenous H 2 S in the pathogenesis of OA and its protective effects on interleukin (IL)-1β-induced chondrocytes were identified. Our data revealed decreased H 2 S expression in both human degenerative OA cartilage tissue and IL-1β-induced chondrocytes. Pretreatment with the H 2 S donor sodium hydrosulfide (NaHS) dramatically attenuated IL-1β-induced overproduction of inflammatory cytokines and improved the balance between anabolic and catabolic chondrocyte capacities, and these effects were dependent on PI3K/ AKT pathway-mediated inhibition of nuclear factor kappa B (NF-κB). Moreover, mitochondrial dysfunction-related apoptosis was significantly reversed by NaHS in IL-1β-stimulated chondrocytes. Mechanistically, NaHS partially suppressed IL-1β-induced phosphorylation of the mitogen-activated protein kinase (MAPK) cascades. Furthermore, in the destabilization of the medial meniscus mouse model, OA progression was ameliorated by NaHS administration. Taken together, these results suggest that H 2 S may antagonize IL-1β-induced inflammation and mitochondrial dysfunction-related apoptosis via selective suppression of the PI3K/Akt/NF-κB and MAPK signalling pathways, respectively, in chondrocytes and may be a potential therapeutic agent for the treatment of OA.

Oxidative stress–induced apoptosis and senescence of nucleus pulposus (NP) cells play a crucial role in the progression of intervertebral disc degeneration (IVDD). Accumulation of studies has shown that activated autophagy and enhanced autophagic flux can alleviate IVDD. In this study, we explored the effects of apigenin on IVDD in vitro and in vivo. Apigenin was found to inhibit tert-butyl hydroperoxide (TBHP)–induced apoptosis, senescence, and ECM degradation in NP cells. In addition, apigenin treatment can restore the autophagic flux blockage caused by TBHP. Mechanistically, we found that TBHP may induce autophagosome and lysosome fusion interruption and lysosomal dysfunction, while apigenin alleviates these phenomena by promoting the nuclear translocation of TFEB via the AMPK/mTOR signaling pathway. Furthermore, apigenin also exerts a protective effect against the progression of IVDD in the puncture-induced rat model. Taken together, these findings indicate that apigenin protects NP cells against TBHP-induced apoptosis, senescence, and ECM degradation via restoration of autophagic flux in vitro, and it also ameliorates IVDD progression in rats in vivo, demonstrating its potential for serving as an effective therapeutic agent for IVDD.

BackgroundMalignant giant cell tumor of bone (MGCTB) is extremely rare. Currently, population-based prognosis studies are lacking. This study aimed to determine the impact of demographics, tumor characteristics, and treatment on prognosis among patients with MGCTB.MethodsThe Surveillance, Epidemiology, and End Results database was used to identify patients with MGCTB from 1984 to 2013. Kaplan-Meier analyses were performed to determine the overall survival (OS). Univariable and multivariable Cox analyses were conducted to identify prognostic factors.ResultsThere were 250 patients with MGCTB included in our study. The multivariate Cox analysis revealed that age at diagnosis (hazard ratio [HR]: 1.09; 95% confidence interval [CI]: 1.07–1.11; P < 0.001), tumor size (HR: 7.04; 95% CI: 2.38–20.77; P < 0.001), tumor extension (regional vs. localized, HR: 2.64; 95% CI: 1.10–6.34; P = 0.030; distant vs. localized, HR: 6.12; 95% CI: 2.27–16.49; P < 0.001), and radiotherapy (HR: 0.41; 95% CI: 0.18–0.89; P = 0.025) were independent risk factors of OS in patients with MGCTB. Notably, tumor site (HR: 1.98; 95% CI: 0.99–4.00; P = 0.055) exhibited borderline significance. Additionally, we found that patients with tumors measuring >70 mm (P = 0.015), located in the axial skeleton (P < 0.001) and presented with distant metastasis (P < 0.001) tended to receive radiotherapy. Moreover, a nomogram model integrating independent predictors was established to estimate the OS of patients with MGCTB.ConclusionThis study provides a population-based assessment of the largest number of patients with MGCTB. We found that older age, larger tumor size, regional or distant metastasis, and lack of radiotherapy was associated with poor OS. Surgical methods were not significantly associated with OS. Furthermore, we built a high-quality nomogram to predict 1-, 3-, and 5-year OS for patients with MGCTB. These findings may assist in the clinical diagnosis and treatment of MGCTB.

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Macrophages are highly heterogeneous and exhibit a diversity of functions and phenotypes. They can be divided into pro‐inflammatory macrophages (M1) and anti‐inflammatory macrophages (M2). Diabetic wounds are characterized by a prolonged inflammatory phase and difficulty in healing due to the accumulation of pro‐inflammatory (M1) macrophages in the wound. Therefore, hydrogel dressings with macrophage heterogeneity regulation function hold great promise in promoting diabetic wound healing in clinical applications. However, the precise conversion of pro‐inflammatory M1 to anti‐inflammatory M2 macrophages by simple and biosafe approaches is still a great challenge. Here, an all‐natural hydrogel with the ability to regulate macrophage heterogeneity is developed to promote angiogenesis and diabetic wound healing. The protocatechuic aldehyde hybridized collagen‐based all‐natural hydrogel exhibits good bioadhesive and antibacterial properties as well as reactive oxygen species scavenging ability. More importantly, the hydrogel is able to convert M1 macrophages into M2 macrophages without the need for any additional ingredients or external intervention. This simple and safe immunomodulatory approach shows great application potential for shortening the inflammatory phase of diabetic wound repair and accelerating wound healing.