Electrospinning-based wound dressings with multifunctional properties, including hemostasis-promoting, antibacterial, drug release, and therapeutic effects, are of great interest in military and civilian trauma healthcare. Herein, we designed lidocaine hydrochloride (LID) and mupirocin-loaded chitosan/polycaprolactone (CSLD-PCLM) scaffolds with multiple functions as wound dressings. Through the dual spinneret electrospinning technique, the scaffolds achieved a nanofiber structure, which enhanced the interfacial interaction between the scaffold and blood cells and showed excellent blood coagulation capacity. In particular, the scaffolds loaded with LID and mupirocin exhibited rapid release of LID and sustained release of mupirocin. The CSLD-PCLM scaffold containing mupirocin exhibited outstanding antibacterial activity. Moreover, the scaffold significantly enhanced the wound healing process with complete re-epithelialization as well as collagen deposition in a full-thickness skin defect model. Thus, CSLD-PCLM nanofibrous scaffolds may ideally meet the various requirements of the wound healing process and are promising candidates for wound dressings in future clinical applications.

Multifunctional Chitosan/Polycaprolactone Nanofiber Scaffolds with Varied Dual-Drug Release for Wound-Healing Applications

Regulation of Runx2 by post-translational modifications in osteoblast differentiation.

Osteoarthritis (OA), which is characterized by proliferation of subchondral bone and the degeneration of articular cartilage, is the most prevalent human arthritis. Nod-like receptor pyrin domain 3 (NLRP3) inflammasome is a hot spot in recent year and has been reported to be associated with OA synovial inflammation. However, there are few studies on NLRP3 inflammasome in chondrocyte. Licochalcone A (Lico A), a compound extracted from Glycyrrhiza species, has various biological effects such as anti-inflammation, anti-apoptotic, anti-cancer and anti-oxidation. In this study, we investigated the protective effect of Lico A on chondrocytes stimulated by lipopolysaccharide (LPS) and surgically induced OA models. In vitro, Lico A could reduce the expression of NLRP3, apoptosis-associated speck-like protein (ASC), Gasdermin D (GSDMD), caspase-1, interleukin-1beta (IL-1β) and IL-18, which indicated that Lico A attenuates LPS-induced chondrocytes pyroptosis. In addition, Lico A ameliorates the degradation of extracellular matrix (ECM) by enhancing the expression of aggrecan and collagen-II. Meanwhile, we found that Lico A inhibits NLRP3 inflammasome via nuclear factor erythroid-2-related factor 2 (Nrf2)/haeme oxygenase-1(HO-1)/nuclear factor kappa-B (NF-κB) axis. And the Nrf2 small interfering RNA (siRNA) could reverse the anti-pyroptosis effects of Lico A in mouse OA chondrocytes. In vivo, Lico A mitigates progression OA in a mouse model and reduces OA Research Society International (OARSI) scores. Thus, Lico A may have therapeutic potential in OA.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/jcmm.15905

Activating Nrf2 signalling alleviates osteoarthritis development by inhibiting inflammasome activation

Current evidence suggests a complex interaction between adipokines and microRNA (miRNA) in osteoarthritis (OA) pathogenesis. The present study explored the role of miR-34a and miR-181a in regulating apoptosis and oxidative stress induced by visfatin in human OA chondrocytes. Chondrocytes were transfected with miR-34a and miR-181a inhibitors and stimulated with visfatin for 24 h, in the presence of nuclear factor (NF)-κB inhibitor (BAY-11-7082, 2 h pre-incubation). Apoptosis and reactive oxygen species (ROS) production were detected by cytometry, miRNA, antioxidant enzymes, nuclear factor erythroid (NRF)2 and B-cell lymphoma (BCL)2 expressions by quantitative real time polymerase chain reaction (real time PCR) and western blot. P50 NF-κB subunit was measured by immunofluorescence. Visfatin significantly induced apoptosis and superoxide anion production, increased miR-34a, miR-181a, superoxide dismutase (SOD)-2, catalase (CAT), NRF2 and decreased BCL2 gene and protein expression in OA chondrocytes. All the visfatin-caused effects were suppressed by using miR-34a and miR-181a inhibitors. Pre-incubation with BAY-11-7082 counteracted visfatin-induced expression of miRNA, BCL2, SOD-2, CAT and NRF2. Inhibition of miR-34a and miR-181a significantly reduced the activation of p50 NF-κB. Visfatin confirms its ability to induce apoptosis and oxidative stress in human OA chondrocytes; these effects appeared mediated by miR-34a and miR-181a via NF-κB pathway. We highlight the relevance of visfatin as potential therapeutic target for OA treatment.

https://www.mdpi.com/2073-4409/8/8/874/pdf

MicroRNA-34a and MicroRNA-181a Mediate Visfatin-Induced Apoptosis and Oxidative Stress via NF-κB Pathway in Human Osteoarthritic Chondrocytes.

Osteoarthritis (OA) is the major course of joint deterioration, in which M1 macrophage-driven synovitis exacerbates the pathological process. However, precise therapies for M1 macrophage to decrease synovitis and attenuate OA progression have been scarcely proposed. Transient receptor potential vanilloid 1 (TRPV1) is a cation channel that has been implicated in pain perception and inflammation. In this study, we investigated the role of TRPV1 in the M1 macrophage polarization and pathogenesis of OA. We demonstrated that TRPV1 expression and M1 macrophage infiltration were simultaneously increased in both human and rat OA synovium. More than 90% of the infiltrated M1 macrophages expressed TRPV1. In the rat OA model, intra-articular injection of capsaicin (CPS), a specific TRPV1 agonist, significantly attenuated OA phenotypes, including joint swelling, synovitis, cartilage damage, and osteophyte formation. CPS treatment markedly reduced M1 macrophage infiltration in the synovium. Further mechanistic analyses showed that TRPV1-evoked Ca2+ influx promoted the phosphorylation of calcium/calmodulin-dependent protein kinase II (CaMKII) and facilitated the nuclear localization of nuclear factor-erythroid 2-related factor 2 (Nrf2), which ultimately resulted in the inhibition of M1 macrophage polarization. Taken together, our findings establish that TRPV1 attenuates the progression of OA by inhibiting M1 macrophage polarization in synovium via the Ca2+/CaMKII/Nrf2 signaling pathway. These results highlight the effect of targeting TRPV1 for the development of a promising therapeutic strategy for OA.

/pdf/trpv1-alleviates-osteoarthritis-by-inhibiting-m1-macrophage-3nmbwr3t32.pdf

TRPV1 alleviates osteoarthritis by inhibiting M1 macrophage polarization via Ca2+/CaMKII/Nrf2 signaling pathway.

Osteoarthritis (OA) is an inflammatory disease of the joints that causes progressive disability in the elderly. Reactive oxygen species (ROS) play an important role in OA development; they may activate the NLRP3 inflammasome, thereby inducing the secretion of proinflammatory IL-1β and IL-18, leading to the aggravation of the downstream inflammatory response. Nrf2 is a key transcription factor that regulates the expression of antioxidant enzymes that protect against oxidative stress and tissue damage. We aimed to explore the underlying mechanism of OA development by investigating NLRP3, ASC, Nrf2, and HO-1 expression in synovia and their regulatory networks in OA. Human total knee replacement samples were subjected to histology and micro-CT analysis to determine the pathological changes in the cartilage and subchondral bone and to assess the expression of inflammation-related markers in the synovial tissue by immunohistochemistry (IHC), qRT-PCR, and Western blot. To investigate these pathological changes in an OA animal model, adult Sprague-Dawley rats were subjected to anterior cruciate ligament transection and medial meniscectomy. Articular cartilage and subchondral bone changes and synovial tissue were also determined by the same methods used for the human samples. Finally, SW982 cells were stimulated with lipopolysaccharide (LPS) as an in vitro inflammatory cell model. The correlation between NLRP3 and Nrf2 expression was confirmed by knocking down NLRP3 or Nrf2. Cartilage destruction and subchondral bone sclerosis were found in the OA patients and OA model rats. Significantly increased expression levels of NLRP3, ASC, Nrf2, and HO-1 were found in the synovial tissue from OA patients. NLRP3, ASC, Nrf2, and HO-1 expression in the synovium was also upregulated in the OA group compared with the sham group. Furthermore, the NLRP3, Nrf2, HO-1, IL-1β, and IL-18 expression in LPS-treated SW982 cells was increased in a dose-dependent manner. As expected, the expression of NLRP3 was upregulated, and the expression of IL-1β and IL-18 was downregulated after Nrf2 silencing. However, knocking down NLRP3 did not affect the expression of Nrf2. ROS-induced oxidative stress may be the main cause of NLRP3 inflammasome activation and subsequent release of downstream factors during OA development. Nrf2/HO-1 signaling could be a key pathway for the activation of the NLRP3 inflammasome, which may contribute to the progression of OA. Herein, we discovered a novel role of Nrf2/HO-1 signaling in the production of NLRP3, which may facilitate the prevention and treatment of OA.

/pdf/inhibition-of-nrf2-ho-1-signaling-leads-to-increased-4aah7hil3d.pdf

Inhibition of Nrf2/HO-1 signaling leads to increased activation of the NLRP3 inflammasome in osteoarthritis

Osteoporosis is characterized by low bone mass and the degeneration of bone structure, conditions which increase the risk of fracture. Aloin has been shown to affect bone metabolism, but its role in osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) remains unclear. The aim of our study was to determine whether aloin promotes the proliferation and osteogenic differentiation of BMSCs and, if so, whether it acts via activation of the ERK1/2-Runx2 signaling pathway. We found that the different concentrations of aloin tested had no obvious cytotoxic effects on the viability of BMSCs. Under osteogenic induction conditions, aloin increased cellular alkaline phosphatase activity, promoted BMSC mineralization, and increased osteogenic-related gene expression. In addition, treating the BMSCs with the signal transduction inhibitor PD98059 (ERK1/2) effectively attenuated Runx2 activation in these cells and also suppressed osteoblastic differentiation. Overall, our study demonstrates that aloin promotes osteogenic differentiation of BMSCs through activation of the ERK1/2-Runx2 signaling pathway.

Aloin promotes osteogenesis of bone-marrow-derived mesenchymal stem cells via the ERK1/2-dependent Runx2 signaling pathway.

Poly-(lactide-co-glycolide acid) (PLGA) has been widely investigated as scaffold material for bone tissue engineering owing to its biosafety, biodegradability, and biocompatibility. However, the bioinert surface of PLGA may fail in regulating cellular behavior and directing osteointegration between the scaffold and the host tissue. In this article, oxidized chondroitin sulfate (oCS) and type I collagen (Col I) were assembled onto PLGA surface via layer by layer technique (LbL) as an adhesive coating for the attachment of inorganic minerals. The multilayer-modified PLGA scaffold was mineralized in vitro to ensure the deposition of nanohydroxyapatite (nHAP). It was found that nHAP crystals were more uniformly and firmly attached on the multilayer-modified PLGA as compared with the pure PLGA scaffold, which remarkably improved PLGA surface and mechanical properties. Additionally, in vitro biocompatibility of PLGA scaffold, in terms of bone mesenchymal stem cells (BMSCs) attachment, spreading and proliferation was greatly enhanced by nHAP coating and multilayer deposition. Furthermore, the fabricated composite scaffold also shows the ability to promote the osteogenic differentiation of BMSCs through the up-regulation of osteogenic marker genes. Thus, this novel biomimetic composite scaffold might achieve a desirable therapeutic result for bone tissue regeneration. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2714-2725, 2018.

Biomineralization improves mechanical and osteogenic properties of multilayer-modified PLGA porous scaffolds.

Gasification of iron coke and cogasification behavior of iron coke and coke under simulated hydrogen-rich blast furnace condition

The invention discloses application of aloin in improvement of osteogenic capability of a bone mesenchymal stem cell (BMSC). According to the application of the invention, the BMSC is treated by aloins with different concentrations, and cell viability of the BMSC is detected; influence of the aloin on osteoblast differentiation of the BMSC is evaluated by adopting alkaline phosphatase activity andmineralization experiments; real-time fluorescent quantitative PCR detection is carried out for detecting expression situation of osteogenesis-related genes such as Runx2, ALP, OCN and OPN; variationof an ERK1/2-Runx2 signal channel is detected by virtue of a Western blotting process and an immumofluorescence process; and results show that the aloin promotes the osteoblast differentiation of theBMSCs by activating the ERK1/2-Runx2 signal channel, the osteogenic capability of the BMSCs is improved, and the research results provide data support for research and development of a new drug usedfor preventing and treating osteoporosis, so that the aloin has a greater application prospect.

Zhuming Chen

Papers

Inhibition of Nrf2/HO-1 signaling leads to increased activation of the NLRP3 inflammasome in osteoarthritis

Aloin promotes osteogenesis of bone-marrow-derived mesenchymal stem cells via the ERK1/2-dependent Runx2 signaling pathway.

Biomineralization improves mechanical and osteogenic properties of multilayer-modified PLGA porous scaffolds.

Gasification of iron coke and cogasification behavior of iron coke and coke under simulated hydrogen-rich blast furnace condition

Application of aloin in improvement of osteogenic capability of bone mesenchymal stem cell