Colloidal Surface Engineering: Growth of Layered Double Hydroxides with Intrinsic Oxidase-Mimicking Activities to Fight Against Bacterial Infection in Wound Healing.

Colloidal surface engineering is of particular importance to impart modular functionalities to the colloidal systems. Here, a layer of Mn/Ni layered hydroxides (Mn/Ni(OH)x LDHs) can be successfully coated on various colloidal particles, such as silica spheres, silica rods, ferrite nanocrystal supraparticles, as well as FeOOH nanorods. Such layered hydroxides have intrinsic oxidase-mimetic activities, as demonstrated by catalytic oxidation of tetramethyl benzidine in the presence of oxygen. Furthermore, Mn/Ni(OH)x LDHs structure seems to capture bacteria (both Gram positive and Gram negative) and exhibit antibacterial properties in vitro. Moreover, local delivery of Mn/Ni-LDH structure fights against infection and reverses delayed wound healing procedures in mice models. Importantly, such hierarchical structures may have strong adhesive properties to the bacteria, which may maximize the contact between Mn/Ni(OH)x LDHs and the bacteria's surface. Overall, the present versatile colloidal surface engineering strategy will bring new insights in the field of antibiotics for its high efficiency toward antibacterial activity.

Cortistatin protects against intervertebral disc degeneration through targeting mitochondrial ROS-dependent NLRP3 inflammasome activation.

Background: Intervertebral disc (IVD) degeneration is a common degenerative disease that can lead to collapse or herniation of the nucleus pulposus (NP) and result in radiculopathy in patients. Methods: NP tissue and cells were isolated from patients and mice, and the expression profile of cortistatin (CST) was analysed. In addition, ageing of the NP was compared between 6-month-old WT and CST-knockout (CST-/-) mice. Furthermore, NP tissues and cells were cultured to validate the role of CST in TNF-α-induced IVD degeneration. Moreover, in vitro and in vivo experiments were performed to identify the potential role of CST in mitochondrial dysfunction, mitochondrial ROS generation and activation of the NLRP3 inflammasome during IVD degeneration. In addition, NF-κB signalling pathway activity was tested in NP tissues and cells from CST-/- mice. Results: The expression of CST in NP cells was diminished in the ageing- and TNF-α-induced IVD degeneration process. In addition, compared with WT mice, aged CST-/- mice displayed accelerated metabolic imbalance and enhanced apoptosis, and these mice showed a disorganized NP tissue structure. Moreover, TNF-α-mediated catabolism and apoptosis were alleviated by exogenous CST treatment. Furthermore, CST inhibited mitochondrial dysfunction in NP cells through IVD degeneration and suppressed activation of the NLRP3 inflammasome. In vitro and ex vivo experiments indicated that increased NF-κB pathway activity might have been associated with the IVD degeneration observed in CST-/- mice. Conclusion: This study suggests the role of CST in mitochondrial ROS and activation of the NLRP3 inflammasome in IVD degeneration, which might shed light on therapeutic targets for IVD degeneration.

Glycitin Suppresses Cartilage Destruction of Osteoarthritis in Mice.

Osteoarthritis (OA), a chronic joint disease, is characterized by cartilage surface erosion, subchondral bone rebuilding, and formation of osteophytes. To date, the nosogenesis and underlying mechanisms of OA have not yet been elucidated. However, it is widely accepted that TNF-α is a crucial cytokine in the development of OA. Glycitin, a natural isoflavone extracted from legumes, affects physiological reactions and pathological responses. Recently, the anti-inflammatory effect of glycitin has been reported. However, the function of glycitin in cartilage degeneration in OA remains to be investigated. In the current study, primary murine chondrocytes were isolated and stimulated by TNF-α to evaluate the anti-inflammatory effects and protective function of glycitin in chondrocytes. In vivo, the ACLT mouse model, a frequently-used OA model, was used to further examine the therapeutic role of glycitin in cartilage degeneration and inflammation in OA. Consequently, glycitin functions were examined both in vivo and in vitro. Moreover, the underlying mechanism of action of glycitin was investigated and was found to involve the NF-κB signaling pathway. Collectively, this study suggests that glycitin can be potentially used for the treatment of joint degenerative diseases, including OA.

Scutellarin suppresses cartilage destruction in osteoarthritis mouse model by inhibiting the NF-κB and PI3K/AKT signaling pathways.

Osteoarthritis (OA), a common and severe disease, is predominantly characterized by cartilage destruction, which results in the degeneration of joint surfaces. Nowadays, it is accepted that TNFα plays a critical role in OA. Scutellarin, the main bioactive flavonoid glycoside extracted form Erigeron breviscapus, has been reported to exert positive effects on anti-inflammatory reactions. However, the effect of scutellarin in OA is still unknown. In this study, we isolated and cultured primary murine chondrocytes, stimulating TNF-α, in the presence or absence of scutellarin treatment. We found that the inflammatory response stimulated by TNF-α was significantly inhibited by the addition of scutellarin. Moreover, we established OA mouse models induced by surgery. In this mouse model, both inflammatory reaction and cartilage degeneration were markedly inhibited by oral administration of scutellarin. Furthermore, the cellular mechanism underlying the protective effect of scutellarin in OA was clearly associated with the NF-κB and PI3K/AKT signaling pathways. Collectively, this study proposes scutellarin as a potential therapeutic to treat joint degenerative diseases, including OA.

Ghrelin protects against contact dermatitis and psoriasiform skin inflammation by antagonizing TNF-α/NF-κB signaling pathways.

Contact dermatitis and psoriasis are skin disorders caused by immune dysregulation, yet much remains unknown about their underlying mechanisms. Ghrelin, a recently discovered novel peptide and potential endogenous anti-inflammatory factor expressed in the epidermis, is involved in skin repair and disease. In this study, we investigated the expression pattern and therapeutic effect of ghrelin in both contact dermatitis and psoriasis mouse models induced by oxazolone (OXA) and imiquimod (IMQ), respectively, and in TNF-α-stimulated RAW264.7 macrophages, NHEKs and skin fibroblasts. Ghrelin expression was reduced in both the OXA-induced contact dermatitis and IMQ-induced psoriasis mouse models. Furthermore, treatment with ghrelin attenuated skin inflammation in both the contact dermatitis and psoriasis mouse models. Mice administered PBS after OXA- or IMQ-induced model generation exhibited typical skin inflammation, whereas ghrelin treatment in these mouse models substantially decreased the dermatitis phenotype. In addition, exogenous ghrelin attenuated the inflammatory reaction induced by TNF-α in RAW264.7 cells. Moreover, ghrelin administration limited activation of NF-κB signaling. In summary, ghrelin may represent a potential molecular target for the prevention and treatment of inflammatory skin diseases, including contact dermatitis and psoriasis.

[Experimental study on the anti-tumor effect of monocytes/macrophages against Tca8113 cells and the secretion of vascular endothelial growth factor in acid microenvironment].

OBJECTIVE: To investigate the anti-tumor effect of monocytes/macrophages against Tca8113 cells and the secretion of vascular endothelial growth factor (VEGF) in acid microenvironment in vitro. METHODS: Peripheral blood mononuclear cells were extracted from healthy person's blood and cultivated to transform into monocytes/macrophages. The monocytes/macrophages were cultured with Tca8113 in acid microenvironment (pH6.6 and pH6.8) and in normal microenvironment (pH7.2). The anti-tumor effect of monocytes/macrophages against Tca8113 cells were examined by MTT assay. The expression of VEGF was detected by enzyme-link immunoassay (ELISA). RESULTS: The anti-tumor effect of monocytes/macrophages against Tca8113 cells in acid environment was lower than in normal environment (P < 0.05). VEGF excreted by mononuclear/macrophage was significantly higher in acid microenvironment than in normal microenvironment. CONCLUSION: Due to acid microenvironment inside tumor, the anti-tumor effect of monocytes/macrophages against tumor cell was decreased, but the secretion of VEGF was gradually increased. However, the function of monocytes/macrophages on anti-tumor need more research.