Salubrinal protects against inflammatory response in macrophage and attenuates psoriasiform skin inflammation by antagonizing NF-κB signaling pathway.

Psoriasiform skin inflammation is the common chronic skin inflammatory disease with no effective clinical therapy. Salubrinal is a multifunctional molecule playing a protective role in several conditions. Recently, studies have reported that Salubrinal is a potential therapeutic agent for inflammatory diseases. However, the protective role of Salubrinal in psoriasis-like skin inflammation remains unknown. In this article, imiquimod (IMQ)-induced psoriasis models were established in wild-type mice to explore the role of Salubrinal in the development of psoriasis. As a result, the IMQ-induced mouse models exhibited typical skin inflammation, which was alleviated by the administration of Salubrinal. Furthermore, RAW264.7 macrophage was stimulated with Lipopolysaccharide(LPS) in the presence or absence of Salubrinal. LPS stimulation elevated the expression of various inflammatory biomarkers, while the administration of Salubrinal abolished the function of LPS in RAW264.7 macrophages. In addition, the activation of the nuclear factor-kappa B (NF-κB) signaling pathway in both the LPS-stimulated RAW264.7 macrophage and psoriasis mouse models was antagonized by the administration of Salubrinal. Collectively, Salubrinal might be considered as a promising therapeutic agent for psoriasis-like skin inflammation.

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.

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.