Ameliorative effects of olibanum essential oil on learning and memory in Aβ1-42-induced Alzheimer’s disease mouse model

Purpose: To study the effect of olibanum essential oil (OEO) on learning and memory in Alzheimer’s disease (AD) mouse.Methods: Mice were administered the 42-amino acid form of amyloid β-peptide (Aβ1-42) to induce AD and then treated with OEO at 150, 300, and 600 mg/kg, p.o. for two weeks. Following treatment, the AD mice were assessed by step-down test (SDT), dark avoidance test (DAT), and Morris water maze test (MWM). Blood and brain tissues were collected for biochemical assessments. Gas chromatographymass spectroscopy was used to analyze the main constituents of OEO.Results: The main constituents of OEO were limonene, α-pinene, and 4-terpineol. Treatment with OEO prolonged t latency in SDT and DAT, but decreased error times. Escape latency decreased and crossing times were rose in the MWM following OEO treatment (p < 0.5). Treatment with OEO also enhanced the acetylcholine levels and decreased the acetylcholinesterase levels in serum and brain tissue (p < 0.5). Additionally, OEO reduced amyloid plaques in the hippocampus and protected hippocampal neurons from damage. Furthermore, OEO decreased c-fos expression in  hippocampus tissues from AD mice (p < 0.5).Conclusion: OEO has significant ameliorative effect AD-induced deterioration in learning and memory in AD mouse induced by Aβ1-42. The mechanisms of these effects are related to increased acetylcholine contents, reduction of amyloid plaques, protection of hippocampal neurons, and downregulation of c-fos in brain tissues. The results justify the need for further investigation of candidate drugs derived from OEO for the  management of AD. Keywords: Olibanum, Essential oil, Learning, Memory, A

Regulation of microglia related neuroinflammation contributes to the protective effect of Gelsevirine on ischemic stroke

Stroke, especially ischemic stroke, is an important cause of neurological morbidity and mortality worldwide. Growing evidence suggests that the immune system plays an intricate function in the pathophysiology of stroke. Gelsevirine (Gs), an alkaloid from Gelsemium elegans, has been proven to decrease inflammation and neuralgia in osteoarthritis previously, but its role in stroke is unknown. In this study, the middle cerebral artery occlusion (MCAO) mice model was used to evaluate the protective effect of Gs on stroke, and the administration of Gs significantly improved infarct volume, Bederson score, neurobiological function, apoptosis of neurons, and inflammation state in vivo. According to the data in vivo and the conditioned medium (CM) stimulated model in vitro, the beneficial effect of Gs came from the downregulation of the over-activity of microglia, such as the generation of inflammatory factors, dysfunction of mitochondria, production of ROS and so on. By RNA-seq analysis and Western-blot analysis, the JAK-STAT signal pathway plays a critical role in the anti-inflammatory effect of Gs. According to the results of molecular docking, inhibition assay, and thermal shift assay, the binding of Gs on JAK2 inhibited the activity of JAK2 which inhibited the over-activity of JAK2 and downregulated the phosphorylation of STAT3. Over-expression of a gain-of-function STAT3 mutation (K392R) abolished the beneficial effects of Gs. So, the downregulation of JAK2-STAT3 signaling pathway by Gs contributed to its anti-inflammatory effect on microglia in stroke. Our study revealed that Gs was benefit to stroke treatment by decreasing neuroinflammation in stroke as a potential drug candidate regulating the JAK2-STAT3 signal pathway

Human Serum Albumin Based Nanodrug Delivery Systems: Recent Advances and Future Perspective

With the success of several clinical trials of products based on human serum albumin (HSA) and the rapid development of nanotechnology, HSA-based nanodrug delivery systems (HBNDSs) have received extensive attention in the field of nanomedicine. However, there is still a lack of comprehensive reviews exploring the broader scope of HBNDSs in biomedical applications beyond cancer therapy. To address this gap, this review takes a systematic approach. Firstly, it focuses on the crystal structure and the potential binding sites of HSA. Additionally, it provides a comprehensive summary of recent progresses in the field of HBNDSs for various biomedical applications over the past five years, categorized according to the type of therapeutic drugs loaded onto HSA. These categories include small-molecule drugs, inorganic materials and bioactive ingredients. Finally, the review summarizes the characteristics and current application status of HBNDSs in drug delivery, and also discusses the challenges that need to be addressed for the clinical transformation of HSA formulations and offers future perspectives in this field

Numerical Simulation of a Sandy Seabed Response to Water Surface Waves Propagating on Current

An integrated numerical model is developed to study wave and current-induced seabed response and liquefaction in a flat seabed. The velocity-inlet wave-generating method is adopted in the present study and the finite difference method is employed to solve the Reynolds-averaged Navier-Stokes equations with k-ε turbulence closure. The model validation demonstrates the capacity of the present model. The parametrical study reveals that the increase of current velocity tends to elongate the wave trough and alleviate the corresponding suction force on the seabed, leading to a decrease in liquefaction depth, while the width of the liquefaction area is enlarged simultaneously. This goes against previous studies, which ignored fluid viscosity, turbulence and bed friction

Bone Regeneration Using MMP-Cleavable Peptides-Based Hydrogels

Accumulating evidence has suggested the significant potential of chemically modified hydrogels in bone regeneration. Despite the progress of bioactive hydrogels with different materials, structures and loading cargoes, the desires from clinical applications have not been fully validated. Multiple biological behaviors are orchestrated precisely during the bone regeneration process, including bone marrow mesenchymal stem cells (BMSCs) recruitment, osteogenic differentiation, matrix calcification and well-organized remodeling. Since matrix metalloproteinases play critical roles in such bone metabolism processes as BMSC commitment, osteoblast survival, osteoclast activation matrix calcification and microstructure remodeling, matrix metalloproteinase (MMP) cleavable peptides-based hydrogels could respond to various MMP levels and, thus, accelerate bone regeneration. In this review, we focused on the MMP-cleavable peptides, polymers, functional modification and crosslinked reactions. Applications, perspectives and limitations of MMP-cleavable peptides-based hydrogels for bone regeneration were then discussed

Bone Regeneration Using MMP-Cleavable Peptides-Based Hydrogels

Accumulating evidence has suggested the significant potential of chemically modified hydrogels in bone regeneration. Despite the progress of bioactive hydrogels with different materials, structures and loading cargoes, the desires from clinical applications have not been fully validated. Multiple biological behaviors are orchestrated precisely during the bone regeneration process, including bone marrow mesenchymal stem cells (BMSCs) recruitment, osteogenic differentiation, matrix calcification and well-organized remodeling. Since matrix metalloproteinases play critical roles in such bone metabolism processes as BMSC commitment, osteoblast survival, osteoclast activation matrix calcification and microstructure remodeling, matrix metalloproteinase (MMP) cleavable peptides-based hydrogels could respond to various MMP levels and, thus, accelerate bone regeneration. In this review, we focused on the MMP-cleavable peptides, polymers, functional modification and crosslinked reactions. Applications, perspectives and limitations of MMP-cleavable peptides-based hydrogels for bone regeneration were then discussed

Advanced multilayer composite dressing with co-delivery of gelsevirine and silk fibroin for burn wound healing

Burn is one of the most common types of injuries worldwide, which remains a clinical challenge due to its progressive exacerbation caused by inflammation and edema that impede the growth and differentiation of fibroblast. To solve this problem, in this study, the anti-inflammatory Gelsvirine (Gs), as a specific STING inhibitor for rheumatoid arthritis pain, is used for inflammation control in burn wound healing. Meanwhile, to improve fibroblast migration, proliferation, and differentiation, the natural protein silk fibroin (SF) was used due to its demonstrated capacity to promote the proliferation of epidermal cells and fibroblasts, facilitate collagen synthesis and further improve wound repair. Through our rational design, a functional dressing for the co-delivery of Gs and SF is developed to improve burn wound healing. A multilayer composite dressing of Polycaprolactone(PCL)/Gs-loaded sodium alginate (SA)/SF-gelatin (Gs@SFD) was prepared using the combination of electrospinning and extrusion method, which contained four layers: PCL-dense barrier layer (to prevent infection), SA-hydrogel layer (to load Gs and keep wound moisture), PCL-loosen support layer (to prevent deformation of bioactive layer and to facilitate Gs release into trauma) and SF/gelatin bioactive layer (to contact with trauma and bioactively induce wound healing). Our data showed that the hydrogel layer realized the sustained release of Gs. As a specific inhibitor of STING signaling pathway, the released Gs inhibited the inflammatory response of macrophages and further reduced the fibroblast damage both in vitro and in vivo. In addition, the bioactive layer promoted cell proliferation, facilitated collagen synthesis, and further improved wound healing in animal model of burn trauma. Therefore, this study provides a novel multilayer composite dressing (Gs@SFD) to facilitate burn wound healing via efficient inflammation control with the sustained release of Gs, and improvement on wound healing due to the bioactive components of silk fibroin, which could serve as a potential therapeutic approach in the future. In addition, our multilayer dressing design provides an advanced drug delivery strategy for burn wound healing