Critical involvement of lysyl oxidase in seizure-induced neuronal damage through ERK-Alox5-dependent ferroptosis and its therapeutic implications

Recent insights collectively suggest the important roles of lysyl oxidase(LysOX)in the pathological processes of several acute and chronic neurological diseases,but the molecular regulatory mechanisms remain elusive.Herein,we explore the regulatory role of LysOX in the seizure-induced ferroptotic cell death of neurons.Mechanistically,LysOX promotes ferroptosis-associated lipid peroxidation in neurons via activating extracellular regulated protein kinase(ERK)-dependent 5-lipoxygenase(Alox5)signaling.In addition,overexpression of LysOX via adeno-associated viral vector(AAV)-based gene transfer enhances ferroptosis sensitivity and aggravates seizure-induced hippocampal damage.Our studies show that pharmacological inhibition of LysOX withβ-aminopropionitrile(BAPN)significantly blocks seizure-induced ferroptosis and thereby alleviates neuronal damage,while the BAPN-associated cardiotoxicity and neurotoxicity could further be reduced through encapsulation with bioresponsive amorphous calcium carbonate-based nanocarriers.These findings unveil a previously unrecognized LysOX-ERK-Alox5 pathway for ferroptosis regulation during seizure-induced neuronal damage.Suppressing this pathway may yield therapeutic implications for restoring seizure-induced neuronal injury.

Constructions of ROS-responsive titanium-hydroxyapatite implant for mesenchymal stem cell recruitment in peri-implant space and bone formation in osteoporosis microenvironment

To solve the issue of unsatisfactory recruitment of mesenchymal stem cells(MSCs)around implant in osteoporotic fractures,we fabricated a ROS-responsive system on titanium surface through hydroxyapatite coating and biomolecule grafting.The porous hydroxyapatite and phosphorylated osteogenic growth peptides(p-OGP)were introduced onto titanium surface to synergistically improve osteogenic differentiation of MSCs.After the p-OGPpromoted expression of osteogenic related proteins,the calcium and phosphate ions were released through the degradation of hydroxyapatite and integrated into bone tissues to boost the mineralization of bone matrix.The ROS-triggered release of DNA aptamer(Apt)19S in the osteoporotic microenvironment guides MSC migration to implant site due to its high affinity with alkaline phosphatase on the membrane of MSCs.Once MSCs reached the implant interface,their osteogenic differentiation potential was enhanced by p-OGP and hydroxyapatite to promote bone regeneration.The study here provided a simple and novel strategy to prepare functional titanium implants for osteoporotic bone fracture repair.

Recent advancements in 2D nanomaterials for cancer therapy

Since mechanical exfoliation of graphene in 2004, unprecedented scientific and technological advances have been achieved in the development of two-dimensional(2 D) nanomaterials. These 2 D nanomaterials exhibit various unique mechanical, physical and chemical properties on account of their ultrathin thickness, which are highly desirable for many applications such as catalysis, optoelectronics, energy storage/conversion, as well as disease diagnosis and therapeutics. In this review, we summarized recent progress on the design and fabrication of functional 2 D nanomaterials capable of being applied for the cancer treatment including drug delivery, photodynamic therapy, and photothermal therapy. Their anticancer mechanisms were discussed in detail, and the related safety concerns were analyzed based on current research developments. This review is expected to provide an insight in the field of 2 D nanostructured materials for anticancer applications.