Role of transforming growth factor-βin peripheral nerve regeneration

Injuries caused by trauma and neurodegenerative diseases can damage the peripheral nervous system and cause functional deficits.Unlike in the central nervous system,damaged axons in peripheral nerves can be induced to regenerate in response to intrinsic cues after reprogramming or in a growth-promoting microenvironment created by Schwann cells.However,axon regeneration and repair do not automatically result in the restoration of function,which is the ultimate therapeutic goal but also a major clinical challenge.Transforming growth factor(TGF)is a multifunctional cytokine that regulates various biological processes including tissue repair,embryo development,and cell growth and differentiation.There is accumulating evidence that TGF-βfamily proteins participate in peripheral nerve repair through various factors and signaling pathways by regulating the growth and transformation of Schwann cells;recruiting specific immune cells;controlling the permeability of the blood-nerve barrier,thereby stimulating axon growth;and inhibiting remyelination of regenerated axons.TGF-βhas been applied to the treatment of peripheral nerve injury in animal models.In this context,we review the functions of TGF-βin peripheral nerve regeneration and potential clinical applications.

A biomimetic nanocomposite with enzyme-like activities and CXCR4 antagonism efficiently enhances the therapeutic efficacy of acute myeloid leukemia

Despite the progress made to improve therapeutic outcomes for acute myeloid leukemia(AML),many unmet clinical needs remain to be resolved.Unlike existing anti-AML strategies,here we developed a biomimetic nanocomposite to efficiently eliminate the leukemia cells in the bone marrow and prevent the homing of AML.To fulfill our design,the ultra-small nanozyme was conjugated onto the surface of an oxygen-carrying nanoparticle,which was further coated with bone marrow stromal cell membrane.After entering the blood,this biomimetic nanocomposite got actively internalized by the leukemia cells in the blood and released the loaded chemotherapeutics and nanozyme inside the leukemia cells to achieve a synergistic antitumor efficacy.Meanwhile,the adhesive properties of the stromal cell membrane enabled the nanocomposite to home to the bone marrow,where the nanocomposite effectively killed the retained leukemia cells.More importantly,the biomimetic cell membrane also acted as a CXCR4 antagonism to block the CXCR4/CXCL12-mediated homing of leukemia cells to the bone marrow and infiltration to other organs like the liver and spleen.In conclusion,this proof-of-concept study demonstrated that our designed platform effectively kills leukemia cells while preventing their infiltration,thus providing a promising prospect for resolving the clinical challenges in current AML treatment.