Metabolic reprogramming: a new option for the treatment of spinal cord injury.

Spinal cord injuries impose a notably economic burden on society, mainly because of the severe after-effects they cause. Despite the ongoing development of various therapies for spinal cord injuries, their effectiveness remains unsatisfactory. However, a deeper understanding of metabolism has opened up a new therapeutic opportunity in the form of metabolic reprogramming.

Silencing circATXN1 in Aging Nucleus Pulposus Cell Alleviates Intervertebral Disc Degeneration via Correcting Progerin Mislocalization.

Circular RNAs (circRNAs) play a critical regulatory role in degenerative diseases; however, their functions and therapeutic applications in intervertebral disc degeneration (IVDD) have not been explored. Here, we identified that a novel circATXN1 highly accumulates in aging nucleus pulposus cells (NPCs) accountable for IVDD. CircATXN1 accelerates cellular senescence, disrupts extracellular matrix organization, and inhibits mitochondrial respiration.

A novel rat model of annulus fibrosus injury for intervertebral disc degeneration.

Background Context: In clinical practice, acute trauma and chronic degeneration of the annulus fibrosus (AF) can promote further degeneration of the intervertebral disc (IVD). Therefore, it is critical to understand the AF repair process and its consequences on IVD. However, the lack of cost-effective and reproducible in vivo animal models of AF injury has limited research development in this field.

Controlled extracellular vesicles release from aminoguanidine nanoparticle-loaded polylysine hydrogel for synergistic treatment of spinal cord injury.

Pharmaceutical treatments are critical for the acute and subacute phases of spinal cord injury (SCI) and significantly impact patients' prognoses. However, there is a lack of a precise, multitemporal, integrated drug delivery system for medications administered in both phases. In this study, we prepare a hybrid polylysine-based hydrogel (PBH@AGN) comprising short-term release of pH-responsive aminoguanidine nanoparticles (AGN) and sustained release of extracellular vesicles (EVs) for synergistic SCI treatment.

Thermosensitive hydrogel-based GPR124 delivery strategy for rebuilding blood-spinal cord barrier.

Spinal cord injury (SCI) causes blood-spinal cord barrier (BSCB) disruption, leading to secondary damage, such as hemorrhagic infiltration, inflammatory response, and neuronal cell death. It is of great significance to rebuild the BSCB at the early stage of SCI to alleviate the secondary injury for better prognosis. Yet, current research involved in the reconstruction of BSCB is insufficient.

Metabolic Glycoengineering: A Promising Strategy to Remodel Microenvironments for Regenerative Therapy.

Cell-based regenerative therapy utilizes the differentiation potential of stem cells to rejuvenate tissues. But the dynamic fate of stem cells is calling for precise control to optimize their therapeutic efficiency. Stem cell fate is regulated by specific conditions called "microenvironments.

Development of Uveal Melanoma-Specific Aptamer for Potential Biomarker Discovery and Targeted Drug Delivery.

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. However, challenges in early diagnosis, high risk of liver metastasis, and lack of effective targeted therapy lead to poor prognosis and high mortality of UM. Therefore, generating an effective molecular tool for UM diagnosis and targeted treatment is of great significance.

Swelling-Mediated Mechanical Stimulation Regulates Differentiation of Adipose-Derived Mesenchymal Stem Cells for Intervertebral Disc Repair Using Injectable UCST Microgels.

Mechanical stimulation is an effective approach for controlling stem cell differentiation in tissue engineering. However, its realization in in vivo tissue repair remains challenging since this type of stimulation can hardly be applied to injectable seeding systems. Here, it is presented that swelling of injectable microgels can be transformed to in situ mechanical stimulation via stretching the cells adhered on their surface.

Collagen Niches Affect Direct Transcriptional Conversion toward Human Nucleus Pulposus Cells via Actomyosin Contractility.

Cellular niches play fundamental roles in regulating cellular behaviors. However, the effect of niches on direct converted cells remains unexplored. In the present study, the specific combination of transcription factors is first identified to directly acquire induced nucleus pulposus-like cells (iNPLCs).

Direct Reprogramming in Bone and Joint Degenerative Diseases: Applications, Obstacles and Directions.

With a booming aging population worldwide, bone and joint degenerative diseases have gradually become a major public health focus, attracting extensive scientific attention. However, the effective treatments of these degenerative diseases have been confined to traditional medications and surgical interventions, which easily lead to the possibility of drug abuse or loss of physiological function to varying degrees. Recently, given that the development of reprogramming has overcome shackles in the field of degenerative diseases, direct reprogramming would provide a new concept to accelerate progress in the therapy of bone and joint degenerative diseases.

A conductive supramolecular hydrogel creates ideal endogenous niches to promote spinal cord injury repair.

The current effective method for treatment of spinal cord injury (SCI) is to reconstruct the biological microenvironment by filling the injured cavity area and increasing neuronal differentiation of neural stem cells (NSCs) to repair SCI. However, the method is characterized by several challenges including irregular wounds, and mechanical and electrical mismatch of the material-tissue interface. In the current study, a unique and facile agarose/gelatin/polypyrrole (Aga/Gel/PPy, AGP3) hydrogel with similar conductivity and modulus as the spinal cord was developed by altering the concentration of Aga and PPy.

Enhancement of nucleus pulposus repair by glycoengineered adipose-derived mesenchymal cells.

Adipose-derived mesenchymal stem cells (ADSCs) are promising candidates for repairing degenerated intervertebral discs through multiple means, including: i. Secretion of bioactive factors to regulate inflammation and, ii. The potential to differentiate into nucleus pulposus (NP)-like cells, which can integrate into host tissues.

Therapeutic difference between orbital decompression and glucocorticoids administration as the first-line treatment for dysthyroid optic neuropathy: a systematic review.

To assess all available data to compare the efficacy of glucocorticoids treatment and orbital decompression for dysthyroid optic neuropathy (DON). PubMed, EMBASE, the Cochrane Library databases as well as other sources were searched by two independent reviewers followed by extensive hand-searching for the identification of relevant studies. The primary outcomes were the improvement in visual acuity and responder rate.

A bioactive injectable self-healing anti-inflammatory hydrogel with ultralong extracellular vesicles release synergistically enhances motor functional recovery of spinal cord injury.

The repair and motor functional recovery after spinal cord injury (SCI) remains a worldwide challenge. The inflammatory microenvironment is one of main obstacles on inhibiting the recovery of SCI. Using mesenchymal stem cells (MSCs) derived extracellular vesicles to replace MSCs transplantation and mimic cell paracrine secretions provides a potential strategy for microenvironment regulation.

Interpreting the Mechanisms by which Integrins Promote the Differentiation of Mesenchymal Stem Cells and Integrin Application Prospects.

Transmembrane integrin receptors represent a major component of cell-extracellular matrix (ECM) communications that mediate cellular biological activities, including proliferation and differentiation. Stem cells, especially mesenchymal stem cells (MSC), have rapidly emerged as promising therapies for various diseases. Dynamic links exist between extracellular and intracellular environments that profoundly influence the cellular activities via integrin receptors, such as cell morphology transformation and differentiation.

Cell Senescence: A Nonnegligible Cell State under Survival Stress in Pathology of Intervertebral Disc Degeneration.

The intervertebral disc degeneration (IDD) with increasing aging mainly manifests as low back pain (LBP) accompanied with a loss of physical ability. These pathological processes can be preliminarily interpreted as a series of changes at cellular level. In addition to cell death, disc cells enter into the stagnation with dysfunction and deteriorate tissue microenvironment in degenerative discs, which is recognized as cell senescence.

Strategies and prospects of effective neural circuits reconstruction after spinal cord injury.

Due to the disconnection of surviving neural elements after spinal cord injury (SCI), such patients had to suffer irreversible loss of motor or sensory function, and thereafter enormous economic and emotional burdens were brought to society and family. Despite many strategies being dealing with SCI, there is still no effective regenerative therapy. To date, significant progress has been made in studies of SCI repair strategies, including gene regulation of neural regeneration, cell or cell-derived exosomes and growth factors transplantation, repair of biomaterials, and neural signal stimulation.

Overexpression of the transcription factors OCT4 and KLF4 improves motor function after spinal cord injury.

Introduction: Astrogliosis and glial scar formation following spinal cord injury (SCI) are viewed as major obstacles that hinder axonal regeneration and functional recovery. Regulating the glial scar and axonal regeneration in the lesion site is important for treating SCI.

Aims: Considering the important role of astrocyte in glial scar formation and subsequent axonal regeneration, we intended to investigate the effect of the transcription factors OCT4 and KLF4 on astrocyte and the underlying mechanism after spinal cord contusion injury in transgenic mice.

Transplantation Strategies for Spinal Cord Injury Based on Microenvironment Modulation.

Spinal cord injury (SCI) is different from peripheral nerve injury; it results in devastating and permanent damage to the spine, leading to severe motor, sensory and autonomic dysfunction. SCI produces a complex microenvironment that can result in hemorrhage, inflammation and scar formation. Not only does it significantly limit regeneration, but it also challenges a multitude of transplantation strategies.

An injectable recombinant human milk fat globule-epidermal growth factor 8-loaded copolymer system for spinal cord injury reduces inflammation through NF-κB and neuronal cell death.

Spinal cord injury (SCI) is a common disease and a major cause of paralysis, carrying much burden around the world. Despite the progress made with growth factors therapy, the response rate of acute SCI treatment still remains unsatisfactory, due largely to complex and severe inflammatory reactions. Herein, we prepare a MFG-E8-loaded copolymer system-based anti-inflammation therapy for SCI treatment.

Effects of Rhizoma Drynariae Cataplasm on Fracture Healing in a Rat Model of Osteoporosis.

BACKGROUND Osteoporosis is an increasingly prevalent disease characterized by decreased bone mass and deterioration of the bone microstructure, which contribute to increased fragility and subsequent fragility fractures, especially in elderly individuals. Rhizoma Drynariae (DRE) is among the most frequently used herbal medicines for the treatment of osteoporosis. Transdermal delivery is a proven novel pathway for drug treatment and has several advantages over traditional drug delivery routes.