Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Dec. 10, 2023

Abstract Ferroptosis, a unique modality of cell death with mechanistic and morphological differences from other modes, plays pivotal role in regulating tumorigenesis offers new opportunity for modulating anticancer drug resistance. Aberrant epigenetic modifications posttranslational (PTMs) promote resistance, cancer progression, metastasis. Accumulating studies indicate that can transcriptionally translationally determine vulnerability to ferroptosis functions as driver nervous system diseases (NSDs), cardiovascular (CVDs), liver diseases, lung kidney diseases. In this review, we first summarize the core molecular mechanisms ferroptosis. Then, roles processes, including histone PTMs, DNA methylation, noncoding RNA regulation such phosphorylation, ubiquitination, SUMOylation, acetylation, ADP-ribosylation, are concisely discussed. The PTMs genesis cancers, NSD, CVDs, well application PTM modulators therapy these then discussed detail. Elucidating mediated by will facilitate development promising combination therapeutic regimens containing or PTM-targeting agents inducers be used overcome chemotherapeutic resistance could prevent addition, highlight potential approaches chemoresistance halt

Language: Английский

---

Recovery of walking after paralysis by regenerating characterized neurons to their natural target region

Science, Journal Year: 2023, Volume and Issue: 381(6664), P. 1338 - 1345

Published: Sept. 21, 2023

Axon regeneration can be induced across anatomically complete spinal cord injury (SCI), but robust functional restoration has been elusive. Whether restoring neurological functions requires directed of axons from specific neuronal subpopulations to their natural target regions remains unclear. To address this question, we applied projection-specific and comparative single-nucleus RNA sequencing identify that restore walking after incomplete SCI. We show chemoattracting guiding the transected these neurons region led substantial recovery SCI in mice, whereas simply lesion had no effect. Thus, reestablishing projections characterized forms an essential part axon strategies aimed at lost functions.

Language: Английский

---

Non-invasive spinal cord electrical stimulation for arm and hand function in chronic tetraplegia: a safety and efficacy trial

Nature Medicine, Journal Year: 2024, Volume and Issue: 30(5), P. 1276 - 1283

Published: May 1, 2024

Abstract Cervical spinal cord injury (SCI) leads to permanent impairment of arm and hand functions. Here we conducted a prospective, single-arm, multicenter, open-label, non-significant risk trial that evaluated the safety efficacy ARC EX Therapy improve functions in people with chronic SCI. involves delivery externally applied electrical stimulation over cervical during structured rehabilitation. The primary endpoints were as measured by whether majority participants exhibited significant improvement both strength functional performance response compared end an equivalent period rehabilitation alone. Sixty completed protocol. No serious adverse events related reported, effectiveness endpoint was met. Seventy-two percent demonstrated improvements greater than minimally important difference criteria for domains. Secondary analysis revealed fingertip pinch force, prehension strength, upper extremity motor sensory abilities self-reported increases quality life. These results demonstrate living ClinicalTrials.gov identifier: NCT04697472 .

Language: Английский

---

Single-cell and spatial atlases of spinal cord injury in the Tabulae Paralytica

Nature, Journal Year: 2024, Volume and Issue: 631(8019), P. 150 - 163

Published: June 19, 2024

Language: Английский

---

Recent advance in bioactive hydrogels for repairing spinal cord injury: material design, biofunctional regulation, and applications

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: July 24, 2023

Abstract Functional hydrogels show potential application in repairing spinal cord injury (SCI) due to their unique chemical, physical, and biological properties functions. In this comprehensive review, we present recent advance the material design, functional regulation, SCI repair applications of bioactive hydrogels. Different from previously released reviews on three-dimensional scaffolds for repair, work focuses strategies design biologically regulation hydrogels, specifically aiming how these significant efforts can promoting performance SCI. We demonstrate various methods techniques fabrication with components such as DNA, proteins, peptides, biomass polysaccharides, biopolymers obtain including cell biocompatibility, self-healing, anti-bacterial activity, injectability, bio-adhesion, bio-degradation, other multi-functions The drugs/growth factors, polymers, nanoparticles, one-dimensional materials, two-dimensional materials highly effective treating are introduced discussed detail. This shows new viewpoints ideas synthesis state-of-the-art knowledges science nanotechnology, will bridge connection biomedicine, further inspire clinical biomedical fields.

Language: Английский

---

Electrical stimulation for therapeutic approach

Deleted Journal, Journal Year: 2023, Volume and Issue: 1(2)

Published: April 1, 2023

Abstract Electrical stimulation as a therapeutic approach is widely applicable in terms of target tissues or effects. This method can be an alternative to conventional therapies for patients who are resistant drugs ineligible surgical operations. In addition, researchers have actively studied how adjust the parameters electrical order improve effectiveness, many already received treatments with stimulation. With respect devices stimulation, recent studies focused on developing reliability safe and long‐term From point view engineers, comprehensive understanding modulates biological system essential develop advanced strategies that provide effective results. Herein, fundamental mechanisms delivering reviewed along requirements need qualified by electrodes. Furthermore, latest advances discussed followed introduction representative applications

Language: Английский

---

Construction of functional neural network tissue combining CBD-NT3-modified linear-ordered collagen scaffold and TrkC-modified iPSC-derived neural stem cells for spinal cord injury repair

Bioactive Materials, Journal Year: 2024, Volume and Issue: 35, P. 242 - 258

Published: Feb. 3, 2024

Induced pluripotent stem cells (iPSCs) can be personalized and differentiated into neural (NSCs), thereby effectively providing a source of transplanted for spinal cord injury (SCI). To further improve the repair efficiency SCI, we designed functional network tissue based on TrkC-modified iPSC-derived NSCs CBD-NT3-modified linear-ordered collagen scaffold (LOCS). We confirmed that transplantation this regenerated neurons synapses, improved microenvironment injured area, enhanced remodeling extracellular matrix, promoted recovery hind limbs in rat SCI model with complete transection. RNA sequencing metabolomic analyses also effect from multiple perspectives revealed its potential mechanism treating SCI. Together, constructed using human iPSCs-derived as seed interaction receptors ligands first time. This therapeutic thus confirming feasibility LOCS valuable direction research.

Language: Английский

---

Transplantation of Neural Stem Cells Loaded in an IGF‐1 Bioactive Supramolecular Nanofiber Hydrogel for the Effective Treatment of Spinal Cord Injury

Advanced Science, Journal Year: 2024, Volume and Issue: 11(17)

Published: March 5, 2024

Abstract Spinal cord injury (SCI) leads to massive cell death, disruption, and demyelination of axons, resulting in permanent motor sensory dysfunctions. Stem transplantation is a promising therapy for SCI. However, owing the poor microenvironment that develops following SCI, bioactivities these grafted stem cells are limited. Cell implantation combined with biomaterial therapies widely studied development tissue engineering technology. Herein, an insulin‐like growth factor‐1 (IGF‐1)‐bioactive supramolecular nanofiber hydrogel (IGF‐1 gel) synthesized can activate IGF‐1 downstream signaling, prevent apoptosis neural (NSCs), improve their proliferation, induce differentiation into neurons oligodendrocytes. Moreover, NSCs carried out gels promotes neurite outgrowth myelin sheath regeneration at lesion sites In addition, enrich extracellular vesicles (EVs) derived from or nerve differentiated via miRNAs related axonal remyelination, even inflammatory environment. These EVs taken up by autologous endogenous regulate differentiation. This study provides adequate evidence treatment potential therapeutic strategy treating

Language: Английский

---

Inhibition of MST1 ameliorates neuronal apoptosis via GSK3β/β-TrCP/NRF2 pathway in spinal cord injury accompanied by diabetes

Redox Biology, Journal Year: 2024, Volume and Issue: 71, P. 103104 - 103104

Published: Feb. 28, 2024

Spinal cord injury (SCI) is a devastating neurological disease that often results in tremendous loss of motor function. Increasing evidence demonstrates diabetes worsens outcomes for patients with SCI due to the higher levels neuronal oxidative stress. Mammalian sterile 20-like kinase (MST1) key mediator stress central nervous system; however, mechanism its action still not clear. Here, we investigated role MST1 activation induced both and diabetes. Diabetes was established mice by diet induction combined intraperitoneal injection streptozotocin (STZ). performed at T10 level through weight dropping. Advanced glycation end products (AGEs) were applied mimic diabetic conditions PC12 cell line vitro. We employed HE, Nissl staining, footprint assessment Basso mouse scale evaluate functional recovery after SCI. Moreover, immunoblotting, qPCR, immunofluorescence protein-protein docking analysis used detect mechanism. Regarding vivo experiments, resulted up-regulation MST1, excessive apoptosis weakened function mice. Furthermore, impeded NRF2-mediated antioxidant defense neurons damaged spinal cord. Treatment AAV-siMST1 could restore properties facilitate reactive oxygen species (ROS) clearance, which subsequently promoted survival improve locomotor recovery. In vitro model found AGEs worsened mitochondrial dysfunction increased cellular While inhibition chemical inhibitor XMU-MP-1 or MST1-shRNA infection restored NRF2 nuclear accumulation transcription downstream enzymes, therefore preventing ROS generation. However, these effects reversed knockdown. Our in-depth studies showed over-activation directly hindered neuroprotective AKT1, fostered ubiquitination degradation via GSK3β/β-TrCP pathway. significantly restores preexisting diabetes, largely attributed GSK3β(Ser 9)/β-TrCP/NRF2 may be promising pharmacological target effective treatment

Language: Английский

---

Edonerpic maleate enhances functional recovery from spinal cord injury with cortical reorganization in non-human primates

Brain Communications, Journal Year: 2025, Volume and Issue: 7(2)

Published: Jan. 1, 2025

Abstract While spinal cord injury (SCI) aggravates the quality of life in humans by severe paralysis, clinical intervention to promote functional recovery from SCI is limited. We recently identified a small compound, edonerpic maleate (edonerpic MA), which accelerates training-dependent motor brain damage rodents (cryo-genic cortical injury) and non-human primates (internal capsule haemorrhage) facilitation experience-dependent synaptic trafficking glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. In present study, we investigated whether MA after primates. Six adult monkeys (Macaca fuscata) received unilateral between C6 C7 segment. After SCI, upper limb function was immediately impaired animals were assigned receive vehicle (n = 3) or 3 mg/kg/day intramuscular injection for 2 months. The rehabilitative training evaluation behaviour using slit task performed 5 days week months SCI. MA-treated group showed significantly improved grasping movements than control group. reached plateau, examined somatotopic map contralesional primary cortex (M1) intracortical microstimulation. representation wrist territory at M1 larger concluded that accompanied reorganization. Since enhances central nervous system multiple levels, treatment with combined may represent novel therapy not only stroke but also

Language: Английский

---