医学最新文献

Neurodegenerative diseases are prevalent conditions that greatly impact human health. These diseases are primarily characterized by the progressive loss and eventual death of neuronal function, although the precise mechanisms underlying these processes remain incompletely understood. Iron is an essential trace element in the human body, playing a crucial role in various biological processes. The maintenance of iron homeostasis relies on the body's intricate and nuanced regulatory mechanisms. In recent years, considerable attention has been directed toward the relationship between dysregulated iron homeostasis and neurodegenerative diseases. The regulation of iron homeostasis within cells is crucial for maintaining proper nervous system function. Research has already revealed that disruptions in iron homeostasis may lead to ferroptosis and oxidative stress, which, in turn, can impact neuronal health and contribute to the development of neurodegenerative diseases. This article primarily explores the intimate relationship between iron homeostasis and neurodegenerative diseases, aiming to provide novel insights and strategies for treating these debilitating conditions.

JOURNAL/nrgr/04.03/01300535-202605000-00037/figure1/v/2025-10-21T121913Z/r/image-tiff Mesenchymal stromal cell transplantation is an effective and promising approach for treating various systemic and diffuse diseases. However, the biological characteristics of transplanted mesenchymal stromal cells in humans remain unclear, including cell viability, distribution, migration, and fate. Conventional cell tracing methods cannot be used in the clinic. The use of superparamagnetic iron oxide nanoparticles as contrast agents allows for the observation of transplanted cells using magnetic resonance imaging. In 2016, the National Medical Products Administration of China approved a new superparamagnetic iron oxide nanoparticle, Ruicun, for use as a contrast agent in clinical trials. In the present study, an acute hemi-transection spinal cord injury model was established in beagle dogs. The injury was then treated by transplantation of Ruicun-labeled mesenchymal stromal cells. The results indicated that Ruicun-labeled mesenchymal stromal cells repaired damaged spinal cord fibers and partially restored neurological function in animals with acute spinal cord injury. T2*-weighted imaging revealed low signal areas on both sides of the injured spinal cord. The results of quantitative susceptibility mapping with ultrashort echo time sequences indicated that Ruicun-labeled mesenchymal stromal cells persisted stably within the injured spinal cord for over 4 weeks. These findings suggest that magnetic resonance imaging has the potential to effectively track the migration of Ruicun-labeled mesenchymal stromal cells and assess their ability to repair spinal cord injury.

Functional neurological recovery remains the primary objective when treating ischemic stroke. However, current therapeutic approaches often fall short of achieving optimal outcomes. One of the most significant challenges in stroke treatment is the effective delivery of neuroprotective agents across the blood-brain barrier to ischemic regions within the brain. The blood-brain barrier, while essential for protecting the brain from harmful substances, also restricts the passage of many therapeutic compounds, thus limiting their efficacy. In this review, we summarizes the emerging role of nanoparticle-based therapies for the treatment of ischemic stroke and investigate their potential to revolutionize drug delivery, enhance neuroprotection, and promote functional recovery. Recent advancements in nanotechnology have led to the development of engineered nanoparticles specifically designed to overcome the blood-brain barrier, thus enabling the targeted delivery of therapeutic agents directly to the affected brain areas. Preclinical studies have demonstrated the remarkable potential of nanoparticle-based therapies to activate key neuroprotective pathways, such as the phosphoinositide 3-kinase/protein kinase B/cAMP response element-binding protein signaling cascade, which is crucial for neuronal survival, synaptic plasticity, and post-stroke recovery. By modulating these pathways, nanoparticles could mitigate neuronal damage, reduce inflammation, and promote tissue repair. Furthermore, nanoparticles offer a unique advantage by enabling multimodal therapeutic strategies that simultaneously target multiple pathological mechanisms of ischemic stroke, including oxidative stress, neuroinflammation, and apoptosis. This multifaceted approach enhances the overall efficacy of treatment, addressing the complex and interconnected processes that contribute to stroke-related brain injury. Surface modifications, such as functionalization with specific ligands or targeting molecules, further improve the precision of drug delivery, enhance targeting specificity, and prolong systemic circulation, thereby optimizing therapeutic outcomes. Nanoparticle-based therapeutics represent a paradigm shift for the management of stroke and provide a promising avenue for reducing post-stroke disability and improving the outcomes of long-term rehabilitation. By combining targeted drug delivery with the ability to modulate critical neuroprotective pathways, nanoparticles hold the potential to transform the treatment landscape for ischemic stroke. However, while preclinical data are highly encouraging, significant challenges remain in translating these advancements into clinical practice. Further research is needed to refine nanoparticle designs, optimize their safety profiles, and ensure their scalability for widespread application. Rigorous clinical trials are essential to validate their efficacy, assess long-term biocompatibility, and address potential off-target effects. The int

Traumatic optic neuropathy is a form of optic neuropathy resulting from trauma. Its pathophysiological mechanisms involve primary and secondary injury phases, leading to progressive retinal ganglion cell loss and axonal degeneration. Contributing factors such as physical trauma, oxidative stress, neuroinflammation, and glial scar formation exacerbate disease progression and retinal ganglion cell death. Multiple forms of cell death-including apoptosis, pyroptosis, necroptosis, and ferroptosis-are involved at different disease stages. Although current treatments, such as corticosteroid therapy and surgical interventions, have limited efficacy, cell-based therapies have emerged as a promising approach that simultaneously promotes neuroprotection and retinal ganglion cell regeneration. This review summarizes recent advances in cell-based therapies for traumatic optic neuropathy. In the context of cell replacement therapy, retinal ganglion cell-like cells derived from embryonic stem cells and induced pluripotent stem cells-via chemical induction or direct reprogramming-have demonstrated the ability to integrate into the host retina and survive for weeks to months, potentially improving visual function. Mesenchymal stem cells derived from various sources, including bone marrow, umbilical cord, placenta, and adipose tissue, have been shown to enhance retinal ganglion cell survival, stimulate axonal regeneration, and support partial functional recovery. Additionally, neural stem/progenitor cells derived from human embryonic stem cells offer neuroprotective effects and function as "neuronal relays," facilitating reconnection between damaged regions of the optic nerve and the visual pathway. Beyond direct cell transplantation, cell-derived products, such as extracellular vesicles and cell-extracted solutions, have demonstrated promising neuroprotective effects in traumatic optic neuropathy. Despite significant progress, several challenges remain, including limited integration of transplanted cells, suboptimal functional vision recovery, the need for precise timing and delivery methods, and an incomplete understanding of the role of the retinal microenvironment and glial cell activation in neuroprotection and neuroregeneration. Furthermore, studies with longer observation periods and deeper mechanistic insights into the therapeutic effects of cell-based therapies remain scarce. Two Phase I clinical trials have confirmed the safety and potential benefits of cell-based therapy for traumatic optic neuropathy, with reported improvements in visual acuity. However, further studies are needed to validate these findings and establish significant therapeutic outcomes. In conclusion, cell-based therapies hold great promise for treating traumatic optic neuropathy, but critical obstacles must be overcome to achieve functional optic nerve regeneration. Emerging bioengineering strategies, such as scaffold-based transplantation, may improve cell survival and axonal

The interleukin-17 family is the key group of cytokines and displays a broad spectrum of biological functions, including regulating the inflammatory cascade in various autoimmune and inflammatory diseases, such as multiple sclerosis, neuromyelitis optica spectrum disorder, myasthenia gravis, Guillain-Barre syndrome, acute disseminated encephalomyelitis, diabetes, inflammatory skin diseases, joint inflammation, and cancer. Although the function of the interleukin-17 family has attracted increasing research attention over many years, the expression, function, and regulation mechanisms of different interleukin-17 members are complicated and still only partially understood. Currently, the interleukin-17A pathway is considered a critical therapeutic target for numerous immune and chronic inflammatory diseases, with several monoclonal antibodies against interleukin-17A having been successfully used in clinical practice. Whether other interleukin-17 members have the potential to be targeted in other diseases is still debated. This review first summarizes the recent advancements in understanding the physicochemical properties, physiological functions, cellular origins, and downstream signaling pathways of different members and corresponding receptors of the interleukin-17 family. Subsequently, the function of interleukin-17 in various immune diseases is discussed, and the important role of interleukin-17 in the pathological process of immune diseases is demonstrated from multiple perspectives. Then, the current status of targeted interleukin-17 therapy is summarized, and the effectiveness and safety of targeted interleukin-17 therapy are analyzed. Finally, the clinical application prospects of targeting the interleukin-17 pathway are discussed.

The capacity of the central nervous system for structural plasticity and regeneration is commonly believed to show a decreasing progression from "small and simple" brains to the larger, more complex brains of mammals. However, recent findings revealed that some forms of neural plasticity can show a reverse trend. Although plasticity is a well-preserved, transversal feature across the animal world, a variety of cell populations and mechanisms seem to have evolved to enable structural modifications to take place in widely different brains, likely as adaptations to selective pressures. Increasing evidence now indicates that a trade-off has occurred between regenerative (mostly stem cell-driven) plasticity and developmental (mostly juvenile) remodeling, with the latter primarily aimed not at brain repair but rather at "sculpting" the neural circuits based on experience. In particular, an evolutionary trade-off has occurred between neurogenic processes intended to support the possibility of recruiting new neurons throughout life and the different ways of obtaining new neurons, and between the different brain locations in which plasticity occurs. This review first briefly surveys the different types of plasticity and the complexity of their possible outcomes and then focuses on recent findings showing that the mammalian brain has a stem cell-independent integration of new neurons into pre-existing (mature) neural circuits. This process is still largely unknown but involves neuronal cells that have been blocked in arrested maturation since their embryonic origin (also termed "immature" or "dormant" neurons). These cells can then restart maturation throughout the animal's lifespan to become functional neurons in brain regions, such as the cerebral cortex and amygdala, that are relevant to high-order cognition and emotions. Unlike stem cell-driven postnatal/adult neurogenesis, which significantly decreases from small-brained, short-living species to large-brained ones, immature neurons are particularly abundant in large-brained, long-living mammals, including humans. The immature neural cell populations hosted in these complex brains are an interesting example of an "enlarged road" in the phylogenetic trend of plastic potential decreases commonly observed in the animal world. The topic of dormant neurons that covary with brain size and gyrencephaly represents a prospective turning point in the field of neuroplasticity, with important translational outcomes. These cells can represent a reservoir of undifferentiated neurons, potentially granting plasticity within the high-order circuits subserving the most sophisticated cognitive skills that are important in the growing brains of young, healthy individuals and are frequently affected by debilitating neurodevelopmental and degenerative disorders.

JOURNAL/nrgr/04.03/01300535-202605000-00035/figure1/v/2025-10-21T121913Z/r/image-tiff The remodeling of axonal connections following injury is an important feature driving functional recovery. The reticulospinal tract is an interesting descending motor tract that contains both excitatory and inhibitory fibers. While the reticulospinal tract has been shown to be particularly prone to axonal growth and plasticity following injuries of the spinal cord, the differential capacities of excitatory and inhibitory fibers for plasticity remain unclear. As adaptive axonal plasticity involves a sophisticated interplay between excitatory and inhibitory input, we investigated in this study the plastic potential of glutamatergic (vGlut2) and GABAergic (vGat) fibers originating from the gigantocellular nucleus and the lateral paragigantocellular nucleus, two nuclei important for locomotor function. Using a combination of viral tracing, chemogenetic silencing, and AI-based kinematic analysis, we investigated plasticity and its impact on functional recovery within the first 3 weeks following injury, a period prone to neuronal remodeling. We demonstrate that, in this time frame, while vGlut2-positive fibers within the gigantocellular and lateral paragigantocellular nuclei rewire significantly following cervical spinal cord injury, vGat-positive fibers are rather unresponsive to injury. We also show that the acute silencing of excitatory axonal fibers which rewire in response to lesions of the spinal cord triggers a worsening of the functional recovery. Using kinematic analysis, we also pinpoint the locomotion features associated with the gigantocellular nucleus or lateral paragigantocellular nucleus during functional recovery. Overall, our study increases the understanding of the role of the gigantocellular and lateral paragigantocellular nuclei during functional recovery following spinal cord injury.