Xinjie Bao

Meningiomas are the most common primary intracranial tumors of the central nervous system. They exhibit highly heterogeneous biological behavior that current histological grading cannot reliably predict. Currently, there are no standardized systemic treatment regimens for recurrent or refractory meningiomas; therefore, molecular subtyping is crucial for assessing prognosis and guiding treatment decisions. Key alterations, including NF2, TERT promoter, CDKN2A/B, AKT1, and SMO, contribute to the proliferation, invasion, and recurrence of meningiomas. This review summarizes the advances in molecular pathological alterations and clinical studies on systemic therapy for meningiomas. Anti-angiogenic agents, immune checkpoint inhibitors, and inhibitors targeting multiple signaling pathways represent promising directions. Anti-angiogenic therapy has demonstrated disease control, whereas PD-1 inhibitors have shown limited benefit in unstratified populations but may be of value in specific molecular subgroups. Molecularly stratified umbrella and basket trials are advancing precision treatment, and peptide receptor radionuclide therapy provides benefit for patients with specific molecular alterations. Some early trials of targeted therapies and immunotherapies have shown positive signals, but the overall level of evidence remains limited. Future studies should employ more rigorous trial designs and encourage patient participation to clarify the clinical value of each strategy and drive the shift from empirical to molecularly guided treatment.

Pituitary neuroendocrine tumors (PitNETs) present significant clinical challenges due to unpredictable invasive behavior and lack of reliable molecular predictors. While the extracellular matrix (ECM), particularly type IV collagen, has emerged as a critical mediator of tumor progression, its mechanistic role in PitNETs remains unclear. Through transcriptomic profiling of patient-derived PitNETs, functional assays in GH3 pituitary tumor cells, and orthotopic allograft models, we identified collagen type IV alpha 3 chain (COL4A3) as a key promoter of tumor invasion. Western blotting and flow cytometry revealed that COL4A3 was markedly upregulated in invasive PitNETs and promoted tumor cell proliferation, invasion, and survival both in vitro and in vivo. Mechanistically, COL4A3 knockdown reduced total FAK, PI3K, and AKT protein levels and altered ERK signaling, suggesting a possible link between COL4A3 and this pathway in promoting invasion, suppressing apoptosis, and driving cell cycle progression. Interestingly, serum COL4A3 levels were paradoxically lower in patients with invasive tumors, suggesting complex ECM remodeling dynamics during invasion that may reflect increased matrix degradation or altered systemic release patterns. These findings establish COL4A3 as a potential regulator of PitNET aggressiveness with dual utility as both a therapeutic target and a potential serum biomarker, offering new molecular insights into ECM-mediated tumor progression and opening avenues for precision diagnostics and treatment strategies.

Extracellular vesicles (EVs) can cross the blood–brain barrier and enter the systemic circulation, potentially acting as peripheral biomarkers of stroke neuropathology. Here, we investigated alterations in EV RNA cargoes extracted from rat brain and plasma before and after stroke induction via middle cerebral artery occlusion and subsequent human neural stem cells (hNSCs) transplantation. EV RNA coexpression profiles were assessed, and digital source tracking was used to determine EV origin. The therapeutic effects of intra‐arterial delivery of hNSCs on ischemic rat brains were quantified, focusing on functional recovery, resolution of ischemic lesions, and the microenvironment. Stroke induced distinct EV secretion patterns, with a notable increase in EV secretion from non‐neuronal cells. hNSCs transplantation caused minimal immune rejection and transplanted cells survived in the brain for over a week. Stem cell‐derived EVs were detected in peripheral blood, indicating prolonged systemic distribution after transplantation. Gene regulatory network analyses identified specific EV miRNAs that play crucial roles in neurogenesis, wound healing, angiogenesis, and blood–brain barrier integrity. An integrated analysis of EV RNAs in brain and plasma samples revealed that stroke increased correlations in RNA expression between brain and plasma and that hNSCs transplantation reversed the effect. Brain‐ and plasma‐derived EVs carry similar molecular information after stroke, suggesting that plasma‐derived EV RNAs reflect stroke pathophysiology. Intra‐arterial transplantation of hNSCs improved outcomes after stroke in rats, by promoting endogenous neurogenesis and maintaining blood–brain barrier integrity. The identified EV miRNAs provided a new mechanism by which hNSCs transplantation regulates neural regeneration through the miR‐204‐5p/EFNB3 axis.

Intracerebral hemorrhage (ICH) carries a substantial global disease burden, and although it occurs less frequently than ischemic stroke, it results in a greater loss of disability-adjusted life years worldwide and is associated with one of the poorest prognoses among stroke patients. Due to the mechanisms of secondary injury following ICH, angiogenesis, inflammation, and oxidative stress (OS) levels in brain tissue are regulated by complex molecular pathways, leading to significant changes in the brain microenvironment (BME). While traditional treatments for ICH improve survival rates, they have notable drawbacks and limitations. Nanomedicines, as a promising approach, offer the potential to gradually overcome these limitations and are becoming increasingly important in ICH treatment research. This review provides an updated overview of the mechanisms behind the formation of the post-ICH BME, focusing on angiogenesis, inflammation, and OS. Conventional diagnostic and therapeutic methods are outlined, along with an analysis of their drawbacks and limitations. In addition, the current research status of nanomedicines targeting the post-ICH BME is systematically summarized from three perspectives: angiogenesis, inflammation, and OS. Finally, the progress of nanomedicines in clinical translation is analyzed, highlighting the challenges, opportunities, and future prospects for their application in the context of ICH.

Stroke has brought about a poor quality of life for patients and a substantial societal burden with high morbidity and mortality. Thus, the efficient stroke treatment has always been the hot topic in the research of medicine. In the past decades, nanobiotechnologies, including natural exosomes and artificial nanomaterials, have been a focus of attention for stroke treatment due to their inherent advantages, such as facile blood - brain barrier traversal and high drug encapsulation efficiency. Recently, thanks to the rapid development of nanobiotechnologies, more and more efforts have been made to study the therapeutic effects of exosomes and artificial nanomaterials as well as relevant mechanisms in stroke treatment. Herein, from recent studies and articles, the application of natural exosomes and artificial nanomaterials in stroke treatment are summarized. And their prospects of clinical translation and future development are also discussed in further detail.

Although thrombolytic therapy has enjoyed relative success, limitations remain, such as a narrow therapeutic window and inconsistent efficacy. Consequently, there is a pressing need to develop novel therapeutic approaches. In recent years, extracellular vesicles (EVs) have garnered increasing attention as a potential alternative to stem cell therapy. Because of their ability to cross the blood–brain barrier and exert neuroprotective effects in cerebral ischemia and hemorrhage, the exploration of EVs for clinical application in stroke treatment is expanding. EVs are characterized by high heterogeneity, with their composition closely mirroring that of their parent cells. This property enables EVs to distinguish between cerebral ischemia and hemorrhage, thus facilitating a more rapid and accurate diagnosis. Additionally, EVs can be engineered to carry specific molecules, such as miRNAs, targeting them to specific cells, potentially enhancing the therapeutic outcome and improving stroke prognosis. In this review, we will also explore the methodologies for the isolation and extraction of EVs, critically evaluating the advantages and disadvantages of various commonly employed separation techniques. Furthermore, we will briefly address current EV preservation and administration methods, providing a comprehensive overview of the state of EV-based therapies in stroke treatment.

Ischemic stroke is a significant global health crisis, frequently resulting in disability or death, with limited therapeutic interventions available. Although various intrinsic reparative processes are initiated within the ischemic brain, these mechanisms are often insufficient to restore neuronal functionality. This has led to intensive investigation into the use of exogenous stem cells as a potential therapeutic option. This comprehensive review outlines the ontogeny and mechanisms of activation of endogenous neural stem cells within the adult brain following ischemic events, with focus on the impact of stem cell-based therapies on neural stem cells. Exogenous stem cells have been shown to enhance the proliferation of endogenous neural stem cells via direct cell-to-cell contact and through the secretion of growth factors and exosomes. Additionally, implanted stem cells may recruit host stem cells from their niches to the infarct area by establishing so-called “biobridges.” Furthermore, xenogeneic and allogeneic stem cells can modify the microenvironment of the infarcted brain tissue through immunomodulatory and angiogenic effects, thereby supporting endogenous neuroregeneration. Given the convergence of regulatory pathways between exogenous and endogenous stem cells and the necessity for a supportive microenvironment, we discuss three strategies to simultaneously enhance the therapeutic efficacy of both cell types. These approaches include: (1) co-administration of various growth factors and pharmacological agents alongside stem cell transplantation to reduce stem cell apoptosis; (2) synergistic administration of stem cells and their exosomes to amplify paracrine effects; and (3) integration of stem cells within hydrogels, which provide a protective scaffold for the implanted cells while facilitating the regeneration of neural tissue and the reconstitution of neural circuits. This comprehensive review highlights the interactions and shared regulatory mechanisms between endogenous neural stem cells and exogenously implanted stem cells and may offer new insights for improving the efficacy of stem cell-based therapies in the treatment of ischemic stroke.