Background: Allergic airway diseases (AADs) such as asthma and allergic rhinitis impose a heavy global health burden, characterized by chronic airway inflammation, airway hyperresponsiveness, and structural remodeling. Endoplasmic reticulum (ER) stress has been increasingly identified as a key driver of AAD pathogenesis. As a well-characterized chemical chaperone, tauroursodeoxycholic acid (TUDCA) exhibits promising therapeutic potential for AADs by regulating immunity, relieving inflammation, and reversing airway pathological lesions. Summary: This review summarizes how ER stress drives AAD development and progression of AADs and details the molecular mechanisms underlying the therapeutic effects of TUDCA by targeting ER stress-related unfolded protein response signaling pathways. Additionally, it highlights preclinical evidence supporting the efficacy of TUDCA and discusses the prospects and challenges associated with its clinical translation. Key Messages: ER stress is a key pathogenic factor in AADs; TUDCA can target ER stress-related signaling pathways to exert therapeutic effects on AADs; preclinical studies confirm the efficacy of TUDCA, and its clinical translation may provide a novel ER stress-targeted strategy to optimize AAD management and improve patient outcomes.
Background: Brain tumor-related edema is a major contributor to morbidity in patients with intracranial neoplasms, arising from interactions between blood-brain barrier (BBB) dysfunction, tumor biology, and dysregulated water transport. Aquaporins (AQPs), and particularly AQP4, are central to cerebral water homeostasis, and alterations in their expression and spatial polarization within and around brain tumors influence both cytotoxic and vasogenic edema. This narrative review synthesizes contemporary evidence on AQP biology in the tumor-bearing brain and critically appraises the translational maturity of AQP-directed therapy. Summary: AQP4 is the predominant central nervous system AQP, concentrated at astrocytic end-feet and essential for water flux across the BBB and along glymphatic pathways. In high-grade gliomas, AQP4 is upregulated and loses perivascular polarity, a pattern that accompanies extensive vasogenic edema, impaired perivascular clearance, and enhanced tumor cell invasion. Low-grade gliomas and meningiomas show more restricted or vascular-predominant AQP expression, including AQP1 in meningioma vasculature, and comparatively less peritumoral edema. Experimental work demonstrates a bidirectional, context-dependent role for AQP4: it promotes astrocytic swelling when the BBB is intact, yet facilitates reabsorption of extracellular fluid once the barrier is disrupted. This duality has not been resolved in human tumor tissue and constrains any single-direction therapeutic strategy. Candidate interventions, including small-molecule inhibitors (AER-270/AER-271), monoclonal antibodies, SUR1–TRPM4 modulation, RNA interference, and CRISPR/Cas9-based editing, have shown activity in rodent injury models but have not been evaluated in brain tumor populations. Key Messages: (1) AQP4 is not uniformly pro-edematous; its net effect depends on BBB integrity, edema phase, and preservation of perivascular polarity, so undifferentiated inhibition risks impairing fluid clearance in precisely the tumors that most need it. (2) The evidence base remains dominated by rodent injury models and small immunohistochemical series rather than human tumor tissue, and no AQP-targeted agent has entered a brain tumor trial. (3) Meaningful progress will require human-tissue studies that quantify AQP4 polarity rather than total expression, prospective imaging biomarkers such as diffusion tensor image analysis along the perivascular space capable of stratifying patients before treatment, and astrocyte-targeted, temporally controlled gene-editing approaches rather than constitutive gene deletion.
Introduction: This research aimed to explore healthcare professional (HCP) students’ dementia knowledge, perceptions of older adults’ digital literacy, and perceived usefulness of digital health interventions for people living with dementia and their caregivers. Methods: Semi-structured interviews were conducted to explore HCP student perceptions of cognitive ageing and their understandings of the relationship between technology and healthcare practice. Researchers also explored students’ knowledge of dementia and their contemporary educational experiences. Results: Findings revealed a lack of formal education regarding the use of technology in cognitive care associated with ageing populations. Students also reported limited experience with the use of technology in care. However, there was a positive response to the future possibility of introducing technologies into healthcare practice. Conclusion: Considering the prevalence of dementia globally, we should increase knowledge of dementia and associated digital health support so that future HCPs can make informed choices regarding the utility and effectiveness of digital tools.
Background:Brain metastases are the most common intracranial malignancy in adults and represent a major source of neurologic morbidity despite advances in surgery and radiotherapy. Immune checkpoint inhibitors (ICIs) have transformed systemic cancer therapy and are increasingly demonstrating intracranial activity, challenging the long-standing view of the central nervous system as an immune-privileged site. Summary:This narrative review synthesizes mechanistic, translational, and clinical evidence from the past decade examining immunotherapeutic strategies for metastatic brain tumors. We review the neuroimmune microenvironment of brain metastases, including blood-brain and blood-tumor barrier remodeling, myeloid and lymphoid immune niches, and factors that modulate intracranial immune responses. Clinical data supporting the use of ICIs, combination strategies with stereotactic radiosurgery and anti-angiogenic agents, and emerging cellular, viral, and locoregional immunotherapies are discussed, with attention to patterns of intracranial response, resistance, and toxicity. We further examine key challenges unique to the CNS, including corticosteroid-associated immunosuppression and immune-related imaging ambiguity. Throughout, we emphasize the expanding role of neurosurgeons in precision neuro-immuno-oncology through tissue-based discovery, perioperative treatment coordination, steroid-sparing strategies, and development of locoregional delivery platforms. Key Messages:Immunotherapy has meaningful intracranial activity in selected patients with brain metastases but remains constrained by CNS-specific biological and clinical barriers. Integrating immunotherapy into neurosurgically centered, tissue-driven care pathways are essential for advancing precision treatment and improving neurologic outcomes.
Introduction:Management strategy to improve cognition is one of the challenges faced by clinicians. Importantly, pioglitazone, a safe and cost-effective medication, has been shown to improve memory dysfunction in both animal and some clinical studies. Thus, the aim of this study was to assess and compare the effect of pioglitazone as an add-on therapy in treating cognitive decline in patients with Parkinson's disease, stroke, and dementia. Methods:This is a randomised double blind controlled trial involving individuals with severe to mild cognitive impairment (MoCA score below 26) associated with either Parkinson's disease, stroke, or dementia. All neurological conditions were clinically diagnosed based on the standard criterions. Participants were randomised 1:1 to orally take 15 mg of pioglitazone once daily for 6 months. A total sample size of 252 participants (42 per group across six groups) was calculated to detect a mean difference of 2 points in MoCA score (SD = 3), with 80% power and 5% significance level, accounting for 15% attrition. The primary outcome measure is the change in MoCA score at 6 months. Secondary outcome measures include the assessment of clinical manifestations, cognitive performance, normal neurological markers, adverse drug reactions, and medication adherence over a follow-up period of 6 months and 12 months. Conclusion:The findings of our study are hypothesis-generating. If positive, this study will support larger multicentre trials to validate efficacy, clarify subgroup responsiveness, and inform future metabolic-targeted therapeutic strategies rather than immediate clinical guideline changes.
