Hydrocephalus is one of the most common brain disorders and a life-long incurable condition. An empirical "one-size-fits-all" approach of cerebrospinal fluid (CSF) shunting remains the mainstay of hydrocephalus treatment and effective pharmacotherapy options are currently lacking. Macrophage-mediated ChP inflammation and CSF hypersecretion have recently been identified as a significant discovery in the pathogenesis of hydrocephalus. In this study, a pioneering DNA nano-drug (TSOs) is developed by modifying S2 ssDNA and S4 ssDNA with SPAK ASO and OSR1 ASO in tetrahedral framework nucleic acids (tFNAs) and synthesis via a one-pot annealing procedure. This construct can significantly knockdown the expression of SPAK and OSR1, along with their downstream ion channel proteins in ChP epithelial cells, thereby leading to a decrease in CSF secretion. Moreover, these findings indicate that TSOs effectively inhibit the M0 to M1 phenotypic switch of ChP macrophages via the MAPK pathways, thus mitigating the cytokine storm. In in vivo post-hemorrhagic hydrocephalus (PHH) models, TSOs significantly reduce CSF secretion rates, alleviate ChP inflammation, and prevent the onset of hydrocephalus. These compelling results highlight the potential of TSOs as a promising therapeutic option for managing hydrocephalus, with significant applications in the future.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11077654 | PMC |
http://dx.doi.org/10.1002/advs.202306622 | DOI Listing |
Neoplasia
December 2024
Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital Hsinchu Branch, Hsinchu, Taiwan.
Leptomeningeal metastasis (LM) is a challenging complication of non-small cell lung cancer (NSCLC). Cerebrospinal fluid (CSF) cell-free DNA (cfDNA) analysis using next-generation sequencing (NGS) offers insights into resistance mechanisms and potential treatment strategies. We conducted a study from February 2022 to April 2023 involving patients from five hospitals in Taiwan who had recurrent or advanced NSCLC with LM.
View Article and Find Full Text PDFNat Cancer
December 2024
Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
The cerebrospinal fluid (CSF) border accommodates diverse immune cells that permit peripheral cell immunosurveillance. However, the intricate interactions between CSF immune cells and infiltrating cancer cells remain poorly understood. Here we use fate mapping, longitudinal time-lapse imaging and multiomics technologies to investigate the precise origin, cellular crosstalk and molecular landscape of macrophages that contribute to leptomeningeal metastasis (LM) progression.
View Article and Find Full Text PDFBMC Infect Dis
December 2024
Central Laboratory, Chongqing Public Health Medical Centre, Chongqing, China.
Background: In acquired immunodeficiency syndrome patients, Talaromyces marneffei infections are mostly disseminated and may involve the skin, mucosa, respiratory system, digestive system, lymphatic system, and as some reports indicate, the nervous system. Mp1p, a cell wall-specific polysaccharide in Talaromyces marneffei, is used for laboratory diagnosis of Talaromyces marneffei in blood and urine samples. However, Cerebrospinal fluid Mp1p diagnosis of Talaromyces marneffei central nervous system infection has not been reported.
View Article and Find Full Text PDFJ Neuroimmunol
December 2024
Department of Neurology, Mayo Clinic, Rochester, MN, USA; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA; Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, MN, USA. Electronic address:
IgLON5 autoimmunity is characterized by a diverse range of clinical presentations, including neuropsychiatric symptoms, sleep disturbances, gait instability, and bulbar symptoms, that are usually insidiously progressive. While some individuals with specific HLA haplotypes may be more susceptible to developing anti-IgLON5 disease, this antibody is typically not associated with a paraneoplastic etiology nor known to be induced by immune checkpoint inhibitors (ICI). We present a clinical and serological workup of a patient who developed symptoms of IgLON5 autoimmunity following treatment with pembrolizumab.
View Article and Find Full Text PDFAlzheimers Res Ther
December 2024
Department of Neurology and Institute on Aging and Brain Disorders, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Lujiang Road 17, Hefei, 230001, China.
Background: Recent research has postulated that the activation of cGAS-STING-interferon signalling pathways could be implicated in the pathogenesis of Alzheimer's disease (AD). However, the precise types of interferons and related cytokines, both from the brain and periphery, responsible for cognitive impairment in patients with AD remain unclear.
Methods: A total of 131 participants (78 [59.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!