Glioblastoma is a highly aggressive primary brain tumor with glioblastoma stem cells (GSCs) enforcing the intra-tumoral hierarchy. Plasma cells (PCs) are critical effectors of the B-lineage immune system, but their roles in glioblastoma remain largely unexplored. Here, we leverage single-cell RNA and B cell receptor sequencing of tumor-infiltrating B-lineage cells and reveal that PCs are aberrantly enriched in the glioblastoma-infiltrating B-lineage population, experience low level of somatic hypermutation, and are associated with poor prognosis.
View Article and Find Full Text PDFTumors reprogram their metabolism to generate complex neoplastic ecosystems. Here, we demonstrate that glioblastoma (GBM) stem cells (GSCs) display elevated activity of the malate-aspartate shuttle (MAS) and expression of malate dehydrogenase 2 (MDH2). Genetic and pharmacologic targeting of MDH2 attenuated GSC proliferation, self-renewal, and in vivo tumor growth, partially rescued by aspartate.
View Article and Find Full Text PDFMYC promotes tumor growth through multiple mechanisms. Here, we show that, in human glioblastomas, the variant transcript encodes a 114-amino acid peptide, MYC pre-mRNA encoded protein (MPEP), from the upstream open reading frame (uORF) . Secreted MPEP promotes patient-derived xenograft tumor growth in vivo, independent of MYC through direct binding, and activation of tropomyosin receptor kinase B (TRKB), which induces downstream AKT-mTOR signaling.
View Article and Find Full Text PDFGlioblastomas (GBM) are incurable central nervous system (CNS) cancers characterized by substantial myeloid cell infiltration. Whether myeloid cell-directed therapeutic targets identified in peripheral non-CNS cancers are applicable to GBM requires further study. Here, we identify that the critical immunosuppressive target in peripheral cancers, triggering receptor expressed on myeloid cells-2 (TREM2), is immunoprotective in GBM.
View Article and Find Full Text PDFEthnopharmacological Relevance: In recent years, Chinese herbal medicine has gained more and more recognition in disease prevention and control due to its low toxicity and comprehensive treatment. C. morifolium (Chrysanthemum morifolium Ramat.
View Article and Find Full Text PDFGlioblastoma (GBM) is the most aggressive malignant primary brain tumor characterized by a highly heterogeneous and immunosuppressive tumor microenvironment (TME). The symbiotic interactions between glioblastoma stem cells (GSCs) and tumor-associated macrophages (TAM) in the TME are critical for tumor progression. Here, we identified that IFI35, a transcriptional regulatory factor, plays both cell-intrinsic and cell-extrinsic roles in maintaining GSCs and the immunosuppressive TME.
View Article and Find Full Text PDFBackground: Adjunctive newer antiseizure medications (ASMs) are being used in patients with treatment-resistant focal-onset seizures (FOS). An updated network meta-analysis (NMA) was necessary to compile evidence in this critical area.
Methods: We systematically searched PubMed, Embase, Cochrane Library, Web of Science, and Scopus from their inception until 17 January 2024, evaluating the efficacy, tolerability, and safety of rufinamide (RUF), brivaracetam (BRV), cenobamate (CNB), eslicarbazepine (ESL), lacosamide (LCM), retigabine (RTG), and perampanel (PER) as adjunctive treatments for FOS.
Int J Biol Macromol
February 2024
TGA transcription factors (TFs), belonging to the D clade of the basic region leucine zipper (bZIP) family, exhibit a specific ability to recognize and bind to regulatory elements with TGACG as the core recognition sequence, enabling the regulation of target gene expression and participation in various biological regulatory processes. In plant growth and development, TGA TFs influence organ traits and phenotypes, including initial root length and flowering time. They also play a vital role in responding to abiotic stresses like salt, drought, and cadmium exposure.
View Article and Find Full Text PDFPreoperative MRI is an essential diagnostic and therapeutic reference for gliomas. This study aims to evaluate the prognostic aspect of a radiomics biomarker for glioma and further investigate its relationship with tumor microenvironment and macrophage infiltration. We covered preoperative MRI of 664 glioma patients from three independent datasets: Jiangsu Province Hospital (JSPH, n = 338), The Cancer Genome Atlas dataset (TCGA, n = 252), and Repository of Molecular Brain Neoplasia Data (REMBRANDT, n = 74).
View Article and Find Full Text PDFPurpose: The dynamic interplay between glioblastoma stem cells (GSC) and tumor-associated macrophages (TAM) sculpts the tumor immune microenvironment (TIME) and promotes malignant progression of glioblastoma (GBM). However, the mechanisms underlying this interaction are still incompletely understood. Here, we investigate the role of CXCL8 in the maintenance of the mesenchymal state of GSC populations and reprogramming the TIME to an immunosuppressive state.
View Article and Find Full Text PDFBackground: Glioblastomas (GBMs) display striking dysregulation of metabolism to promote tumor growth. Glioblastoma stem cells (GSCs) adapt to regions of heterogeneous nutrient availability, yet display dependency on de novo cholesterol biosynthesis. The transcription factor Sterol Regulatory Element-Binding Protein 2 (SREBP2) regulates cholesterol biosynthesis enzymes and uptake receptors.
View Article and Find Full Text PDFUnlabelled: Radiotherapy is a major component of standard-of-care treatment for gliomas, the most prevalent type of brain tumor. However, resistance to radiotherapy remains a major concern. Identification of mechanisms governing radioresistance in gliomas could reveal improved therapeutic strategies for treating patients.
View Article and Find Full Text PDFEthnopharmacological Relevance: Bamboos are perennial evergreen plants that belong to the subfamily Bambusoideae of the true grass family Poaceae, with more than thousands of species distributed around the world. They are used as a traditional medicine with demonstrated effects of anti-oxidation, free radical scavenging, anti-inflammatory, liver protection and ameliorating cognitive deficits. Bamboo leaf is mainly used for the treatment of atherosclerotic, diabetic and nervous system diseases.
View Article and Find Full Text PDFUnlabelled: Glioblastoma (GBM) is a complex ecosystem that includes a heterogeneous tumor population and the tumor-immune microenvironment (TIME), prominently containing tumor-associated macrophages (TAM) and microglia. Here, we demonstrated that β2-microglobulin (B2M), a subunit of the class I major histocompatibility complex (MHC-I), promotes the maintenance of stem-like neoplastic populations and reprograms the TIME to an anti-inflammatory, tumor-promoting state. B2M activated PI3K/AKT/mTOR signaling by interacting with PIP5K1A in GBM stem cells (GSC) and promoting MYC-induced secretion of transforming growth factor-β1 (TGFβ1).
View Article and Find Full Text PDFCineraria () is an ornamental plant with pure colour and bicolour cultivars, widely used for landscaping. Anthocyanin biosynthesis influences coloration patterns in cineraria. However, how anthocyanins accumulate and distribute in cineraria is poorly understood.
View Article and Find Full Text PDFBackground: PCSK9 gene expression is associated with biological processes such as lipid metabolism, glucose metabolism, and inflammation. In the present study, our primary objective was to assess the association between the single-nucleotide polymorphisms in the PCSK9 gene and type 2 diabetes in Uygur subjects, in Xinjiang, China.
Methods: We designed a case-control study including 662 patients diagnosed with T2DM and 1220 control subjects.
We develop a method for lattice QCD calculation of the two-photon exchange contribution to the muonic-hydrogen Lamb shift. To demonstrate its feasibility, we present the first lattice calculation with a gauge ensemble at m_{π}=142 MeV. By adopting the infinite-volume reconstruction method along with an optimized subtraction scheme, we obtain with statistical uncertainty ΔE_{TPE}=-28.
View Article and Find Full Text PDFForensic firearm analysis concerns an attempt to determine if ammunition is associated with a specific firearm based on tool-marks produced by it. A feature-based method using the Scale Invariant Feature Transform (SIFT) and RANdom SAmple Consensus (RANSAC) integration algorithm had been suggested to allow the automated comparison of breech face impressions. In this paper, an estimation method is proposed to establish a correspondence function among the features of comparison impression pairs, aiming to further improve the robustness and repeatability of automated feature matching.
View Article and Find Full Text PDFCarotenoids are one of the most important pigments for the coloring in many plants, fruits and flowers. Recently, significant progress has been made in carotenoid metabolism. However, the specific understanding on transcriptional regulation controlling the expression of carotenoid metabolic genes remains extremely limited.
View Article and Find Full Text PDFCultivated chrysanthemum (Chrysanthemum × morifolium Ramat.) is a beloved ornamental crop due to the diverse capitula types among varieties, but the molecular mechanism of capitulum development remains unclear. Here, we report a 2.
View Article and Find Full Text PDFAnthocyanins are important flavonoid pigments involved in the colouring of flowers and fruits. They are synthesized on the cytoplasmic surface of the endoplasmic reticulum and transported into the vacuole for storage. Previous reports have suggested that glutathione S-transferase (GST) is involved in anthocyanin transport.
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