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Hereditary spastic paraplegia (HSP) encompasses a group of rare genetic diseases primarily affecting motor neurons. Among these, spastic paraplegia type 11 (SPG11) represents a complex form of HSP caused by deleterious variants in the SPG11 gene, which encodes the spatacsin protein. Previous studies have described several potential roles for spatacsin, including its involvement in lysosome and autophagy mechanisms, neuronal and neurites development or mitochondria function.
View Article and Find Full Text PDFInterplay of Light, Melatonin, and Circadian Genes in Skin Pigmentation Regulation.
Pigment Cell Melanoma Res
January 2025
Department of Cell Biology and Anatomy, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.
Circadian regulation of skin pigmentation is essential for thermoregulation, ultraviolet (UV) protection, and synchronization of skin cell renewal. This regulation involves both cell-autonomous photic responses and non-cell-autonomous hormonal control, particularly through melatonin produced in a light-sensitive manner. Photosensitive opsins, cryptochromes, and melatonin regulate circadian rhythms in skin pigment cells.
View Article and Find Full Text PDFConcurrent RB1 and P53 pathway disruption predisposes to the development of a primitive neuronal component in high-grade gliomas depending on MYC-driven EBF3 transcription.
Acta Neuropathol
January 2025
Pathology Unit, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
The foremost feature of glioblastoma (GBM), the most frequent malignant brain tumours in adults, is a remarkable degree of intra- and inter-tumour heterogeneity reflecting the coexistence within the tumour bulk of different cell populations displaying distinctive genetic and transcriptomic profiles. GBM with primitive neuronal component (PNC), recently identified by DNA methylation-based classification as a peculiar GBM subtype (GBM-PNC), is a poorly recognized and aggressive GBM variant characterised by nodules containing cells with primitive neuronal differentiation along with conventional GBM areas. In addition, the presence of a PNC component has been also reported in IDH-mutant high-grade gliomas (HGGs), and to a lesser extent to other HGGs, suggesting that regardless from being IDH-mutant or IDH-wildtype, peculiar genetic and/or epigenetic events may contribute to the phenotypic skewing with the emergence of the PNC phenotype.
View Article and Find Full Text PDFHER2-Positive Breast Cancer Treatment and Resistance.
Adv Exp Med Biol
January 2025
Lester & Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.
HER2-positive (+) breast cancer is an aggressive disease with poor prognosis, a narrative that changed drastically with the advent and approval of trastuzumab, the first humanized monoclonal antibody targeting HER2. In addition to another monoclonal antibody, more classes of HER2-targeted agents, including tyrosine kinase inhibitors, and antibody-drug conjugates were developed in the years that followed. While these potent therapies have substantially improved the outcome of patients with HER2+ breast cancer, resistance has prevailed as a clinical challenge ever since the arrival of targeted agents.
View Article and Find Full Text PDFIncreased pro-SFTPB in HDL promotes the pro-inflammatory transition of HDL and represents a sign of poor prognosis in ARDS patients.
J Transl Med
January 2025
Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital, Capital Medical University, N0.5 Jingyuan Road, Beijing, China.
Background: Acute respiratory distress syndrome (ARDS) is causatively associated with excessive alveolar inflammation involving deregulated pro-inflammatory macrophage polarization. High-density lipoprotein (HDL) showed critical anti-inflammatory roles by modulating macrophage function, and its adverse transition to pro-inflammation has an important role in the pathogenesis of ARDS. However, the relationship between HDL protein constituents and functional remodeling is unknown in ARDS.
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