Traumatic brain injury (TBI), particularly at high altitudes (HA-TBI), is a leading cause of mortality and disability, yet clear diagnostic and treatment protocols are lacking. This study explores the early pathophysiological changes occurring within 24 h following HA-TBI, with a focus on differentially expressed proteins (DEPs) and phosphorylated proteins (DEPPs). Using a low-pressure hypoxic chamber to simulate high-altitude conditions combined with a controllable cortical impact (CCI) model, we established a rat model of HA-TBI. Neurological function was evaluated using the modified Neurologic Severity Score (mNSS), while neuropathological and inflammatory responses following HA-TBI were evaluated through hematoxylin and eosin (HE) staining, immunofluorescence, Western blot (WB), and Enzyme-Linked Immunosorbent Assay (ELISA). In-depth proteomic and phosphoproteomic analyses were performed on the cerebral cortex at 6, 12, and 24 h post-injury. Bioinformatic analysis identified time-dependent DEPs, revealing dynamic changes in mRNA metabolism, ATP metabolism, and MAPK signaling during the early stages of HA-TBI. Common DEPs at 6, 12, and 24 h post-injury were linked to complement and coagulation cascades. Time-dependent DEPPs influenced synaptic structure and neurotransmission, with early changes in glutamatergic synapses being especially pronounced. Key pathways, including the complement and coagulation cascades and dopaminergic synapses, emerged as central to the injury response. Furthermore, proteins such as AHSG, APOA1, GRIN2B, phospho-GSK3β-S9, and CAMK2G were identified as critical regulators in these pathways. WB validated these findings, offering new insights into the mechanisms underlying HA-TBI and highlighting potential therapeutic targets for early intervention in high-altitude trauma.
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http://dx.doi.org/10.1016/j.expneurol.2025.115147 | DOI Listing |
Exp Neurol
January 2025
Department of Military Traffic Injury Prevention and Control, Daping Hospital, Army Medical University, Chongqing, China. Electronic address:
Traumatic brain injury (TBI), particularly at high altitudes (HA-TBI), is a leading cause of mortality and disability, yet clear diagnostic and treatment protocols are lacking. This study explores the early pathophysiological changes occurring within 24 h following HA-TBI, with a focus on differentially expressed proteins (DEPs) and phosphorylated proteins (DEPPs). Using a low-pressure hypoxic chamber to simulate high-altitude conditions combined with a controllable cortical impact (CCI) model, we established a rat model of HA-TBI.
View Article and Find Full Text PDFSci Rep
January 2025
Amsterdam UMC, Location VUmc, Cancer Center Amsterdam, de Boelelaan 1117, 1018 HV, Amsterdam, The Netherlands.
Bladder cancer often recurs, necessitating innovative treatments to reduce recurrence. We investigated non-thermal plasma's potential as a novel anti-cancer therapy, focusing on plasma-activated solution (PAS), created by exposing saline to non-thermal plasma. Our study aims to elucidate the biological effects of PAS on bladder cancer cell lines in vitro, as well as the combination with mitomycin C (MMC), using clinically relevant settings.
View Article and Find Full Text PDFAm J Hum Genet
January 2025
Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany; Center for Rare Disease, University of Tübingen, Tübingen, Germany; Genomics for Health in Africa (GHA), Africa-Europe Cluster of Research Excellence (CoRE). Electronic address:
Nutrient-dependent mTORC1 regulation upon amino acid deprivation is mediated by the KICSTOR complex, comprising SZT2, KPTN, ITFG2, and KICS2, recruiting GATOR1 to lysosomes. Previously, pathogenic SZT2 and KPTN variants have been associated with autosomal recessive intellectual disability and epileptic encephalopathy. We identified bi-allelic KICS2 variants in eleven affected individuals presenting with intellectual disability and epilepsy.
View Article and Find Full Text PDFFood Chem
January 2025
College of Food Science, Shenyang Agricultural University, Shenyang 110866, PR China. Electronic address:
This study employed proteomics and phosphoproteomics to compare protein expression and phosphorylation modifications in the milk fat globule membrane (MFGM) of human and bovine mature milk. A total of 410 proteins and 73 phosphorylation sites on 49 proteins were identified in the MFGM of bovine and human mature milk, respectively. Differential analysis revealed 40 differentially expressed proteins and 8 differentially phosphorylated sites, followed by bioinformatics analysis.
View Article and Find Full Text PDFAnal Chem
January 2025
Research Unit of Environmental Toxicology, School of Public Health, China Medical University, Shenyang 110122, China.
Although cathepsin S is transported from the spleen to the liver, where it cleaves collagen XVIII to produce endostatin and plays a critical role in the onset of early liver fibrosis, the relationship between liver fibrosis and spleen function remains underexplored. Given the roles of phosphorylation in disease, understanding its regulatory mechanism in early liver fibrosis is crucial. Despite advances in mass spectrometry enhancing phosphoproteomics, its application is limited by small clinical samples and subtle protein changes.
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