Diagnostic and Therapeutic Challenges of Rare Concurrent Intracranial Meningioma and Oligodendroglioma.

Introduction: Concurrent primary brain tumors are rare clinical entities, with a prevalence ranging from 0.1 to 0.5% of all diagnosed brain tumors.

Deciphering Distinct Genetic Risk Factors for FTLD-TDP Pathological Subtypes via Whole-Genome Sequencing.

Frontotemporal lobar degeneration with neuronal inclusions of the TAR DNA-binding protein 43 (FTLD-TDP) is a fatal neurodegenerative disorder with only a limited number of risk loci identified. We report our comprehensive genome-wide association study as part of the International FTLD-TDP Whole-Genome Sequencing Consortium, including 985 cases and 3,153 controls, and meta-analysis with the Dementia-seq cohort, compiled from 26 institutions/brain banks in the United States, Europe and Australia. We confirm as the strongest overall FTLD-TDP risk factor and identify as a novel FTLD-TDP risk factor.

BI-7273, a BRD9 inhibitor, reduces lipid accumulation by downregulating the AKT/mTOR/SREBP1 signaling pathway.

Increases in de novo lipogenesis that disturbed lipid homeostasis and caused lipid accumulation are a major cause of NAFLD and obesity. SREBP1 is a crucial regulatory factor controlling the expression of rate-limiting enzymes of lipid synthesis. A reduction in SREBP1expression can reduce lipid accumulation.

Production and characterization of novel monoclonal antibodies against pathological human TDP-43 proteins.

The RNA/DNA-binding protein TDP-43 plays a pivotal role in the ubiquitinated inclusions characteristic of TDP-43 proteinopathies, including most cases of frontotemporal lobar degeneration (FTLD-TDP) and Alzheimer disease (AD). To understand the mechanisms of pathological TDP-43 processing and identify potential biomarkers, we generated novel phosphorylation-independent monoclonal antibodies (MAbs) using bacteria-expressed human full-length recombinant TDP-43. Remarkably, we identified a distinctive MAb, No.

EGFR/CEP7 high polysomy is separate and distinct from EGFR amplification in glioblastoma as determined by fluorescence in situ hybridization.

EGFR amplification in gliomas is commonly defined by an EGFR/CEP7 ratio of ≥2. In testing performed at a major reference laboratory, a small subset of patients had ≥5 copies of both EGFR and CEP7 yet were not amplified by the EGFR/CEP7 ratio and were designated high polysomy cases. To determine whether these tumors are more closely related to traditionally defined EGFR-amplified or nonamplified gliomas, a retrospective search identified 22 out of 1143 (1.

FAM76B regulates PI3K/Akt/NF-κB-mediated M1 macrophage polarization by influencing the stability of PIK3CD mRNA.

Macrophage polarization is closely related to inflammation development, yet how macrophages are polarized remains unclear. In our study, the number of M1 macrophages was markedly increased in Fam76b knockout U937 cells vs. wild-type U937 cells, and FAM76B expression was decreased in M1 macrophages induced from different sources of macrophages.

Expression and functional analysis of fam76b in zebrafish.

FAM76B is nuclear speckle-localized protein with a molecular weight of 39 kDa. The amino sequence of FAM76B protein is highly conserved among species, suggesting that FAM76B has important biological functions. However, the biological function of FAM76B is currently still unclear.

FAM76B regulates NF-κB-mediated inflammatory pathway by influencing the translocation of hnRNPA2B1.

FAM76B has been reported to be a nuclear speckle-localized protein with unknown function. In this study, FAM76B was first demonstrated to inhibit the NF-κB-mediated inflammatory pathway by affecting the translocation of hnRNPA2B1 in vitro. We further showed that FAM76B suppressed inflammation in vivo using a traumatic brain injury (TBI) mouse model.

Distinct Patterns of Hippocampal Pathology in Alzheimer's Disease with Transactive Response DNA-binding Protein 43.

Objective: Age-related dementia syndromes are often not related to a single pathophysiological process, leading to multiple neuropathologies found at autopsy. An amnestic dementia syndrome can be associated with Alzheimer's disease (AD) with comorbid transactive response DNA-binding protein 43 (TDP-43) pathology (AD/TDP). Here, we investigated neuronal integrity and pathological burden of TDP-43 and tau, along the well-charted trisynaptic hippocampal circuit (dentate gyrus [DG], CA3, and CA1) in participants with amnestic dementia due to AD/TDP, amnestic dementia due to AD alone, or non-amnestic dementia due to TDP-43 proteinopathy associated with frontotemporal lobar degeneration (FTLD-TDP).

Clinical utility of whole-genome DNA methylation profiling as a primary molecular diagnostic assay for central nervous system tumors-A prospective study and guidelines for clinical testing.

Background: Central nervous system (CNS) cancer is the 10th leading cause of cancer-associated deaths for adults, but the leading cause in pediatric patients and young adults. The variety and complexity of histologic subtypes can lead to diagnostic errors. DNA methylation is an epigenetic modification that provides a tumor type-specific signature that can be used for diagnosis.

Role of neuroinflammation in neurodegeneration development.

Studies in neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and Amyotrophic lateral sclerosis, Huntington's disease, and so on, have suggested that inflammation is not only a result of neurodegeneration but also a crucial player in this process. Protein aggregates which are very common pathological phenomenon in neurodegeneration can induce neuroinflammation which further aggravates protein aggregation and neurodegeneration. Actually, inflammation even happens earlier than protein aggregation.

Mechanisms regulating the loss of Tregs in HUPO mice that develop spontaneous inflammatory arthritis.

T regulatory cells (Tregs) are a potential therapeutic target in many autoimmune diseases including rheumatoid arthritis (RA). The mechanisms responsible for the maintenance of Tregs in chronic inflammatory conditions such as RA are poorly understood. We employed our mouse model of RA in which, the following deletion of Flice-like inhibitory protein in CD11c cells, CD11c-FLIP-KO (HUPO) mice develop spontaneous, progressive, erosive arthritis, with reduced Tregs, and the adoptive transfer of Tregs ameliorates the arthritis.

Lycium barbarum polysaccharide alleviates dextran sodium sulfate-induced inflammatory bowel disease by regulating M1/M2 macrophage polarization via the STAT1 and STAT6 pathways.

Disruption of colonic homeostasis caused by aberrant M1/M2 macrophage polarization contributes to the development of inflammatory bowel disease (IBD). Lycium barbarum polysaccharide (LBP) is the primary active constituent of traditional Chinese herbal , which has been widely demonstrated to have important functions in regulating immune activity and anti-inflammatory. Thus, LBP may protect against IBD.

LATE-NC staging in routine neuropathologic diagnosis: an update.

An international consensus report in 2019 recommended a classification system for limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes (LATE-NC). The suggested neuropathologic staging system and nomenclature have proven useful for autopsy practice and dementia research. However, some issues remain unresolved, such as cases with unusual features that do not fit with current diagnostic categories.