TRAIL (TNF-alpha-Related Apoptosis-Inducing Ligand) is a promising anticancer agent. In fact, it induces apoptosis in cancer cells and not in most normal cells. Nevertheless, certain cancer cells are resistant to TRAIL-induced apoptosis and this could limit TRAIL's efficiency in cancer therapy. To overcome TRAIL resistance, a combination of TRAIL with chemotherapy could be used in cancer treatment. However, sensitivity of human normal cells to such combinations is not well known. We showed in this study that TRAIL/cisplatin, in contrast to TRAIL/5-fluorouracil, was toxic toward human primary hepatocytes and resting lymphocytes. Furthermore, both combinations are toxic toward PHA-IL2-activated lymphocytes. In contrast, freshly isolated neutrophils are resistant to TRAIL in combination or not with anticancer drugs.
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http://dx.doi.org/10.1196/annals.1378.023 | DOI Listing |
Alzheimers Dement
December 2024
Imperial College London, London, United Kingdom; Division of Neurology, Department of Brain Sciences, Imperial College London, United Kingdom, London, London, United Kingdom.
Background: Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue licensed for the treatment of type 2 diabetes mellitus (T2DM). Preclinical evidence in transgenic models of Alzheimer's disease suggests that liraglutide exerts neuroprotective effects by reducing amyloid oligomers, normalising synaptic plasticity and cerebral glucose uptake, and increasing the proliferation of neuronal progenitor cells.
Method: This is a multi-centre, randomised, double-blind, placebo-controlled, phase IIb trial of liraglutide in participants with mild to moderate Alzheimer's dementia, conducted at several centres in the UK.
Alzheimers Dement
December 2024
Afe Babalola University, Ado-Ekiti (ABUAD), Ado-Ekiti, Ekiti state, Nigeria.
Background: The impact of probiotics as gut and immunological modulator in restoring gut microbial balance and immune cells expression have generated much attention in the health sector. Its inhibitory effect on bacterial translocation and associated neural inflammatory processes has been reported. However, there is scarcity of data on its neuroprotective impact against neuroinflammation-associated neurodegeneration and memory impairment.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Indiana University School of Medicine, Indianapolis, IN, USA.
Background: The goal of the TREAT-AD Center is to enable drug discovery by developing assays and providing tool compounds for novel and emerging targets. The role of microglia in neuroinflammation has been implicated in the pathogenesis of Alzheimer's disease (AD). Genome-wide association studies, whole genome sequencing, and gene-expression network analyses comparing normal to AD brain have identified risk and protective variants in genes essential to microglial function.
View Article and Find Full Text PDFBackground: TAR-DNA-binding protein 43 (TDP43), is a pathologic marker in neurodegenerative diseases including frontotemporal lobar degeneration and amyotrophic lateral sclerosis. The aggregation of TDP-43, a crucial RNA-binding protein, is a consequence of post-translational modifications (PTMs) that disrupt its normal function. PTMs such as phosphorylation and ubiquitination contribute to the aberrant accumulation of TDP-43 aggregates, leading to neurodegenerative disorders like amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD).
View Article and Find Full Text PDFCurr Pharm Des
January 2025
Department of Pharmacy, Delhi Pharmaceutical Sciences and Research University, New Delhi, India.
Background: The metal oxide nanoparticles possess unique properties such as biological compatibility, superior reactivity, and capacity to develop reactive oxygen species, due to this they have drawn significant interest in cancer treatment. The various MONPs such as cerium oxide, Copper oxide, Iron oxide, Titanium dioxide, and Zinc oxide have been investigated for several types of cancers including brain, breast, cervical, colon, leukemia, liver, lung, melanoma, ovarian, and prostate cancers. However, traditional physiochemical synthetic methods for MONPs commonly include toxic materials, a major concern that raises questions regarding their biocompatibility and safety.
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