Objective: Colorectal cancer progression involves complex cellular mechanisms. This study examines the effects of Lactobacillus plantarum-derived extracellular vesicles (LEVs) on the SIRT5/p53 axis, focusing on glycolytic metabolic reprogramming and abnormal proliferation in intestinal epithelial cells.
Methods: LEVs were isolated from Lactobacillus plantarum and incubated with Caco-2 cells. Differential gene expression was analyzed through RNA sequencing and compared with TCGA-COAD data. Key target genes and pathways were identified using PPI network and pathway enrichment analysis. Various assays, including RT-qPCR, EdU staining, colony formation, flow cytometry, and Western blotting, were used to assess gene expression, cell proliferation, and metabolic changes. Co-immunoprecipitation confirmed the interaction between SIRT5 and p53, and animal models were employed to validate in vivo effects.
Results: Bioinformatics analysis indicated the SIRT5/p53 axis as a critical pathway in LEVs' modulation of colorectal cancer. LEVs were found to inhibit colorectal cancer cell proliferation and glycolytic metabolism by downregulating SIRT5, influencing p53 desuccinylation. In vivo, LEVs regulated this axis, reducing tumor formation in mice. Clinical sample analysis showed that SIRT5 and p53 succinylation levels correlated with patient prognosis.
Conclusion: Lactobacillus-derived extracellular vesicles play a pivotal role in suppressing colonic tumor formation by modulating the SIRT5/p53 axis. This results in decreased glycolytic metabolic reprogramming and reduced proliferation in intestinal epithelial cells.
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http://dx.doi.org/10.1007/s10565-024-09897-y | DOI Listing |
Alzheimers Dement
December 2024
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Background: Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is a common neuropathologic finding at advanced age that associates with hippocampal sclerosis (HS) and is often comorbid with AD pathology. Neuroimaging measurements of LATE-NC-associated limbic degeneration have been proposed as indirect biomarkers, but molecular-specific biomarkers for LATE-NC are still lacking. Here we used combined ante-mortem blood and MRI data to study TDP-43 levels in plasma-derived small extracellular vesicles (sEV-TDP-43) and hippocampal volume (HV) in relation to LATE-NC and HS at autopsy.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
All India Institute of Medical Sciences, New Delhi, New Delhi, India.
Background: Alzheimer's disease (AD) is a neurodegenerative disease characterized by Aβ plaques and neurofibrillary tangles, with chronic inflammation and synaptic dysfunction playing a significant contributor to disease progression and cognitive decline. Small extracellular vesicles (sEVs) are implicated in AD progression by facilitating the spread of pathological proteins and inflammatory cytokines. This study investigates the role of plasma-derived sEVs (PsEVs) in synaptic dysfunction and neuroinflammation and their association with amyloid-β and tau pathologies in AD progression.
View Article and Find Full Text PDFBackground: Brain derived Extracellular Vesicles (EVs) was isolated from blood and their containing pthogenic proteins were quantified to develop a biomarker signature for the classification of Tau aggregation in the brain.
Method: Brain derived EVs and their cargo were measured directly in the plasma of patients with AD and determined to be Tau-PET positive (visual read) (n=10) and other age matched healthy controls (n = 22) at one time-point. AD pathogenic proteins bound to EVs were quantified by in-house custom developed immunoassays.
Alzheimers Dement
December 2024
Osaka University Graduate School of Medicine, Toyonaka, Japan.
Background: We have developed a technology for isolating extracellular vesicles (EVs) released from the central nervous system present in plasma.
Method: Initially, we differentiated induced pluripotent stem cells (iPS) into neurons to examine the membrane surface molecules of neuron-derived EVs in culture media. Our analysis revealed a specific interest in neuron-specific APLP1.
Alzheimers Dement
December 2024
Wake Forest University School of Medicine, Winston Salem, NC, USA.
Background: Insulin signaling deregulation in the brain is a critical risk factor for Alzheimer's disease (AD); however, molecular changes in this pathway during AD pathogenesis cannot be currently accessed in clinical setting due to lack of brain tissues. Here, we propose small extracellular vesicles (sEV) characterization as a non-invasive approach to assess the status of insulin signaling in the AD brain.
Method: In postmortem brain tissues of cognitively normal (CN) and AD (n=5 each) subjects, expression of 84 genes, involved in insulin signaling and resistance was analyzed using pathway specific PCR array.
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