04.03.2022

Mitochondrial functional and structural impairment is involved in the... Mitochondrial functional and structural impairment is involved in the...

Abstract The therapeutic options for castration-resistant prostate cancer (CRPC) are still limited. Natural bioactive compounds were shown to possess pro-death properties in different tumors. We previously reported that δ-tocotrienol (δ-TT) induces apoptosis, paraptosis and autophagy in CRPC cells. Here, we investigated whether δ-TT might exert its activity by impairing mitochondrial functions. We demonstrated that, in PC3 and DU145 cells, δ-TT impairs mitochondrial respiration and structural dynamics. In both cell...

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25.02.2022

Imaging Glioblastoma With 18F-Fluciclovine Amino Acid Positron Emissio... Imaging Glioblastoma With 18F-Fluciclovine Amino Acid Positron Emissio...

Introduction: Conventional methods of imaging brain tumors fail to assess metabolically active tumor regions, which limits their capabilities for tumor detection, localization, and response assessment. Positron emission tomography (PET) with 18F-fluciclovine (fluciclovine) provides regional assessment of amino acid uptake in tumors that could overcome some of the limitations of conventional imaging. However, the biological basis of enhanced fluciclovine uptake is insufficiently characterized in brain tumors, which confounds clinical i...

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18.02.2022

Detection of H3K4me3 Identifies NeuroHIV Signatures, Genomic Effects o... Detection of H3K4me3 Identifies NeuroHIV Signatures, Genomic Effects o...

Abstract Human postmortem specimens are extremely valuable resources for investigating translational hypotheses. Tissue repositories collect clinically assessed specimens from people with and without HIV, including age, viral load, treatments, substance use patterns and cognitive functions. One challenge is the limited number of specimens suitable for transcriptional studies, mainly due to poor RNA quality resulting from long postmortem intervals. We hypothesized that epigenomic signatures would be more stable than RNA for assessing global...

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11.02.2022

Attenuated fusogenicity and pathogenicity of SARS-CoV-2 Omicron varian... Attenuated fusogenicity and pathogenicity of SARS-CoV-2 Omicron varian...

Abstract The emergence of a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, Omicron, is an urgent global health concern (ref.1). Our statistical modelling suggests that Omicron has spread more rapidly than the Delta variant in several countries including South Africa. Cell culture experiments show that Omicron is less fusogenic than Delta and an ancestral SARS-CoV-2 strain. Although the spike (S) protein of Delta is efficiently cleaved into two subunits, which facilitates cell–cell fusion2,3, Omicron S is le...

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28.01.2022

Effect of various weight loss interventions on serum NT-proBNP concent... Effect of various weight loss interventions on serum NT-proBNP concent...

Abstract Obesity is associated with a "natriuretic handicap" indicated by reduced N-terminal fragment of proBNP (NT-proBNP) concentration. While gastric bypass surgery improves the natriuretic handicap, it is presently unclear if sleeve gastrectomy exhibits similar effects. We examined NT-proBNP serum concentration in n = 72 obese participants without heart failure before and 6 months after sleeve gastrectomy (n = 28), gastric bypass surgery (n = 19), and 3-month 800 kcal/day very-low calorie diet (n = 25). A signi...

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17.12.2021

Systematic insight into the active constituents and mechanism of Guiqi... Cancer Science, 2021

Abstract Traditional Chinese medicine treatment of diseases has been recognized, but the material basis and mechanisms are not clear. In this study, target prediction of the antigastric cancer (GC) effect of Guiqi Baizhu (GQBZP) and the analysis of potential key compounds, key targets, and key pathways for the therapeutic effects against GC were carried out based on the method of network analysis and Kyoto Encyclopedia of Genes and Genomes enrichment. There were 33 proteins shared between GQBZP and GC, and 131 compounds of GQBZP had a high...

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10.12.2021

The endocytic pathway taken by cationic substances requires Rab14 but...

Abstract Endocytosis and endosome dynamics are controlled by proteins of the small GTPase Rab family. Besides possible recycling routes to the plasma membrane and various organelles, previously described endocytic pathways (e.g., clathrin-mediated endocytosis, macropinocytosis, CLIC/GEEC pathway) all appear to funnel the endocytosed material to Rab5-positive early endosomes that then mature into Rab7-positive late endosomes/lysosomes. By studying the uptake of a series of cell-penetrating peptides (CPPs), we identify an endocytic pathway t...

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10.12.2021

Identification of a choroid plexus vascular barrier closing during int... Science, 2021

Abstract Up to 40% of patients with inflammatory bowel disease present with psychosocial disturbances. We previously identified a gut vascular barrier that controls the dissemination of bacteria from the intestine to the liver. Here, we describe a vascular barrier in the brain choroid plexus (PVB) that is modulated in response to intestinal inflammation through bacteria-derived lipopolysaccharide. The inflammatory response induces PVB closure after gut vascular barrier opening by the up-regulation of the wingless-type, cat...

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03.12.2021

Cathepsin C promotes breast cancer lung metastasis by modulating neutr... Cancer Cell, 2021

Abstract Lung metastasis is the major cause of breast cancer-related mortality. The neutrophil-associated inflammatory microenvironment aids tumor cells in metastatic colonization in lungs. Here, we show that tumor-secreted protease cathepsin C (CTSC) promotes breast-to-lung metastasis by regulating recruitment of neutrophils and formation of neutrophil extracellular traps (NETs). CTSC enzymatically activates neutrophil membrane-bound proteinase 3 (PR3) to facilitate interleukin-1β (IL-1β) processing and nuclear factor κB a...

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26.11.2021

Patient-derived iPSC-cerebral organoid modeling of the 17q11.2 microde... Patient-derived iPSC-cerebral organoid modeling of the 17q11.2 microde...

Abstract Neurodevelopmental disorders are often caused by chromosomal microdeletions comprising numerous contiguous genes. A subset of neurofibromatosis type 1 (NF1) patients with severe developmental delays and intellectual disability harbors such a microdeletion event on chromosome 17q11.2, involving the NF1 gene and flanking regions (NF1 total gene deletion [NF1-TGD]). Using patient-derived human induced pluripotent stem cell (hiPSC)-forebrain cerebral organoids (hCOs), we identify both neural stem cell (NSC) proliferation and neuronal...

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