| 1. |
- Bravo, L, et al.
(author)
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- 2021
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swepub:Mat__t
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| 2. |
- Thomas, HS, et al.
(author)
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- 2019
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swepub:Mat__t
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| 3. |
- Tabiri, S, et al.
(author)
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- 2021
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swepub:Mat__t
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| 4. |
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| 5. |
- Jones, Benedict C, et al.
(author)
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To which world regions does the valence-dominance model of social perception apply?
- 2021
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In: Nature Human Behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 5:1, s. 159-169
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Journal article (peer-reviewed)abstract
- Over the past 10 years, Oosterhof and Todorov's valence-dominance model has emerged as the most prominent account of how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov's methodology across 11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov's original analysis strategy, the valence-dominance model generalized across regions. When we used an alternative methodology to allow for correlated dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence-dominance model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed when we use different extraction methods and correlate and rotate the dimension reduction solution. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 5 November 2018. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.7611443.v1 .
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| 6. |
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| 7. |
- Lakens, Daniel, et al.
(author)
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Justify your alpha
- 2018
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In: Nature Human Behaviour. - : Nature Publishing Group. - 2397-3374. ; 2:3, s. 168-171
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Journal article (peer-reviewed)abstract
- In response to recommendations to redefine statistical significance to P ≤ 0.005, we propose that researchers should transparently report and justify all choices they make when designing a study, including the alpha level.
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| 8. |
- Smati, S., et al.
(author)
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Integrative study of diet-induced mouse models of NAFLD identifies PPARα as a sexually dimorphic drug target
- 2022
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In: Gut. - : BMJ Publishing Group. - 0017-5749 .- 1468-3288. ; 71:4, s. 807-821
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Journal article (peer-reviewed)abstract
- We evaluated the influence of sex on the pathophysiology of non-alcoholic fatty liver disease (NAFLD). We investigated diet-induced phenotypic responses to define sex-specific regulation between healthy liver and NAFLD to identify influential pathways in different preclinical murine models and their relevance in humans. Different models of diet-induced NAFLD (high-fat diet, choline-deficient high-fat diet, Western diet or Western diet supplemented with fructose and glucose in drinking water) were compared with a control diet in male and female mice. We performed metabolic phenotyping, including plasma biochemistry and liver histology, untargeted large-scale approaches (liver metabolome, lipidome and transcriptome), gene expression profiling and network analysis to identify sex-specific pathways in the mouse liver. The different diets induced sex-specific responses that illustrated an increased susceptibility to NAFLD in male mice. The most severe lipid accumulation and inflammation/fibrosis occurred in males receiving the high-fat diet and Western diet, respectively. Sex-biased hepatic gene signatures were identified for these different dietary challenges. The peroxisome proliferator-activated receptor α (PPARα) co-expression network was identified as sexually dimorphic, and in vivo experiments in mice demonstrated that hepatocyte PPARα determines a sex-specific response to fasting and treatment with pemafibrate, a selective PPARα agonist. Liver molecular signatures in humans also provided evidence of sexually dimorphic gene expression profiles and the sex-specific co-expression network for PPARα. These findings underscore the sex specificity of NAFLD pathophysiology in preclinical studies and identify PPARα as a pivotal, sexually dimorphic, pharmacological target. NCT02390232.
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| 9. |
- Das, P., et al.
(author)
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Exotic decay of 115Cs
- 2023
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In: Physical Review C. - 2469-9985. ; 108:6
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Journal article (peer-reviewed)abstract
- The detailed study of the β+/EC decay of the very neutron-deficient and alpha-unbound nucleus 115Cs is presented. The measurement was performed at the ISOLDE, CERN where delayed charged particles and γ rays were detected. The observed delayed γ rays are in agreement with the previously reported characteristics γ rays of 115Xe. Based on the experimental observations, the tentative ground-state spin of 115Cs is suggested to be 7/2+ or 9/2+. Furthermore, the measured decay branching ratio of delayed protons exceeds the previously reported value. Additionally, new delayed α-branching ratio and several reconstructed proton and α-unbound excited states of 115Xe are being reported for the first time. The properties of proton-unbound states at excitation energies from 3.9–7.9 MeV have been obtained by fitting the delayed proton spectrum via the Bayesian method. The measured lifetimes of these proton-unbound states are in the order of zeptoseconds.
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| 10. |
- Turkez, H., et al.
(author)
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In vitro transcriptome response to propolis in differentiated SH-SY5Y neurons
- 2021
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In: Journal of food biochemistry. - : Wiley. - 0145-8884 .- 1745-4514. ; 45:12
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Journal article (peer-reviewed)abstract
- Propolis is the extract of a resinous compound that protects plants from both cold and microorganism attack and has gained a strong and sticky property because it is transformed after being collected by honey bees. Up to date, many studies have shown that propolis exhibited various beneficial biological activities, such as antifungal, antibacterial, antiviral, antioxidant, antimutagenic, and antitumor effects. Recent reports propounded the in vitro and in vivo neuroprotective effect of propolis; however, the exact molecular genetic mechanisms are still unclear. Therefore, we aimed to investigate the toxicogenomic and beneficial properties, including cytotoxic, antioxidant, apoptotic/necrotic as well as genotoxic effects of propolis (1.56–200 µg/ml) on differentiated SH-SY5Y neuronal cells. Additionally, microarray analysis was conducted on cell cultures following propolis application to explore gene differentiation. Differentially expressed genes were further analyzed using string software to characterize protein–protein interactions between gene pathways. Our results revealed that propolis applications could not have a prominent effect on cell viability even at concentrations up to 200 µg/ml. The highest propolis concentration induced apoptotic rather than necrotic cell death. The alterations in gene expression profiles, including CYP26A1, DHRS2, DHRS3, DYNC1I1, IGF2, ITGA4, SVIL, TGFβ1, and TGM2 could participate in the neuroprotective effects of propolis. In conclusion, propolis supplementation exerted remarkable advantageous; thus, it may offer great potential as a natural component in the prevention and treatment of neurodegenerative disorders. Whole-genome gene expression pattern following propolis application was investigated for the first time in neuronal cell culture to fill a gap in the literature about propolis toxicogenomics. Practical applications: Propolis is a very rich product in terms of benefits. In addition to its antibacterial, antiviral, antifungal, and anti-inflammatory content, it is known to have preventive and therapeutic properties for many different ailments. On the other hand, molecular mechanisms of propolis on gene expression differentiations haven't been investigated until now. Moreover, gene expression pattern is vital for all living organisms to maintain homeostasis. Thus, we conduct an experiment series for analyzing gene expression differentiation effects on neuronal cells to understand beneficial properties of propolis. Hence, it could be possible to comment on the use of propolis as a nutritional factor and beneficial diet.
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| 11. |
- Heinonen, S., et al.
(author)
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Mitochondria-related transcriptional signature is downregulated in adipocytes in obesity: a study of young healthy MZ twins
- 2017
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In: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 60:1, s. 169-181
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Journal article (peer-reviewed)abstract
- Low mitochondrial activity in adipose tissue is suggested to be an underlying factor in obesity and its metabolic complications. We aimed to find out whether mitochondrial measures are downregulated in obesity also in isolated adipocytes. We studied young adult monozygotic (MZ) twin pairs discordant (n = 14, intrapair difference Delta BMI ae 3 kg/m(2)) and concordant (n = 5, Delta BMI
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| 12. |
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| 13. |
- Pettersen, Emily, 1996, et al.
(author)
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Regenerative Peripheral Nerve Interface: Surgical Protocol for a Randomized Controlled Trial in Postamputation Pain
- 2024
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In: JOVE-JOURNAL OF VISUALIZED EXPERIMENTS. - 1940-087X. ; :205
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Journal article (peer-reviewed)abstract
- Surgical procedures, including nerve reconstruction and end -organ muscle reinnervation, have become more prominent in the prosthetic field over the past decade. Primarily developed to increase the functionality of prosthetic limbs, these surgical procedures have also been found to reduce postamputation neuropathic pain. Today, some of these procedures are performed more frequently for the management and prevention of postamputation pain than for prosthetic fitting, indicating a significant need for effective solutions to postamputation pain. One notable emerging procedure in this context is the Regenerative Peripheral Nerve Interface (RPNI). RPNI surgery involves an operative approach that entails splitting the nerve end longitudinally into its main fascicles and implanting these fascicles within free denervated and devascularized muscle grafts. The RPNI procedure takes a proactive stance in addressing freshly cut nerve endings, facilitating painful neuroma prevention and treatment by enabling the nerve to regenerate and innervate an end organ, i.e., the free muscle graft. Retrospective studies have shown RPNI's effectiveness in alleviating postamputation pain and preventing the formation of painful neuromas. The increasing frequency of utilization of this approach has also given rise to variations in the technique. This article aims to provide a step-by-step description of the RPNI procedure, which will serve as the standardized procedure employed in an international, randomized controlled trial (ClinicalTrials.gov, NCT05009394). In this trial, RPNI is compared to two other surgical procedures for postamputation pain management, specifically, Targeted Muscle Reinnervation (TMR) and neuroma excision coupled with intra-muscular transposition and burying.
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| 14. |
- Turkez, H., et al.
(author)
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Combined metabolic activators improve metabolic functions in the animal models of neurodegenerative diseases
- 2023
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In: Life Sciences. - : Elsevier BV. - 0024-3205 .- 1879-0631. ; 314
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Journal article (peer-reviewed)abstract
- Background: Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), are associated with metabolic abnormalities. Integrative analysis of human clinical data and animal studies have contributed to a better understanding of the molecular and cellular pathways involved in the progression of NDDs. Previously, we have reported that the combined metabolic activators (CMA), which include the precursors of nicotinamide adenine dinucleotide and glutathione can be utilized to alleviate metabolic disorders by acti-vating mitochondrial metabolism. Methods: We first analysed the brain transcriptomics data from AD patients and controls using a brain-specific genome-scale metabolic model (GEM). Then, we investigated the effect of CMA administration in animal models of AD and PD. We evaluated pathological and immunohistochemical findings of brain and liver tissues. Moreover, PD rats were tested for locomotor activity and apomorphine-induced rotation. Findings: Analysis of transcriptomics data with GEM revealed that mitochondrial dysfunction is involved in the underlying molecular pathways of AD. In animal models of AD and PD, we showed significant damage in the high-fat diet groups' brain and liver tissues compared to the chow diet. The histological analyses revealed that hyperemia, degeneration and necrosis in neurons were improved by CMA administration in both AD and PD animal models. These findings were supported by immunohistochemical evidence of decreased immunoreactivity in neurons. In parallel to the improvement in the brain, we also observed dramatic metabolic improvement in the liver tissue. CMA administration also showed a beneficial effect on behavioural functions in PD rats.Interpretation: Overall, we showed that CMA administration significantly improved behavioural scores in parallel with the neurohistological outcomes in the AD and PD animal models and is a promising treatment for improving the metabolic parameters and brain functions in NDDs.
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| 15. |
- Yulug, B., et al.
(author)
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Combined metabolic activators improve cognitive functions in Alzheimer's disease patients: a randomised, double-blinded, placebo-controlled phase-II trial
- 2023
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In: Translational Neurodegeneration. - : Springer Science and Business Media LLC. - 2047-9158. ; 12:1
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Journal article (peer-reviewed)abstract
- Background Alzheimer's disease (AD) is associated with metabolic abnormalities linked to critical elements of neurodegeneration. We recently administered combined metabolic activators (CMA) to the AD rat model and observed that CMA improves the AD-associated histological parameters in the animals. CMA promotes mitochondrial fatty acid uptake from the cytosol, facilitates fatty acid oxidation in the mitochondria, and alleviates oxidative stress.Methods Here, we designed a randomised, double-blinded, placebo-controlled phase-II clinical trial and studied the effect of CMA administration on the global metabolism of AD patients. One-dose CMA included 12.35 g L-serine (61.75%), 1 g nicotinamide riboside (5%), 2.55 g N-acetyl-L-cysteine (12.75%), and 3.73 g L-carnitine tartrate (18.65%). AD patients received one dose of CMA or placebo daily during the first 28 days and twice daily between day 28 and day 84. The primary endpoint was the difference in the cognitive function and daily living activity scores between the placebo and the treatment arms. The secondary aim of this study was to evaluate the safety and tolerability of CMA. A comprehensive plasma metabolome and proteome analysis was also performed to evaluate the efficacy of the CMA in AD patients.Results We showed a significant decrease of AD Assessment Scale-cognitive subscale (ADAS-Cog) score on day 84 vs day 0 (P = 0.00001, 29% improvement) in the CMA group. Moreover, there was a significant decline (P = 0.0073) in ADAS-Cog scores (improvement of cognitive functions) in the CMA compared to the placebo group in patients with higher ADAS-Cog scores. Improved cognitive functions in AD patients were supported by the relevant alterations in the hippocampal volumes and cortical thickness based on imaging analysis. Moreover, the plasma levels of proteins and metabolites associated with NAD + and glutathione metabolism were significantly improved after CMA treatment.Conclusion Our results indicate that treatment of AD patients with CMA can lead to enhanced cognitive functions and improved clinical parameters associated with phenomics, metabolomics, proteomics and imaging analysis.
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| 16. |
- Zhang, Xiang, et al.
(author)
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Identification of discriminating metabolic pathways and metabolites in human PBMCs stimulated by various pathogenic agents
- 2018
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In: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 9:FEB
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Journal article (peer-reviewed)abstract
- Immunity and cellular metabolism are tightly interconnected but it is not clear whether different pathogens elicit specific metabolic responses. To address this issue, we studied differential metabolic regulation in peripheral blood mononuclear cells (PBMCs) of healthy volunteers challenged by Candida albicans, Borrelia burgdorferi, lipopolysaccharide, and Mycobacterium tuberculosis in vitro. By integrating gene expression data of stimulated PBMCs of healthy individuals with the KEGG pathways, we identified both common and pathogen-specific regulated pathways depending on the time of incubation. At 4 h of incubation, pathogenic agents inhibited expression of genes involved in both the glycolysis and oxidative phosphorylation pathways. In contrast, at 24 h of incubation, particularly glycolysis was enhanced while genes involved in oxidative phosphorylation remained unaltered in the PBMCs. In general, differential gene expression was less pronounced at 4 h compared to 24 h of incubation. KEGG pathway analysis allowed differentiation between effects induced by Candida and bacterial stimuli. Application of genome-scale metabolic model further generated a Candida-specific set of 103 reporter metabolites (e.g., desmosterol) that might serve as biomarkers discriminating Candida-stimulated PBMCs from bacteria-stimuated PBMCs. Our analysis also identified a set of 49 metabolites that allowed discrimination between the effects of Borrelia burgdorferi, lipopolysaccharide and Mycobacterium tuberculosis. We conclude that analysis of pathogen-induced effects on PBMCs by a combination of KEGG pathways and genome-scale metabolic model provides deep insight in the metabolic changes coupled to host defense.
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| 17. |
- Adil, Mohammed Yasin, et al.
(author)
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Meibomian Gland Morphology Is a Sensitive Early Indicator of Meibomian Gland Dysfunction
- 2019
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In: American Journal of Ophthalmology. - : ELSEVIER SCIENCE INC. - 0002-9394 .- 1879-1891. ; 200, s. 16-25
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Journal article (peer-reviewed)abstract
- PURPOSE: To investigate the relationship between meibomian gland (MG) morphology and clinical dry eye tests in patients with meibomian gland dysfunction (MGD). DESIGN: Cross-sectional study. SUBJECTS: Total 538 MGD patients and 21 healthy controls. METHODS: MG loss on meibography images of upper (UL) and lower lids (LL) was graded on a scale of 0 (lowest degree of MG loss) to 3. MG length, thickness, and interglandular space in the UL were measured. Clinical tests included meibum expression and quality, tear film break-up time, ocular staining, osmolarity, Schirmer I, blink interval timing, and Ocular Surface Disease Index (OSDI) questionnaire. RESULTS: Mean UL and LL meibogrades were significantly higher in MGD patients compared to controls (P amp;lt; .001 for UL and LL). The sensitivity and specificity of the meibograde as a diagnostic parameter for MGD was 96.7% and 85%, respectively. Schirmer I was significantly increased in MGD patients with meibograde 1 compared to patients with meibograde 0, 2, and 3 in the UL (P amp;lt; .05 ). MG thickness increased with higher meibograde (P amp;lt; .001). MG morphology correlated significantly but weakly with several clinical parameters (P amp;lt; .05). OSDI did not correlate with any MG morphologic parameter. CONCLUSIONS: Grading of MG loss using meibograde effectively diagnoses MGD. Compensatory mechanisms such as increased aqueous tear production and dilation of MGs make early detection of MGD difficult by standard clinical measures of dry eye, whereas morphologic analysis of MGs reveals an early stage of MGD, and therefore represents a complementary clinical parameter with diagnostic potential. (C) 2018 Elsevier Inc. All rights reserved.
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| 18. |
- Babiker, Adil A., et al.
(author)
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Prothrombotic effect of prostasomes of metastatic cell and seminal origin
- 2007
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In: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 67:4, s. 378-388
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Journal article (peer-reviewed)abstract
- BACKGROUND. Prostasomes are secretory granules produced by the glandular epithelial cells of the prostate. Seminal prostasomes contain high amounts of Tissue Factor (TF) but no studies of TF on malignant cell prostasomes have been made. Here we compare the expression, phosphorylation, and function of TF on prostasomes of different origin. METHODS. TF was detected on prostasomes isolated from seminal fluid and human prostate cancer cell lines (PC-3, DU145, and LNCaP) using FACS and enzyme immunoassay (EIA). Incubation of prostasomes with radioactive ATP under conditions favoring protein kinase A activity led to phosphorylation of TF as detected by immunoprecipitation and SDS-PAGE. The prothrombotic effect of prostasomes was investigated in whole blood and recalcified plasma. Blocking experiments were performed using anti-TF antibodies and corn trypsin inhibitor. RESULTS. TF was expressed on all tested prostasome preparations with lowest values found for seminal ones. Prostasomal TF was the main endogenous substrate for prostasomal protein kinase A. All tested prostasome preparations greatly enhanced the rate of clot formation in a dose-dependent fashion, that is, the clotting capability of prostasomes seemed to be related to the extent of their expression of TF. In addition, the density of the clot varied between different prostasome preparations. When incubated in whole blood, prostasomes were found to associate to WBC thereby inducing them to express and release TF. CONCLUSIONS. These data show that TF is overexpressed and also subjected to phosphorylation by malignant cell prostasomes. This suggests major roles for prostasomes in thrombotic events that occur in some advanced cases of prostate cancer.
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| 19. |
- Baboota, Ritesh, et al.
(author)
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BMP4 and Gremlin 1 regulate hepatic cell senescence during clinical progression of NAFLD/NASH
- 2022
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In: Nature Metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 4:8, s. 1007-21
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Journal article (peer-reviewed)abstract
- The role of hepatic cell senescence in human non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) is not well understood. To examine this, we performed liver biopsies and extensive characterization of 58 individuals with or without NAFLD/NASH. Here, we show that hepatic cell senescence is strongly related to NAFLD/NASH severity, and machine learning analysis identified senescence markers, the BMP4 inhibitor Gremlin 1 in liver and visceral fat, and the amount of visceral adipose tissue as strong predictors. Studies in liver cell spheroids made from human stellate and hepatocyte cells show BMP4 to be anti-senescent, anti-steatotic, anti-inflammatory and anti-fibrotic, whereas Gremlin 1, which is particularly highly expressed in visceral fat in humans, is pro-senescent and antagonistic to BMP4. Both senescence and anti-senescence factors target the YAP/TAZ pathway, making this a likely regulator of senescence and its effects. We conclude that senescence is an important driver of human NAFLD/NASH and that BMP4 and Gremlin 1 are novel therapeutic targets. Baboota et al. investigate senescence as a driver of human NAFLD/NASH and show the roles of BMP4 and its antagonist Gremlin 1 as anti-senescent and pro-senescent molecules, respectively.
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| 20. |
- Cacciatore, I., et al.
(author)
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Boron-based hybrids as novel scaffolds for the development of drugs with neuroprotective properties
- 2021
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In: RSC Medicinal Chemistry. - : Royal Society of Chemistry (RSC). - 2632-8682. ; 12:11, s. 1944-1949
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Journal article (peer-reviewed)abstract
- Novel boron-based compounds (BBCs) were synthesized and evaluated as potential candidates for the development of novel drugs against Alzheimer's disease (AD). The neuroprotective profile of novel BBCs was evaluated using Aβ1-42-treated-SH-SY5Y cells while their antioxidant activity was evaluated by total antioxidant capacity (TAC) and total oxidative status (TOS) assays. Results showed that BLA (a novel boron-based hybrid containing an antioxidant portion) inhibited cell death induced by Aβ1-42-exposure in differentiated SH-SY5Y cells, resulting in an increase in cell viability by 25-33% (MTT assay) and by 63-71% (LDH assay) in a concentration range of 25-100 μM. Antioxidant assays demonstrated a good capability of BLA to counteract the oxidative status. Moreover, BLA possessed a significant ability to inhibit acetylcholinesterase (AChE) (22.96% at 50 μM), an enzyme whose enzymatic activity is increased in AD patients. In the present work, absorption and distribution properties of boron-based hybrids were predicted using Pre-ADMET software. In vitro preliminary results suggested that boron-based hybrids could be new structural scaffolds for the development of novel drugs for the management of AD.
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| 21. |
- Cornacchia, C., et al.
(author)
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Development of L-Dopa-containing diketopiperazines as blood-brain barrier shuttle
- 2022
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In: European Journal of Medicinal Chemistry. - : Elsevier BV. - 0223-5234 .- 1768-3254. ; 243
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Journal article (peer-reviewed)abstract
- In our overall goal to develop anti-Parkinson drugs, we designed novel diketopiperazines (DKP1-6) aiming to both reach the blood-brain barrier and counteract the oxidative stress related to Parkinson's Disease (PD). The anti-Parkinson properties of DKP 1–6 were evaluated using neurotoxin-treated PC12 cells, as in vitro model of PD, while their cytotoxicity and genotoxicity potentials were investigated in newborn rat cerebral cortex (RCC) and primary human whole blood (PHWB) cell cultures. The response against free radicals was evaluated by the total antioxidant capacity (TAC) assay. Comet assay was used to detect DNA damage while the content of 8-hydroxyl-2′-deoxyguanosine (8-OH-dG) was determined as a marker of oxidative DNA damage. PAMPA-BBB and Caco-2 assays were employed to evaluate the capability of DKP1-6 to cross the membranes. Stability studies were conducted in simulated gastric and intestinal fluids and human plasma. Results showed that DKP5-6 attenuate the MPP + -induced cell death on a nanomolar scale, but a remarkable effect was observed for DKP6 on Nrf2 activation that leads to the expression of genes involved in oxidative stress response thus increasing glutathione biosynthesis and ROS buffering. DKP5-6 resulted in no toxicity for RCC neurons and PHWB cells exposed to 10–500 nM concentrations during 24 h as determined by MTT and LDH assays and TAC levels were not altered in both cultured cell types. No significant difference in the induction of DNA damage was observed for DKP5-6. Both DKPs resulted stable in simulated gastric fluids (t1/2 > 22h). In simulated intestinal fluids, DKP5 underwent immediate hydrolysis while DKP6 showed a half-life higher than 3 h. In human plasma, DKP6 resulted quite stable. DKP6 displayed both high BBB and Caco-2 permeability confirming that the DKP scaffold represents a useful tool to improve the crossing of drugs through the biological membranes.
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| 22. |
- Hambsch, F. -J, et al.
(author)
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Investigation of the Fission Process at IRMM
- 2011
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In: Journal of the Korean Physical Society. - : Korean Physical Society. - 0374-4884 .- 1976-8524. ; 59:2, s. 1654-1659
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Journal article (peer-reviewed)abstract
- The investigation of the fission process is and has been a major undertaking at IRMM. The most recent investigations concerned the reaction (234)U(n,f) and (238)U(n,f) around vibrational resonances at the barrier of the fission cross-section. Furthermore prompt neutron emission of (252)Cf(SF) has been investigated understanding for the first time the prompt neutron multiplicity as a function of total kinetic energy (TKE). Theoretical modelling of reaction cross sections as well as prompt neutron multiplicity and spectra has been performed using the experimental data as input parameters. Also instrument developments for correlation measurements of fission fragment properties has been pursued in recent years with the time-of-flight spectrometer VERDI and detectors for prompt fission gamma-ray.
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| 23. |
- Mardinoglu, Adil, 1982, et al.
(author)
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Elevated Plasma Levels of 3-Hydroxyisobutyric Acid Are Associated With Incident Type 2 Diabetes
- 2018
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In: Ebiomedicine. - : Elsevier BV. - 2352-3964. ; 27, s. 151-155
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Journal article (peer-reviewed)abstract
- Branched-chain amino acids (BCAAs) metabolite, 3-Hydroxyisobutyric acid (3-HIB) has been identified as a secreted mediator of endothelial cell fatty acid transport and insulin resistance (IR) using animal models. To identify if 3-HIB is a marker of human IR and future risk of developing Type 2 diabetes (T2D), we measured plasma levels of 3-HIB and associated metabolites in around 10,000 extensively phenotyped individuals. The levels of 3-HIB were increased in obesity but not robustly associated with degree of IR after adjusting for BMI. Nevertheless, also after adjusting for obesity and plasma BCAA, 3-HIB levels were associated with future risk of incident T2D. We also examined the effect of 3-HIB on fatty acid uptake in human cells and found that both HUVEC and human cardiac endothelial cells respond to 3-HIB whereas human adipose tissue-derived endothelial cells do not respond to 3-HIB. In conclusion, we found that increased plasma level of 3-HIB is a marker of future risk of T2D and 3-HIB may be important for the regulation of metabolic flexibility in heart and muscles.
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| 24. |
- Mardinoglu, Adil, 1982, et al.
(author)
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Plasma Mannose Levels Are Associated with Incident Type 2 Diabetes and Cardiovascular Disease
- 2017
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In: Cell Metabolism. - : Elsevier BV. - 1932-7420 .- 1550-4131. ; 26:2, s. 281-283
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Journal article (other academic/artistic)abstract
- Plasma mannose levels are elevated in subjects with insulin resistance independently of obesity. Here, we found that elevated plasma mannose levels are strong markers of future risk of several chronic diseases including T2D, CVD, and albuminuria, and that it may contribute to their development rather than just being a novel biomarker.
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| 25. |
- Pagoni, A., et al.
(author)
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Novel anti-Alzheimer phenol-lipoyl hybrids : Synthesis, physico-chemical characterization, and biological evaluation
- 2020
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In: European Journal of Medicinal Chemistry. - : Elsevier Masson SAS. - 0223-5234 .- 1768-3254. ; 186
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Journal article (peer-reviewed)abstract
- To date, drugs that hit a single target are inadequate for the treatment of neurodegenerative diseases, such as Alzheimer's or Parkinson's diseases. The development of multitarget ligands, able to interact with the different pathways involved in the progession of these disorders, represents a great challenge for medicinal chemists. In this context, we report here the synthesis and biological evaluation of phenol-lipoyl hybrids (SV1-13), obtained via a linking strategy, to take advantage of the synergistic effect due to the antioxidant portions and anti-amyloid properties of the single constituents present in the hybrid molecule. Biological results showed that SV5 and SV10 possessed the best protective activity against Aβ1-42 induced neurotoxicity in differentiated SH-SY5Y cells. SV9 and SV10 showed remarkable antioxidant properties due to their ability to counteract the damage caused by H2O2 in SHSY-5Y-treated cells. Hovewer, SV5, showing moderate antioxidant and good neuroprotective activities, resulted the best candidate for further experiments since it also resulted stable both simulated and plasma fluids.
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| 26. |
- Pettersen, Emily, 1996, et al.
(author)
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Targeted Muscle Reinnervation: Surgical Protocol for a Randomized Controlled Trial in Postamputation Pain
- 2024
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In: Journal of Visualized Experiments. - 1940-087X. ; 2024:205
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Journal article (peer-reviewed)abstract
- Over the past decade, the field of prosthetics has witnessed significant progress, particularly in the development of surgical techniques to enhance the functionality of prosthetic limbs. Notably, novel surgical interventions have had an additional positive outcome, as individuals with amputations have reported neuropathic pain relief after undergoing such procedures. Subsequently, surgical techniques have gained increased prominence in the treatment of postamputation pain, including one such surgical advancement-targeted muscle reinnervation (TMR). TMR involves a surgical approach that reroutes severed nerves as a type of nerve transfer to "target" motor nerves and their accompanying motor end plates within nearby muscles. This technique originally aimed to create new myoelectric sites for amplified electromyography (EMG) signals to enhance prosthetic intuitive control. Subsequent work showed that TMR also could prevent the formation of painful neuromas as well as reduce postamputation neuropathic pain (e.g., Residual and Phantom Limb Pain). Indeed, multiple studies have demonstrated TMR's effectiveness in mitigating postamputation pain as well as improving prosthetic functional outcomes. However, technical variations in the procedure have been identified as it is adopted by clinics worldwide. The purpose of this article is to provide a detailed step-by-step description of the TMR procedure, serving as the foundation for an international, randomized controlled trial (ClinicalTrials.gov, NCT05009394), including nine clinics in seven countries. In this trial, TMR and two other surgical techniques for managing postamputation pain will be evaluated.
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| 27. |
- Riaux-Gobin, C., et al.
(author)
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Planothidium juandenovense sp. nov. (Bacillariophyta) from Juan de Nova (Scattered Islands, Mozambique Channel) and other tropical environments: A new addition to the Planothidium delicatulum complex
- 2018
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In: Fottea. - : Palacky University Olomouc. - 1802-5439 .- 1805-4927. ; 18:1, s. 106-119
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Journal article (peer-reviewed)abstract
- Planothidium juandenovense sp. nov. (Bacillariophyta) is described from the marine tropical environments of Juan de Nova I. (Mozambique Channel), Rodrigues I. (Mascarene Archipelago) and from Guam (Northern Mariana Is., Pacific). This small and relatively rare taxon has short multiseriate striae on the sternum valve (SV), hooked raphe valve (RV) terminal raphe endings and no SV cavum or hoof-shaped area. This taxon has similarities with Planothidium delicatulum (Kütz.) Round et Bukht. and Planothidium septentrionale (Østrup) Round et Bukht. ex Rumrich et al., but also differences: e.g. a relatively narrow and rhombic SV sternum, void of areolae, with vestigial radiate structures and an uninterrupted marginal SV elevated crest or ‘crista marginalis’. P. juandenovense sp. nov. is compared to some other Achnanthales with short SV striae. Cocconeis quarnerensis var. lanceolata Jurilj and Planothidium quarnerense f. rhombica (Giffen) comb. nov. may be close to our new taxon. © Czech Phycological Society (2018).
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| 28. |
- Rutten, Martijn G. S., et al.
(author)
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Normalization of hepatic ChREBP activity does not protect against liver disease progression in a mouse model for Glycogen Storage Disease type Ia
- 2023
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In: Cancer & Metabolism. - : Springer Nature. - 2049-3002. ; 11:1
-
Journal article (peer-reviewed)abstract
- BackgroundGlycogen storage disease type 1a (GSD Ia) is an inborn error of metabolism caused by a defect in glucose-6-phosphatase (G6PC1) activity, which induces severe hepatomegaly and increases the risk for liver cancer. Hepatic GSD Ia is characterized by constitutive activation of Carbohydrate Response Element Binding Protein (ChREBP), a glucose-sensitive transcription factor. Previously, we showed that ChREBP activation limits non-alcoholic fatty liver disease (NAFLD) in hepatic GSD Ia. As ChREBP has been proposed as a pro-oncogenic molecular switch that supports tumour progression, we hypothesized that ChREBP normalization protects against liver disease progression in hepatic GSD Ia.MethodsHepatocyte-specific G6pc knockout (L-G6pc−/−) mice were treated with AAV-shChREBP to normalize hepatic ChREBP activity.ResultsHepatic ChREBP normalization in GSD Ia mice induced dysplastic liver growth, massively increased hepatocyte size, and was associated with increased hepatic inflammation. Furthermore, nuclear levels of the oncoprotein Yes Associated Protein (YAP) were increased and its transcriptional targets were induced in ChREBP-normalized GSD Ia mice. Hepatic ChREBP normalization furthermore induced DNA damage and mitotic activity in GSD Ia mice, while gene signatures of chromosomal instability, the cytosolic DNA-sensing cGAS-STING pathway, senescence, and hepatocyte dedifferentiation emerged.ConclusionsIn conclusion, our findings indicate that ChREBP activity limits hepatomegaly while decelerating liver disease progression and protecting against chromosomal instability in hepatic GSD Ia. These results disqualify ChREBP as a therapeutic target for treatment of liver disease in GSD Ia. In addition, they underline the importance of establishing the context-specific roles of hepatic ChREBP to define its therapeutic potential to prevent or treat advanced liver disease.
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| 29. |
- Walsh, F., et al.
(author)
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Artificial backbone neuronal network for nano scale sensors
- 2011
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In: 2011 IEEE Conference on Computer Communications Workshops, INFOCOM WKSHPS 2011. Shanghai, 10-15 April 2011. - 9781457702488 ; , s. 449-454
-
Conference paper (peer-reviewed)abstract
- Communication between biological based nano scale devices is a crucial component of future applications in nanotechnology. This paper explores the creation of a backbone communication network for nano scale sensors using neurons. We investigate how neuron cell characteristics affect the performance of neuronal based network and highlight several key characteristics compared to conventional wire based networks. Finally, we investigate four network topologies through simulation.
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| 30. |
- Xiao, Jiaxin, et al.
(author)
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Diagnostic Test Efficacy of Meibomian Gland Morphology and Function
- 2019
-
In: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 9
-
Journal article (peer-reviewed)abstract
- Meibomian gland dysfunction (MGD) is the leading cause of dry eye and proposed treatments are based on disease severity. Our purpose was to establish reliable morphologic measurements of meibomian glands for evaluating MGD severity. This retrospective, cross-sectional study included 100 MGD patients and 20 controls. The patients were classified into dry eye severity level (DESL) 1-4 based on symptoms and clinical parameters including tear-film breakup time, ocular staining and Schirmer I. The gland loss, length, thickness, density and distortion were analyzed. We compared the morphology between patients and controls; examined their correlations to meibum expressibility, quality, and DESL. Relative to controls, the gland thickness, density and distortion were elevated in patients (p amp;lt; 0.001 for all tests). The area under the receiver operating characteristic curve was 0.98 (95% confidence interval [CI], 0.96-1.0) for gland loss, and 0.96 (CI 0.91-1.0) for gland distortion, with a cutoff value of six distorted glands yielding a sensitivity of 93% and specificity of 97% for MGD diagnosis. The gland distortion was negatively correlated to the meibum expressibility (r = -0.53; p amp;lt; 0.001) and DESL (r = -0.22, p = 0.018). In conclusion, evaluation of meibomian gland loss and distortion are valuable complementary clinical parameters to assess MGD status.
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| 31. |
- Xiao, Jiaxin, et al.
(author)
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Functional and Morphological Evaluation of Meibomian Glands in the Assessment of Meibomian Gland Dysfunction Subtype and Severity
- 2020
-
In: American Journal of Ophthalmology. - : ELSEVIER SCIENCE INC. - 0002-9394 .- 1879-1891. ; 209, s. 160-167
-
Journal article (peer-reviewed)abstract
- PURPOSE: To classify subtypes of meibomian gland dysfunction (MGD) and evaluate the dependency of dry eye signs, symptoms, and parameters on MGD subtype. DESIGN: Cross-sectional study. Study Population: the right eyes of 447 patients with MGD of various subtypes and 20 healthy volunteers. METHODS: Patients were divided into 4 subtypes of MGD based on meibum expression, meibum quality, and MG loss on meibography images (meibograde of 0-6). Subtypes were patients with high meibum delivery (hypersecretory and nonobvious MGD) and those with low meibum delivery (hyposecretory and obstructive MGD). Additional clinical tests included tear film break-up time (TFBUT), ocular staining, osmolarity, Schirmer I, blink interval timing and the Ocular Surface Disease Index (OSDI) questionnaire. RESULTS: A total of 78 eyes had hypersecretory MGD; 49 eyes had nonobvious MGD; 66 eyes had hyposecretory MGD; and 254 eyes had obstructive MGD. Increased tear film osmolarity and lower TFBUT were found in the low-delivery groups; hyposecretory (P = 0.006, P = 0.016) and obstructive MGD (P = 0.008, P = 0.006) relative to high-delivery MGD (hypersecretory and nonobvious groups, respectively). Worse ocular symptoms and ocular staining were also found in low-delivery MGD groups than the high delivery MGD groups (P amp;lt; 0.01 and P amp;lt; 0.006, respectively). " CONCLUSIONS: Patients with low-delivery MGD had worse dry eye parameters and ocular symptoms than those with high meibum delivery, indicating the pivotal role of meibum secretion in ocular surface health that should be targeted in MGD therapy. Furthermore, nonobvious MGD cannot be diagnosed using conventional dry eye tests and requires morphologic assessment of meibography images to confirm MG loss. ((C) 2019 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)
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| 32. |
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| 33. |
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| 34. |
- Aarrestad, Thea, et al.
(author)
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Benchmark data and model independent event classification for the large hadron collider
- 2022
-
In: SciPost Physics. - 2542-4653. ; 12:1
-
Journal article (peer-reviewed)abstract
- We describe the outcome of a data challenge conducted as part of the Dark Machines (https://www.darkmachines.org) initiative and the Les Houches 2019 workshop on Physics at TeV colliders. The challenged aims to detect signals of new physics at the Large Hadron Collider (LHC) using unsupervised machine learning algorithms. First, we propose how an anomaly score could be implemented to define model-independent signal regions in LHC searches. We define and describe a large benchmark dataset, consisting of > 1 billion simulated LHC events corresponding to 10 fb−1 of proton-proton collisions at a center-of-mass energy of 13 TeV. We then review a wide range of anomaly detection and density estimation algorithms, developed in the context of the data challenge, and we measure their performance in a set of realistic analysis environments. We draw a number of useful conclusions that will aid the development of unsupervised new physics searches during the third run of the LHC, and provide our benchmark dataset for future studies at https://www.phenoMLdata.org. Code to reproduce the analysis is provided at https://github.com/bostdiek/DarkMachines-UnsupervisedChallenge.
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| 35. |
- Akbas, Esvet, et al.
(author)
-
Synthesis and Biological Evaluation of Novel Benzylidene Thiazolo Pyrimidin-3(5H)-One Derivatives
- 2024
-
In: Polycyclic aromatic compounds (Print). - : Informa UK Limited. - 1040-6638 .- 1563-5333. ; 44:5, s. 3061-3078
-
Journal article (peer-reviewed)abstract
- Starting compound 1 was synthesized according to reference. 1 Benzylidene thiazole pyrimidin-3(5H)-ones were synthesized reactions of 1 with bromoacetic acid and various aryl-aldehydes in the same vessel via one-step, unlike studies in the literature. Quantum chemical parameters and full geometry optimizations for all compounds were computed using DFT based on B3LYP. Cytotoxic action potential of synthesized compounds was evaluated using trypan blue dye exclusion and MTT assays in different cell lines including adenocarcinoma alveolar basal epithelial-like adherent A549 cells, the colon adenocarcinoma HT-29 cells, prostate adenocarcinoma DU-145 cells, and diploid ARPE-19 retinal pigment epithelial cells. Embryotoxicity and genotoxicity assessments were performed on pluripotent human embryonal carcinoma NT2 and human lymphocyte cells, respectively. Compound A1 exhibited good anticancer activity on A549 and DU-145 cell lines, and the compounds including A3, 4, 6, and 9 induced cytotoxicity on A549 cells. The compounds A1-10 also showed a good biosafety profile at relatively lower concentrations.
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| 36. |
- Akbas, Esvet, et al.
(author)
-
Synthesis, Characterization, Theoretical Studies and in Vitro Embriyotoxic, Genotoxic and Anticancer Effects of Novel Phenyl(1,4,6-Triphenyl-2-Thioxo-1,2,3,4-Tetrahydropyrimidin-5-yl)Methanone
- 2023
-
In: Polycyclic aromatic compounds (Print). - : Informa UK Limited. - 1040-6638 .- 1563-5333. ; , s. 1-18
-
Journal article (peer-reviewed)abstract
- In this study, phenyl (1,4,6-triphenyl-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl)methanone was obtained by using the Biginelli reaction method. The structure of this compound was analyzed using elemental analysis, IR, 1H, and 13C NMR. The quantum chemical calculations (QCC) of this compound were performed density functional theory (DFT) method, 6–31 G (d, p) base set, and B3LYP functions with the Gaussian09W software package. Literature shows that pyrimidine-derived compounds have very active biological properties. For this reason, the biologically active properties of the synthesized compound were also examined. To determine embryotoxic, genotoxic, and cytotoxic effects of compound, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), lactate dehydrogenase (LDH) release, micronucleus (MN) and 8-OH-dG assays were carried out. On the other hand, pharmacokinetic and toxicity properties (ADMET) were predicted in silico via SwissADME and Protox-II web tools. In silico estimates of this compound used in the study showed that the compound has the covetable physicochemical properties for bioavailability. In conclusion, the obtained results of our study clearly showed that this compound exerted strong toxicity potential.
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| 37. |
- Al-Handal, Adil Y, 1952, et al.
(author)
-
Fallacia fawensis sp. nov., a new brackish water diatom (Bacillariophyceae) from Southern Iraq
- 2022
-
In: Phytotaxa. - : Magnolia Press. - 1179-3155 .- 1179-3163. ; 550:1, s. 71-78
-
Journal article (peer-reviewed)abstract
- The diatom genus Fallacia includes species having a conopeum which is a perforated thin sheath of silica lying along the apical axis on the external valve face and a hyaline lateral area in the internal valve face. In surveying the benthic diatoms of Basra, a new small brackish water species, Fallacia fawensis was found associated with fine-grained substrata on the western bank of Shatt Al???Arab River, Southern Iraq. This epipelic species is described based on light and scanning electron microscopy and characterized by having a porous conopeum covering the area between raphe sterna and mantle, narrow elongated marginal striae, and a structure similar to lateral hyaline areas in the valve internal side. The terminal raphe endings on the external valve face, below valve apex, the raphe sternum inner margins come close to each other, blocking raphe canal but leaving a lacuna-like thin groove for connection with the deflected upper part of the open raphe canal. These features separated this species from allied taxa of the genus and also from closely related genera, Pseudofallacia and Germaniella. Notes on the ecology and distribution of the new species as well as the associated diatom taxa are provided.
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| 38. |
- Al-Handal, Adil Y, 1952, et al.
(author)
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Observations on diatoms inhabiting natural and artificial substrates in Kongsfjorden, Svalbard, the Arctic
- 2016
-
In: Polar Biology. - : Springer Science and Business Media LLC. - 0722-4060 .- 1432-2056. ; 39:11, s. 1913-1932
-
Journal article (peer-reviewed)abstract
- The most dramatic effects of global climate change are predicted for the Arctic, and there is a raising concern about the lack of baseline information on microalgal biodiversity. The present study was motivated by the general lack of information on species distribution of Arctic benthic diatoms and particularly studies providing photographs to facilitate morphological species identification. Diatoms were studied in samples collected from Ny lesund, Spitsbergen, Svalbard, during summer 2006 and spring 2008. Two types of samples were examined: diatoms scraped from ceramic tiles, immersed at 0.5 m depth (2006), and diatoms extracted from surface sediment, collected at 0.5 to 3 m depth (2008). A total number of 75 taxa belonging to 45 genera were encountered. Sixty-eight species were found in the sediment samples and 48 on the ceramic tiles, of which 41 species were found on both substrata. Common species of the tile assemblages were Fragilariopsis spp., Licmophora spp., Odontella aurita, Synedropsis hyperborea and Trachyneis aspera, while Thalassiosira spp., Diploneis spp. and Navicula spp. were common in the sediment samples. Twenty-five percent of the observed diatom species belonged to freshwater taxa brought to the fjord from surrounding meltwater and river discharges. ELMANN A, 1992, DEEP-SEA RESEARCH PART A-OCEANOGRAPHIC RESEARCH PAPERS, V39, PS525
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| 39. |
- Al-Handal, Adil Y, 1952, et al.
(author)
-
Synedropsis abuflosensis sp. nov., a new araphid diatom (Bacillariophyceae) from the Shatt Al-Arab River, Southern Iraq
- 2022
-
In: Cryptogamie Algologie. - : Museum National d'Histoire Naturelle, Paris, France. - 0181-1568. ; 43:2, s. 31-39
-
Journal article (peer-reviewed)abstract
- Synedropsis abuflosensis sp. nov. is the third species of the genus recorded from a sub-tropical brackish water habitat as opposed to a polar distribution. This species is differentiated from others in the genus by having a different number of slits in the apical slit field at opposite ends of the valve (i.e., 4 at the end possessing a rimoportula versus 5 at the end lacking a rimoportula), an apically oriented rimoportula and 3-4 non-porous cingular bands. Its habitat is different than that of all known Synedropsis Hasle, Medlin & Syvertsen species as it is either benthic or epiphytic in algal mats rather than planktonic or associated with sea ice. The new species was found in waters with a conductivity of 7.1 mu S (cm-1) (salinity 3.3 psu) and a temperature of 33 degrees C. Morphological characters of the new species are described based on light and scanning electron microscopy observations. A comparison of S. abuflosensis sp. nov. with morphologically similar species is provided.
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| 40. |
- Al-Handal, Adil Y, 1952, et al.
(author)
-
Two new marine species of Cocconeis (Bacillariophyceae) from the west coast of Sweden
- 2019
-
In: European Journal of Taxonomy. - : Museum National D'Histoire Naturelle. - 2118-9773. ; 497, s. 1-16
-
Journal article (peer-reviewed)abstract
- This paper is part of a project of studying benthic diatom biodiversity on marine coastal regions of Sweden with focus on rare and less known species. Two new species of Cocconeis Ehrenb. are described from Vrango, a small island in the west coast of Sweden. Both species were found as epiphytic on the green alga Ulva intestinalis L. Cocconeis magnoareolata Al-Handal, Riaux-Gob., R.Jahn & A.K.Wulff sp. nov. is a small species not exceeding 9 mu m in length and characterized by having large subquadrangular areolae on the sternum valve. Cocconeis vrangoensis Al-Handal & Riaux-Gob. sp. nov. appears similar to some taxa of the 'Cocconeis scutellum complex', but differs by its stria density on both valves and variable features of the areola and valvocopula ultrastructure. Detailed descriptions based on light and electron microscopy examination, a comparison with closely related taxa, as well as a description of the habitat of both species are here presented.
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| 41. |
- Babiker, Adil A., et al.
(author)
-
Mapping pro- and antiangiogenic factors on the surface of prostasomes of normal and malignant cell origin
- 2010
-
In: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 70:8, s. 834-847
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Angiogenesis is the formation of new blood vessels by capillary sprouting from pre-existing vessels. Tumor growth is angiogenesis-dependent and the formation of new blood vessels is associated with the increased expression of angiogenic factors. Prostasomes are secretory granules produced, stored and released by the glandular epithelial cells of the prostate. We investigated the expression of selected angiogenic and anti-angiogenic factors on the surface of prostasomes of different origins as well as the direct effect of prostasomes on angiogenesis. METHODS: VEGF, endothelin-1, endostatin, and thrombospondin-1 were determined on prostasomes from seminal fluid and human prostate cancer cell lines (DU145,PC-3,LNCaP) using different immunochemical techniques. Human dermal microvascular endothelial cells were incubated with seminal and DU145 cell-prostasomes and with radioactive thymidine. The effect of prostasomes on angiogenesis was judged by measuring the uptake of labeled thymidine. The presence of any deleterious effects of prostasomes on the endothelial cells was investigated using thymidine assay and confocal laser microscopy. RESULTS: VEGF and endothelin-1 were determined on malignant cell-prostasomes (no difference between cell lines) but not determined on seminal prostasomes. The same applies for the expression of endostatin but with much higher expression on malignant cell-prostasomes with obvious differences between them. Seminal and DU145 cell-prostasomes were found to have anti-angiogenic effect which was more expressed by DU145 cell-prostasomes. No deleterious effect of prostasomes on endothelial function was detected using either thymidine assay or microscopy. CONCLUSIONS: Prostasomes contain pro- and anti-angiogenic factors that function to counteract each other unless the impact from one side exceeds the other to bring about dysequilibrium.
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| 42. |
- Babiker, Adil A., et al.
(author)
-
Overexpression of ecto-protein kinases in prostasomes of metastatic cell origin
- 2006
-
In: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 66:7, s. 675-686
-
Journal article (peer-reviewed)abstract
- BACKGROUND:Prostasomes are secretory granules produced, stored, and released by the glandular epithelial cells of the prostate. They express numerous enzymes whose physiological roles have so far not been fully evaluated. In this study, we investigated the expression and function of prostasomal protein kinases and ATPase.METHODS:The protein kinase activities of prostasomes isolated from seminal fluid and malignant prostate cell lines (PC-3, DU145, and LNCaP) were investigated using the model phosphorylation substrates histone and casein, as well as the plasma proteins C3 and fibrinogen, in combination with specific protein kinase inhibitors. The prostasomal ATPase activity was also evaluated. The expression of protein kinases and ATPase on prostasomes was verified by flow cytometry.RESULTS:Prostasomes (intact or solubilized with octylglucoside or saponin) from prostate cancer cells had higher expression of protein kinases A, C, and casein kinase II compared to prostasomes isolated from seminal plasma, resulting in higher phosphorylation of both exogenous and endogenous substrates. Using intact prostasomes, it was found that prostasomes of metastatic origin had lower ATPase activity, resulting in higher residual ATP available for the phosphorylation reaction. Finally, complement component C3 and fibrinogen (two proteins whose activities are modulated by phosphorylation) were identified as physiologically relevant phosphorylation substrates.CONCLUSIONS:These results indicate that prostasomes are capable of modifying proteins possibly involved in the innate response by extracellular phosphorylation mediated by ecto-kinases. This is a novel mechanism by which prostatic malignant cells may interact with their environment.
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| 43. |
- Babiker, Adil A., et al.
(author)
-
Prostasome Involvement in the Development and Growth of Prostate Cancer
- 2010
-
In: The Open Prostate Cancer Journal. - : Bentham Science Publishers Ltd.. - 1876-8229. ; 3, s. 1-13
-
Research review (peer-reviewed)abstract
- Prostasomes are extracellularly occurring submicron, membrane-surrounded organelles produced by the epithelial cells of the prostate and present in semen after secretion. Even dedifferentiated prostate cancer cells have preserved their ability to produce and export prostasomes to the extracellular space. The precise physiological role of prostasomes is not known, although some of their properties assign them to important physiological and patho-physiological functions that could be exploited in prostate cancer growth and development. In this review, some new properties of seminal and malignant cell line (DU145, PC-3 and LNCaP) prostasomes will be discussed. There are typical differences in the expressions and activities of prostasomal CD59, ATPase, protein kinases and tissue factor (TF) as well as in the transfer of prostasomal CD59 to CD59-deficient erythrocytes (rabbit and human PNH erythrocytes). CD59, protein kinases and TF exhibit characteristic patterns of overexpression by malignant cell prostasomes. A high ATPase activity is recognized on seminal prostasomes with minimal activity on malignant cell prostasomes resulting in more residual ATP available for phosphorylation reactions. Several proteins are phosphorylated by prostasomal protein kinases, namely, complement component C3, fibrinogen, vitronectin and E-cadherin. Furthermore, TF is identified as the main endogenous phosphorylation substrate on prostasomes. In addition, prothrombotic effects of prostasomes are demonstrated. DU145 and PC-3 cell-derived prostasomes exert a higher clotting effect on whole blood and plasma compared to LNCaP cell-derived and seminal prostasomes. In conclusion, malignant cell prostasomes show an increased ability to interact with the biological system in favor of prostate cancer cell promotion and survival. The roles played by prostasomes in this context may improve the understanding of the mechanisms that help the prostate cancer cells to avoid the complement attack (CD59 transfer and phosphorylation and inactivation of C3), to promote angiogenesis (TF) and to metastasize. It may also provide a better understanding of some of the complications usually seen in some terminal prostate cancer patients like thrombotic events and tendency to develop disseminated intravascular coagulation.
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| 44. |
- Babiker, Adil A., et al.
(author)
-
Prothrombotic effects of prostasomes isolated from prostatic cancer cell lines and seminal plasma
- 2007
-
In: Seminars in Thrombosis and Hemostasis. - : Georg Thieme Verlag KG. - 0094-6176 .- 1098-9064. ; 33:1, s. 80-86
-
Research review (peer-reviewed)abstract
- Thromboembolism is well recognized as a major complication of cancer. Many tumor cells overexpress tissue factor (TF), which activates blood coagulation in cancer patients. Inflammatory cells expressing TF are also contributors to this activation. In prostate cancer, we believe that prostasomes may also be involved in the initiation of blood coagulation. Prostasomes are submicron secretory granules derived from the prostate gland. They are surrounded by membrane and their extracellular appearance and membrane architecture are complex. Seminal prostasomes are believed to be necessary for successful fertilization and act as protectors of the spermatozoa in the lower and upper female genital tract. Cells from prostate cancer and its metastases are able to produce and export prostasomes to the extracellular environment. These prostasomes may differ quantitatively rather than qualitatively from their normal counterparts with regard to protein composition and function. A majority of human prostate cancers have been found to overexpress TF, and we have demonstrated by various methods that prostasomes derived from prostate cancer cells express considerably higher levels of TF compared with prostasomes of nonmalignant cell origin. The mechanism related to thromboembolic disease generated by prostasomes in prostatic cancer patients may be the early release of prostasomes from prostate cancer cells into the blood circulation, where they will evoke their blood-clotting effects.
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| 45. |
- Babiker, Adil A., et al.
(author)
-
Transfer of functional prostasomal CD59 of metastatic prostatic cancer cell origin protects cells against complement attck
- 2005
-
In: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 62:2, s. 105-114
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Prostasomes are secretory granules produced, stored, and released, by the glandular epithelial cells of the prostate. They express the glycosylphosphatidylinositol (GPI)-anchored complement regulatory protein CD59, which has been shown to be transferred to spermatozoa and erythrocytes.METHODS: The CD59 content of prostasomes isolated from seminal fluid and malignant prostate cells (PC-3, DU145, and LNCaP) and the transfer of prostasomal CD59 to rabbit erythrocytes (RE) and to PIPLC-treated and unmanipulated cancer cells were investigated using FACS. All prostasomes were also incubated with RE and tested in a hemolytic assay.RESULTS: Prostasomes from cancer cells had higher expression of CD59 than those of normal cells. Prostasomal CD59 of different origin could be transferred to RE, malignant cell lines stripped of CD59 by PIPLC, or unmanipulated LNCaP cells. Malignant cell prostasomes had an increased ability to inhibit complement-mediated lysis compared to those from non-malignant cells.CONCLUSIONS: These results point to a novel mechanism by which prostasomes can protect prostatic malignant cells from complement attack.
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| 46. |
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| 47. |
- Battisti, Umberto Maria, et al.
(author)
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Ellagic Acid and Its Metabolites as Potent and Selective Allosteric Inhibitors of Liver Pyruvate Kinase
- 2023
-
In: Nutrients. - : MDPI AG. - 2072-6643. ; 15:3
-
Journal article (peer-reviewed)abstract
- Liver pyruvate kinase (PKL) has recently emerged as a new target for non-alcoholic fatty liver disease (NAFLD), and inhibitors of this enzyme could represent a new therapeutic option. However, this breakthrough is complicated by selectivity issues since pyruvate kinase exists in four different isoforms. In this work, we report that ellagic acid (EA) and its derivatives, present in numerous fruits and vegetables, can inhibit PKL potently and selectively. Several polyphenolic analogues of EA were synthesized and tested to identify the chemical features responsible for the desired activity. Molecular modelling studies suggested that this inhibition is related to the stabilization of the PKL inactive state. This unique inhibition mechanism could potentially herald the development of new therapeutics for NAFLD.
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| 48. |
- Braeckman, U., et al.
(author)
-
Glacial melt disturbance shifts community metabolism of an Antarctic seafloor ecosystem from net autotrophy to heterotrophy
- 2021
-
In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 4:1
-
Journal article (peer-reviewed)abstract
- Climate change-induced glacial melt affects benthic ecosystems along the West Antarctic Peninsula, but current understanding of the effects on benthic primary production and respiration is limited. Here we demonstrate with a series of in situ community metabolism measurements that climate-related glacial melt disturbance shifts benthic communities from net autotrophy to heterotrophy. With little glacial melt disturbance (during cold El Nino spring 2015), clear waters enabled high benthic microalgal production, resulting in net autotrophic benthic communities. In contrast, water column turbidity caused by increased glacial melt run-off (summer 2015 and warm La Nina spring 2016) limited benthic microalgal production and turned the benthic communities net heterotrophic. Ongoing accelerations in glacial melt and run-off may steer shallow Antarctic seafloor ecosystems towards net heterotrophy, altering the metabolic balance of benthic communities and potentially impacting the carbon balance and food webs at the Antarctic seafloor. Ulrike Braeckman et al. use in situ benthic community and benthic biogeochemistry measurements in Potter Cove on the Antarctic Peninsula to show that climate-related glacial melt disturbance shifts benthic communities from net autotrophy to heterotrophy. This study sheds light on how future glacial melt and run-off may affect the metabolic balance of Antarctic benthic communities.
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| 49. |
- Chapman, Mark A., et al.
(author)
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Skeletal Muscle Transcriptomic Comparison between Long-Term Trained and Untrained Men and Women
- 2020
-
In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 31:12
-
Journal article (peer-reviewed)abstract
- To better understand the health benefits of lifelong exercise in humans, we conduct global skeletal muscle transcriptomic analyses of long-term endurance- (9 men, 9 women) and strength-trained (7 men) humans compared with age-matched untrained controls (7 men, 8 women). Transcriptomic analysis, Gene Ontology, and genome-scale metabolic modeling demonstrate changes in pathways related to the prevention of metabolic diseases, particularly with endurance training. Our data also show prominent sex differences between controls and that these differences are reduced with endurance training. Additionally, we compare our data with studies examining muscle gene expression before and after a months-long training period in individuals with metabolic diseases, This analysis reveals that training shifts gene expression in individuals with impaired metabolism to become more similar to our endurance-trained group. Overall, our data provide an extensive examination of the accumulated transcriptional changes that occur with decades-long training and identify important "exercise-responsive" genes that could attenuate metabolic disease.
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| 50. |
- De Tommasi, E., et al.
(author)
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Underwater Light Manipulation by the Benthic Diatom Ctenophora pulchella: From PAR Efficient Collection to UVR Screening
- 2021
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In: Nanomaterials. - : MDPI AG. - 2079-4991. ; 11:11
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Journal article (peer-reviewed)abstract
- Several species of diatoms, unicellular microalgae which constitute the main component of phytoplankton, are characterized by an impressive photosynthetic efficiency while presenting a noticeable tolerance versus exposure to detrimental UV radiation (UVR). In particular, the growth rate of the araphid diatom Ctenophora pulchella is not significantly affected by harsh treatments with UVR, even in absence of detectable, specific UV-absorbing pigments and even if it is not able to avoid high UV exposure by motility. In this work we applied a multi-disciplinary approach involving numerical computation, photonics, and biological parameters in order to investigate the possible role of the frustule, micro- and nano-patterned silica shell which encloses the cell, in the ability of C. pulchella to efficiently collect photosynthetic active radiation (PAR) and to simultaneously screen the protoplasm from UVR. The characterization of the photonic properties of the frustule has been accompanied by in vivo experiments conducted in water in order to investigate its function as optical coupler between light and plastids.
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