| 1. |
- Visuttijai, Kittichate, 1979-, et al.
(författare)
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Lowered Expression of Tumor Suppressor Candidate MYO1C Stimulates Cell Proliferation, Suppresses Cell Adhesion and Activates AKT
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 11:10
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Tidskriftsartikel (refereegranskat)abstract
- Myosin-1C (MYO1C) is a tumor suppressor candidate located in a region of recurrent losses distal to TP53. Myo1c can tightly and specifically bind to PIP2, the substrate of Phosphoinositide 3-kinase (PI3K), and to Rictor, suggesting a role for MYO1C in the PI3K pathway. This study was designed to examine MYO1C expression status in a panel of well-stratified endometrial carcinomas as well as to assess the biological significance of MYO1C as a tumor suppressor in vitro. We found a significant correlation between the tumor stage and lowered expression of MYO1C in endometrial carcinoma samples. In cell transfection experiments, we found a negative correlation between MYO1C expression and cell proliferation, and MYO1C silencing resulted in diminished cell migration and adhesion. Cells expressing excess of MYO1C had low basal level of phosphorylated protein kinase B (PKB, a.k.a. AKT) and cells with knocked down MYO1C expression showed a quicker phosphorylated AKT (pAKT) response in reaction to serum stimulation. Taken together the present study gives further evidence for tumor suppressor activity of MYO1C and suggests MYO1C mediates its tumor suppressor function through inhibition of PI3K pathway and its involvement in loss of contact inhibition.
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| 2. |
- Nawaz, Muhammad, et al.
(författare)
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Lipid Nanoparticles Deliver the Therapeutic VEGFA mRNA In Vitro and In Vivo and Transform Extracellular Vesicles for Their Functional Extensions
- 2023
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Ingår i: Advanced Science. - : John Wiley & Sons. - 2198-3844. ; 10:12
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Tidskriftsartikel (refereegranskat)abstract
- Lipid nanoparticles (LNPs) are currently used to transport functional mRNAs, such as COVID-19 mRNA vaccines. The delivery of angiogenic molecules, such as therapeutic VEGF-A mRNA, to ischemic tissues for producing new blood vessels is an emerging strategy for the treatment of cardiovascular diseases. Here, the authors deliver VEGF-A mRNA via LNPs and study stoichiometric quantification of their uptake kinetics and how the transport of exogenous LNP-mRNAs between cells is functionally extended by cells’ own vehicles called extracellular vesicles (EVs). The results show that cellular uptake of LNPs and their mRNA molecules occurs quickly, and that the translation of exogenously delivered mRNA begins immediately. Following the VEGF-A mRNA delivery to cells via LNPs, a fraction of internalized VEGF-A mRNA is secreted via EVs. The overexpressed VEGF-A mRNA is detected in EVs secreted from three different cell types. Additionally, RNA-Seq analysis reveals that as cells’ response to LNP-VEGF-A mRNA treatment, several overexpressed proangiogenic transcripts are packaged into EVs. EVs are further deployed to deliver VEGF-A mRNA in vitro and in vivo. Upon equal amount of VEGF-A mRNA delivery via three EV types or LNPs in vitro, EVs from cardiac progenitor cells are the most efficient in promoting angiogenesis per amount of VEGF-A protein produced. Intravenous administration of luciferase mRNA shows that EVs could distribute translatable mRNA to different organs with the highest amounts of luciferase detected in the liver. Direct injections of VEGF-A mRNA (via EVs or LNPs) into mice heart result in locally produced VEGF-A protein without spillover to liver and circulation. In addition, EVs from cardiac progenitor cells cause minimal production of inflammatory cytokines in cardiac tissue compared with all other treatment types. Collectively, the data demonstrate that LNPs transform EVs as functional extensions to distribute therapeutic mRNA between cells, where EVs deliver this mRNA differently than LNPs.
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| 3. |
- Frykholm, Karolin, 1977, et al.
(författare)
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Fast size-determination of intact bacterial plasmids using nanofluidic channels
- 2015
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Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0189 .- 1473-0197. ; 15:13, s. 2739-2743
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate how nanofluidic channels can be used as a tool to rapidly determine the number and sizes of plasmids in bacterial isolates. Each step can be automated at low cost, opening up opportunities for general use in microbiology labs.
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| 4. |
- Javeed, Ashir, 1989-, et al.
(författare)
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Breaking barriers : a statistical and machine learning-based hybrid system for predicting dementia
- 2023
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Ingår i: Frontiers in Bioengineering and Biotechnology. - : Frontiers Media S.A.. - 2296-4185. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Dementia is a condition (a collection of related signs and symptoms) that causes a continuing deterioration in cognitive function, and millions of people are impacted by dementia every year as the world population continues to rise. Conventional approaches for determining dementia rely primarily on clinical examinations, analyzing medical records, and administering cognitive and neuropsychological testing. However, these methods are time-consuming and costly in terms of treatment. Therefore, this study aims to present a noninvasive method for the early prediction of dementia so that preventive steps should be taken to avoid dementia. Methods: We developed a hybrid diagnostic system based on statistical and machine learning (ML) methods that used patient electronic health records to predict dementia. The dataset used for this study was obtained from the Swedish National Study on Aging and Care (SNAC), with a sample size of 43040 and 75 features. The newly constructed diagnostic extracts a subset of useful features from the dataset through a statistical method (F-score). For the classification, we developed an ensemble voting classifier based on five different ML models: decision tree (DT), naive Bayes (NB), logistic regression (LR), support vector machines (SVM), and random forest (RF). To address the problem of ML model overfitting, we used a cross-validation approach to evaluate the performance of the proposed diagnostic system. Various assessment measures, such as accuracy, sensitivity, specificity, receiver operating characteristic (ROC) curve, and Matthew’s correlation coefficient (MCC), were used to thoroughly validate the devised diagnostic system’s efficiency. Results: According to the experimental results, the proposed diagnostic method achieved the best accuracy of 98.25%, as well as sensitivity of 97.44%, specificity of 95.744%, and MCC of 0.7535. Discussion: The effectiveness of the proposed diagnostic approach is compared to various cutting-edge feature selection techniques and baseline ML models. From experimental results, it is evident that the proposed diagnostic system outperformed the prior feature selection strategies and baseline ML models regarding accuracy.
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| 5. |
- Enroth, Helena, et al.
(författare)
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Evaluation of QuickFISH and maldi Sepsityper for identification of bacteria in bloodstream infection
- 2019
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Ingår i: Infectious Diseases. - : Taylor & Francis. - 2374-4235 .- 2374-4243. ; 51:4, s. 249-258
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early detection of bacteria and their antibiotic susceptibility patterns are critical to guide therapeutic decision-making for optimal care of septic patients. The current gold standard, blood culturing followed by subculture on agar plates for subsequent identification, is too slow leading to excessive use of broad-spectrum antibiotic with harmful consequences for the patient and, in the long run, the public health. The aim of the present study was to assess the performance of two commercial assays, QuickFISH® (OpGen) and Maldi Sepsityper™ (Bruker Daltonics) for early and accurate identification of microorganisms directly from positive blood cultures.Materials and methods: During two substudies of positive blood cultures, the two commercial assays were assessed against the routine method used at the clinical microbiology laboratory, Unilabs AB, at Skaraborg Hospital, Sweden.Results: The Maldi Sepsityper™ assay enabled earlier microorganism identification. Using the cut-off for definite species identification according to the reference method (>2.0), sufficiently accurate species identification was achieved, but only among Gram-negative bacteria. The QuickFISH®assay was time-saving and showed high concordance with the reference method, 94.8% (95% CI 88.4–98.3), when the causative agent was covered by the QuickFISH® assay.Conclusions: The use of the commercial assays may shorten the time to identification of causative agents in bloodstream infections and can be a good complement to the current clinical routine diagnostics. Nevertheless, the performance of the commercial assays is considerably affected by the characteristics of the causative agents.
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