| 1. |
- Altay, Özlem, et al.
(författare)
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Combined Metabolic Activators Accelerates Recovery in Mild-to-Moderate COVID-19
- 2021
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Ingår i: Advanced Science. - : Wiley. - 2198-3844. ; 8:17
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Tidskriftsartikel (refereegranskat)abstract
- COVID-19 is associated with mitochondrial dysfunction and metabolic abnormalities, including the deficiencies in nicotinamide adenine dinucleotide (NAD+) and glutathione metabolism. Here it is investigated if administration of a mixture of combined metabolic activators (CMAs) consisting of glutathione and NAD+ precursors can restore metabolic function and thus aid the recovery of COVID-19 patients. CMAs include l-serine, N-acetyl-l-cysteine, nicotinamide riboside, and l-carnitine tartrate, salt form of l-carnitine. Placebo-controlled, open-label phase 2 study and double-blinded phase 3 clinical trials are conducted to investigate the time of symptom-free recovery on ambulatory patients using CMAs. The results of both studies show that the time to complete recovery is significantly shorter in the CMA group (6.6 vs 9.3 d) in phase 2 and (5.7 vs 9.2 d) in phase 3 trials compared to placebo group. A comprehensive analysis of the plasma metabolome and proteome reveals major metabolic changes. Plasma levels of proteins and metabolites associated with inflammation and antioxidant metabolism are significantly improved in patients treated with CMAs as compared to placebo. The results show that treating patients infected with COVID-19 with CMAs lead to a more rapid symptom-free recovery, suggesting a role for such a therapeutic regime in the treatment of infections leading to respiratory problems.
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| 2. |
- Abdellah, Tebani, et al.
(författare)
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Integration of molecular profiles in a longitudinal wellness profiling cohort.
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies andimmune cell profiling, complementedwith gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.
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| 3. |
- Grishenkov, Dmitry, 1983-, et al.
(författare)
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Acoustic properties of polymer-shelled ultrasound contrast agents. Bulk volume vs. microcapillary
- 2009
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Ingår i: 16th International Congress on Sound and Vibration 2009, ICSV 2009. - Krakow. - 9781615677368 ; , s. 2515-2522
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Konferensbidrag (refereegranskat)abstract
- The focus of contrast-enhanced ultrasound research has developed beyond detecting the blood pool to new areas such as perfusion imaging, drug and gene therapy, and targeted imaging. Polymer-shelled microbubbles are proposed as a new generation of ultrasound contrast agents (UCAs) which fulfil the requirements of these applications. With a shelf-life of several months and possibility to conjugate pharmacological molecules to their surface, these UCAs will allow not only to enhance the contrast of ultrasound images, but also to function as carriers of drugs to be delivered locally. In this study, the results of an experimental investigation of three types of UCAs stabilized by thick poly vinyl alcohol (PVA) shell are presented. These UCAs are synthesized from a PVA aqueous solution under varied pH values and temperature. The UCAs differ from each other in their average diameter, shell thickness and polydispersity. Knowledge of the peak negative pressure at which the solid shell fractures is paramount for a proper use of UCAs. Therefore, the dependence of this quantity on temperature and number of cycles in the incident pulse is examined. Much of the blood volume resides in the microcirculation, with capillaries playing a particularly important role in patho-physiology and drug delivery. In this sense in vitro characterization of the UCAs oscillation was moved from bulk volume to the capillary scale, where tissue-bubble interaction takes place. The main conclusion to be drawn from these results is that the shell of the UCAs begin to fracture at values of mechanical index (MI) approved for clinical applications. The fatigue, i.e. the accumulation of damage within the shell of the UCAs, is found to play an important role in fracturing the shell. Finally adhesion of the UCAs to the elastic wall is studied and correlated with estimates of the shell’s visco-elastic constants. Open questions arising from this comparison are briefly discussed.
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| 4. |
- Björnson, Elias, 1988, et al.
(författare)
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Personalized Cardiovascular Disease Prediction and Treatment-A Review of Existing Strategies and Novel Systems Medicine Tools
- 2016
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Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 7:JAN
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Forskningsöversikt (refereegranskat)abstract
- Cardiovascular disease (CVD) continues to constitute the leading cause of death globally. CVD risk stratification is an essential tool to sort through heterogeneous populations and identify individuals at risk of developing CVD. However, applications of current risk scores have recently been shown to result in considerable misclassification of high-risk subjects. In addition, despite long standing beneficial effects in secondary prevention, current CVD medications have in a primary prevention setting shown modest benefit in terms of increasing life expectancy. A systems biology approach to CVD risk stratification may be employed for improving risk-estimating algorithms through addition of high-throughput derived omics biomarkers. In addition, modeling of personalized benefit-of-treatment may help in guiding choice of intervention. In the area of medicine, realizing that CVD involves perturbations of large complex biological networks, future directions in drug development may involve moving away from a reductionist approach toward a system level approach. Here, we review current CVD risk scores and explore how novel algorithms could help to improve the identification of risk and maximize personalized treatment benefit. We also discuss possible future directions in the development of effective treatment strategies for CVD through the use of genome-scale metabolic models (GEMs) as well as other biological network-based approaches.
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| 5. |
- Klevstig, Martina, et al.
(författare)
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Cardiac expression of the microsomal triglyceride transport protein protects the heart function during ischemia
- 2019
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Ingår i: Journal of Molecular and Cellular Cardiology. - : Elsevier BV. - 0022-2828 .- 1095-8584. ; 137, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The microsomal triglyceride transport protein (MTTP) is critical for assembly and secretion of apolipoprotein B (apoB)-containing lipoproteins and is most abundant in the liver and intestine. Surprisingly, MTTP is also expressed in the heart. Here we tested the functional relevance of cardiac MTTP expression. Materials and methods: We combined clinical studies, advanced expression analysis of human heart biopsies and analyses in genetically modified mice lacking cardiac expression of the MTTP-A isoform of MTTP. Results: Our results indicate that lower cardiac MTTP expression in humans is associated with structural and perfusion abnormalities in patients with ischemic heart disease. MTTP-A deficiency in mice heart does not affect total MTTP expression, activity or lipid concentration in the heart. Despite this, MTTP-A deficient mice displayed impaired cardiac function after a myocardial infarction. Expression analysis of MTTP indicates that MTTP expression is linked to cardiac function and responses in the heart. Conclusions: Our results indicate that MTTP may play an important role for the heart function in conjunction to ischemic events.
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| 6. |
- Wang, Chunliang, 1980-, et al.
(författare)
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An interactive software module for visualizing coronary arteries in CT angiography
- 2008
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Ingår i: International Journal of Computer Assisted Radiology and Surgery. - Heidelberg/Berlin : Springer. - 1861-6410 .- 1861-6429. ; 3:1-2, s. 11-18
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Tidskriftsartikel (refereegranskat)abstract
- A new software module for coronary artery segmentation and visualization in CT angiography (CTA) datasets is presented, which aims to interactively segment coronary arteries and visualize them in 3D with maximum intensity projection (MIP) and volume rendering (VRT).Materials and Methods: The software was built as a plug-in for the open-source PACS workstation OsiriX. The main segmentation function is based an optimized “virtual contrast injection” algorithm, which uses fuzzy connectedness of the vessel lumen to separate the contrast-filled structures from each other. The software was evaluated in 42 clinical coronary CTA datasets acquired with 64-slice CT using isotropic voxels of 0.3–0.5 mm.Results: The median processing time was 6.4 min, and 100% of main branches (right coronary artery, left circumflex artery and left anterior descending artery) and 86.9% (219/252) of visible minor branches were intact. Visually correct centerlines were obtained automatically in 94.7% (321/339) of the intact branches.Conclusion: The new software is a promising tool for coronary CTA post-processing providing good overviews of the coronary artery with limited user interaction on low-end hardware, and the coronary CTA diagnosis procedure could potentially be more time-efficient than using thin-slab technique.
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| 7. |
- Wang, Chunliang, 1980-, et al.
(författare)
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Integrating automatic and interactive method for coronary artery segmentation : let PACS workstation think ahead
- 2010
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Ingår i: International Journal of Computer Assisted Radiology and Surgery. - : Springer Science and Business Media LLC. - 1861-6410 .- 1861-6429. ; 5:3, s. 275-285
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To provide an efficient method to extract useful information from the increasing amount of coronary CTA.Methods: A quantitative coronary CTA analysis tool was built on OsiriX, which integrates both fully automatic and interactive methods for coronary artery extraction. The computational power of an ordinary PC is exploited by running the non-supervised coronary artery segmentation and centerline tracking in the background as soon as the images are received. When the user opens the data, the software provides a real-time interactive analysis environment.Results: The average overlap between the centerline created in our software and the reference standard was 96.0%. The average distance between them was 0.38 mm. The automatic procedure runs for 3-5 min as a single-thread application in background. Interactive processing takes 3 min in average.Conclusion: In preliminary experiments, the software achieved higher efficiency than the former interactive method, and reasonable accuracy compared to manual vessel extraction.
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| 8. |
- Ritsinger, V., et al.
(författare)
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Elevated levels of insulin-like growth factor-binding protein 1 predict outcome after acute myocardial infarction : A long-term follow-up of the glucose tolerance in patients with acute myocardial infarction (GAMI) cohort
- 2018
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Ingår i: Diabetes & Vascular Disease Research. - : SAGE Publications Ltd. - 1479-1641 .- 1752-8984. ; 15:5, s. 387-395
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the long-term prognostic value of insulin-like growth factor-binding protein 1 in patients with acute myocardial infarction. Methods: Patients (n = 180) with admission glucose < 11 mmol/L without previously known diabetes admitted for an acute myocardial infarction in 1998–2000 were followed for mortality and cardiovascular events (first of cardiovascular mortality/acute myocardial infarction/stroke/severe heart failure) until the end of 2011 (median 11.6 years). Fasting levels of insulin-like growth factor-binding protein 1 at day 2 were related to outcome in Cox proportional hazard regression analyses. Results: Median age was 64 years, 69% were male and median insulin-like growth factor-binding protein 1 was 20 µg/L. Total mortality was 34% (n = 61) and 44% (n = 80) experienced a cardiovascular event during a median follow-up time of 11.6 years. After age adjustment, insulin-like growth factor-binding protein 1 was associated with all-cause (1.40; 1.02–1.93, p = 0.039) and cancer mortality (2.09; 1.15–3.79, p = 0.015) but not with cardiovascular death (p = 0.29) or cardiovascular events (p = 0.57). After adjustments also for previous myocardial infarction, previous heart failure and body mass index, insulin-like growth factor-binding protein 1 was still associated with all-cause mortality (1.38; 1.01–1.89, p = 0.046). Conclusion: In patients with acute myocardial infarction without previously known diabetes, high insulin-like growth factor-binding protein 1 was associated with long-term all-cause and cancer mortality but not with cardiovascular events.
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| 9. |
- Li, Yanhong, et al.
(författare)
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Urinary aquaporin-2 excretion during ibuprofen or indomethacin treatment in preterm infants with patent ductus arteriosus
- 2011
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Ingår i: Acta Paediatrica. - : Wiley-Blackwell. - 0803-5253 .- 1651-2227. ; 100:1, s. 59-66
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Water channel AQP2 is the target for vasopressin (AVP) and a major determinant of urinary concentrating capacity. In mature kidneys, prostaglandins counteract the effect of AVP on AQP2 expression at functional sites. We investigated whether disturbances in water homeostasis in infants with patent ductus arteriosus (PDA) treated with prostaglandin inhibitors can be attributed to activation of AQP2. Methods: In 53 infants with symptomatic PDA (gestational age 24-33 weeks), 30 receiving ibuprofen and 23 indomethacin starting at 2-15 days of life, clinical and biochemical data were collected before treatment and after each dose of the drugs. Urinary AQP2 was determined by dot immunoblotting. Results: Urinary AQP2 level and osmolality were decreased in both groups. Urinary osmolality was overall low and correlated inversely with fluid uptake. In ibuprofen group, there was no correlation of AQP2 level with urinary osmolality. Conclusion: There was no AQP2 upregulation in the infants. The low urinary osmolality and dissociation between urinary osmolality and urinary AQP2 level indicate that the fluid retention sometimes observed in PDA infants treated with prostaglandin inhibitors is not caused by increased levels of functional AQP2. Thus, knowledge about the renal physiology of the adult cannot always be transferred to the infant kidney.
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| 10. |
- Yang, Zhijian, et al.
(författare)
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Genetic Landscape of the ACE2 Coronavirus Receptor
- 2022
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Ingår i: Circulation. - : Ovid Technologies (Wolters Kluwer Health). - 0009-7322 .- 1524-4539. ; 30:SUPPL 1, s. 36-36
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Tidskriftsartikel (refereegranskat)abstract
- Background: SARS-CoV-2, the causal agent of COVID-19, enters human cells using the ACE2 (angiotensin-converting enzyme 2) protein as a receptor. ACE2 is thus key to the infection and treatment of the coronavirus. ACE2 is highly expressed in the heart and respiratory and gastrointestinal tracts, playing important regulatory roles in the cardiovascular and other biological systems. However, the genetic basis of the ACE2 protein levels is not well understood.Methods: We have conducted the largest genome-wide association meta-analysis of plasma ACE2 levels in >28 000 individuals of the SCALLOP Consortium (Systematic and Combined Analysis of Olink Proteins). We summarize the cross-sectional epidemiological correlates of circulating ACE2. Using the summary statistics-based high-definition likelihood method, we estimate relevant genetic correlations with cardiometabolic phenotypes, COVID-19, and other human complex traits and diseases. We perform causal inference of soluble ACE2 on vascular disease outcomes and COVID-19 severity using mendelian randomization. We also perform in silico functional analysis by integrating with other types of omics data.Results: We identified 10 loci, including 8 novel, capturing 30% of the heritability of the protein. We detected that plasma ACE2 was genetically correlated with vascular diseases, severe COVID-19, and a wide range of human complex diseases and medications. An X-chromosome cis-protein quantitative trait loci-based mendelian randomization analysis suggested a causal effect of elevated ACE2 levels on COVID-19 severity (odds ratio, 1.63 [95% CI, 1.10-2.42]; P=0.01), hospitalization (odds ratio, 1.52 [95% CI, 1.05-2.21]; P=0.03), and infection (odds ratio, 1.60 [95% CI, 1.08-2.37]; P=0.02). Tissue- and cell type-specific transcriptomic and epigenomic analysis revealed that the ACE2 regulatory variants were enriched for DNA methylation sites in blood immune cells.Conclusions: Human plasma ACE2 shares a genetic basis with cardiovascular disease, COVID-19, and other related diseases. The genetic architecture of the ACE2 protein is mapped, providing a useful resource for further biological and clinical studies on this coronavirus receptor.
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