| 1. |
- Sliz, E., et al.
(author)
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Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
- 2023
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
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Journal article (peer-reviewed)abstract
- Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.
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| 2. |
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| 3. |
- Zhao, L, et al.
(author)
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Transcriptomic Profiling the Effects of Airway Exposure of Zinc Oxide and Silver Nanoparticles in Mouse Lungs
- 2023
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In: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 24:6
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Journal article (peer-reviewed)abstract
- Consumers and manufacturers are exposed to nanosized zinc oxide (nZnO) and silver particles (nAg) via airways, but their biological effects are still not fully elucidated. To understand the immune effects, we exposed mice to 2, 10, or 50 μg of nZnO or nAg by oropharyngeal aspiration and analyzed the global gene expression profiles and immunopathological changes in the lungs after 1, 7, or 28 days. Our results show that the kinetics of responses varied in the lungs. Exposure to nZnO resulted in the highest accumulation of F4/80- and CD3-positive cells, and the largest number of differentially expressed genes (DEGs) were identified after day 1, while exposure to nAg caused peak responses at day 7. Additionally, nZnO mainly activated the innate immune responses leading to acute inflammation, whereas the nAg activated both innate and adaptive immune pathways, with long-lasting effects. This kinetic-profiling study provides an important data source to understand the cellular and molecular processes underlying nZnO- and nAg-induced transcriptomic changes, which lead to the characterization of the corresponding biological and toxicological effects of nZnO and nAg in the lungs. These findings could improve science-based hazard and risk assessment and the development of safe applications of engineered nanomaterials (ENMs), e.g., in biomedical applications.
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| 4. |
- Agustin, Melissa B., et al.
(author)
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Enzymatic crosslinking of lignin nanoparticles and nanocellulose in cryogels improves adsorption of pharmaceutical pollutants
- 2024
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In: International Journal of Biological Macromolecules. - : Elsevier BV. - 0141-8130 .- 1879-0003. ; 266
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Journal article (peer-reviewed)abstract
- Pharmaceuticals, designed for treating diseases, ironically endanger humans and aquatic ecosystems as pollutants. Adsorption-based wastewater treatment could address this problem, however, creating efficient adsorbents remains a challenge. Recent efforts have shifted towards sustainable bio-based adsorbents. Here, cryogels from lignin-containing cellulose nanofibrils (LCNF) and lignin nanoparticles (LNPs) were explored as pharmaceuticals adsorbents. An enzyme-based approach using laccase was used for crosslinking instead of fossil-based chemical modification. The impact of laccase treatment on LNPs alone produced surface-crosslinked water-insoluble LNPs with preserved morphology and a hemicellulose-rich, water-soluble LNP fraction. The water-insoluble LNPs displayed a significant increase in adsorption capacity, up to 140 % and 400 % for neutral and cationic drugs, respectively. The crosslinked cryogel prepared by one-pot incubation of LNPs, LCNF and laccase showed significantly higher adsorption capacities for various pharmaceuticals in a multi-component system than pure LCNF or unmodified cryogels. The crosslinking minimized the leaching of LNPs in water, signifying enhanced binding between LNPs and LCNF. In real wastewater, the laccase-modified cryogel displayed 8–44 % removal for cationic pharmaceuticals. Overall, laccase treatment facilitated the production of bio-based adsorbents by improving the deposition of LNPs to LCNF. Finally, this work introduces a sustainable approach for engineering adsorbents, while aligning with global sustainability goals.
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| 7. |
- Jarvilehto, J., et al.
(author)
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Serum Creatine, Not Neurofilament Light, Is Elevated in CHCHD10-Linked Spinal Muscular Atrophy
- 2022
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In: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 13
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Journal article (peer-reviewed)abstract
- ObjectiveTo characterize serum biomarkers in mitochondrial CHCHD10-linked spinal muscular atrophy Jokela (SMAJ) type for disease monitoring and for the understanding of pathogenic mechanisms. MethodsWe collected serum samples from a cohort of 49 patients with SMAJ, all carriers of the heterozygous c.197G>T p.G66V variant in CHCHD10. As controls, we used age- and sex-matched serum samples obtained from Helsinki Biobank. Creatine kinase and creatinine were measured by standard methods. Neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) were measured with single molecule array (Simoa), fibroblast growth factor 21 (FGF-21), and growth differentiation factor 15 (GDF-15) with an enzyme-linked immunosorbent assay. For non-targeted plasma metabolite profiling, samples were analyzed with liquid chromatography high-resolution mass spectrometry. Disease severity was evaluated retrospectively by calculating a symptom-based score. ResultsAxon degeneration marker, NfL, was unexpectedly not altered in the serum of patients with SMAJ, whereas astrocytic activation marker, GFAP, was slightly decreased. Creatine kinase was elevated in most patients, particularly men. We identified six metabolites that were significantly altered in serum of patients with SMAJ in comparison to controls: increased creatine and pyruvate, and decreased creatinine, taurine, N-acetyl-carnosine, and succinate. Creatine correlated with disease severity. Altered pyruvate and succinate indicated a metabolic response to mitochondrial dysfunction; however, lactate or mitochondrial myopathy markers FGF-21 or GDF-15 was not changed. ConclusionsBiomarkers of muscle mass and damage are altered in SMAJ serum, indicating a role for skeletal muscle in disease pathogenesis in addition to neurogenic damage. Despite the minimal mitochondrial pathology in skeletal muscle, signs of a metabolic shift can be detected.
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| 8. |
- Lehtonen, T, et al.
(author)
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SLEEP PROBLEMS IN EARLY RHEUMATOID ARTHRITIS
- 2020
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In: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 614-614
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Conference paper (other academic/artistic)abstract
- It is well known that patients with established RA suffer from problems with sleep quality[1]. There are however few, if any, studies on sleep quality among newly diagnosed patients.Objectives:To investigate the sleep quality among patients newly diagnosed with RA.Methods:We used the Swedish study Epidemiological Investigation of RA (EIRA) including patients at the time of diagnosis, based on the 1987 ACR criteria during 2008-2016. At 1 and 3 years after diagnosis, the patients were sent a questionnaire in which they were asked to rate their sleep quality on 10 different questions. We then calculated 6 different sleep components consisting of insomnia, non-restorative sleep, sleep problems, general quality of sleep, if poor sleep affected the health and if they were getting enough sleep[2].Sleep problems were defined as mostly or always having problems with either of the following: falling asleep, many awakenings with difficulties to go back to sleep, waking up early or having disturbed/restless sleep. Insomnia was defined as answering mostly or always on either problem with falling asleep, many awakenings with difficulties to go back to sleep or waking up early, in combination with mostly or always being tired during the day.Having problems with non-restorative sleep was defined as mostly or always having trouble waking up or not feeling well rested when waking up. We defined having problem with not getting enough sleep, sleep quality affecting the health and poor sleep quality as reporting any of the two highest scores on the corresponding questions.We then calculated the proportion of people experiencing no problems at 1 or 3 years after RA diagnosis, developing problems, improving or always having problems with their sleep.Results:We identified 1483 patients with data at either one or both time points. The mean age was 59 years (IQR 19), and 1063 (72%) were women. At 1 year, 36% of the patients reported having at least one type of sleep problem, after 3 years, this figure was 29%. Over 20% of the patients reported having “Rather big” or “Very big” problems with sleep after one year (Table 1) and 31% had problems at one or both time points (Table 2). Disturbed sleep was a problem for their health in 20% of the patients and 11% reported having “poor” or “very poor” sleep quality at both times. Insomnia was experienced by 118 (10%) patients at 1 year and 112 (11%) at 3 years.Table 1.Sleep problems at 1 and 3 years after diagnosis of RA.1 year3 yearsInsomnia118 (9%)112 (11%)Not getting enough sleep102 (8%)113 (11%)Problems with sleep in general270 (22%)231 (22%)Sleep quality affecting health238 (19%)197 (19%)Poor sleep quality218 (17%)209 (20%)Problem with non-restorative sleep218 (17%)154 (14%)Table 2.Individuals experiencing no problems, developing problems, improving or always having problems with their sleep at 1 and 3 years after diagnosis of RA.No problems at any time pointImprovedDeveloped problemsProblems at both 1 and 3 yearsInsomnia702 (85%)43 (5%)46 (6%)39 (5%)Not getting enough sleep719 (86%)36 (4%)47 (6%)34 (4%)Problems with sleep in general576 (69%)81 (10%)78 (9%)103 (12%)Sleep quality affecting health616 (74%)65 (8%)70 (8%)85 (10%)Poor sleep quality623 (74%)57 (7%)66 (8%)91 (11%)Problem with non-restorative sleep654 (78%)71 (8%)46 (5%)67 (8%)Conclusion:In a population-based early RA cohort receiving today’s standard care, 30% of the patients reported some type of sleep problem during the first 3 years. Although this is a lower rate than has been reported in established RA, this is a significant proportion of RA patients, and these findings warrant further studies to closer identify the course of sleep problems and the factors influencing it such as pain.References:[1]Bourguignon C et al PMID 14596374[2]Akerstedt T et al PMID 18484368Acknowledgments:The authors wish to acknowledge the EIRA study group and the EIRA data collectors.Disclosure of Interests:Tiina Lehtonen: None declared, Torbjörn Åkerstedr: None declared, Lauren Lyne: None declared, Lars Klareskog: None declared, Saedis Saevarsdottir Employee of: Part-time at deCODE Genetics/Amgen Inc, working on genetic research unrelated to this project, Lars Alfredsson: None declared, Helga Westerlind: None declared
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| 9. |
- Lyne, L, et al.
(author)
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Sleep problems in rheumatoid arthritis over 12 years from diagnosis: results from the Swedish EIRA study
- 2022
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In: RMD open. - : BMJ. - 2056-5933. ; 8:1
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Journal article (peer-reviewed)abstract
- Most studies of rheumatoid arthritis (RA) and sleep have focused on established RA. We here investigate sleep quality and sleep duration in patients with newly diagnosed RA and during 1–12 years after diagnosis.MethodsData were collected on sleep 1–12 years after diagnosis from patients diagnosed 1998–2018 in the Swedish study Epidemiological Investigation of RA. Six sleep domains (sleep problems, non-restorative sleep, insomnia, insufficient sleep, sleep quality perceived as poor and sleep considered a health problem); a global sleep score and time spent in bed were estimated. Using logistic regression, ORs were calculated for each sleep outcome by disease duration. We explored whether pain (low (Visual Analogue Scale=0–20 mm, reference), intermediate=21–70, high=71–100) or functional impairment (Health Assessment Questionnaire>1.0) was associated with problems.ResultsWe had sleep data on 4131 observations (n=3265 individuals). Problems with ≥1 sleep domain (global sleep score) was reported in 1578 observations (38%) and increased with disease duration (OR 1.04, 95% CI 1.02 to 1.07). Median time in bed was 8 hours (Q1-Q3: 7.5–9.0). High-grade pain increased the likelihood of sleep problems ~3–9 fold, and increased functional impairment ~4–8 fold.ConclusionIn this cohort of newly diagnosed patients with RA with access to the current treatment from diagnosis, we did not find any major problems with sleep, and existing sleep problems related mainly to pain and reduced function. Treatment of sleep problems in RA should be guided towards treating the underlying problem causing the sleep disturbance.
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