| 1. |
- Börgeson, Emma, et al.
(författare)
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Challenges in PhD education due to COVID-19-disrupted supervision or business as usual: a cross-sectional survey of Swedish biomedical sciences graduate students
- 2021
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Ingår i: Bmc Medical Education. - : Springer Science and Business Media LLC. - 1472-6920. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background It remains unclear to what extent the SARS-CoV-2/COVID-19 pandemic disrupted the normal progression of biomedical and medical science graduate programs and if there was a lasting impact on the quality and quantity of supervision of PhD-students. To date, multiple editorials and commentaries indicate the severity of the disruption without providing sufficient evidence with quantifiable data. Methods An online survey was submitted to the administrative offices of biomedical and medical PhD-programs at eight major universities in Sweden to gauge the impact of the pandemic on the students. It consisted of multiple-choice and open-ended questions where students could provide examples of positive and/or negative supervision strategies. Open answered questions were coded as either examples of positive or negative support. Results PhD students were divided into two groups: those with improved or unchanged supervision during the pandemic (group 1, n = 185), versus those whose supervision worsened (group 2, n = 69). Group 1 received more help from supervisors and more frequent supervision via both online and alternative platforms (email/messages and telephone). There was no significant difference in educational-stage, gender or caretaking responsibilities between the groups. Conclusions It is important for the scientific community to learn how to provide the best possible supervision for PhD students during the pandemic. Our data suggests that more frequent supervision, and using a diverse array of meeting platforms is helpful. In addition, it is important for the students to feel that they have their supervisor's emotional support. Several students also expressed that they would benefit from an extension of their PhD programs due to delays caused by the pandemic.
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| 2. |
- Kraft, Jamie D., et al.
(författare)
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Lipoxins modulate neutrophil oxidative burst, integrin expression and lymphatic transmigration differentially in human health and atherosclerosis
- 2022
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Ingår i: FASEB Journal. - Hoboken, NJ, United States : John Wiley & Sons. - 0892-6638 .- 1530-6860. ; 36:3
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Tidskriftsartikel (refereegranskat)abstract
- Dysregulated chronic inflammation plays a crucial role in the pathophysiology of atherosclerosis and may be a result of impaired resolution. Thus, restoring levels of specialized pro-resolving mediators (SPMs) to promote the resolution of inflammation has been proposed as a therapeutic strategy for patients with atherosclerosis, in addition to standard clinical care. Herein, we evaluated the effects of the SPM lipids, lipoxin A4 (LXA4) and lipoxin B4 (LXB4), on neutrophils isolated from patients with atherosclerosis compared with healthy controls. Patients displayed altered endogenous SPM production, and we demonstrated that lipoxin treatment in whole blood from atherosclerosis patients attenuates neutrophil oxidative burst, a key contributor to atherosclerotic development. We found the opposite effect in neutrophils from healthy controls, indicating a potential mechanism whereby lipoxins aid the endogenous neutrophil function in health but reduce its excessive activation in disease. We also demonstrated that lipoxins attenuated upregulation of the high-affinity conformation of the CD11b/CD18 integrin, which plays a central role in clot activation and atherosclerosis. Finally, LXB4 enhanced lymphatic transmigration of human neutrophils isolated from patients with atherosclerosis. This finding is noteworthy, as impaired lymphatic function is now recognized as an important contributor to atherosclerosis. Although both lipoxins modulated neutrophil function, LXB4 displayed more potent effects than LXA4 in humans. This study highlights the therapeutic potential of lipoxins in atherosclerotic disease and demonstrates that the effect of these SPMs may be specifically tailored to the need of the individual. © 2022 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.
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| 3. |
- Lange, Stefan, 1948, et al.
(författare)
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Students at a crossroad: A cross-sectional survey gauging the impact of COVID-19 on medical and biomedical graduates in the United States and Sweden
- 2023
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Ingår i: Biochemistry and Molecular Biology Education. - 1470-8175. ; 51:5, s. 508-519
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Tidskriftsartikel (refereegranskat)abstract
- Graduate programs in medicine and biomedical sciences have been severely impacted by the SARS-CoV-2/COVID-19 pandemic over the last 2 years. Following 2 years since beginning of the pandemic, data on student support, educational and academic performance as well as sentiment on changes to educational programs are starting to emerge. We performed and compared results of two cross-sectional surveys of Swedish and U.S.-based medical and biomedical graduate students on how the pandemic has affected their studies, research productivity and career trajectory. Students were also asked to assess support provided by the university and supervisors. The surveys also captured student demographics and a range of other factors, such as pressures brought on by caretaking and financial responsibilities. We analyzed answers from 264 and 106 students attending graduate programs in universities in Sweden and the United States, respectively. U.S.-based students faced more severe restrictions on their research program compared to students in Sweden, reporting more delays in productivity, scientific output and graduation, and increased worries about their career trajectory. Swedish students had more caretaking responsibilities, although these did not cause any delays in graduation. While support by universities and supervisors was comparable between the countries, financial worries and mental health concerns were particularly prominent in the U.S. cohort. Student performance and outlook was hugely dependent on the breadth of the restrictions and the available support. Besides the governmental and university-led approach to counter the pandemic, societal differences also played a role in how well students were handling effects of the pandemic.
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| 4. |
- Pacha, J., et al.
(författare)
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Circadian regulation of transporter expression and implications for drug disposition
- 2021
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Ingår i: Expert Opinion on Drug Metabolism & Toxicology. - : Informa UK Limited. - 1742-5255 .- 1744-7607. ; 17:4, s. 425-439
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Solute Carrier (SLC) and ATP-binding cassette (ABC) transporters expressed in the intestine, liver, and kidney determine the absorption, distribution, and excretion of drugs. In addition, most molecular and cellular processes show circadian rhythmicity controlled by circadian clocks that leads to diurnal variations in the pharmacokinetics and pharmacodynamics of many drugs and affects their therapeutic efficacy and toxicity. Area covered: This review provides an overview of the current knowledge on the circadian rhythmicity of drug transporters and the molecular mechanisms of their circadian control. Evidence for coupling drug transporters to circadian oscillators and the plausible candidates conveying circadian clock signals to target drug transporters, particularly transcription factors operating as the output of clock genes, is discussed. Expert opinion: The circadian machinery has been demonstrated to interact with the uptake and efflux of various drug transporters. The evidence supports the concept that diurnal changes that affect drug transporters may influence the pharmacokinetics of the drugs. However, more systematic studies are required to better define the timing of pharmacologically important drug transporter regulation and determine tissue- and sex-dependent differences. Finally, the transfer of knowledge based on the results and conclusions obtained primarily from animal models will require careful validation before it is applied to humans.
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| 5. |
- Rohin Rajan, Meenu, et al.
(författare)
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Comparative analysis of obesity-related cardiometabolic and renal biomarkers in human plasma and serum.
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- The search for biomarkers associated with obesity-related diseases is ongoing, but it is not clear whether plasma and serum can be used interchangeably in this process. Here we used high-throughput screening to analyze 358 proteins and 76 lipids, selected because of their relevance to obesity-associated diseases, in plasma and serum from age- and sex-matched lean and obese humans. Most of the proteins/lipids had similar concentrations in plasma and serum, but a subset showed significant differences. Notably, a key marker of cardiovascular disease PAI-1 showed a difference in concentration between the obese and lean groups only in plasma. Furthermore, some biomarkers showed poor correlations between plasma and serum, including PCSK9, an important regulator of cholesterol homeostasis. Collectively, our results show that the choice of biofluid may impact study outcome when screening for obesity-related biomarkers and we identify several markers where this will be the case.
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| 6. |
- Sotak, Matus, et al.
(författare)
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Healthy Subcutaneous and Omental Adipose Tissue Is Associated with High Expression of Extracellular Matrix Components
- 2022
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is associated with extensive expansion and remodeling of the adipose tissue architecture, including its microenvironment and extracellular matrix (ECM). Although obesity has been reported to induce adipose tissue fibrosis, the composition of the ECM under healthy physiological conditions has remained underexplored and debated. Here, we used a combination of three established techniques (picrosirius red staining, a colorimetric hydroxyproline assay, and sensitive gene expression measurements) to evaluate the status of the ECM in metabolically healthy lean (MHL) and metabolically unhealthy obese (MUO) subjects. We investigated ECM deposition in the two major human adipose tissues, namely the omental and subcutaneous depots. Biopsies were obtained from the same anatomic region of respective individuals. We found robust ECM deposition in MHL subjects, which correlated with high expression of collagens and enzymes involved in ECM remodeling. In contrast, MUO individuals showed lower expression of ECM components but elevated levels of ECM cross-linking and adhesion proteins, e.g., lysyl oxidase and thrombospondin. Our data suggests that subcutaneous fat is more prone to express proteins involved in ECM remodeling than omental adipose tissues. We conclude that a more dynamic ability to deposit and remodel ECM may be a key signature of healthy adipose tissue, and that subcutaneous fat may adapt more readily to changing metabolic conditions than omental fat.
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| 7. |
- Sotak, Matus, et al.
(författare)
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Intestinal sodium/glucose cotransporter 3 expression is epithelial and downregulated in obesity.
- 2021
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Ingår i: Life sciences. - : Elsevier BV. - 1879-0631 .- 0024-3205. ; 267
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to determine whether the sodium/glucose cotransporter family member SGLT3, a proposed glucose sensor, is expressed in the intestine and/or kidney, and if its expression is altered in mouse models of obesity and in humans before and after weight-loss surgery.We used in-situ hybridization and quantitative PCR to determine whether the Sglt3 isoforms 3a and 3b were expressed in the intestine and kidney of C57, leptin-deficient ob/ob, and diabetic BTBR ob/ob mice. Western blotting and immunohistochemistry were also used to assess SGLT3 protein levels in jejunal biopsies from obese patients before and after weight-loss Roux-en-Y gastric bypass surgery (RYGB), and in lean healthy controls.Sglt3a/3b mRNA was detected in the small intestine (duodenum, jejunum and ileum), but not in the large intestine or kidneys of mice. Both isoforms were detected in epithelial cells (confirmed using intestinal organoids). Expression of Sglt3a/3b mRNA in duodenum and jejunum was significantly lower in ob/ob and BTBR ob/ob mice than in normal-weight littermates. Jejunal SGLT3 protein levels in aged obese patients before Roux-en-Y gastric bypass (RYGB) were lower than in lean individuals, but substantially upregulated 6months post-RYGB.Our study shows that Sglt3a/3b is expressed primarily in epithelial cells of the small intestine in mice. Furthermore, we observed an association between intestinal mRNA Sglt3a/3b expression and obesity in mice, and between jejunal SGLT3 protein levels and obesity in humans. Further studies are required to determine the possible role of SGLT3 in obesity.
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| 8. |
- Sotak, Matus, et al.
(författare)
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Lipoxins reduce obesity-induced adipose tissue inflammation in 3D-cultured human adipocytes and explant cultures
- 2022
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Ingår i: iScience. - : Elsevier BV. - 2589-0042. ; 25:7
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Tidskriftsartikel (refereegranskat)abstract
- Adipose tissue inflammation drives obesity-related cardiometabolic diseases. Enhancing endogenous resolution mechanisms through administration of lipoxin A4, a specialized pro-resolving lipid mediator, was shown to reduce adipose inflammation and subsequently protects againstobesity-inducedsystemic disease inmice. Here, we demonstrate that lipoxins reduce inflammation in 3D-cultured human adipocytes and adipose tissue explants from obese patients. Approximately 50% of patients responded particularlywell to lipoxins by reducing inflammatory cytokines and promoting an anti-inflammatory M2 macrophage phenotype. Responding patients were characterized by elevated systemic levels of C-reactive protein, which causes inflammation in cultured human adipocytes. Responders appeared more prone to producing anti-inflammatory oxylipins and displayed elevated prostaglandin D2 levels, which has been interlinked with transcription of lipoxin-generatingenzymes. Using explant cultures, this study provides the first proof-of-concept evidence supporting the therapeutic potential of lipoxins in reducing human adipose tissue inflammation. Our data further indicate that lipoxin treatment may require a tailored personalized-medicine approach.
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