| 1. |
- Avram, Vlad Florian, et al.
(författare)
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Improvement of platelet respiration by cell-permeable succinate in diabetic patients treated with statins
- 2021
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Ingår i: Life. - : MDPI AG. - 0024-3019 .- 2075-1729. ; 11:4
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Tidskriftsartikel (refereegranskat)abstract
- Diabetes mellitus (DM) is the most severe metabolic disease that reached the level of a global pandemic and is associated with high cardiovascular morbidity. Statins are the first-line lipid- lowering therapy in diabetic patients with or without a history of atherosclerotic disease. Although well tolerated, chronic treatment may result in side effects that lead to treatment interruption. Mitochondrial dysfunction has emerged as a central pathomechanism in DM- and statin-induced side effects. Assessment of mitochondrial respiration in peripheral platelets has been increasingly used as a mirror of organ mitochondrial dysfunction. The present study aimed to assess the: (i) changes in mitochondrial respiration elicited by statins in patients with type 2 DM and (ii) the effects of cell-permeable succinate (NV118) on respiratory parameters in platelets harvested from these patients. No significant changes were found in global mitochondrial respiration of intact platelets isolated from diabetic patients treated with either atorvastatin or rosuvastatin. Similarly, no significant changes in mitochondrial respiration of permeabilized platelets were found between diabetic patients treated with atorvastatin and healthy controls. Acute ex vivo administration of NV118 significantly improved respiration in isolated platelets. These results prompt further research on the role of permeable succinate as a therapeutic alternative for improving mitochondrial function in metabolic pathologies and point to the role of peripheral platelets as a potential biomarker of treatment response.
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| 2. |
- Barbara Sahlin, K., et al.
(författare)
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Short-term effect of induced alterations in testosterone levels on fasting plasma amino acid levels in healthy young men
- 2021
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Ingår i: Life. - : MDPI AG. - 0024-3019 .- 2075-1729. ; 11:11
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Tidskriftsartikel (refereegranskat)abstract
- Long term effect of testosterone (T) deficiency impairs metabolism and is associated with muscle degradation and metabolic disease. The association seems to have a bidirectional nature and is not well understood. The present study aims to investigate the early and unidirectional metabolic effect of induced T changes by measuring fasting amino acid (AA) levels in a human model, in which short-term T alterations were induced. We designed a human model of 30 healthy young males with pharmacologically induced T changes, which resulted in three time points for blood collection: (A) baseline, (B) low T (3 weeks post administration of gonadotropin releasing hormone antagonist) and (C) restored T (2 weeks after injection of T undecanoate). The influence of T on AAs was analyzed by spectrophotometry on plasma samples. Levels of 9 out of 23 AAs, of which 7 were essential AAs, were significantly increased at low T and are restored upon T supplementation. Levels of tyrosine and phenylalanine were most strongly associated to T changes. Short-term effect of T changes suggests an increased protein breakdown that is restored upon T supplementation. Fasting AA levels are able to monitor the early metabolic changes induced by the T fluctuations.
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| 3. |
- Demi, Selina, et al.
(författare)
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Doctor at your fingertips : An exploration of digital visits from stakeholders’ perspectives
- 2021
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Ingår i: Life. - : MDPI AG. - 0024-3019 .- 2075-1729. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Technological advances and the evolution of mobile technologies enable patients to meet their doctors through their smartphones. While offering the opportunity of digital visits to patients, there are also challenges for this development. The purpose of this study is to enhance the understanding of digital visits, as perceived by experts working in telemedicine companies. To serve this purpose, the authors conducted semi-structured interviews with managers and employees in eight telemedicine companies. The analysis of the empirical data confirmed the importance of digital visits and their efficiency. The potential of digital visits is expected to increase significantly, should they make use of remote devices to transfer real-time data from patients to physicians. In such a case, digital visits are expected to cover approximately 70–75% of medical cases. However, the use of remote devices must be taken with caution and specific conditions need to be taken into account. We encourage researchers to perform research on promising technologies such as artificial intelligence and remote diagnostic devices, which could make more diagnoses and conditions possible to be treated by digital visits. This is even more important in light of the ongoing Covid-19 pandemic.
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| 4. |
- Jakobsson, Magnus E.
(författare)
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Structure, activity and function of the dual protein lysine and protein n‐terminal methyltransferase mettl13
- 2021
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Ingår i: Life. - : MDPI AG. - 0024-3019 .- 2075-1729. ; 11:11
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Forskningsöversikt (refereegranskat)abstract
- METTL13 (also known as eEF1A‐KNMT and FEAT) is a dual methyltransferase reported to target the N‐terminus and Lys55 in the eukaryotic translation elongation factor 1 alpha (eEF1A). METTL13‐mediated methylation of eEF1A has functional consequences related to translation dynamics and include altered rate of global protein synthesis and translation of specific codons. Aberrant regulation of METTL13 has been linked to several types of cancer but the precise mechanisms are not yet fully understood. In this article, the current literature related to the structure, activity, and function of METTL13 is systematically reviewed and put into context. The links between METTL13 and diseases, mainly different types of cancer, are also summarized. Finally, key challenges and opportunities for METTL13 research are pinpointed in a prospective outlook.
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| 5. |
- Sharma, Siddhant, et al.
(författare)
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Automated exploration of prebiotic chemical reaction space: progress and perspectives
- 2021
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Ingår i: Life. - : MDPI AG. - 0024-3019 .- 2075-1729. ; 11:11
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Tidskriftsartikel (refereegranskat)abstract
- Prebiotic chemistry often involves the study of complex systems of chemical reactions that form large networks with a large number of diverse species. Such complex systems may have given rise to emergent phenomena that ultimately led to the origin of life on Earth. The environmental conditions and processes involved in this emergence may not be fully recapitulable, making it difficult for experimentalists to study prebiotic systems in laboratory simulations. Computational chemistry offers efficient ways to study such chemical systems and identify the ones most likely to display complex properties associated with life. Here, we review tools and techniques for modelling prebiotic chemical reaction networks and outline possible ways to identify self-replicating features that are central to many origin-of-life models.
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| 6. |
- Hedman, Christel, et al.
(författare)
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Deprescribing in Palliative Cancer Care
- 2022
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Ingår i: Life. - : MDPI AG. - 0024-3019 .- 2075-1729. ; 12:5
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Forskningsöversikt (refereegranskat)abstract
- The aim of palliative care is to maintain as high a quality of life (QoL) as possible despite a life-threatening illness. Thus, the prescribed medications need to be evaluated and the benefit of each treatment must be weighed against potential side effects. Medications that contribute to symptom relief and maintained QoL should be prioritized. However, studies have shown that treatment with preventive drugs that may not benefit the patient in end-of-life is generally deprescribed very late in the disease trajectory of cancer patients. Yet, knowing how and when to deprescribe drugs can be difficult. In addition, some drugs, such as beta-blockers, proton pump inhibitors, anti-depressants and cortisone need to be scaled down slowly to avoid troublesome withdrawal symptoms. In contrast, other medicines, such as statins, antihypertensives and vitamins, can be discontinued directly. The aim of this review is to give some advice according to when and how to deprescribe medications in palliative cancer care according to current evidence and clinical praxis. The review includes antihypertensive drugs, statins, anti-coagulants, aspirin, anti-diabetics, proton pump inhibitors, histamin-2-blockers, bisphosphonates denosumab, urologicals, anti-depressants, cortisone, thyroxin and vitamins.
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| 7. |
- Jacobs, Rita, et al.
(författare)
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Fluid Management, Intra-Abdominal Hypertension and the Abdominal Compartment Syndrome : A Narrative Review
- 2022
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Ingår i: Life. - : MDPI AG. - 0024-3019 .- 2075-1729. ; 12:9
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Forskningsöversikt (refereegranskat)abstract
- Background: General pathophysiological mechanisms regarding associations between fluid administration and intra-abdominal hypertension (IAH) are evident, but specific effects of type, amount, and timing of fluids are less clear. Objectives: This review aims to summarize current knowledge on associations between fluid administration and intra-abdominal pressure (IAP) and fluid management in patients at risk of intra-abdominal hypertension and abdominal compartment syndrome (ACS). Methods: We performed a structured literature search from 1950 until May 2021 to identify evidence of associations between fluid management and intra-abdominal pressure not limited to any specific study or patient population. Findings were summarized based on the following information: general concepts of fluid management, physiology of fluid movement in patients with intra-abdominal hypertension, and data on associations between fluid administration and IAH. Results: We identified three randomized controlled trials (RCTs), 38 prospective observational studies, 29 retrospective studies, 18 case reports in adults, two observational studies and 10 case reports in children, and three animal studies that addressed associations between fluid administration and IAH. Associations between fluid resuscitation and IAH were confirmed in most studies. Fluid resuscitation contributes to the development of IAH. However, patients with IAH receive more fluids to manage the effect of IAH on other organ systems, thereby causing a vicious cycle. Timing and approach to de-resuscitation are of utmost importance, but clear indicators to guide this decision-making process are lacking. In selected cases, only surgical decompression of the abdomen can stop deterioration and prevent further morbidity and mortality. Conclusions: Current evidence confirms an association between fluid resuscitation and secondary IAH, but optimal fluid management strategies for patients with IAH remain controversial.
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| 8. |
- Luo, Cui, et al.
(författare)
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Identification and Current Palaeobiological Understanding of “Keratosa”-Type Nonspicular Demosponge Fossils in Carbonates : With a New Example from the Lowermost Triassic, Armenia
- 2022
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Ingår i: Life. - : MDPI AG. - 0024-3019 .- 2075-1729. ; 12:9
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Tidskriftsartikel (refereegranskat)abstract
- Structures similar to fossilized nonspicular demosponges have been reported in carbonates throughout the Phanerozoic and recently in rocks dating back to 890 Ma ago. Interpretation of these records is increasingly influential to our understanding of metazoans in multiple aspects, including their early evolution, the ecology in fossil reefs, and recovery after mass extinction events. Here, we propose six identification criteria of “Keratosa”-type nonspicular demosponge fossils based on the well-established taphonomical models and their biological characteristics. Besides, sponge fossils of this kind from the lowermost Triassic of Chanakhchi (Armenia) are described with a 3-D reconstruction to exemplify the application of these criteria in recognition of such organisms. Subsequently, the state-of-the-art understanding of the taxonomy and evolution of these fossil sponges, a previously poorly addressed topic, is summarized. The morphology of the Triassic Chanakhchi fossils indicates an affinity with verongimorphs, a group that may have evolved by Cambrian Age 3. Other than that, further efforts are encouraged to forge quantitative criteria based on the here proposed descriptive version and to explore the taxonomic diversity and evolutionary details of these fossil nonspicular demosponges.
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| 9. |
- Pla, Indira, et al.
(författare)
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Proteomic Alterations in Follicular Fluid of Human Small Antral Follicles Collected from Polycystic Ovaries—A Pilot Study
- 2022
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Ingår i: Life. - : MDPI AG. - 0024-3019 .- 2075-1729. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- Polycystic ovaries (PCO) contain antral follicles that arrest growing around 3–11 mm in diameter, perturbing the dominant follicle’s selection and the subsequent ovulatory process. Proteomic alterations of PCO follicular fluid (FF) (i.e., microenvironment in which the oocyte develops until ovulation) have been studied from large follicles in connection with oocyte pickup during ovarian stimulation. The present study aimed to detect proteomic alterations in FF from unstimulated human small antral follicles (hSAF) obtained from PCO. After performing deep-sequencing label-free proteomics on 10 PCO and 10 non-PCO FF samples from unstimulated hSAF (4.6–9.8 mm), 1436 proteins were identified, of which 115 were dysregulated in PCO FF samples. Pathways and processes related to the immune system, inflammation, and oxidative stress appeared to be upregulated in PCO, while extracellular matrix receptors interactions, the collagens-containing extracellular matrix, and the regulation of signaling were downregulated. The secreted proteins SFRP1, THBS4, and C1QC significantly decreased their expression in PCO FF, and this downregulation was suggested to affect future oocyte competence. In conclusion, our study revealed, for the first time, evidence of proteomic alterations occurring in the FF of PCO hSAF that may be related to the dysfunction of follicular growth and subsequent oocyte competence.
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| 10. |
- Tsochantaridis, Ilias, et al.
(författare)
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The Concept of Cancer Stem Cells : Elaborating on ALDH1B1 as an Emerging Marker of Cancer Progression
- 2023
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Ingår i: Life. - : MDPI AG. - 0024-3019 .- 2075-1729. ; 13:1
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Forskningsöversikt (refereegranskat)abstract
- Cancer is a multifactorial, complex disease exhibiting extraordinary phenotypic plasticity and diversity. One of the greatest challenges in cancer treatment is intratumoral heterogeneity, which obstructs the efficient eradication of the tumor. Tumor heterogeneity is often associated with the presence of cancer stem cells (CSCs), a cancer cell sub-population possessing a panel of stem-like properties, such as a self-renewal ability and multipotency potential. CSCs are associated with enhanced chemoresistance due to the enhanced efflux of chemotherapeutic agents and the existence of powerful antioxidant and DNA damage repair mechanisms. The distinctive characteristics of CSCs make them ideal targets for clinical therapeutic approaches, and the identification of efficient and specific CSCs biomarkers is of utmost importance. Aldehyde dehydrogenases (ALDHs) comprise a wide superfamily of metabolic enzymes that, over the last years, have gained increasing attention due to their association with stem-related features in a wide panel of hematopoietic malignancies and solid cancers. Aldehyde dehydrogenase 1B1 (ALDH1B1) is an isoform that has been characterized as a marker of colon cancer progression, while various studies suggest its importance in additional malignancies. Here, we review the basic concepts related to CSCs and discuss the potential role of ALDH1B1 in cancer development and its contribution to the CSC phenotype.
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