| 1. |
- Afewerki, Samson, 1985-, et al.
(författare)
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In vitro high-content tissue models to address precision medicine challenges
- 2023
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Ingår i: Molecular Aspects of Medicine. - : Elsevier. - 0098-2997 .- 1872-9452. ; 91
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Tidskriftsartikel (refereegranskat)abstract
- The field of precision medicine allows for tailor-made treatments specific to a patient and thereby improve the efficiency and accuracy of disease prevention, diagnosis, and treatment and at the same time would reduce the cost, redundant treatment, and side effects of current treatments. Here, the combination of organ-on-a-chip and bioprinting into engineering high-content in vitro tissue models is envisioned to address some precision medicine challenges. This strategy could be employed to tackle the current coronavirus disease 2019 (COVID-19), which has made a significant impact and paradigm shift in our society. Nevertheless, despite that vaccines against COVID-19 have been successfully developed and vaccination programs are already being deployed worldwide, it will likely require some time before it is available to everyone. Furthermore, there are still some uncertainties and lack of a full understanding of the virus as demonstrated in the high number new mutations arising worldwide and reinfections of already vaccinated individuals. To this end, efficient diagnostic tools and treatments are still urgently needed. In this context, the convergence of bioprinting and organ-on-a-chip technologies, either used alone or in combination, could possibly function as a prominent tool in addressing the current pandemic. This could enable facile advances of important tools, diagnostics, and better physiologically representative in vitro models specific to individuals allowing for faster and more accurate screening of therapeutics evaluating their efficacy and toxicity. This review will cover such technological advances and highlight what is needed for the field to mature for tackling the various needs for current and future pandemics as well as their relevancy towards precision medicine.
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| 2. |
- Andersson, Daniel, 1979, et al.
(författare)
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Liquid biopsy analysis in cancer diagnostics.
- 2020
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Ingår i: Molecular aspects of medicine. - : Elsevier BV. - 1872-9452 .- 0098-2997. ; 72
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 3. |
- Andersson, Daniel, 1979, et al.
(författare)
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Principles of digital sequencing using unique molecular identifiers
- 2024
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Ingår i: Molecular Aspects of Medicine. - 0098-2997 .- 1872-9452. ; 96
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Forskningsöversikt (refereegranskat)abstract
- Massively parallel sequencing technologies have long been used in both basic research and clinical routine. The recent introduction of digital sequencing has made previously challenging applications possible by significantly improving sensitivity and specificity to now allow detection of rare sequence variants, even at single molecule level. Digital sequencing utilizes unique molecular identifiers (UMIs) to minimize sequencing-induced errors and quantification biases. Here, we discuss the principles of UMIs and how they are used in digital sequencing. We outline the properties of different UMI types and the consequences of various UMI approaches in relation to experimental protocols and bioinformatics. Finally, we describe how digital sequencing can be applied in specific research fields, focusing on cancer management where it can be used in screening of asymptomatic individuals, diagnosis, treatment prediction, prognostication, monitoring treatment efficacy and early detection of treatment resistance as well as relapse.
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| 4. |
- Appelkvist, E L, et al.
(författare)
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Regulation of coenzyme Q biosynthesis
- 1994
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Ingår i: Molecular Aspects of Medicine. - 0098-2997 .- 1872-9452. ; 15:Suppl., s. 37-46
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Forskningsöversikt (refereegranskat)abstract
- The side-chain moiety of coenzyme Q is synthesized by a trans-prenyltransferase present in microsomes. Condensation of this moiety with the precursor ring takes place in the Golgi system. The enzymes involved, as well as the cytosolic geranylgeranyl-PP synthase, are regulated in an independent fashion. When the size of the farnesyl-PP pool is decreased or increased by employing appropriate inhibitors, the rate of CoQ synthesis is modified accordingly, indicating the dependence of trans-prenyltransferase activity on the level of intracellular substrate concentrations. Administration of peroxisome proliferators elevates CoQ concentrations not only in blood, but also in various tissues. Thus, it may be possible in the future to selectively increase CoQ concentrations in certain organs, without increasing the level of cholesterol.
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| 5. |
- Banerjee, Partha S., et al.
(författare)
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Roles of O-GlcNAc in chronic diseases of aging
- 2016
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Ingår i: Molecular Aspects of Medicine. - : Elsevier. - 0098-2997 .- 1872-9452. ; 51, s. 1-15
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Forskningsöversikt (refereegranskat)abstract
- O-GlcNAcylation, a dynamic nutrient and stress sensitive post-translational modification, occurs on myriad proteins in the cell nucleus, cytoplasm and mitochondria. O-GlcNAcylation serves as a nutrient sensor to regulate signaling, transcription, translation, cell division, metabolism, and stress sensitivity in all cells. Aberrant protein O-GlcNAcylation plays a critical role both in the development, as well as in the progression of a variety of age related diseases. O-GlcNAcylation underlies the etiology of diabetes, and changes in specific protein O-GlcNAc levels and sites are responsible for insulin expression and sensitivity and glucose toxicity. Abnormal O-GlcNAcylation contributes directly to diabetes related dysfunction of the heart, kidney and eyes and affects progression of cardiomyopathy, nephropathy and retinopathy. O-GlcNAcylation is a critical modification in the brain and plays a role in both plaque and tangle formation, thus making its study important in neurodegenerative disorders. O-GlcNAcylation also affects cellular growth and metabolism during the development and metastasis of cancer. Finally, alterations in O-GlcNAcylation of transcription factors in macrophages and lymphocytes affect inflammation and cytokine production. Thus, O-GlcNAcylation plays key roles in many of the major diseases associated with aging. Elucidation of its specific functions in both normal and diseased tissues is likely to uncover totally novel avenues for therapeutic intervention.
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| 6. |
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| 7. |
- Bjorkhem, I, et al.
(författare)
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Oxysterols and neurodegenerative diseases
- 2009
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Ingår i: Molecular aspects of medicine. - : Elsevier BV. - 1872-9452 .- 0098-2997. ; 30:3, s. 171-179
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Tidskriftsartikel (refereegranskat)
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| 8. |
- Di Pede, Giuseppe, et al.
(författare)
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Revisiting the bioavailability of flavan-3-ols in humans: A systematic review and comprehensive data analysis
- 2023
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Ingår i: Molecular Aspects of Medicine. - : Elsevier BV. - 1872-9452 .- 0098-2997. ; 89
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Forskningsöversikt (refereegranskat)abstract
- This systematic review summarizes findings from human studies investigating the different routes of absorption, metabolism, distribution and excretion (ADME) of dietary flavan-3-ols and their circulating metabolites in healthy subjects. Literature searches were performed in PubMed, Scopus and the Web of Science. Human intervention studies using single and/or multiple intake of flavan-3-ols from food, extracts, and pure compounds were included. Forty-nine human intervention studies met inclusion criteria. Up to 180 metabolites were quantified from blood and urine samples following intake of flavan-3-ols, mainly as phase 2 conjugates of microbial catabolites (n = 97), with phenyl-γ-valerolactones being the most representative ones (n = 34). Phase 2 conjugates of monomers and phenyl-γ-valerolactones, the main compounds in both plasma and urine, reached two peak plasma concentrations (Cmax) of 260 and 88 nmol/L at 1.8 and 5.3 h (Tmax) after flavan-3-ol intake. They contributed to the bioavailability of flavan-3-ols for over 20%. Mean bioavailability for flavan-3-ols was moderate (31 ± 23%, n bioavailability values = 20), and it seems to be scarcely affected by the amount of ingested compounds. While intra- and inter-source differences in flavan-3-ol bioavailability emerged, mean flavan-3-ol bioavailability was 82% (n = 1) and 63% (n = 2) after (−)-epicatechin and nut (hazelnuts, almonds) intake, respectively, followed by 25% after consumption of tea (n = 7), cocoa (n = 5), apples (n = 3) and grape (n = 2). This highlights the need to better clarify the metabolic yield with which monomer flavan-3-ols and proanthocyanidins are metabolized in humans. This work clarified in a comprehensive way for the first time the ADME of a (poly)phenol family, highlighting the pool of circulating compounds that might be determinants of the putative beneficial effects linked to flavan-3-ol intake. Lastly, methodological inputs for implementing well-designed human and experimental model studies were provided.
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| 9. |
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| 10. |
- Eckhard, Andreas, et al.
(författare)
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Water channel proteins in the inner ear and their link to hearing impairment and deafness
- 2012
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Ingår i: Molecular Aspects of Medicine. - : Elsevier BV. - 0098-2997 .- 1872-9452. ; 33:5-6, s. 612-637
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Tidskriftsartikel (refereegranskat)abstract
- The inner ear is a fluid-filled sensory organ that transforms mechanical stimuli into the senses of hearing and balance. These neurosensory functions depend on the strict regulation of the volume of the two major extracellular fluid domains of the inner ear, the perilymph and the endolymph. Water channel proteins, or aquaporins (AQPs), are molecular candidates for the precise regulation of perilymph and endolymph volume. Eight AQP subtypes have been identified in the membranous labyrinth of the inner ear. Similar AQP subtypes are also expressed in the kidney, where they function in whole-body water regulation. In the inner ear, AQP subtypes are ubiquitously expressed in distinct cell types, suggesting that AQPs have an important physiological role in the volume regulation of perilymph and endolymph. Furthermore, disturbed AQP function may have pathophysiological relevance and may turn AQPs into therapeutic targets for the treatment of inner ear diseases. In this review, we present the currently available knowledge regarding the expression and function of AQPs in the inner ear. We give special consideration to AQP subtypes AQP2, AQP4 and AQP5, which have been studied most extensively. The potential functions of AQP2 and AQP5 in the resorption and secretion of endolymph and of AQP4 in the equilibration of cell volume are described. The pathophysiological implications of these AQP subtypes for inner ear diseases, that appear to involve impaired fluid regulation, such as Menière's disease and Sjögren's syndrome, are discussed.
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