| 1. |
- Baruah, Kartik
(författare)
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Structure-Functional Activity Relationship of beta-Glucans From the Perspective of Immunomodulation: A Mini-Review
- 2020
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 11
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Forskningsöversikt (refereegranskat)abstract
- beta-Glucans are a heterogeneous group of glucose polymers with a common structure comprising a main chain of beta-(1,3) and/or beta-(1,4)-glucopyranosyl units, along with side chains with various branches and lengths. beta-Glucans initiate immune responses via immune cells, which become activated by the binding of the polymer to specific receptors. However, beta-glucans from different sources also differ in their structure, conformation, physical properties, binding affinity to receptors, and thus biological functions. The mechanisms behind this are not fully understood. This mini-review provides a comprehensive and up-to-date commentary on the relationship between beta-glucans' structure and function in relation to their use for immunomodulation.
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| 2. |
- Okamoto, Sadahisa, et al.
(författare)
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Development of cardiomyopathy after liver transplantation in Swedish hereditary transthyretin amyloidosis (ATTR) patients
- 2011
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Ingår i: Amyloid. - London : Informa Healthcare. - 1350-6129 .- 1744-2818. ; 18:4, s. 200-205
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recent studies of liver transplanted (LTx) familial amyloidotic polyneuropathy (FAP) patients have shown a progression of cardiomyopathy in some patients after LTx, but knowledge of the underlying factors remains limited.Methods: Seventy-five patients, who had undergone LTx from 1996 to 2008, were included. They had all been examined by echocardiography 1-16 months before LTx. Fifty-four had been re-examined 7-34 months, and forty-two 36-137 months after LTx.Results: A significant increase in interventricular septum (IVS) thickness occurred after LTx (p < 0.01), particularly in males (p = 0.002) and late onset patients (p = 0.003). The development of post-LTx cardiomyopathy was related to patient's age at onset of the disease, male gender and pre-LTx IVS thickness. On multivariate regression analysis, however, age at onset was the only significant predictor for the development of cardiomyopathy (odds ratio = 1.14, 95% confident interval 1.01-1.30, p = 0.04).Conclusion: An increase of IVS thickness can be observed in FAP patients after LTx. Age at onset of the disease is the main predictor for increased IVS thickness and for the development of cardiomyopathy after liver transplantation.
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| 3. |
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| 4. |
- Desbans, Coraline, et al.
(författare)
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Accurate prediction of variability in CLint and Fm via 3A4 is only obtained by assessing a series of individual cryopreserved human hepatocyte batches
- 2010
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Ingår i: Drug metabolism reviews (Softcover ed.). - New York : Informa Healthcare. - 0360-2532 .- 1097-9883. ; 42:Suppl. 1, s. 274-274
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Tidskriftsartikel (refereegranskat)abstract
- Multiple in-vitro and in-vivo methods are currently assessed and under discussion to predict human clearance and pharmacokinetics from preclinical studies. A combination of high fm with a high fraction metabolism via a single pathway, e.g. via CYP3A4 (fmCYP3A4), has been recognized as a high risk factor for Drug Drug Interactions (DDI) in the clinical setting[1],[2],[3],[4] . Thus, an early predictive tool to allow for appropriate modeling of this potential risk for DDI is highly warranted. Hepatocytes, capable of both phase I and phase II reactions, are an attractive system to study fraction metabolized (fm) via a single pathway. In the present study, intrinsic clearance (CLint) was determined in cryopreserved human hepatocytes in suspension for a set of five compounds with known and variable fm via CYP3A4 (amitriptyline, loratadine, methylprednisolone, midazolam, and tacrolimus) in the absence or presence of ketoconazole. In order to get an insight into the influence of inter-individual variability, twelve batches of cryopreserved human hepatocytes with either high, moderate or low CYP3A4-dependent activity towards midazolam (MDZ) were chosen. Clint values were determined as substrate depletion under shaking conditions (900rpm) using an elliptic shaker as previously reported[5]. For all compounds, the mean CLint for individual donors in absence of ketoconazole correlated very well with literature data on the mean of individual donors1,2,3, and/or pools of donors5. Average fmCYP3A4 for midazolam was 83%, tacrolimus 64%, methylprednisolone 55%, amitriptyline 28%, and loratadine 19% are also well within the literature data2,3,4. Interestingly, the results obtained for a homogenous subpopulation regarding MDZ CLint and percent inhibition by ketoconazole, were not directly related to the ketoconazole sensitive CLint for the other CYP3A4 substrates tested. The variability in CYP3A4 contribution for compounds having multiple metabolic pathways cannot be predicted by the fm3A4 for MDZ. This suggests that an overall prediction of CLint or fm via CYP3A4 for compounds partially metabolized by this enzyme is not possible. Thus, the individual differences in CLint for a given compound and fmCYPi can only be well covered by assessing a series of individual cryopreserved human hepatocyte batches.[1] Lu, C., Miwa, G. T., Prakash, S. R., Gan, L-S. and Balani, S. K. (2007), Drug Metabolism And Disposition, 35: 1, 79–85[2] Lu, C., Hatsis,P., Berg,C., Lee, F. W. and Balani, S. K. (2008), Drug Metabolism And Disposition, 36: 7, 1255–1260[3] Lu, C., Hatsis,P., Berg,C., Lee, F. W. and Balani, S. K. (2008), Drug Metabolism And Disposition, 36: 7, 1261–1266[4] Emoto, C., Murase, S. and Iwasaki, K.(2006), Xenobiotica, 36: 8, 671 — 683[5] Simon ,S., Blanchard, N., Alexandre, E., Hewitt, N. J., Bachellier, P., Heyd, B., Coassolo, P., Schuler, F., Richert, L., (2009) ‘MV-HUF Copenhagen’
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| 5. |
- El-Kafrawy, SA, et al.
(författare)
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Genomic profiling and network-level understanding uncover the potential genes and the pathways in hepatocellular carcinoma
- 2022
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Ingår i: Frontiers in genetics. - : Frontiers Media SA. - 1664-8021. ; 13, s. 880440-
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Tidskriftsartikel (refereegranskat)abstract
- Data integration with phenotypes such as gene expression, pathways or function, and protein-protein interactions data has proven to be a highly promising technique for improving human complex diseases, particularly cancer patient outcome prediction. Hepatocellular carcinoma is one of the most prevalent cancers, and the most common cause is chronic HBV and HCV infection, which is linked to the majority of cases, and HBV and HCV play a role in multistep carcinogenesis progression. We examined the list of known hepatocellular carcinoma biomarkers with the publicly available expression profile dataset of hepatocellular carcinoma infected with HCV from day 1 to day 10 in this study. The study covers an overexpression pattern for the selected biomarkers in clinical hepatocellular carcinoma patients, a combined investigation of these biomarkers with the gathered temporal dataset, temporal expression profiling changes, and temporal pathway enrichment following HCV infection. Following a temporal analysis, it was discovered that the early stages of HCV infection tend to be more harmful in terms of expression shifting patterns, and that there is no significant change after that, followed by a set of genes that are consistently altered. PI3K, cAMP, TGF, TNF, Rap1, NF-kB, Apoptosis, Longevity regulating pathway, signaling pathways regulating pluripotency of stem cells, Cytokine-cytokine receptor interaction, p53 signaling, Wnt signaling, Toll-like receptor signaling, and Hippo signaling pathways are just a few of the most commonly enriched pathways. The majority of these pathways are well-known for their roles in the immune system, infection and inflammation, and human illnesses like cancer. We also find that ADCY8, MYC, PTK2, CTNNB1, TP53, RB1, PRKCA, TCF7L2, PAK1, ITPR2, CYP3A4, UGT1A6, GCK, and FGFR2/3 appear to be among the prominent genes based on the networks of genes and pathways based on the copy number alterations, mutations, and structural variants study.
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| 6. |
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| 7. |
- Pain, Adam, et al.
(författare)
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Secondary Forests and Agrarian Transitions: Insights from Nepal and Peru
- 2021
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Ingår i: Human Ecology. - : Springer Science and Business Media LLC. - 0300-7839 .- 1572-9915. ; 49, s. 249-258
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Tidskriftsartikel (refereegranskat)abstract
- We provide an analytical contrast of the dynamics of secondary forest regeneration in Nepal and Peru framed by a set of common themes: land access, boundaries, territories, and rights, seemingly more secure in Nepal than Peru; processes of agrarian change and their consequences for forest-agriculture interactions and the role of secondary forest in the landscape, more marked in Peru, where San Martin is experiencing apparent agricultural intensification, than in Nepal; and finally processes of social differentiation that have consequences for different social groups, livelihood construction and their engagement with trees, common to both countries. These themes address the broader issue of the necessary conditions for secondary forest regeneration and the extent to which the rights and livelihood benefits of those actively managing it are secured.
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| 8. |
- Perkoulidis, G., et al.
(författare)
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Integrated assessment of a new Waste-to-Energy facility in Central Greece in the context of regional perspectives
- 2010
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Ingår i: Waste Management. - : Elsevier. - 0956-053X .- 1879-2456. ; 30:7, s. 1395-1406
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Tidskriftsartikel (refereegranskat)abstract
- The main aim of this study is the integrated assessment of a proposed Waste-to-Energy facility that could contribute in the Municipal Solid Waste Management system of the Region of Central Greece. In the context of this paper alternative transfer schemes for supplying the candidate facility were assessed considering local conditions and economical criteria. A mixed-integer linear programming model was applied for the determination of optimum locations of Transfer Stations for an efficient supplying chain between the waste producers and the Waste-to-Energy facility. Moreover different Regional Waste Management Scenarios were assessed against multiple criteria, via the Multi Criteria Decision Making method ELECTRE III. The chosen criteria were total cost, Biodegradable Municipal Waste diversion from landfill, energy recovery and Greenhouse Gas emissions and the analysis demonstrated that a Waste Management Scenario based on a Waste-to-Energy plant with an adjacent landfill for disposal of the residues would be the best performing option for the Region, depending however on the priorities of the decision makers. In addition the study demonstrated that efficient planning is necessary and the case of three sanitary landfills operating in parallel with the WtE plant in the study area should be avoided. Moreover alternative cases of energy recovery of the candidate Waste-to-Energy facility were evaluated against the requirements of the new European Commission Directive on waste in order for the facility to be recognized as recovery operation. The latter issue is of high significance and the decision makers in European Union countries should take it into account from now on, in order to plan and implement facilities that recover energy efficiently. Finally a sensitivity check was performed in order to evaluate the effects of increased recycling rate, on the calorific value of treated Municipal Solid Waste and the gate fee of the candidate plant and found that increased recycling efforts would not diminish the potential for incineration with energy recovery from waste and neither would have adverse impacts on the gate fee of the Waste-to-Energy plant. In general, the study highlighted the need for efficient planning in solid waste management, by taking into account multiple criteria and parameters and utilizing relevant tools and methodologies into this context
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| 9. |
- Formosa, MM, et al.
(författare)
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A Roadmap to Gene Discoveries and Novel Therapies in Monogenic Low and High Bone Mass Disorders
- 2021
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Ingår i: Frontiers in endocrinology. - : Frontiers Media SA. - 1664-2392. ; 12, s. 709711-
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Tidskriftsartikel (refereegranskat)abstract
- Genetic disorders of the skeleton encompass a diverse group of bone diseases differing in clinical characteristics, severity, incidence and molecular etiology. Of particular interest are the monogenic rare bone mass disorders, with the underlying genetic defect contributing to either low or high bone mass phenotype. Extensive, deep phenotyping coupled with high-throughput, cost-effective genotyping is crucial in the characterization and diagnosis of affected individuals. Massive parallel sequencing efforts have been instrumental in the discovery of novel causal genes that merit functional validation using in vitro and ex vivo cell-based techniques, and in vivo models, mainly mice and zebrafish. These translational models also serve as an excellent platform for therapeutic discovery, bridging the gap between basic science research and the clinic. Altogether, genetic studies of monogenic rare bone mass disorders have broadened our knowledge on molecular signaling pathways coordinating bone development and metabolism, disease inheritance patterns, development of new and improved bone biomarkers, and identification of novel drug targets. In this comprehensive review we describe approaches to further enhance the innovative processes taking discoveries from clinic to bench, and then back to clinic in rare bone mass disorders. We highlight the importance of cross laboratory collaboration to perform functional validation in multiple model systems after identification of a novel disease gene. We describe the monogenic forms of rare low and high rare bone mass disorders known to date, provide a roadmap to unravel the genetic determinants of monogenic rare bone mass disorders using proper phenotyping and genotyping methods, and describe different genetic validation approaches paving the way for future treatments.
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