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排序方式: 共有353条查询结果,搜索用时 13 毫秒
1.
Eleni Papakonstantinou Dimitrios Vlachakis Trias Thireou Panayiotis G. Vlachoyiannopoulos Elias Eliopoulos 《International journal of molecular sciences》2021,22(6)
Monocarboxylate transporters (MCTs) are of great research interest for their role in cancer cell metabolism and their potential ability to transport pharmacologically relevant compounds across the membrane. Each member of the MCT family could potentially provide novel therapeutic approaches to various diseases. The major differences among MCTs are related to each of their specific metabolic roles, their relative substrate and inhibitor affinities, the regulation of their expression, their intracellular localization, and their tissue distribution. MCT4 is the main mediator for the efflux of L-lactate produced in the cell. Thus, MCT4 maintains the glycolytic phenotype of the cancer cell by supplying the molecular resources for tumor cell proliferation and promotes the acidification of the extracellular microenvironment from the co-transport of protons. A promising therapeutic strategy in anti-cancer drug design is the selective inhibition of MCT4 for the glycolytic suppression of solid tumors. A small number of studies indicate molecules for dual inhibition of MCT1 and MCT4; however, no selective inhibitor with high-affinity for MCT4 has been identified. In this study, we attempt to approach the structural characteristics of MCT4 through an in silico pipeline for molecular modelling and pharmacophore elucidation towards the identification of specific inhibitors as a novel anti-cancer strategy. 相似文献
2.
The mechanical property and phase structures of wheat proteins/polyvinyl alcohol blends studied by high-resolution solid-state NMR 总被引:1,自引:0,他引:1
The phase structures of thermally processed wheat proteins (WP) and polyvinyl alcohol (PVOH) blends were studied by solid-state high-resolution NMR spectroscopy. The intermolecular interactions among the multi-component systems and the behavior of each component in the blends on scales of nanometers were examined. The mechanical properties of the blends were also measured and related to the phase structure studies. The results indicated that the polymer chains of WP could be homogeneously mobilized when thermally processed with glycerol and water as plasticisers, but the glycerol predominately associated with WP rather than PVOH in the blends. The intermolecular hydrogen bonding interactions between WP and PVOH caused some extent of miscibility in the system on scales of nanometers especially when the PVOH content was low. The tensile strength and modulus of the blends were improved as compared to WP. However, the intermolecular interactions were relatively weak and could not be further enhanced by increasing PVOH component in the blends. The particle miscible WP/PVOH blends contained plasticised WP and PVOH phases in conjunction with the miscible WP/PVOH phase. Increasing the PVOH content in the blends did not result in an increase of the percentage of the miscible phase and the blends tented to be immiscible while the elongation of the blends was reduced when increasing the PVOH content in the blends. 相似文献
3.
Giannakis E Samuel CS Hewitson TD Boon WM Macris M Reeve S Lawrence J Ian Smith A Tregear GW Wade JD 《Proteomics. Clinical applications》2009,3(10):1211-1224
Kidney failure is a major health problem worldwide. Patients with end-stage renal disease require intensive medical support by dialysis or kidney transplantation. Current methods for diagnosis of kidney disease are either invasive or insensitive, and renal function may decline by as much as 50% before it can be detected using current techniques. The goal of this study was, therefore, to identify biomarkers of kidney disease (associated with renal fibrosis) that can be used for the development of a non-invasive clinical test for early disease detection. We utilized two protein-profiling technologies (SELDI-TOF MS and 2-D) to screen the plasma and kidney proteome for aberrantly expressed proteins in an experimental mouse model of unilateral uretric obstruction, which mimics the pathology of human renal disease. Several differentially regulated proteins were detected at the plasma level of day-3-obstructed animals, which included serum amyloid A1, fibrinogen α, haptoglobin precursor protein, haptoglobin and major urinary proteins 11 and 8. Differentially expressed proteins detected at the tissue level included ras-like activator protein 2, haptoglobin precursor protein, malate dehydrogenase, α enolase and murine urinary protein (all p<0.05 versus controls). Immunohistochemistry was used to confirm the up-regulation of fibrinogen. Interestingly, these proteins are largely separated into four major classes: (i) acute-phase reactants (ii) cell-signaling molecules (iii) molecules involved in cell growth and metabolism and (iv) urinary proteins. These results provide new insights into the pathology of obstructive nephropathy and may facilitate the development of specific assay(s) to detect and monitor renal fibrosis. 相似文献
4.
Konstantinos Agathos Eleni Chatzi Stéphane P. A. Bordas Demosthenes Talaslidis 《International journal for numerical methods in engineering》2016,105(9):643-677
A variation of the extended finite element method for three‐dimensional fracture mechanics is proposed. It utilizes a novel form of enrichment and point‐wise and integral matching of displacements of the standard and enriched elements in order to achieve higher accuracy, optimal convergence rates, and improved conditioning for two‐dimensional and three‐dimensional crack problems. A bespoke benchmark problem is introduced to determine the method's accuracy in the general three‐dimensional case where it is demonstrated that the proposed approach improves the accuracy and reduces the number of iterations required for the iterative solution of the resulting system of equations by 40% for moderately refined meshes and topological enrichment. Moreover, when a fixed enrichment volume is used, the number of iterations required grows at a rate which is reduced by a factor of 2 compared with standard extended finite element method, diminishing the number of iterations by almost one order of magnitude. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
5.
Stavropoulou EA Dafalias YF Sokolis DP 《Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine》2012,226(6):477-490
The zero-stress state of the mucosa-submucosa and two muscle esophageal layers has been delineated, but their multi-axial response has not, because muscle dissection may not leave tubular specimens intact for inflation/extension testing. The histomechanical behavior of the three-layered porcine esophagus was investigated in this study, through light microscopic examination and uniaxial tension, with two-dimensional strain measurement in pairs of orthogonally oriented specimens. The two-dimensional Fung-type strain-energy function described suitably the pseudo-elastic tissue response, affording faithful simulations to our data. Differences in the scleroprotein content and configuration were identified as a function of layer, topography, and orientation, substantiating the macromechanical differences found. In view of the failure and optimized material parameters, the mucosa-submucosa was stronger and stiffer than muscle, associating it with a higher collagen content. A notable topographical distribution was apparent, with data for the abdominal region differentiated from that for the cervical region, owing to the existence of inner muscle with a circumferential arrangement and of outer muscle with a longitudinal arrangement in the former region, and of both muscle layers with oblique arrangement in the latter region, with thoracic esophagus being a transition zone. Tissue from the mucosa-submucosa was stronger and stiffer longitudinally, relating with a preferential collagen reinforcement along that axis, but more extensible in the orthogonal axis. 相似文献
6.
Eleni Gavriilaki Anna Papakonstantinou Konstantinos A. Agrios 《International journal of molecular sciences》2022,23(13)
Complement-mediated diseases or complementopathies, such as Paroxysmal nocturnal hemoglobinuria (PNH), cold agglutinin disease (CAD), and transplant-associated thrombotic microangiopathy (TA-TMA), demand advanced complement diagnostics and therapeutics be adopted in a vast field of medical specialties, such as hematology, transplantation, rheumatology, and nephrology. The miracle of complement inhibitors as “orphan drugs” has dramatically improved morbidity and mortality in patients with otherwise life-threatening complementopathies. Efficacy has been significantly improved by upstream inhibition in patients with PNH. Different molecules may exert diverse characteristics in vitro and in vivo. Further studies remain to show safety and efficacy of upstream inhibition in other complementopathies. In addition, cost and availability issues are major drawbacks of current treatments. Therefore, further developments are warranted to address the unmet clinical needs in the field of complementopathies. This state-of-the-art narrative review aims to delineate novel insights into factor D inhibition as a promising target for complementopathies. 相似文献
7.
Eleni Koliakou Manthou Maria Eleni Ioanna Koumentakou Nikolaos Bikiaris Polyanthi Konstantinidou Patricia Rousselle Doxakis Anestakis Elisabeth Lazaridou Evangelia Kalloniati Dimosthenis Miliaras Anna Michopoulou 《International journal of molecular sciences》2022,23(12)
Syndecans act as independent co-receptors to exert biological activities and their altered function is associated with many pathophysiological conditions. Here, syndecan-1 and -4 were examined in lesional skin of patients with psoriasis. Immunohistochemical staining confirmed altered syndecan-1 distribution and revealed absence of syndecan-4 expression in the epidermis. Fibronectin (FN)—known to influence inflammation and keratinocyte hyperproliferation via α5β1 integrin in psoriasis—was also decreased. Syndecan-1 and -4 expression was analyzed in freshly isolated lesional psoriatic human keratinocytes (PHK) characterized based on their proliferation and differentiation properties. mRNA levels of syndecan-1 were similar between healthy and PHK, while syndecan-4 was significantly decreased. Cell growth and release of the pro-inflammatory Tumor Necrosis Factor-alpha (TNFα) were selectively and significantly induced in PHKs plated on FN. Results from co-culture of healthy keratinocytes and psoriatic fibroblasts led to the speculation that at least one factor released by fibroblasts down-regulate syndecan-1 expression in PHK plated on FN. To assay if biological treatments for psoriasis target keratinocyte proliferation, gelatin-based patches enriched with inteleukin (IL)-17α or TNFα blockers were prepared and tested using a full-thickness healthy epidermal model (Phenion®). Immunohistochemistry analysis showed that both blockers impacted the localisation of syndecan-1 within the refined epidermis. These results provide evidence that syndecans expression are modified in psoriasis, suggesting that they may represent markers of interest in this pathology. 相似文献
8.
9.
Angelika Zimmermann Ilan Oshri Eleni Lioliou Alexandra Gerbasi 《The Journal of Strategic Information Systems》2018,27(1):82-100
The sharing of knowledge between a firm and its internal or external service suppliers has become an important element of contemporary sourcing arrangements. Moreover, the knowledge based view (KBV) has long suggested that due to stronger cognitive links within firms, internal compared to external service provision creates better conditions for knowledge sharing. Empirical evidence for this claim is however scarce, and the KBV does not explain the mechanisms for more knowledge sharing in internal sourcing in detail. Moreover, there is now some evidence to suggest that firms’ relationships with external sourcing partners are becoming more similar to those with captive centres, which represent a less traditional form of insourcing setting. To scrutinize the possible knowledge sharing advantages of internal sourcing in more depth, we turn to social capital (SC) research. There are some theoretical claims that SC and knowledge sharing are stronger within than between firms, and there is ample evidence that SC facilitates knowledge sharing. Our survey results suggest that the extent of knowledge sharing and SC are indeed stronger in a captive than in an external sourcing mode, and that structural (tie strength), cognitive (shared understanding), and relational (trust) aspects of SC mediate the effect of sourcing mode on the extent of knowledge sharing. By contrast, network stability (a structural aspect) mediated knowledge sharing only indirectly, by reinforcing the other SC aspects. We highlight important contributions to research and practice of IS outsourcing and social capital. 相似文献
10.
Mehran Oraee M. Reza Hosseini David J. Edwards Heng Li Eleni Papadonikolaki Dongping Cao 《International Journal of Project Management》2019,37(6):839-854
Building information modelling (BIM) teams, hereafter referred to as BIM-based construction networks, are teams whose possibly geographically dispersed members from various organisations and disciplines, perform project tasks on BIM-enabled projects. In recent years, BIM-based construction networks have progressively become the norm in executing BIM activities on projects. However, even though achieving BIM's full capabilities relies on effective collaboration among the team members in BIM-based construction networks, it is still a struggle for these members to collaborate. Nonetheless, only a few studies have been conducted to identify the barriers to strengthening team collaboration in BIM-based construction networks. To address this gap, the current study, by examining 73 journal articles on collaboration in BIM-based construction networks, builds upon a theoretical review of the literature. A conceptual model is presented to capture the main barriers to collaboration in BIM-based construction networks. The study benefits researchers as well as project managers. For researchers, the conceptual model provides an intermediate theory, namely, a theoretical basis to direct further knowledge creation attempts on the topic. In addition, the conceptual model supports project managers on BIM-enabled projects. That is, it simplifies the knowledge now available for practical applications enabling it to be translated into guidelines and practical instructions on real-life projects. 相似文献