| 1. |
- Wu, Biying, et al.
(författare)
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Megakaryocytes Mediate Hyperglycemia-Induced Tumor Metastasis
- 2021
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Ingår i: Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 0008-5472 .- 1538-7445. ; 81:21, s. 5506-5522
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Tidskriftsartikel (refereegranskat)abstract
- High blood glucose has long been established as a risk factor for tumor metastasis, yet the molecular mechanisms underlying this association have not been elucidated. Here we describe that hyperglycemia promotes tumor metastasis via increased platelet activity. Administration of glucose, but not fructose, reprogrammed the metabolism of megakaryocytes to indirectly prime platelets into a prometastatic phenotype with increased adherence to tumor cells. In megakaryocytes, a glucose metabolism-related gene array identified the mitochondrial molecular chaperone glucose-regulated protein 75 (GRP75) as a trigger for platelet activation and aggregation by stimulating the Ca2+-PKC alpha pathway. Genetic depletion of Glut1 in megakaryocytes blocked MYC-induced GRP75 expression. Pharmacologic blockade of platelet GRP75 compromised tumor-induced platelet activation and reduced metastasis. Moreover, in a pilot clinical study, drinking a 5% glucose solution elevated platelet GRP75 expression and activated platelets in healthy volunteers. Platelets from these volunteers promoted tumor metastasis in a plateletadoptive transfer mouse model. Together, under hyperglycemic conditions, MYC-induced upregulation of GRP75 in megakaryocytes increases platelet activation via the Ca2+-PKC alpha pathway to promote cancer metastasis, providing a potential new therapeutic target for preventing metastasis. Significance: This study provides mechanistic insights into a glucose-megakaryocyte-platelet axis that promotes metastasis and proposes an antimetastatic therapeutic approach by targeting the mitochondrial protein GRP75.
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| 2. |
- Ali, Zaheer, et al.
(författare)
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Synchronized tissue-scale vasculogenesis and ubiquitous lateral sprouting underlie the unique architecture of the choriocapillaris
- 2020
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Ingår i: Developmental Biology. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0012-1606 .- 1095-564X. ; 457:2, s. 206-214
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Tidskriftsartikel (refereegranskat)abstract
- The choriocapillaris is an exceptionally high density, two-dimensional, sheet-like capillary network, characterized by the highest exchange rate of nutrients for waste products per area in the organism. These unique morphological and physiological features are critical for supporting the extreme metabolic requirements of the outer retina needed for vision. The developmental mechanisms and processes responsible for generating this unique vascular network remain, however, poorly understood. Here we take advantage of the zebrafish as a model organism for gaining novel insights into the cellular dynamics and molecular signaling mechanisms involved in the development of the choriocapillaris. We show for the first time that zebrafish have a choriocapillaris highly similar to that in mammals, and that it is initially formed by a novel process of synchronized vasculogenesis occurring simultaneously across the entire outer retina. This initial vascular network expands by un-inhibited sprouting angiogenesis whereby all endothelial cells adopt tip-cell characteristics, a process which is sustained throughout embryonic and early post-natal development, even after the choriocapillaris becomes perfused. Ubiquitous sprouting was maintained by continuous VEGF-VEGFR2 signaling in endothelial cells delaying maturation until immediately before stages where vision becomes important for survival, leading to the unparalleled high density and lobular structure of this vasculature. Sprouting was throughout development limited to two dimensions by Bruchs membrane and the sclera at the anterior and posterior surfaces respectively. These novel cellular and molecular mechanisms underlying choriocapillaris development were recapitulated in mice. In conclusion, our findings reveal novel mechanisms underlying the development of the choriocapillaris during zebrafish and mouse development. These results may explain the uniquely high density and sheet-like organization of this vasculature.
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| 3. |
- Ji, Guomin, et al.
(författare)
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Enhanced rectifying performance by asymmetrical gate voltage for BDC20 molecular devices
- 2014
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Ingår i: RSC Advances. - : Royal Society of Chemistry. - 2046-2069. ; 4:32, s. 16537-16544
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Tidskriftsartikel (refereegranskat)abstract
- By applying the asymmetrical gate voltage on the 1,4-bis (fullero[c]pyrrolidin-1-yl) benzene BDC20 molecule, we investigate theoretically its electronic transport properties using the density functional theory and nonequilibrium Greens function formalism for a unimolecule device with metal electrodes. Interestingly, the rectifying characteristic with very high rectification ratio, 91.7 and 24.0, can be obtained when the gate voltage is asymmetrically applied on the BDC20 molecular device. The rectification direction can be tuned by the different gate voltage applying regions. The rectification behavior is understood in terms of the evolution of the transmission spectrum and projected density of states spectrum with applied bias combined with molecular projected self-consistent Hamiltonian states analyses. Our finding implies that to realize and greatly promote rectifying performance of the BDC20 molecule the variable gate voltage applying position might be a key
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| 4. |
- Ji, Guomin, et al.
(författare)
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Rectifying behaviors of an Au/(C-20)(2)/Au molecular device induced by the different positions of gate voltage
- 2012
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Ingår i: RSC ADVANCES. - : RSC Publishing. - 2046-2069. ; 2:30, s. 11349-11353
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Tidskriftsartikel (refereegranskat)abstract
- The electronic transport properties of a gated Au/(C-20)(2)/Au molecular device are studied using nonequilibrium Greens function in combination with density functional theory. The results show that different applied positions of the external transverse gate voltage can effectively tune the current-voltage (I-V) characteristic of molecular devices. Rectifying behaviors of the device can be realized when the gate voltage is applied asymmetrically on the left C-20 molecule, and the rectification directions can also be modulated by the positive or negative value of the gate voltage. These results provide an important theoretical support to experiments and the design of a molecular rectifier.
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| 5. |
- Yang, Yunlong, et al.
(författare)
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Up-to-date molecular medicine strategies for management of ocular surface neovascularization
- 2023
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Ingår i: Advanced Drug Delivery Reviews. - : ELSEVIER. - 0169-409X .- 1872-8294. ; 201
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Forskningsöversikt (refereegranskat)abstract
- Ocular surface neovascularization and its resulting pathological changes significantly alter corneal refraction and obstruct the light path to the retina, and hence is a major cause of vision loss. Various factors such as infection, irritation, trauma, dry eye, and ocular surface surgery trigger neovascularization via angiogenesis and lym-phangiogenesis dependent on VEGF-related and alternative mechanisms. Recent advances in antiangiogenic drugs, nanotechnology, gene therapy, surgical equipment and techniques, animal models, and drug delivery strategies have provided a range of novel therapeutic options for the treatment of ocular surfaceneovascularization. In this review article, we comprehensively discuss the etiology and mechanisms of corneal neovascularization and other types of ocular surface neovascularization, as well as emerging animal models and drug delivery strategies that facilitate its management.
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