Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Due to the unique anatomical structure of the eye, ocular drug delivery is a promising delivery route for the treatment of several ocular diseases, such as the ocular neovascularization that contributes to diabetic retinopathy. This disease is triggered by inflammation, retinal ischemia, and/or deposits of advanced-glycation end-products (AGEs), as well as increased levels of vascular endothelial growth factor (VEGF), interleukins, or reactive oxygen species (ROS). Gold has unique antioxidant and antiangiogenic properties and can inhibit angiogenic molecules. Furthermore, gold nanoparticles (GNPs) are not only biocompatible, they are easy to synthesize, they absorb and scatter visible light, and they can be made with precise control over size and shape. GNPs are an excellent candidate for ocular drug delivery because they can be conjugated to an extraordinarily diverse array of different biomolecules, and surface functionalization can improve the mobility of GNPs across the physiological barriers of the eye, such as the vitreous humour or the inner limiting membrane. For this purpose, we employed low molecular weight hyaluronan (HA) to increase the mobility of the nanoparticles as well as target them to HA receptors that are expressed in different cells of the eye. In this study, the combination of gold and HA enhanced the stability of the whole carrier and promoted their distribution across ocular tissues and barriers to reach the retina. Moreover, analysis in vitro, ex vivo, and in ovo revealed the protective and antiangiogenic effect of GNPs as inhibitors of AGEs-mediated- retinal pigment epithelial cell death and neovascularization. We demonstrated that conjugation with HA enhances GNP stability and distribution due to a specific CD44 receptor interaction. The capacity of HA-GNPs to distribute through the vitreous humour and their avidity for the deeper retinal layers ex vivo, suggest that HA-GNPs are a promising delivery system for the treatment of ocular neovascularization and related disorders.
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PMID:Hyaluronic acid coating of gold nanoparticles for intraocular drug delivery: Evaluation of the surface properties and effect on their distribution. 3272 26

Angiogenesis is required for normal development and occurs as a pathological step in a variety of disease settings, such as cancer, ocular diseases, and ischemia. Recent studies have revealed the role of CD44, a widely expressed cell surface adhesion molecule, in promoting pathological angiogenesis and the development of its associated diseases through its regulation of diverse function of endothelial cells, such as proliferation, migration, adhesion, invasion, and communication with the microenvironment. Conversely, the absence of CD44 expression or inhibition of its function impairs pathological angiogenesis and disease progression. Here, we summarize the current understanding of the roles of CD44 in pathological angiogenesis and the underlying cellular and molecular mechanisms.
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PMID:The role of CD44 in pathological angiogenesis. 3283 Mar 49

Acute kidney injury (AKI) is thought to be a reversible condition; however, growing evidence has suggested that AKI may be associated with subsequent development of chronic kidney disease. Although renal tubules have intrinsic regeneration capacity, disruption of the regeneration mechanisms leads to irreversible interstitial fibrosis. In this study, we investigated immunohistochemical markers of renal tubules in adaptive and maladaptive repair processes to predict AKI reversibility. Histopathological analysis demonstrated that regenerative tubules and dilated tubules were observed in the kidneys of AKI model rats after ischemia/reperfusion (I/R). Regenerative tubules gradually redifferentiated after I/R, whereas dilated tubules exhibited no tendency for redifferentiation. In fibrotic areas of the kidney in renal fibrosis model rats subjected to I/R, renal tubules were dilated or atrophied. There results suggested that the histopathological features of renal tubules in the maladaptive repair were dilation or atrophy. From microarray data of regenerative tubules, survivin, SOX9, and CD44 were extracted as candidate markers. Immunohistochemical analysis demonstrated that survivin and SOX9 were expressed in regenerative tubules, whereas SOX9 was also detected in renal tubules in fibrotic areas. These findings indicated that survivin and SOX9 contributed to renal tubular regeneration, whereas sustained SOX9 expression may be associated to fibrosis. CD44 was expressed in dilated tubules in the kidneys of AKI model rats and in the tubules of fibrotic areas of renal fibrosis model rats, suggesting that CD44 was expressed in renal tubules in maladaptive repair. Thus, these factors could be useful markers for detecting disruption of the regenerative mechanisms of renal tubules.
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PMID:Specific expression of survivin, SOX9, and CD44 in renal tubules in adaptive and maladaptive repair processes after acute kidney injury in rats. 3296 66


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