alpha-klotho was identified as a gene associated with premature aging-like phenotypes characterized by short lifespan. In mice, we found the molecular association of alpha-Klotho (alpha-Kl) and Na+,K+-adenosine triphosphatase (Na+,K+-ATPase) and provide evidence for an increase of abundance of Na+,K+-ATPase at the plasma membrane. Low concentrations of extracellular free calcium ([Ca2+]e) rapidly induce regulated parathyroid hormone (PTH) secretion in an alpha-Kl- and Na+,K+-ATPase-dependent manner. The increased Na+ gradient created by Na+,K+-ATPase activity might drive the transepithelial transport of Ca2+ in cooperation with ion channels and transporters in the choroid plexus and the kidney. Our findings reveal fundamental roles of alpha-Kl in the regulation of calcium metabolism.
Sonoelastography had high accuracy (92%) in the differentiation of benign and metastatic cervical LNs in patients suspected of having thyroid or hypopharyngeal cancer.
The current regenerative technique avoided tracheotomy, a second operation, and deformity. Good epithelialization has been observed on the tracheal luminal surface without any complications for 2 years. Although long-term observation is required, regenerative medicine of the tracheal tissue appears feasible for airway reconstruction.
Photoreceptor degeneration is the most critical cause of visual impairment in age-related macular degeneration (AMD). In neovascular form of AMD, severe photoreceptor loss develops with subretinal hemorrhage due to choroidal neovascularization (CNV), growth of abnormal blood vessels from choroidal circulation. However, the detailed mechanisms of this process remain elusive. Here we demonstrate that neovascular AMD with subretinal hemorrhage accompanies a significant increase in extracellular ATP, and that extracellular ATP initiates neurodegenerative processes through specific ligation of Purinergic receptor P2X, ligand-gated ion channel, 7 (P2RX7; P2X7 receptor). Increased extracellular ATP levels were found in the vitreous samples of AMD patients with subretinal hemorrhage compared to control vitreous samples. Extravascular blood induced a massive release of ATP and photoreceptor cell apoptosis in co-culture with primary retinal cells. Photoreceptor cell apoptosis accompanied mitochondrial apoptotic pathways, namely activation of caspase-9 and translocation of apoptosis-inducing factor (AIF) from mitochondria to nuclei, as well as TUNEL-detectable DNA fragmentation. These hallmarks of photoreceptor cell apoptosis were prevented by brilliant blue G (BBG), a selective P2RX7 antagonist, which is an approved adjuvant in ocular surgery. Finally, in a mouse model of subretinal hemorrhage, photoreceptor cells degenerated through BBG-inhibitable apoptosis, suggesting that ligation of P2RX7 by extracellular ATP may accelerate photoreceptor cell apoptosis in AMD with subretinal hemorrhage. Our results indicate a novel mechanism that could involve neuronal cell death not only in AMD but also in hemorrhagic disorders in the CNS and encourage the potential application of BBG as a neuroprotective therapy.
The aim of this study was to evaluate the elastic moduli of thyroid tissues under uniaxial compression and to establish the biomechanical fundamentals for accurate interpretation of thyroid elastograms. A total of 67 thyroid samples (24 samples of normal thyroid tissue, 2 samples of thyroid tissue with chronic thyroiditis, 12 samples of adenomatous goiter lesions and 7 samples of follicular adenoma, 19 samples of papillary adenocarcinoma (PAC) and 3 samples of follicular adenocarcinoma (FAC)) obtained from 36 patients who had received thyroid surgery were subjected to biomechanical testing within three hours after surgical resection at precompression strains of 5%, 10% and 20% and applied strains of 1%, 2%, 5% and 10% of sample height. As a result, the mean values of elastic moduli for benign thyroid lesions at all examined precompression levels were significantly higher than those for normal thyroid tissue measured at the same load (p<0.01). At low precompression (5%) and compression (1-2%) levels, benign thyroid nodule samples were 1.7 times harder than normal thyroid tissue. At high precompression (20%) and compression (10%) levels, this difference increased to 2.4 times. Stiffness of PAC samples was significantly higher than those for normal thyroid tissue and benign thyroid tumors measured at the same load (p<0.01). At low precompression (5%) and compression (1-2%) levels, PAC samples were 5.0 times harder than normal thyroid tissue. At high precompression (20%) and compression (10%) levels, this difference increased to 17.7 times. In contrast, samples of FAC were much softer than PAC (p<0.05) and were comparable in stiffness to normal thyroid tissues. The significant differences in the stiffness between normal thyroid tissue and thyroid tumors may provide useful information for accurate interpretation of thyroid elastograms.
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