Glomerular hypertension is a major determinant advancing progression to end-stage renal failure. Podocytes, which are thought to counteract pressure-mediated capillary expansion, are increasingly challenged in glomerular hypertension. Studies in animal models of glomerular hypertension indicate that glomerulosclerosis develops from adhesions of the glomerular tuft to Bowman's capsule due to progressive podocyte loss. However, the molecular alterations of podocytes in glomerular hypertension are unknown. In this study, we determined the changes in gene expression in podocytes induced by mechanical stress in vitro (cyclic biaxial stretch, 0.5 Hz, 5% linear strain, 3 days) using cDNA arrays (6144 clones). Sixteen differentially regulated genes were identified, suggesting alterations of cell-matrix interaction, mitochondrial/metabolic function, and protein synthesis/degradation in stretched podocytes. The transcript for the matricellular protein osteopontin (OPN) was most strongly up-regulated by stretch (approximately threefold). By reverse transcriptase-polymer chain reaction, up-regulation of OPN mRNA was also detected in glomeruli of rats treated for 2.5 wk with desoxycorticosterone acetate-salt, an animal model of glomerular hypertension. In cultured podocytes, OPN coating induced a motile phenotype increasing actin nucleation proteins at cell margins and reducing stress fibers and focal adhesions. Intriguingly, additional OPN coating of collagen IV-coated membranes accelerated stretch-induced actin reorganization and markedly diminished podocyte loss at higher strain. This study delineates the molecular response of podocytes to mechanical stress and identifies OPN as a stretch-adapting molecule in podocytes.
The mental artery displays several branches internal to the anterior region of the mandible as confirmed by macroscopic observation and computed tomography. The inferior alveolar artery formed complex branches and divided into mental and incisive branches, which were found in the right internal side of the mandible of one male cadaver (88 years old). The branches of these two arteries ran through the bony lingual canal to the lingual foramen between the canine and premolar region of the inner surface of the mandible body, where they emerged to enter the mylohyoid and anterior belly of the digastric muscles and communicate with the submental artery. The observation of the anastomotic artery is considered important for surgical placement of dental implants in the mandibular region.
Drug resistance to anti-cancer agents is a major concern regarding the successful treatment of malignant tumors. Recent studies have suggested that acquired resistance to anti-epidermal growth factor receptor (EGFR) therapies such as cetuximab are in part caused by genetic alterations in patients with oral squamous cell carcinoma (OSCC). However, the molecular mechanisms employed by other complementary pathways that govern resistance remain unclear. In the current study, we performed gene expression profiling combined with extensive molecular validation to explore alternative mechanisms driving cetuximab-resistance in OSCC cells. Among the genes identified, we discovered that a urokinase-type plasminogen activator receptor (uPAR)/integrin β1/Src/FAK signal circuit converges to regulate ERK1/2 phosphorylation and this pathway drives cetuximab-resistance in the absence of EGFR overexpression or acquired EGFR activating mutations. Notably, the polyphenolic phytoalexin resveratrol, inhibited uPAR expression and consequently the signaling molecules ERK1/2 downstream of EGFR thus revealing additive effects on promoting OSCC cetuximab-sensitivity in vitro and in vivo . The current findings indicate that uPAR expression plays a critical role in acquired cetuximab resistance of OSCC and that combination therapy with resveratrol may provide an attractive means for treating these patients.
The formation of the maxillary sinus (MS) is tied to the maturation of the craniofacial bones during development. The MS and surrounding bone matrices in Japanese foetal specimens were inspected using cone beam computed tomography relative to the nasal cavity (NC) and the surrounding bones, including the palatine bone, maxillary process, inferior nasal concha and lacrimal bone. The human foetuses analysed were 223.2 ± 25.9 mm in crown-rump length (CRL) and ranged in estimated age from 20 to 30 weeks of gestation. The amount of bone in the maxilla surrounding the MS increased gradually between 20 and 30 weeks of gestation. Various calcified structures that formed the bone matrix were found in the cortical bone of the maxilla, and these calcified structures specifically surrounded the deciduous tooth germs. By 30 weeks of gestation, the uncinate process of the ethmoid bone formed a border with the maxilla. The distance from the midline to the maximum lateral surface border of the MS combined with the width from the midline to the maximum lateral surface border of the inferior nasal concha showed a high positive correlation with CRL in Japanese foetuses. There appears to be a complex correlation between the MS and NC formation during development in the Japanese foetus. Examination of the surrounding bone indicated that MS formation influences maturation of the maxilla and the uncinate process of the ethmoid bone during craniofacial bone development.
Summary: The lingual canal with foramen displays different appearances on the internal surfaces of mandible as confirmed by macroscopic observation and computerized tomography (CT). The lingual canal was observed in the inside of mental region run to the outside of lingual foramen, which is extend internally from mandibular canal in right and left sides of the mandible in cadavers (13 sides out of 88 sides) and in dry skulls (43 out of 94 sides) examined. The spinal foramen connected with mental canal occurred at the midline of mandible in 6 cases (6 out of 47 cases) in dry skulls. In this small foramen, the inferior alveolar artery give some branches to the inside of mental region at the anterior mandible and which may be run pass through the lingual canal to the lingual foramen, where they emerge to enter the mylohyoid or anterior belly of digastric muscles. The observations of these are important considerations for surgical placement of dental implants in the region in the mandible.The anatomical location, course and arrangement of branches of the incisive artery and nerve should be given more attention for dental implantology. A supplementary branch of the mylohyoid nerve entered the mandible through accessory foramina in the lingual side of the mandibular symphysis in 50% of the cases7). This was also confirmed by studies using dry skulls11) and CT imaging5). Numerous reported have described accessory mandibular foramens1,8,11,12). However, there are considerable confusions for variability in distribution, incidence, size, and contents of the accessory lingual foramina. Appearance of lingual foramen and course of lingual canal between cadaver and dry skull has not been identified by dental CT and anatomical observation. Although CT observation has been made on various incisive branches at the anterior mandible, more detailed information is needed on the lingual foramen which contain lingual branch connected with arty and nerve, they use to traverse the mandible for purposes of dental treatments. In this study we identified the appearance of lingual and spinal foramen and course of lingual canal at the mental region of human mandible using CT from cadavers and dry skulls. This study focused on the anatomic peculiarities of the anterior mandible and implant related with clinical implications. Materials and MethodsA total of 91 mandibles were used from adult Japanese cadavers (44 cases: 24 males; 20 females from The Donation for Human Dissection) and adult Japanese dry skulls (47 cases: 36 males; 11 females from a collection at Nippon Dental University) for this study. Three-dimensional images of the mandible were obtained from reconstruction of CT images using a CT apparatus (Toshiba Medical Co. Ltd, Tokyo, Japan, 120 kV; 50 mA; slice, 1 mm; table speed, 0.75 sec/mm). CT examination 83Correspondence to: Iwao Sato, Ph.D
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