Oxysophocarpine Retards the Growth and Metastasis of Oral Squamous Cell Carcinoma by Targeting the Nrf2/HO-1 Axis

Background/Aims: Nuclear factor erythroid 2-related factor 2 (Nrf2) is an oncogene in various types of cancers, including oral squamous cell carcinoma (OSCC). Oxysophocarpine (OSC) is a natural alkaloid that has multiple pharmacological activities. However, the biological functions and molecular mechanism underlying the effects of OSC on the growth and metastasis of OSCC are unclear. Methods: Nrf2 levels were determined in OSCC tissues and non-cancerous specimens by quantitative real-time PCR, western blotting, and immunohistochemistry (IHC) assays. The effects of OSC on OSCC cell growth and metastasis were explored (1) using 5-ethynyl-20-deoxyuridine staining and Cell Counting Kit-8, colony formation, flow cytometry, wound-healing, Transwell, and tube formation assays in vitro; and (2) by establishing a xenograft nude mouse model in vivo. The molecular mechanisms underlying the effects of OSC on the growth and metastasis of OSCC were investigated in vitro by western blotting, caspase-3 activity, and enzyme-linked immunosorbent assays, and in vivo by western blotting and IHC assays. Results: The expression levels of Nrf2 in OSCC tissues and in cell lines were much higher than in non-cancerous tissues and normal oral keratinocytes. The upregulation of Nrf2 was positively correlated with a high incidence of lymph node metastasis and advanced histological grade and TNM stage, but inversely associated with differentiation and survival of OSCC patients. OSC reduced the expression of Nrf2 and heme oxygenase 1 (HO-1) in OSCC cells. OSC also inhibited proliferation, migration, invasion, and pro-angiogenesis of OSCC cells. Moreover, OSC induced cell cycle arrest, enhanced apoptosis of OSCC cells in vitro, and decreased OSCC tumor growth in vivo. Mechanically, OSC reduced the aggressive behavior of OSCC cells by inactivation of the Nrf2/HO-1 signaling pathway. Conclusion: Our findings provide evidence that OSC inhibits the growth and metastasis of OSCC by targeting the Nrf2/ HO-1 axis, suggesting that OSC may be a potential therapeutic agent for OSCC

Research Progress on regarding the torque control of upper anterior teeth with a lip appliance

The normal torque angle of the maxillary anterior teeth is an important factor in the aesthetics and func⁃ tion of the anterior teeth, and torque control of the front teeth is an extremely important aspect of the correction process. At present, the normal torque angle of the front teeth is among the phase Ⅲ clinical test items recognized by the Ameri⁃ can orthodontic professional committee; consequently, good control of front teeth torque is of great significance to the aesthetics of the upper anterior teeth. In this paper, the influence of a lip appliance on the bad torque of upper anterior teeth and the associated methods of control are reviewed in detail. The advantages and disadvantages of various control methods for the anterior teeth and the significance of correct anterior teeth torque angle are summarized. The existing re⁃ search results indicate that the torsion of a straight arch wire applied directly to individual teeth is too great, making it difficult to enter the groove. Although the bending of the arch wire overcomes these shortcomings, the procedure is cum⁃ bersome; it stimulates the soft tissue of the vestibular groove and increases the patients discomfort. The bending mecha⁃ nism of the rocking chair is more complicated; it is greatly affected by the friction between the arch wire and the brack⁃ et and is not conducive to closing the tooth extraction gap using the sliding method. The portal auxiliary arch and the single bending torque are suitable for correcting the torque angle of a single tooth. Auxiliary arch torque can be used to correct the upright upper anterior teeth during the process of closing the extraction space and after adduction; therefore, this procedure is worth popularizing. However, the accuracy of orthodontic control of anterior teeth torque requires fur⁃ ther study

Dynamic expression of Mage-D1 in rat dental germs and potential role in mineralization of ectomesenchymal stem cells

Abstract Mage-D1 (MAGE family member D1) is involved in a variety of cell biological effects. Recent studies have shown that Mage-D1 is closely related to tooth development, but its specific regulatory mechanism is unclear. The purpose of this study was to investigate the expression pattern of Mage-D1 in rat dental germ development and its differential mineralization ability to ectomesenchymal stem cells (EMSCs), and to explore its potential mechanism. Results showed that the expression of Mage-D1 during rat dental germ development was temporally and spatially specific. Mage-D1 promotes the proliferation ability of EMSCs but inhibits their migration ability. Under induction by mineralized culture medium, Mage-D1 promotes osteogenesis and tooth-forming ability. Furthermore, the expression pattern of Mage-D1 at E19.5 d rat dental germ is similar to p75 neurotrophin receptor (p75NTR), distal-less homeobox 1 (Dlx1) and msh homeobox 1 (Msx1). In addition, Mage-D1 is binding to p75NTR, Dlx1, and Msx1 in vitro. These findings indicate that Mage-D1 is play an important regulatory role in normal mineralization of teeth. p75NTR, Dlx1, and Msx1 seem to be closely related to the underlying mechanism of Mage-D1 action

Finite element analysis of torque control efficiency of a homemade four ⁃ curved auxiliary arch for anterior teeth

Objective To analyze the initial displacement of the upper central incisor and stress distribution of periodontal ligament under different torque values of upper incisors under the action of a four⁃curved auxiliary arch to provide a reliable basis for the safety of clinical application of four⁃curved auxiliary arches. Methods A three⁃dimen⁃ sional finite element model for torque control of upper anterior teeth with a homemade quadrilateral auxiliary arch was established. Four different states were analyzed: molar ligation without extraction space (group A), microimplant ligation without extraction space (group B), molar recovery with extraction space closure (group C) (the adductive traction force was set at 115 g) and microimplant recovery with extraction space closure (group D) (the adductive traction force was set at 115 g). When four types of torque (0.5 N, 1.0 N, 1.5 N, and 2.0 N) were applied. The initial displacement of upper central incisors and the stress distribution of periodontal ligament in 16 groups (A1⁃A4, B1⁃B4, C1⁃C4, D1⁃D4) were ob⁃ served. Results Under different conditions, as the strength of the four⁃curve auxiliary arch increases, the maxillary an⁃ terior teeth has crown labial inclination and a root lingual inclination. The displacement of the incisor tip increases with the increase in the loading force of the torque auxiliary arch, and the displacement of the incisor root apex increases as the force increases. The difference in incisor⁃apex displacement distance in A1⁃A4, B1⁃B4, C1⁃C4, D2 and D4 groups increased as the torque force increases, while the difference between the D3 group and D1 and D2 groups decreased slightly. The stress of the cervical periodontal ligament of the upper central incisor did not exceed the stress of the peri⁃ odontal ligament in the following groups: A1, A2, B1, B2, B3, C1, C2, D1, and D2. The stress of the lip side of the up⁃ per central incisor did exceed the stress of the periodontal ligament in the following groups: A3, A4, B4, C3, C4, D3, and D4. In other words, when using the four⁃curved auxiliary arch as an implant anchorage, the force applied in the ab⁃ sence of extraction space should not exceed 1.5 N, and the force applied in the adduction of extraction space should not exceed 1.0 N. When using the nonimplant anchorage, the force applied in the absence of extraction space and the ad⁃ duction of extraction space should not exceed 1.0 N. In addition, the range of force should not exceed the maximum stress of the periodontal ligament in the cervical region such that the effective and safe torque movement can be achieved. Under other stress conditions, the stress of the labial and cervical periodontal ligament of the upper central in⁃ cisor exceeded the stress value (2.6 × 10 ⁃ 2 MPa). The stress value of periodontal ligament was 2.6 × 10 ⁃ 2 MPa in all groups. Conclusion A four⁃curved auxiliary arch has a significant effect on the upper anterior teeth, and the use of mi⁃ croimplants can better control root movement such that the crown of upper central incisors cannot be excessively lip in⁃ clined

Delayed and highly specific antibody response to nonstructural protein 1 (NS1) revealed during natural human ZIKV infection by NS1-based capture ELISA

Abstract Background Zika virus (ZIKV) had spread rapidly in the past few years in southern hemisphere where dengue virus (DENV) had caused epidemic problems for over half a century. The high degree of cross-reactivity of Envelope (E) protein specific antibody responses between ZIKV and DENV made it challenging to perform differential diagnosis between the two infections using standard ELISA method for E protein. Methods Using an IgG capture ELISA, we investigated the kinetics of nonstructural protein 1 (NS1) antibody response during natural ZIKV infection and the cross-reactivity to NS1 proteins using convalescent sera obtained from patients infected by either DENV or ZIKV. Results The analyses of the sequential serum samples from ZIKV infected individuals showed NS1 specific Abs appeared 2 weeks later than E specific Abs. Notably, human sera from ZIKV infected individuals did not contain cross-reactivity to NS1 proteins of any of the four DENV serotypes. Furthermore, four out of five NS1-specific monoclonal antibodies (mAbs) isolated from ZIKV infected individuals did not bind to DENV NS1 proteins. Only limited amount of cross-reactivity to ZIKV NS1 was displayed in 108 DENV1 immune sera at 1:100 dilution. Conclusions The high degree of NS1-specific Abs in both ZIKV and DENV infection revealed here suggest that NS1-based diagnostics would significantly improve the differential diagnosis between DENV and ZIKV infections

The Long Noncoding RNA MALAT-1 Is Highly Expressed in Ovarian Cancer and Induces Cell Growth and Migration

<div><p>Background</p><p>Metastasis associated in lung adenocarcinoma transcript-1 (MALAT-1) is overexpressed during cancer progression and promotes cell migration and invasion in many solid tumors. However, its role in ovarian cancer remains poorly understood.</p><p>Methods</p><p>Expressions of MALAT-1 were detected in 37 normal ovarian tissues and 45 ovarian cancer tissues by reverse transcription polymerase chain reaction (RT-PCR). Cell proliferation was observed by CCK-8 assay; Flow cytometry was used to measure cell cycle and apoptosis; Cell migration was detected by transwell migration and invasion assay. In order to evaluate the function of MALAT-1, shRNA combined with DNA microarray and Functional enrichment analysis were performed to determine the transcriptional effects of MALAT-1 silencing in OVCAR3 cells. RNA and protein expression were measured by qRT-PCR and Western blotting, respectively.</p><p>Results</p><p>We found that upregulation of MALAT-1 mRNA in ovarian cancer tissues and enhanced MALAT-1 expression was associated with FIGO stage. Knockdown of MALAT-1 expression in OVCAR3 cells inhibited cell proliferation, migration, and invasion, leading to G0/G1 cell cycle arrest and apoptosis. Overexpressed MALAT-1 expression in SKOV3 cells promoted cell proliferation, migration and invasion. Downregulation of MALAT-1 resulted in significant change of gene expression (at least 2-fold) in 449 genes, which regulate proliferation, cell cycle, and adhesion. As a consequence of MALAT-1 knockdown, MMP13 protein expression decreased, while the expression of MMP19 and ADAMTS1 was increased.</p><p>Conclusions</p><p>The present study found that MALAT-1 is highly expressed in ovarian tumors. MALAT-1 promotes the growth and migration of ovarian cancer cells, suggesting that MALAT-1 may be an important contributor to ovarian cancer development.</p></div

Triaxial shape in Os-Pt region from ground states to collective rotational states

In order to study the deformation of the nuclei which belongs to the transitional region between strongly deformed and spherical nuclei, the calculations of the total Routhian surfaces by means of the pairing-deformation- frequency self-consistent cranked shell model were carried out in order to investigate shape evolution in even-mass Os and Pt isotopes ( 176-202Os and 182-204Pt) starting from the static nuclear ground states. It is found that some nuclear ground states such as in 196Os and 188-194Pt are neither oblate nor prolate. Instead, the ground-state minima in these nuclei are axially asymmetric in shape. In addition, a complementary approach is used to extract equilibrium γ0 value (nonaxially symmetric equilibrium shape parameter), which support our predictions. © 2010 World Scientific Publishing Company