Activation of β-catenin and Akt pathways by Twist are critical for the maintenance of EMT associated cancer stem cell-like characters

<p>Abstract</p> <p>Background</p> <p>Epithelial-mesenchymal transition (EMT) not only confers tumor cells with a distinct advantage for metastatic dissemination, but also it provides those cells with cancer stem cell-like characters for proliferation and drug resistance. However, the molecular mechanism for maintenance of these stem cell-like traits remains unclear.</p> <p>Methods</p> <p>In this study, we induced EMT in breast cancer MCF7 and cervical cancer Hela cells with expression of Twist, a key transcriptional factor of EMT. The morphological changes associated with EMT were analyzed by immunofluorescent staining and Western blotting. The stem cell-like traits associated with EMT were determined by tumorsphere-formation and expression of ALDH1 and CD44 in these cells. The activation of β-catenin and Akt pathways was examined by Western blotting and luciferase assays.</p> <p>Results</p> <p>We found that expression of Twist induced a morphological change associated with EMT. We also found that the cancer stem cell-like traits, such as tumorsphere formation, expression of ALDH1 and CD44, were significantly elevated in Twist-overexpressing cells. Interestingly, we showed that β-catenin and Akt pathways were activated in these Twist-overexpressing cells. Activation of β-catenin correlated with the expression of CD44. Knockdown of β-catenin expression and inhibition of the Akt pathway greatly suppressed the expression of CD44.</p> <p>Conclusions</p> <p>Our results indicate that activation of β-catenin and Akt pathways are required for the sustention of EMT-associated stem cell-like traits.</p

RESEARCH ON THE FLUID-INDUCED EXCITATION CHARACTERISTICS OF THE CENTRIFUGAL PUMP CONSIDERING THE COMPOUND WHIRL EFFECT

In order to study the correlation mechanism between the flow characteristics and the fluid-induced force under the compound whirl motion in the centrifugal pump, the RNG k-ε model is selected in this paper to simulate a low specific speed centrifugal pump with impeller eccentricity based on the N-S equation. The changes of fluid-induced force with impeller eccentricity and the unsteady flow characteristics of the internal flow field of centrifugal pump under different flow conditions and rotation speeds are investigated, and the relationship between the fluid-induced force of the impeller and the internal flow field characteristics is discussed. The results show that the trend of fluid-induced force and the pressure coefficient is similar. When the rotation speed changes and when the flow is similar, the pressure coefficient under different rotation speeds almost coincides. With the increase of impeller speed and impeller eccentricity, the dynamic and static interferences between the impeller and the volute tongue are more significant, the uneven distribution of the pressure around the impeller makes the internal flow of centrifugal pump more disordered and increases the fluid-induced force near the volute tongue. The research results can provide important reference value for accurately grasping the internal flow excitation principle of the centrifugal pump

Auricle shaping using 3D printing and autologous diced cartilage.

ObjectiveTo reconstruct the auricle using a porous, hollow, three-dimensional (3D)-printed mold and autologous diced cartilage mixed with platelet-rich plasma (PRP).MethodsMaterialise Magics v20.03 was used to design a 3D, porous, hollow auricle mold. Ten molds were printed by selective laser sintering with polyamide. Cartilage grafts were harvested from one ear of a New Zealand rabbit, and PRP was prepared using 10 mL of auricular blood from the same animal. Ear cartilage was diced into 0.5- to 2.0-mm pieces, weighed, mixed with PRP, and then placed inside the hollow mold. Composite grafts were then implanted into the backs of respective rabbits (n = 10) for 4 months. The shape and composition of the diced cartilage were assessed histologically, and biomechanical testing was used to determine stiffness.ResultsThe 3D-printed auricle molds were 0.6-mm thick and showed connectivity between the internal and external surfaces, with round pores of 0.1 to 0.3 cm. After 4 months, the diced cartilage pieces had fused into an auricular shape with high fidelity to the anthropotomy. The weight of the diced cartilage was 5.157 ± 0.230 g (P &gt; 0.05, compared with preoperative). Histological staining showed high chondrocyte viability and the production of collagen II, glycosaminoglycans, and other cartilaginous matrix components. In unrestricted compression tests, auricle stiffness was 0.158 ± 0.187 N/mm, similar to that in humans.ConclusionAuricle grafts were constructed successfully through packing a 3D-printed, porous, hollow auricle mold with diced cartilage mixed with PRP. The auricle cartilage contained viable chondrocytes, appropriate extracellular matrix components, and good mechanical properties.Levels of evidenceNA. Laryngoscope, 129:2467-2474, 2019

Spotlight on iron and ferroptosis: research progress in diabetic retinopathy

Iron, as the most abundant metallic element within the human organism, is an indispensable ion for sustaining life and assumes a pivotal role in governing glucose and lipid metabolism, along with orchestrating inflammatory responses. The presence of diabetes mellitus (DM) can induce aberrant iron accumulation within the corporeal system. Consequentially, iron overload precipitates a sequence of important adversities, subsequently setting in motion a domino effect wherein ferroptosis emerges as the utmost pernicious outcome. Ferroptosis, an emerging variant of non-apoptotic regulated cell death, operates independently of caspases and GSDMD. It distinguishes itself from alternative forms of controlled cell death through distinctive morphological and biochemical attributes. Its principal hallmark resides in the pathological accrual of intracellular iron and the concomitant generation of iron-driven lipid peroxides. Diabetic retinopathy (DR), established as the predominant cause of adult blindness, wields profound influence over the well-being and psychosocial strain experienced by afflicted individuals. Presently, an abundance of research endeavors has ascertained the pervasive engagement of iron and ferroptosis in the microangiopathy inherent to DR. Evidently, judicious management of iron overload and ferroptosis in the early stages of DR bears the potential to considerably decelerate disease progression. Within this discourse, we undertake a comprehensive exploration of the regulatory mechanisms governing iron homeostasis and ferroptosis. Furthermore, we expound upon the subsequent detriments induced by their dysregulation. Concurrently, we elucidate the intricate interplay linking iron overload, ferroptosis, and DR. Delving deeper, we engage in a comprehensive deliberation regarding strategies to modulate their influence, thereby effecting prospective interventions in the trajectory of DR’s advancement or employing them as therapeutic modalities