Canonical Wnt signaling is antagonized by noncanonical Wnt5a in hepatocellular carcinoma cells

<p>Abstract</p> <p>Background</p> <p>β-catenin mutations that constitutively activate the canonical Wnt signaling have been observed in a subset of hepatocellular carcinomas (HCCs). These mutations are associated with chromosomal stability, low histological grade, low tumor invasion and better patient survival. We hypothesized that canonical Wnt signaling is selectively activated in well-differentiated, but repressed in poorly differentiated HCCs. To this aim, we characterized differentiation status of HCC cell lines and compared their expression status of Wnt pathway genes, and explored their activity of canonical Wnt signaling.</p> <p>Results</p> <p>We classified human HCC cell lines into "well-differentiated" and "poorly differentiated" subtypes, based on the expression of hepatocyte lineage, epithelial and mesenchymal markers. Poorly differentiated cell lines lost epithelial and hepatocyte lineage markers, and overexpressed mesenchymal markers. Also, they were highly motile and invasive. We compared the expression of 45 Wnt pathway genes between two subtypes. TCF1 and TCF4 factors, and LRP5 and LRP6 co-receptors were ubiquitously expressed. Likewise, six Frizzled receptors, and canonical Wnt3 ligand were expressed in both subtypes. In contrast, canonical ligand Wnt8b and noncanonical ligands Wnt4, Wnt5a, Wnt5b and Wnt7b were expressed selectively in well- and poorly differentiated cell lines, respectively. Canonical Wnt signaling activity, as tested by a TCF reporter assay was detected in 80% of well-differentiated, contrary to 14% of poorly differentiated cell lines. TCF activity generated by ectopic mutant β-catenin was weak in poorly differentiated SNU449 cell line, suggesting a repressive mechanism. We tested Wnt5a as a candidate antagonist. It strongly inhibited canonical Wnt signaling that is activated by mutant β-catenin in HCC cell lines.</p> <p>Conclusion</p> <p>Differential expression of Wnt ligands in HCC cells is associated with selective activation of canonical Wnt signaling in well-differentiated, and its repression in poorly differentiated cell lines. One potential mechanism of repression involved Wnt5a, acting as an antagonist of canonical Wnt signaling. Our observations support the hypothesis that Wnt pathway is selectively activated or repressed depending on differentiation status of HCC cells. We propose that canonical and noncanonical Wnt pathways have complementary roles in HCC, where the canonical signaling contributes to tumor initiation, and noncanonical signaling to tumor progression.</p

Ameliorative impacts of floral extract of Salvia species on oxidative stress and inflammation in rats renal ischemia/reperfusion

91-100I/R injury is a potentially serious problem that is encountered during a variety of medical and surgical procedures, such as thrombolytic therapy, organ transplantation and coronary angioplasty, The basic pathophysiology of I/R injury is microvascular dysfunction which is developed following reperfusion of ischemic tissues. It has clinical importance because of its frequent occurrence and mortality in some surgical conditions such as renal transplantation. Here, we investigated the protective effect of Salvia extracts on kidneys against I/R injury. Forty Spraque Dawley rats were divided into 5 groups. Right nephrectomy was performed to all groups. Gr. I, control; Gr. II, I/R; Gr. III & IV, I/R+50 and I/R+100 mg/kg Salvia floral extract; and Gr. V with I/R+50 mg/kg Rosmarinic acid. Salvia and Rosmarinic acid for 7 days was given single dose as a gavage.60 min ischemia, 60 min reperfusion were applied to groups except control. Intracardiac blood samples were taken, Blood urea nitrogen, creatine, malondialdehyde, myeloperoxidase, nitric oxide and chitotriosidase levels were detected. Mean values were evaluated by statistical analysis. The renal tissues were examined under light microscopy. Based on our biochemical and histological data, Salvia floral extract has potent anti-inflammatory and antioxidant effects against renal structure and function

Evaluation of low tidal volume with positive end-expiratory pressure application effects on arterial blood gases during laparoscopic surgery

Abstract Background: Pneumoperitoneum (PNP) and patient positions required for laparoscopy can induce pathophysiological changes that complicate anesthetic management during laparoscopic procedures. This study investigated whether low tidal volume and positive end-expiratory pressure (PEEP) application can improve ventilatory and oxygenation parameters during laparoscopic surgery. Methods: A total of 60 patients undergoing laparoscopic surgery were randomized to either the conventional group (n ¼ 30, tidal volume ¼ 10 mL/kg, rate ¼ 12/minute, PEEP ¼ 0 cm H 2 O) or the low tidal group with PEEP group (n ¼ 30, tidal volume ¼ 6 mL/kg, rate ¼ 18/minute, PEEP ¼ 5 cm H 2 O) at maintenance of anesthesia. Hemodynamic parameters, peak plateau pressure (Pplat) and arterial blood gases results were recorded before and after PNP. Results: There was a significant increase in the partial pressure of arterial carbon dioxide (PaCO 2 ) values after PNP in the conventional group in the reverse Trendelenburg (41.28 mmHg) and Trendelenburg positions (44.80 mmHg; p ¼ 0.001), but there was no difference in the low tidal group at any of the positions (36.46 and 38.56, respectively). We saw that PaO 2 values recorded before PNP were significantly higher than the values recorded 1 hour after PNP in the two groups at all positions. No significant difference was seen in peak inspiratory pressure (Ppeak) at the reverse Trendelenburg position before and after PNP between the groups, but there was a significant increase at the Trendelenburg position in both groups (conventional; 21.67 cm H 2 O, p ¼ 0.041, low tidal; 23.67 cm H 2 O, p ¼ 0.004). However, Pplat values did not change before and after PNP in the two groups at all positions. Conclusion: The application of low tidal volume þ PEEP þ high respiratory rate during laparoscopic surgeries may be considered to improve good results of arterial blood gases

Mn4+-, Tb-3+,Tb-4+-, and Er3+-activated red phosphors in the MgAl2Si2O8 system

Mn4+ doped and Tb-3+,Tb-4+, Er3+ co-doped MgAl2Si2O8-based phosphors were prepared by conventional solid-state synthesis at 1,300 A degrees C. They were characterized by thermogravimetry, differential thermal analysis, X-ray powder diffraction, photoluminescence, and scanning electron microscopy. The luminescence mechanism of the phosphors, which showed broad red emission bands in the range of 600-715 nm and had different maximum intensities when activated by UV illumination, was discussed. Such a red emission can be attributed to the intrinsic E-2 -> (4)A(2) transitions of Mn4+

High-performance thienothiophene and single wall carbon nanotube-based supercapacitor as a free-standing and flexible hybrid energy storage material

Long cycle life and high energy/power density are imperative for energy storage systems. Similarly, flexible and free-standing electrodes are important for supercapacitor applications. Herein, we report, for the first time, use of thienothiophene (TT) and a single-walled carbon nanotube (SWCNT)-based free-standing and flexible hybrid material (TT-TPA-SWCNT) as a high-performance supercapacitor. The synthesized TT derivative, TT-TPA, was directly attached to SWCNT through noncovalent interactions to obtain the TT-based SWCNT hybrid, TT-TPA-SWCNT, as a flexible film. The hybrid film was clarified by surface analysis methods of scanning electron microscopy and atomic force microscopy. TT-TPA-SWCNT was used as a flexible and free-standing electrode in a two-electrode system for supercapacitor and energy storage applications. It displayed a high energy storage capacity of 83.2 F g-1 at 5 mV s-1 scan rate, an excellent cyclic stability with 110% retention of its initial specific capacitance after 7000 cycles and a long power density ranged from 100 to 3000 W·kg-1, demonstrating that TT-TPA-SWCNT is a promising hybrid nanomaterial for high-performance energy storage applications