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Background and Aim: Intestinal ischemia/reperfusion (II/R) can cause injury of remote organs, including acute renal injury. All of these, in turn, increase the rate of disability and mortality. Anwulignan (Anwu) is an active monomer from Schisandra sphenanthera, which has been used for thousands of years in China as a medical herb. In our previous study, we found that Anwu can improve the intestinal function after ischemia/reperfusion. Therefore, we were curious to know if Anwu can have a protective effect on remote organ injury after II/R. The purpose of the present study was to examine the effect of Anwu on the remote renal injury induced by II/R in rats and investigate its mechanism. Materials and Methods: Forty Sprague Dawley (SD) rats were divided into four groups, and they were sham operation (Sham), sham + Anwu, II/R, and II/R + Anwu groups. After reperfusion or sham operation, blood and kidneys were collected from the rats for the detection of relative biochemical parameters. Results: Renal indexes were not significantly different among all groups. In the II/R group the following were the findings: blood urea nitrogen and creatinine levels were increased, kidney injury score was increased, renal superoxide dismutase was reduced, the activities of reduced glutathione and catalase were decreased, the renal malondialdehyde content was increased, there was an improvement in the levels of renal proinflammatory cytokines, interleukin-6, tumor necrosis factor-α, and interleukin-1β, the expressions of renal oxidative stress-related p-Nrf2 and heme oxygenase (decycling) 1 (HO-1) were decreased, and the Kelch-like ECH-associated protein 1 (Keap1) expression was increased. The expression levels of the apoptotic protein, cleaved caspase-3, were raised, while the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated x protein (Bax) ratio was reduced. However, the administration of Anwu before the surgery significantly reversed the above changes. Conclusion: Anwu has a protective effect against the II/R-induced remote renal injury in rats, which may be related to its regulation of antioxidant, anti-inflammatory, and antiapoptotic pathways. [ABSTRACT FROM AUTHOR]

Background and purpose Sorafenib, a potent inhibitor that targets several kinases associated with tumourigenesis and cell survival, has been approved for clinical treatment as a single agent. However, combining sorafenib with other agents improves its anti-tumour efficacy in various preclinical tumour models. ABT-263, a second-generation BH3 mimic, binds to the anti-apoptotic family members Bcl-2, Bcl-xL and Bcl-w, and has been demonstrated to enhance TNFSF10 (TRAIL)-induced apoptosis in human hepatocarcinoma cells. Hence, we investigated the effects of ABT-263 treatment combined with sorafenib. Experimental Approach The effects of ABT-263 combined with sorafenib were investigated in vitro, on cell viability, clone formation and apoptosis, and the mechanism examined using western blot and flow cytometry. This combination was also evaluated in vivo, in a mouse xenograft model; tumour growth, volume and weights were measured and a TUNEL assay performed. Key Results ABT-263 enhanced sorafenib-induced apoptosis while sparing non-tumourigenic cells. Although ABT-263 plus sorafenib significantly stimulated intracellular reactive oxygen species production and subsequent mitochondrial depolarization, this was not sufficient to trigger cell apoptosis. ABT-263 plus sorafenib significantly decreased Akt activity, which was, at least partly, involved in its effect on apoptosis. Bax and p21 ( CIP1/WAF1) were shown to play a critical role in ABT-263 plus sorafenib-induced apoptosis. Combining sorafenib with ABT-263 dramatically increased its efficacy in vivo. Conclusion and Implications The anti-tumour activity of ABT-263 plus sorafenib may involve the induction of intrinsic cell apoptosis via inhibition of Akt, and reduced Bax and p21 expression. Our findings offer a novel effective therapeutic strategy for tumour treatment. [ABSTRACT FROM AUTHOR]

Background & Aims: Hepatocellular carcinoma (HCC) is the third most common cause of cancer death worldwide. Improved treatments for advanced HCC are urgently needed. The recently identified human sulfatase 1 enzyme (SULF1) desulfates cell surface heparan sulfate glycosaminoglycans and down-regulates cell growth signaling in HCC cells in vitro. While investigating the epigenetic regulation of SULF1, we discovered that histone H4 acetylation is up-regulated by SULF1 in HCC cells. Histone deacetylase (HDAC) inhibitors reprogram cellular gene expression through the acetylation of nucleosomal histones and promote cell growth arrest and apoptosis. Hence, they are a promising modality for cancer treatment. Methods: To explore the interaction between SULF1 expression and HDAC inhibitor action, we examined the effects of SULF1 expression on HCC cells and xenografts treated with HDAC inhibitors. Results: (1) Forced expression of SULF1 significantly delayed the growth of Huh7 and Hep3B xenografts in nude mice in vivo. (2) SULF1 increased histone H4 acetylation by modulation of cellular HDAC and histone acetyltransferase activities. (3) SULF1 enhanced the induction of apoptosis by the HDAC inhibitors apicidin and scriptaid. (4) SULF1 enhanced the inhibition of tumor growth, migration, and angiogenesis by HDAC inhibitors. We also demonstrate that knockdown of SULF1 with shRNA constructs up-regulates phosphorylation of AKT and Erk and attenuates apicidin-induced apoptosis. The interaction between SULF1 and apicidin was confirmed in vivo in Huh7 and Hep3B xenografts. Conclusions: These results show that SULF1 promotes histone H4 acetylation, potentiates the effects of HDAC inhibitors, and inhibits HCC tumorigenesis. [Copyright &y& Elsevier]

• A guideline to optimize the structure of 3DCOHP was proposed, which can enhance the heat transfer performance significantly. • Reducing the top bend curvature radius of 3DCOHP with asymmetric heating mode can promote the formation of unidirectional flow without check valve. • The existence of unequal flow pressure drop between the push-up and push-down causes the formation of unidirectional flow in 3DCOHP. The effects of the bend curvature radius and tube diameter on the heat transfer performance of the three-dimensional coil oscillating heat pipe (3DCOHP) were experimentally studied in asymmetric heating mode. Three types of copper 3DCOHPs using water as the working fluid were studied in vertical orientation. And the filling ratio of each 3DCOHP was set to 50%. It was found that reducing the top bend curvature radius and increasing the tube diameter can both strengthen the formation of unidirectional flow and significantly improve the heat transfer performance of the 3DCOHP. The heat transfer performance of the OHP with a tube diameter of 1.90 mm increased by up to 34.6% when the heating power was set to 40 W. At the same time, the reason of the unidirectional flow in asymmetric heating mode was theoretically analyzed. It was shown that the calculated pressure drops in liquid slug flowing from the evaporation section to both sides powered by vapor expansion are different, which develops the unidirectional flow. These findings provide a guideline to optimize the structure of OHP to enhance its heat transfer capacity. [ABSTRACT FROM AUTHOR]

Background & Aims: The mammalian target of rapamycin (mTOR) plays a pivotal role in hepatocellular carcinoma (HCC). Previous studies indicated that inhibition of mTORC1 enhanced histone deacetylase inhibitors (HDACis)-mediated anti-tumor activity, accompanied with feedback activation of AKT. Therefore, dual targeting of mTORC1/C2 should be more efficient in suppressing AKT activity and in enhancing the anti-tumor activity of HDACi in HCC. Methods: The interactions between mTOR kinase inhibitors (mTORKis) (i.e., Pp242, AZD8055, OSI027) and HDACis (i.e., SAHA, LBH589) were examined in vitro using HCC cell lines and in vivo using patient-derived primary HCC xenografts on SCID mice. Results: mTORKis significantly enhanced HDACi-induced apoptosis in HCC cells. The inhibition of both mTORC1/2 not only efficiently blocked mTORC1 signaling, but also abrogated AKT-feedback activation caused by selective mTORC1 inhibition. The co-treatment of mTORKi and HDACi further inhibited AKT signaling and upregulated Bim. Dysfunction of mTORC2 by shRNA significantly lowered the threshold of HDACi-induced cytotoxicity by abrogating AKT activation. Knockdown of AKT1 sensitized Pp242/HDACi-induced apoptosis and ectopic expression of constitutively active AKT1 abrogated the combination-induced cytotoxicity, indicating AKT plays a vital role in the combination-induced effects. Knockdown of Bim prevented Pp242/HDACis-induced cytotoxicity in HCC. Lastly, in vivo studies indicated that the combination of AZD8055 and SAHA almost completely inhibited tumor-growth, without obvious adverse effects, by abrogating AKT and upregulating Bim; while either agent alone shows only 30% inhibition in primary HCC xenografts. Conclusions: Our findings suggest that a combining-regimen of mTORKi and HDACi may be an effective therapeutic strategy for HCC. [ABSTRACT FROM AUTHOR]

Abstract: An acoustic-optic Q-switched YAG laser is newly developed for truing and dressing of bronze-bonded diamond grinding wheels through ablation in the radial direction. The laser ablation merges truing and dressing as a single process and can be easily controlled through an online closed-loop control system. The laser truing and dressing characteristics are investigated by wheel surface topography and a high-speed grinding test. A two-dimensional mathematical model is developed to simulate laser truing and dressing of bronze-bonded diamond grinding wheel. Based on the model, the ablation depth produced on bond and diamond abrasives by a pulsed laser under different parameters as well as the temperature field on grinding wheel surface produced in the laser ablation process are numerically simulated. Both the experimental results and the theoretical analysis indicate that the truing and dressing processes can be simultaneously realized with the laser ablation. [Copyright &y& Elsevier]

• A liquid metal high temperature OHP (LMHOHP) was first developed. • The LMHOHP that can function at a temperature of over 500 °C. • The LMHOHP can transport heat of 3169 W and achieve a thermal resistance of 0.08 °C/W. This paper introduces the development of a liquid metal high-temperature oscillating heat pipe (LMHOHP) that can function under high-temperature conditions (over 500 °C). The LMHOHP has six turns with a total height of 310 mm. The sodium-potassium alloy (potassium 78%) was used as the working fluid, and the 310S stainless steel tube with an inner diameter of 6 mm as the shell tube. The LMHOHP heat transfer performance was investigated experimentally with a filling ratio of 45% at different input powers. Experimental results show that the LMHOHP can effectively generate steady-state oscillating motions at a working temperature of over 500 °C. When the steady-state oscillating motions exist, the temperature difference and thermal resistance between the evaporator and condenser were reduced significantly. At a heat input of 3169 W, the LMHOHP presents a minimum thermal resistance of 0.08 °C/W. This LMHOHP provides a new approach to next-generation high-temperature cooling devices. [ABSTRACT FROM AUTHOR]