TPX2 enhances the transcription factor activation of PXR and enhances the resistance of hepatocellular carcinoma cells to antitumor drugs.

The pregnane X receptor (PXR) is an important regulator of hepatocellular carcinoma cellular resistance to antitumor drugs. Activation of PXR was modulated by the co-regulators. The target protein for the Xenopus plus end-directed kinesin-like protein (Xklp2) known as TPX2 that was previously considered as a tubulin regulator, also functions as the regulator of some transcription factors and pro-oncogenes in human malignances. However, the actions of TPX2 on PXR and HCC cells are still unclear. In the present study, our results demonstrate that the high expression of endogenous mRNA level of TPX2 not only correlated with the poor prognosis of advanced HCC patients who received sorafenib treatment but also with expression of PXR's downstream genes, cyp3a4 and/or mdr-1. Results from luciferase and real-time polymerase chain reaction (qPCR) showed that TPX2 leads to enhancement of the transcription factor activation of PXR. Protein-protein interactions between PXR and TPX2 were identified using co-immunoprecipitation. Mechanically, overexpression of TPX2 led to enhancement of PXR recruitment to its downstream gene cyp3a4's promoter region (the PXRE region) or enhancer region (the XREM region). Treatment of HCC cells with paclitaxel, a microtubule promoter, led to enhancement of the effects of TPX2, whereas vincristine, a microtubule depolymerizing agent caused a decrease in TPX2-associated effects. TPX2 was found to cause acceleration of the metabolism or clearance of sorafenib, a typical tyrosine kinase inhibitor (TKI) in HCC cells and in turn led to the resistance to sorafenib by HCC cells. By establishing novel actions of TXP2 on PXR in HCC cells, the results indicate that TPX2 could be considered a promising therapeutic target to enhance HCC cells sensitivity to antitumor drugs.

The Combination of AFP and "Up-To-Seven" Criteria May Be a Better Strategy for Liver Transplantation in Chinese Cirrhotic HCC Patients.

Background: Orthotopic liver transplantation (OLT) is a life-saving option for patients with hepatocellular carcinoma (HCC), but the expanded OLT criteria remain controversial. Objective: The study aimed to explore whether expanded OLT criteria can be applied to Chinese cirrhotic patients with HCC. Methods: This retrospective study analyzed risk factors for HCC recurrence and death and compared patients' tumor characteristics and outcomes in groups of Milan, "Up-to-seven," and Hangzhou criteria, and groups between met and unmet the combinative criteria of "Up-to-seven" and AFP of < 1000 ng/mL. Results: Among 153 patients who underwent OLT for HCC from January 2015 to February 2019 in 4 years of follow-up, 20 (13.1%) patients had HCC recurrence, and 11 (7.2%) had HCC-related death. Multivariate Cox regression analysis showed that preoperative alpha-fetoprotein (AFP) of > 1000 ng/mL (hazard ratio [HR]: 10.05, 95% confidence interval [CI]: 2.45-41.13, P = 0.001) was an independent risk factor for HCC recurrence and HCC-related death (HR: 6.63, 95%CI: 1.31-33.52, P = 0.022). Patients who did not meet Milan criteria but satisfied the "Up-to-seven" criteria had no differences in overall survival (OS) (P = 0.69) and disease-free survival (DFS) (P = 0.35) than patients who met the Milan criteria. The combination of "Up-to-seven" criteria and AFP of < 1000 ng/mL differed significantly (HR: 18.9; 95% CI: 4.0-89.2; P < 0.001). Patients with HCC who met the "Up-to-seven" criteria and AFP of < 1000 ng/mL (n = 121) had excellent survival with 4-year OS of 91.6% (P < 0.001) and DFS of 90.8% (P < 0.001), which is significantly better compared to the other group (n = 32) (OS of 67.5% and DFS of 46.5%) and patients who met the Milan criteria (n = 108, OS of 89.8%, DFS of 89.6%), allowing 28.9% (13/45) of patients who did not meet the Milan criteria to benefit from OLT. Conclusion: Chinese cirrhotic patients with HCC who met the combinative criteria of "Up-to-seven" and AFP of < 1000 ng/mL had better survival than those who met the Milan criteria, and these combinative criteria benefited more patients and may become a better option for OLT.

MicroRNA-22 inhibition prevents doxorubicin-induced cardiotoxicity via upregulating SIRT1.

Oxidative stress and cardiomyocyte apoptosis contributed to the progression of doxorubicin (Dox)-induced cardiotoxicity. Recent studies identified microRNA-22 (miR-22) as a cardiac- and skeletal muscle-enriched microRNA that functioned as a key regulator in stress-induced cardiac injury. The present study aimed to investigate the role and possible mechanism of miR-22 on Dox-induced oxidative stress and cardiomyocyte apoptosis. Mice were exposed to reduplicative injections of Dox (i.p., 4 mg/kg) weekly for consecutive 4 weeks to generate Dox-induced cardiotoxicity. Herein, we found that miR-22 level was significantly increased in murine hearts subjected to chronic Dox treatment. MiR-22 inhibition attenuated oxidative stress and cardiomyocyte apoptosis in vivo and in vitro, thereby preventing Dox-induced cardiac dysfunction. Mechanistically, we observed that miR-22 directly bound to the 3'-UTR of Sirt1 and caused SIRT1 downregulation. Conversely, miR-22 antagomir upregulated SIRT1 expression and SIRT1 inhibitor abolished the beneficial effects of miR-22 antagomir. In conclusion, miR-22 inhibition prevented oxidative stress and cardiomyocyte apoptosis via upregulating SIRT1 and miR-22 might be a new target for treating Dox-induced cardiotoxicity.

Conductive elastomers with autonomic self-healing properties.

Healable, electrically conductive materials are highly desirable and valuable for the development of various modern electronics. But the preparation of a material combining good mechanical elasticity, functional properties, and intrinsic self-healing ability remains a great challenge. Here, we design composites by connecting a polymer network and single-walled carbon nanotubes (SWCNTs) through host-guest interactions. The resulting materials show bulk electrical conductivity, proximity sensitivity, humidity sensitivity and are able to self-heal without external stimulus under ambient conditions rapidly. Furthermore, they also possess elasticity comparable to commercial rubbers.

An efficient multiple healing conductive composite via host-guest inclusion.

A self-healable conductive composite is developed by combining the small molecules and nanotubes through host-guest interactions. This material shows uniform conductivity, microwave absorption and humidity sensing properties, and can be rapidly healed to over 90% electrical and mechanical properties with the aid of water multiple times. In addition, the produced material is also remouldable and recyclable.

Syntheses of tanshinone anhydrides and their suppression on oxidized LDL uptake in macrophages and foam cell formation.

We synthesized eight tanshinone anhydrides and the alcoholytic derivatives through a mild oxygen-insertion under Pd/C catalytic hydrogenation conditions. The suppressive effects of the anhydrides on the oxidized low-density lipoprotein (oxLDL) uptake and the oxLDL-induced macrophage-derived foam cell formation were studied. Our results revealed that both anhydrides 1a and 2a could significantly suppress the oxLDL uptake in macrophages and the foam cell formation at micromolar level, which might be partially attributed to their inhibition of oxLDL-induced LOX-1 expression in macrophages.

Syntheses of diacyltanshinol derivatives and their suppressive effects on macrophage foam cell formation by reducing oxidized LDL uptake.

A series of diacyltanshinol derivatives were synthesized by esterifying the corresponding o-hydroquinones of tanshinones. The suppressive effects of the synthesized compounds on oxidized low-density lipoprotein (oxLDL) uptake and oxLDL-induced macrophage-derived foam cell formation were evaluated. Our results indicated that the nicotinate derivatives 1a and 2a, modified from tanshinone IIA and cryptotanshinone, showed stronger suppressive activity on oxLDL uptake and the resultant foam cell formation relative to tanshinone IIA. Western Blot analysis indicated that derivatives 1a and 2a could dose-dependently inhibit the expression of oxLDL-induced LOX-1, implying that the suppressive effects of 1a and 2a on oxLDL uptake and foam cell formation could be at least partially attributed to the inhibition of LOX-1 expression in macrophages.

Ultra-precision measurement and control of angle motion in piezo-based platforms using strain gauge sensors and a robust composite controller.

The measurement and control strategy of a piezo-based platform by using strain gauge sensors (SGS) and a robust composite controller is investigated in this paper. First, the experimental setup is constructed by using a piezo-based platform, SGS sensors, an AD5435 platform and two voltage amplifiers. Then, the measurement strategy to measure the tip/tilt angles accurately in the order of sub-µrad is presented. A comprehensive composite control strategy design to enhance the tracking accuracy with a novel driving principle is also proposed. Finally, an experiment is presented to validate the measurement and control strategy. The experimental results demonstrate that the proposed measurement and control strategy provides accurate angle motion with a root mean square (RMS) error of 0.21 µrad, which is approximately equal to the noise level.

Oxygen insertion of o-quinone under catalytic hydrogenation conditions.

An oxygen-insertion reaction that transforms an o-quinone and a conjugated α-diketone substrate into an anhydride product or derivative under catalytic hydrogenation conditions is reported. The experiments and computations indicate that the oxygen insertion proceeds via a radical mechanism mediated by an acetoxyl radical.

Ethyl 9-fluoro-5,12-dioxo-5,12-dihydro-indolizino[2,3-g]quinoline-6-carboxyl-ate.

In the title mol-ecule, C(18)H(11)FN(2)O(4), the fused four- ring system is essentially planar, with an r.m.s. deviation of 0.032 Å. In the crystal, mol-ecules are connected by π-π stacking inter-actions [centroid-centroid distances = 3.5684 (9) and 3.8247 (9) Å] into chains along [100].

[Effect of ginsenosides on level of sex hormone receptors in human liver cell line HL-7702].

OBJECTIVE: To investigate the effect of ginsenoside (GSS) in regulating level of sex hormone receptors in human liver cell line HL-7702. METHODS: The growth of HL-7702 were detected by MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay for choosing the available concentration of GSS; and the effect of GSS on sex hormone receptors in HL-7702 cells were detected by immuno-histochemistry, Western blot and RT-PCR. RESULTS: GSS significantly enhance the protein and mRNA expressions of estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR) in HL7702 cell in a dose-dependent manner, the levels of expressions in the GSS treated group were higher than those in the solvent control group respectively (P < 0.05). CONCLUSION: GSS can up-regulate the protein and mRNA expressions of sex hormone receptors in HL-7702.

[Experimental study on the survival of venous flap with different pedicle styles].

OBJECTIVE: To study a new method of venous flap that is improved on its persistence and quality. METHODS: New Zealand white rabbits were subdivided randomly into 4 groups. All rabbits were operated by harvesting a flap from the latero-abdominal wall and then sutured it in the original position. Group A: the superficial epigastric vein in the pedicle was left open (only one inflow vein remained). Group B: the pedicle vein of the proximal and distant end were left open (keeping an inflow vein and a principal out). Group C: the pedicle vein and a tributary vein were left open (keeping an inflow vein and a tributary outflow vein). Group D: the pedicle vein and two tributary veins were left open (keeping an inflow vein and two tributary outflow veins). Survival rate, MDA of the tissue, histology and ultra-microstructure were examined. RESULTS: Survival rate of A, B, C, D were improved in order. Statistic difference is significant (P < 0.05) between group and group other than C and D. The content of MDA was heightened with statistically significant differences (A > B > C > D) among the four groups 8 hours postoperatively, but fell back to the normal level in group D and C and kept a high level in group A and B at 72 hour postoperatively. Histology and ultra-microstructure exam showed that degeneration of collagen fiber and karyopyknosis of cell is more obvious in Group A and Group B than Group C and Group D. CONCLUSIONS: The higher survival rate of venous flap is possible by designing the more reasonable venous flap outputs pedicles which can alleviate the high tension dropsy and maintain the valid equilibrium of pour with flow in the venous flap.