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Hepatocellular carcinoma(HCC)is the third leading cause of cancer death worldwide.Ginsenoside Rk3,an important and rare saponin in heat-treated ginseng,is generated from Rg1 and has a smaller mo-lecular weight.However,the anti-HCC efficacy and mechanisms of ginsenoside Rk3 have not yet been characterized.Here,we investigated the mechanism by which ginsenoside Rk3,a tetracyclic triterpenoid rare ginsenoside,inhibits the growth of HCC.We first explored the possible potential targets of Rk3 through network pharmacology.Both in vitro(HepG2 and HCC-LM3 cells)and in vivo(primary liver cancer mice and HCC-LM3 subcutaneous tumor-bearing mice)studies revealed that Rk3 significantly inhibits the proliferation of HCC.Meanwhile,Rk3 blocked the cell cycle in HCC at the G1 phase and induced autophagy and apoptosis in HCC.Further proteomics and siRNA experiments showed that Rk3 regulates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway to inhibit HCC growth,which was validated by molecular docking and surface plasmon resonance.In conclusion,we report the discovery that ginsenoside Rk3 binds to PI3K/AKT and promotes autophagy and apoptosis in HCC.Our data strongly support the translation of ginsenoside Rk3 into novel PI3K/AKT-targeting ther-apeutics for HCC treatment with low toxic side effects.
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Early diagnosis, treatment and evaluation of therapeutic effect are important for improving prognosis of patients with pancreatic cancer. CT perfusion (CTP) have made great progresses in diagnosis, differential diagnosis of pancreatic cancer and evaluation of hemodynamic changes after treatment and efficacy with the development of technology. The progresses of application of CTP in pancreatic cancer were reviewed in this article.
ABSTRACT
Purpose To analyze the perfusion differences of different pancreatic diseases using the low-dose whole organ dynamic volume CT perfusion imaging, and to provide the evidence for the clinical application. Materials and Methods Twenty-eight patients suspected as pancreatic disease were applied by 640 layer volume CT perfusion imaging for the pancreas. Data were collected at the same time of bolus injection of contrast agent, then were analyzed by spatial alignment and perfusion calculation using the perfusion software. The time-density curve, blood perfusion flow diagram and tissue artery blood flow were obtained using the maximum slope method. Results Normal pancreatic tissue (n=9) blood flow was (117.04±12.05) ml/(min?100 ml), pancreatitis organizations (6 cases with acute pancreatitis and 3 cases with chronic pancreatitis) (118.67±37.18) ml/(min?100 ml), pancreatic carcinoma tissue (n=10) was (67.16±18.94) ml/(min?100 ml). There was significant difference among three groups (F=8.59, P0.05). The total dose of X-rays in the whole scanning process was 21.5-23.9 mSv. Conclusion Low-dose whole pancreas organ CT perfusion scan can quantitatively analyze the hemodynamic changes in pancreatic disease, which be of great value for evaluating changes in microcirculation during the treatment of pancreatic cancer.
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In order to improve tensile property of vascular scaffold, we blended silk fibroin with novel human-like collagen with the mass ratio of 9:1, 7:3 and 5:5 (W/W), and then fabricated blood vessel tubular graft by freeze-drying process. We studied microstructure, mechanical properties, elements composites, degradability and biocompatibility of vascular scaffolds. These results showed that tubular scaffold with mass ratio 7:3 exhibited interconnected porous structure with pore size at (60 +/- 5) microm and porosity of 85%; achieved the desirable mechanical property (strain of 50% +/- 5% and stress of 332 +/- 16 kPa); had relatively slow degradation rate; could enhance cell adhesion and proliferation and had superior biocompatibility.
Subject(s)
Humans , Biocompatible Materials , Chemistry , Biomechanical Phenomena , Blood Vessels , Physiology , Collagen , Chemistry , Fibroins , Chemistry , Materials Testing , Porosity , Tissue Engineering , Methods , Tissue ScaffoldsABSTRACT
Human-like collagen (HLC) was cross-linked with hyaluronic acid by genipin in different ratio. The concentrations of hyaluronic acid in the mixture were 0, 0.01%, 0.05% and 0.1%. The blood vessel tubular grafts were then fabricated by freeze-drying. Microstructure, element composite, mechanical properties, cytotoxicity grade, and biocompatibility of different vascular scaffold groups were studied by scanning electron microscope (SEM), X-ray photoelectron spectroscopy (XPS), tensile test, burst pressure experiment, cytotoxicity experiment, endothelial cells planted in blood vessel scaffolds and hypodermic embedding of mice. The results showed that HLC-HA (0.05%) tubular scaffold exhibited interconnected well-distributed and porous structure and porosity of 94.38%; achieved the desirable mechanical property with stress of (1000.8 +/- 7.9) kPa and burst pressure of (1058.6 +/- 8.2) kPa, hypocytotoxicity, favourable cytocompatibility, hisocompatibility and disposition of degradation.
Subject(s)
Animals , Humans , Mice , Adhesives , Chemistry , Biocompatible Materials , Chemistry , Biomimetic Materials , Chemistry , Blood Vessels , Physiology , Collagen , Chemistry , Hyaluronic Acid , Chemistry , Iridoid Glycosides , Iridoids , Chemistry , Materials Testing , Tissue Engineering , Methods , Tissue ScaffoldsABSTRACT
Strains from the cellulose-containing environment were collected. Primary screening(by filter-paper Hutchison solid culture medium and sodium carboxymethylcellulose solid culture medium) and reelection(by filter-paper inorganic salt culture medium and sodium carboxymethylcellulosc Congo red coltnre medium) indicated that five strains obtained were best suited for high performance cellulose degradation. Determination of sodium carboxymethylcellulose activity(CMCA) and filter paper activity(FPA) was accomplished for each of the five. The strongest of the five in CMCA and FPA was applied to the production of cellulose bioethanol by separate hydrolysis and fermentation(SHF) and simultaneous saccharification and fermentation(SSF) respectively.
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This research adopted silt as the sample,and the five highest hydrogen production performing strains contained in the sample were isolated. The strain whose hydrogen production was the highest was identified as Enterobacter cloacae by the analysis of 16S rDNA sequencing and comparison. It is showed by Plackett-Burman Experimental Design that only glucose,citric buffer and reducing agent had significant effects on hydrogen production by Enterobacter cloacae FML-C1. The path of steepest ascent was undertaken to approach the optimal response region of those three factors. Central Composite Design(CCD) and Response Surface Methodology(RSM) were employed to investigate the interaction of the variables and to ascertain the optimal values of the factors,which finally led to the maximum hydrogen production(VH2) . The theoretical optimal medium conditions were:glucose 21.5 g/L,citric buffer 13.6 mL/L,reducing agent10.0 mL/L. The five tentative tests matched this model well. The final VH2 was up to 2347.4 mL/L,which was 127.42% enhanced in comparison to the original. The result shows that PB experiment design and RSM analytical method work well in selecting factors which have significant influences on the hydrogen production and,moreover,achieve the ideal optimal result.
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To study and optimize the fermentation parameters for expressing human-like collagenⅡduring E. coli high-density fermentation. The effects of pH, temperature, dissolved oxygen and induction instant on the cell growth and human-like collagenⅡproduction were investigated to optimize the fermentation conditions. The results demonstrated that the following conditions were beneficial for cell growth and foreign gene expression, controlling pH in phase induction at 6.8 and initial pH at 6.5, maintaining fermentation temperature and dissolved oxygen concentration was controlled at 34?C and 20% respectively, and implementing induction at the later logarithmic growth phase. Under the optimized condition, the cell density and human-like collagenⅡyield could reach 88.4 g/L and 14.2 g/L, respectively.