Engineering the Vasculature of Stem-Cell-Derived Liver Organoids.

The vasculature of stem-cell-derived liver organoids can be engineered using methods that recapitulate embryonic liver development. Hepatic organoids with a vascular network offer great application prospects for drug screening, disease modeling, and therapeutics. However, the application of stem cell-derived organoids is hindered by insufficient vascularization and maturation. Here, we review different theories about the origin of hepatic cells and the morphogenesis of hepatic vessels to provide potential approaches for organoid generation. We also review the main protocols for generating vascularized liver organoids from stem cells and consider their potential and limitations in the generation of vascularized liver organoids.

Salvianolic Acids: Potential Source of Natural Drugs for the Treatment of Fibrosis Disease and Cancer.

Salvianolic acids, the most effective and abundant compounds extracted from Salvia miltiorrhiza (Danshen), are well known for its good anti-oxidative activity. Danshen has been extensively used as a traditional medicine to treat cardiovascular-related diseases in China and other Asian countries for hundreds of years. Recently, more and more studies have demonstrated that salvianolic acids also have a good effect on the alleviation of fibrosis disease and the treatment of cancer. In vivo and in vitro experiments have demonstrated that salvianolic acids can modulate signal transduction within fibroblasts and cancer cells. It is discovered that the cancer treatment of salvianolic acids is not only because salvianolic acids promote the apoptosis of cancer cells, but also due to the inhibition of cancer-associated epithelial-mesenchymal transition processes. In this article, we review a variety of studies focusing on the comprehensive roles of salvianolic acids in the treatment of fibrosis disease and cancer. These perspectives on the therapeutic potential of salvianolic acids highlight the importance of these compounds, which could be the novel and attractive drugs for fibrosis disease and cancer.

Bioengineered 3D Scaffolds in Cancer Research: Focus on Epithelial to Mesenchymal Transition and Drug Screening.

BACKGROUND: The living environment of cancer cells is complicated and information-rich. Thus, traditional 2D culture mold in vitro cannot mimic the microenvironment of cancer cells exactly. Currently, bioengineered 3D scaffolds have been developed which can better simulate the microenvironment of tumors and fill the gap between 2D culture and clinical application. CONCLUSION: In this review, we discuss the scaffold materials used for fabrication techniques, biological behaviors of cancer cells in 3D scaffolds and the scaffold-based drug screening. A major emphasis is placed on the description of scaffold-based epithelial to mesenchymal transition and drug screening in 3D culture. By overcoming the defects of traditional 2D culture, 3D scaffolds culture can provide a simpler, safer and more reliable approach for cancer research.

Fabrication of selenium-deposited and chitosan-coated titania nanotubes with anticancer and antibacterial properties.

To exploit titanium materials with anticancer and antibacterial properties, TiO(2) nanotubes arrays as nanoreservoirs for deposition of selenium were generated onto titanium substrates and then covered with chitosan layer. The deposition of selenium in TiO(2) nanotubes was performed with electrodeposition. The physical properties (surface morphologies, chemical compositions and wettability) of the substrates were characterized by field-emission scanning electron microscopy (FE-SEM) equipped with energy dispersive X-ray spectroscopy (EDS) and contact angle measurement, respectively. The growth behaviors of both healthy osteoblasts and cancerous osteoblasts on the substrates were investigated in vitro. The selenium-deposited and chitosan-coated TiO(2) nanotubes substrates (TiO(2) nanotubes-Se-Chi) demonstrated great potential for promoting the proliferation of healthy osteoblasts and inhibiting the growth of cancerous osteoblasts. Meanwhile, the TiO(2) nanotubes-Se-Chi substrates displayed a sustained release of selenium for 21 days. The antibacterial properties of the prepared substrates were evaluated with Escherichia coli (E. coli). The result showed that TiO(2) nanotubes-Se-Chi substrates had long term antibacterial capacity. The approach in this study provides an alternative to fabricate anticancer and antibacterial titanium-based implants for potential clinical application.

[A new progress of cancer therapy: irreversible electrical breakdown of pulse therapy].

Depending on the specified electric field parameters such as electrical field strength and duration, electrical pulses have generally been applied in biomedical fields. Conventional electroporation is commonly used for cell fusion, transfection, electrochemotherapy and so on. Recently, pulse electric fields with high strength (MV/cm) and duration of several tens of nanoseconds can affect intracellular signal transduction and intracellular structures with plasma intact, owing to the application of intracellular manipulation. Most researches indicate that parameters between those two ranges could be used to result in an inreversible apoptosis of cancer cells. The procedure between electroporation and intracellular manipulation is irreversible electrical breakdown (IREB). IREB selectively kills tumor cells by inducing cell apoptosis; thus it might provide a new method for cancer therapy.

Apoptosis induction with electric pulses - a new approach to cancer therapy with drug free.

Electrical pulses have been widely used in biomedical fields, whose applications depend on the parameters such as durations and electric intensity. Conventional electroporation (0.1-1kV/cm, 100micros) has been used in cell fusion, transfection and electrochemotherapy. Recent studies with high-intensity (MV/cm) electric field applications with durations of several tens of nanoseconds can affect intracellular signal transduction and intracellular structures with plasma intact, resulting in an application of intracellular manipulation. The most recent development is the finding that parameters between those two ranges could be used to induce apoptosis of cancer cells. Proposal of apoptosis induction and tumor inhibition has advantages to pursue the treatment of cancer free of cytotoxic drugs.

Pharmacokinetic properties of S-adenosylmethionine after oral and intravenous administration of its tosylate disulfate salt: a multiple-dose, open-label, parallel-group study in healthy Chinese volunteers.

BACKGROUND: S-adenosylmethionine (SAMe) is an endogenous molecule that plays an important role in cellular metabolism. Despite being widely used as a dietary supplement with claimed benefits for numerous conditions, there is little information about the pharmacokinetic properties of exogenous SAMe. OBJECTIVES: One aim of this study was to characterize the pharmacokinetic properties of SAMe after administration of single and multiple doses of orally and intravenously administered SAMe tosylate disulfate (STD) in healthy male and female Chinese volunteers. Because men have higher erythrocyte levels of endogenous SAMe than do women, we also assessed the effects of sex on the disposition of SAMe. METHODS: A simple and sensitive assay for SAMe based on liquid chromatography-mass spectrometry using selected-ion monitoring of analyte and acyclovir as internal standard was developed and validated. The assay was used to study the pharmacokinetic properties of SAMe. STD was administered as single and multiple doses of enteric-coated tablets and IV infusion of STD to groups of healthy native Chinese volunteers. After an overnight fast, male and female Chinese volunteers were assigned to receive STD 1000 mg for 5 days, either in enteric-coated tablet formulation or as a 250-mL IV infusion. Blood samples were collected 24 hours after the first and last dose and used for determining plasma SAMe concentrations and pharmacokinetic parameters. For the oral formulation, SAMe concentrations were corrected for concentrations of endogenous SAMe. Pharmacokinetic parameters were calculated for men and women separately and for the total group of volunteers. Adverse events were monitored using a physician during blood collection and by spontaneous reporting. RESULTS: Twenty healthy volunteers were enrolled (oral formulation: 5 men, 5 women; mean [SD] age, 24.1 [4.7] years [range, 21-37 years]; mean [SD] weight, 59.9 [4.8] kg [range, 54-70 kg]; IV formulation: 5 men, 5 women; mean [SD] age, 22.6 [1.8] years [range, 21-27 years]; mean [SD] weight, 59.5 [5.4] kg [range, 53-67 kg]). None of the between-sex differences in SAMe pharmacokinetic properties were significant. The (mean [SD]) pharmacokinetic properties of singledose oral SAMe in men and women, respectively, were as follows: C(max), 2.37 (1.58) and 2.50 (1.83) micromol/L; T(max), 5.40 (1.14) and 5.20 (1.48) hours; AUC(0-24), 8.56 (5.16) and 10.3 (8.0) micromol/L/h; and t(1/2beta), 6.06 (1.80) and 6.28 (2.60) hours. Corresponding values with the single-dose IV formulation were: C(max), 127 (49) and 211 (94) micromol/L; T(max), 1.90 (0.22) and 1.60 (0.22) hours; AUC(0-24), 329 (84) and 480 (176) micromol/L/h; and t(1/2beta), 4.34 (0.57) and 3.83 (0.78) hours. The single-dose oral:IV ratios of AUC(0-24) in men and women, respectively, were 2.60% and 2.14% (degrees of fluctuation: 4.96 [1.77] and 9.49 [0.91]). The pharmacokinetic properties of multiple-dose oral and IV SAMe were not significantly different from those with single-dose administration. None of the volunteers reported any adverse events during the study. CONCLUSIONS: In this small study in healthy Chinese volunteers, there were no significant differences in the pharmacokinetic parameters of SAMe between men and women or between single- and multiple-dose administration of STD 1000 mg administered orally or intravenously. No evidence of accumulation of SAMe in plasma was found on multiple dosing. Both enteric-coated tablets and the IV infusion were well tolerated in these volunteers.