The intestinal absorption mechanism of chicoric acid and its bioavailability improvement with chitosan.

Chicoric acid (CA), an active phenolic acid of Echinacea purpurea (Linn.) Moench, has been demonstrated to exhibit antioxidative, antiviral and immunological activities. A prior study showed that CA is a water-soluble compound with low bioavailability. The current study was performed to study the intestinal absorption mechanism of CA and improve its bioavailability using natural biodegradable chitosan. A Caco-2 monolayer cell model was established to characterise the mechanisms involved in the intestinal absorption of CA. The bioavailability improvement of CA was studied in Sprague-Dawley rats after oral (20 mg/kg) administration of 0.5% chitosan. In vitro, the results showed that the absorption transport of CA was fairly poor, with Papp values of 8.2 × 10-8 to 2.1 × 10-7 cm/s in the absorption direction and 1.5 × 10-7 to 2.6 × 10-7 cm/s in the secretory direction. The permeability was increased by EDTA and chitosan in both directions. Moreover, the transport through the intestinal monolayer was H+ dependent, and P-glycoprotein and OATP2B1 transporters were involved in the intestinal transport of CA. In vivo, the absorption of CA was increased and accelerated with chitosan in rats because the bioavailability was 1.74-fold that of the prototype drug. The above mentioned results indicated that CA was a poor absorption drug and that paracellular and carrier-mediated trancellular transport both participated in its transport route. Chitosan is an excellent absorption enhancer for CA. The transport characteristics uncovered in this study lay the groundwork for further studies directed toward the development and utilisation of its new formulations.

Wedge-shaped vertebrae is a risk factor for symptomatic upper lumbar disc herniation.

BACKGROUND: At present, much is unknown about the etiology and pathogenesis of ULDH. However, it is interesting to note that many ULDH patients have a radiographic feature of adjacent vertebral wedge deformation. The purpose of this study is to investigate the relationship between symptomatic upper lumbar disc herniation (ULDH) and wedge-shaped vertebrae (WSV). METHODS: This was a retrospective study of 65 patients with single-level ULDH, who had undergone surgery at our medical center between January 2012 and December 2016. Clinical data including clinical and radiological evaluation results were performed. RESULTS: The incidence of WSV in the ULDH group (44.6%, 29/65) was more than in the lower lumbar disc herniation group (21.5%, 14/65). And there were statistically significant differences in WSV (χ2 = 7.819, P = 0.005), wedging angle of the vertebrae (WAV) (t = 9.013, P < 0.001), and thoracolumbar kyphotic angle (TL) (t = 8.618, P < 0.001) between two groups. Based on multivariate logistic regression analysis, WAV (OR = 0.783, 95% CI = 0.687-0.893, P < 0.001) and TL (OR = 0.831, 95% CI = 0.746-0.925, P = 0.001) were independently associated with ULDH. The cutoff values of WAV and TL were 5.35° and 8.35°, which were significantly associated with ULDH (OR = 3.667, 95% CI = 1.588-8.466, P = 0.002). CONCLUSION: The WSV is an independent risk factor for ULDH. WAV > 5.35° and TL > 8.35° were the predictors for ULDH. It should be noted that the patients with vertebral wedge deformation combined with thoracolumbar kyphosis have a higher risk of ULDH.

Lack of hepatic stimulator substance expression promotes hepatocellular carcinoma metastasis partly through ERK-activated epithelial-mesenchymal transition.

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies due to its high frequency of metastasis via the epithelial-mesenchymal transition (EMT) pathway. Hepatic stimulator substance (HSS) can protect hepatocytes from injury and promote liver growth. Recent studies indicated that HSS expression is increased in HCC tissues; however, whether HSS expression is potentially associated with HCC metastasis, particularly through the EMT pathway, remains largely unknown. In this study, the relationship between HSS expression and HCC metastasis was investigated in clinical samples of HCC. Meanwhile, the regulation of HCC metastasis and EMT progression by HSS were also analyzed in both in vitro and in vivo models. The results showed that the expression of 23 kDa HSS was significantly decreased among HCC tissues with angioinvasion. A decrease in HSS predicted poor prognosis with a lower survival rate. Furthermore, the growth of xenograft tumors after inoculating MHCC97H-HSS-shRNA (HCC) cells into nude mice was notably accelerated compared to those inoculated with HSS-expressing cells. Further analysis revealed that knockdown of HSS expression in both MHCC97H and HepG2 cells could enhance the migration of these HCC cells. Concurrently, interference of HSS expression by shRNA promoted conversion of morphologically epithelial-like HCC cells into mesenchymal-like cells, together with downregulations of epithelial markers (such as E-cadherin and zonula occludens-1) and upregulation of mesenchymal-like makers (such as α-SMA, ß-catenin, and fibronectin). Furthermore, it was demonstrated that, as well as promoting EMT, HSS-shRNA induced the phosphorylation of extracellular signal-regulated kinase (ERK) and elevated the expression of the EMT-related transcription factor Snail. Specific inhibition of HSS-shRNA-induced ERK phosphorylation by PD98059 attenuated HCC cell migration in a dose-dependent manner. In conclusion, we demonstrated that downregulation of HSS expression contributes to HCC metastasis partially through the ERK-activated EMT pathway.

[Establishment of neuritis migration model induced by Slit 2N and silk fibroin mixture in the rat hippocampal neurons in vitro].

OBJECTIVE: To explore a simply feasible and affordable method to establish neuritis migration model induced by Slit 2N and silk fibroin mixture in the rat hippocampal neurons in vitro. METHODS: Neurons were derived from SD rat hippocampal tissues and cultured with a special cell culture-plate in vitro. The cultured neurons were divided into four groups, named as control group, pure silk fibroin, pure Slit 2N and Slit 2N mixture with silk fibroin (mixture group), and 50 different neurons were randomly selected in each group. Moreover, we photographed and recorded the soma coordinate and added the silk fibroin, Slit 2N and mixture to each neurite with a distance of 100 µm, except control group. Record again after 30 min. Property and positive rate of cells were identified by immunofluorescence staining. RESULTS: Neurites of the pure Slit 2N group and the mixture group became shorter, and there was no significant change in the pure silk fibroin and control groups. The results showed that the average duration and length difference before and after changed were in descending order of mixture group, Slit 2N group, silk fibroin group (P<0.05), and the silk fibroin and control groups were no significant change (P>0.05). The positive rate of MAP-2 in four groups was more than 90%. CONCLUSIONS: There were no significant effects of Silk fibroin on induced by Slit 2N in rat hippocampal neuron migration. It had an effect on reducing Slit 2N diffusion rate and extending its working time. It provides an advantageous construction method in vitro on based 3D directed neural repair for the treatment of central nervous system diseases.

Two new 13,14:14,15-disecopregnane-type compounds from the roots of Cynanchum paniculatum.

Two new 13,14:14,15-disecopregnane-type compounds glaucogenin F (1), glaucogenin F 3-O-ß-D-oleandropyranoside (2), together with three known compounds cynapanoside A (3), cynatratoside A (4), and neocynapanogenin F 3-O-ß-D-oleandropyranoside (5) were isolated from the 95% ethanol extract of the roots of Cynanchum paniculatum. The structures of new compounds were elucidated on the basis of extensive spectroscopic analyses, including 1D and 2D NMR, HRESIMS and NOESY.

Raman Spectra of Bredigite at High Temperature and High Pressure.

Bredigite was synthesized by using the Piston-Cylinder in 1.2 GPa and 1 473 K. With external heating device and diamond anvil cell, high temperature and high pressure Raman spectra of bredigite were collected at temperatures 298, 353, 463, 543, 663, 773 and 873 K and with pressure from 1 atm up to 14.36 GPa (room temperature). The SEM image showed that the sample consisted of one crystalline phase with grain size ranging from 10～20 µm. The EPMA data suggest a chemical formula of Ca7.03(2)Mg0.98(2)Si3.94(2)O16 which was identical to the theoretical component of bredigite. The Raman spectroscopic results indicate there were 29 vibration bands of bredigite at high temperature. Some bands were merging, weakening and disappearing increasingly with the temperature, which was obvious in the range of 800~1 200 cm-1. The vibration bands of 909, 927 and 950 cm-1 disappeared at 873, 773 and 873 K, respectively. The results primarily indicated that the structure of bredigite was stable under experimental condition. In addition, isobaric mode-Grüneisen parameters and isothermal mode-Grüneisen parameters were calculated, yielding 1.47(2) and 0.45(3) as their mean values, respectively. Anharmonic coefficients were estimated based on the high temperature and high pressure Raman experiments, showing that the contributions to anharmonic-effect induced with the Si­O vibration modes were smaller than other modes.

Co-culture of oligodendrocytes and neurons can be used to assess drugs for axon regeneration in the central nervous system.

We present a novel in vitro model in which to investigate the efficacy of experimental drugs for the promotion of axon regeneration in the central nervous system. We co-cultured rat hippocampal neurons and cerebral cortical oligodendrocytes, and tested the co-culture system using a Nogo-66 receptor antagonist peptide (NEP1-40), which promotes axonal growth. Primary cultured oligodendrocytes suppressed axonal growth in the rat hippocampus, but NEP1-40 stimulated axonal growth in the co-culture system. Our results confirm the validity of the neuron-oligodendrocyte co-culture system as an assay for the evaluation of drugs for axon regeneration in the central nervous system.

Interface engineering to enhance the efficiency of conventional polymer solar cells by alcohol-/water-soluble C60 materials doped with alkali carbonates.

Two new C60-based n-type materials, EGMC-OH and EGMC-COOH, functionalized with hydrophilic triethylene glycol groups (TEGs), have been synthesized and employed in conventional polymer solar cells. With the assistance of the TEG-based surfactant, EGMC-OH and EGMC-COOH can be dissolved in highly polar solvents to implement the polar/nonpolar orthogonal solvent strategy, forming an electron modification layer (EML) without eroding the underlying active layer. Multilayer conventional solar cells on the basis of ITO/PEDOT:PSS/P3HT:PC61BM/EML/Ca/Al configuration with the insertion of the EGMC-OH and EGMC-COOH EML between the active layer and the electrode have thus been successfully realized by cost-effective solution processing techniques. Moreover, the electron conductivity of the EML can be improved by incorporating alkali carbonates into the EGMC-COOH EML. Compared to the pristine device with a PCE of 3.61%, the devices modified by the Li2CO3-doped EGMC-COOH EML achieved a highest PCE of 4.29%. Furthermore, we demonstrated that the formation of the EGMC-COOH EML can be utilized as a general approach in the fabrication of highly efficient multilayer conventional devices. With the incorporation of the EGMC-COOH doped with 40 wt % Li2CO3, the PCDCTBT-C8:PC71BM-based device exhibited a superior PCE of 4.51%, which outperformed the corresponding nonmodified device with a PCE of 3.63%.