Grape seed procyanidin B2 promotes the autophagy and apoptosis in colorectal cancer cells via regulating PI3K/Akt signaling pathway.

Aim: Colorectal cancer (CRC) is a major malignancy in China, which is the critical risk of people health. Many natural herbs extracts have been found to exhibit good therapeutic effect on CRC. Our previous study found that grape seed procyanidins B2 (PB2) would induce CRC cell death. However, the molecular mechanism underlying its anti-tumor effect on CRC remains unclear. Thereby, this study aimed to investigate the anti-tumor mechanism of PB2 on CRC. Methods: CCK-8, western blotting, flow cytometry, qRT-PCR and animal study were used in the current study. Results: The in vitro and in vivo data demonstrated that PB2 could promote the apoptosis of CRC cells in a dose-dependent manner, which was significantly reversed by caspase 3 inhibitor. Meanwhile, PB2 dose-dependently induced autophagy in CRC cells, which was markedly attenuated by autophagy inhibitor 3-MA. In addition, PB2 dose-dependently inhibited the expressions of p-PI3K, p-Akt and p-mTOR in the cells. Conclusion: PB2 dose-dependently induced apoptosis and autophagy in CRC cells via downregulation of PI3K/Akt pathway. This study provided the experimental basis for further development of PB2 as a new effective anticancer drug for the patients with CRC.

Inhibition of CCL19 benefits non­alcoholic fatty liver disease by inhibiting TLR4/NF­κB­p65 signaling.

Non­alcoholic fatty liver disease (NAFLD), which affects approximately one­third of the general population, has become a global health problem. Thus, more effective treatments for NAFLD are urgently required. In the present study, high levels of C­C motif ligand 19 (CCL19), signaling pathways such as Toll­like receptor 4 (TLR4)/nuclear factor­κB (NF­κB), and proinflammatory factors including interleukin­6 (IL­6) and tumor necrosis factor­α (TNF­α) were detected in NAFLD patients, thereby indicating that there may be an association between CCL19 and these factors in NAFLD progression. Using a high­fat diet (HFD), the present study generated a Sprague­Dawley rat model of NAFLD, which displayed dyslipidemia with increased levels of plasma aspartate aminotransferase, alanine aminotransferase, total cholesterol and triglyceride. Dyslipidemia, liver histopathology and gene expression analyses indicated that the NAFLD model was successfully induced by HFD, and metformin and berberine (BBR) were effective treatments for NAFLD. HFD­induced CCL19 levels and associated factors were markedly reduced by the two drug treatments. In addition, metformin or BBR alone significantly promoted adenosine monophosphate­activated protein kinase (AMPK) phosphorylation, which was inhibited by HFD. These results demonstrated that metformin and BBR could improve NAFLD, which may be via the activation of AMPK signaling, and the high expression of CCL19 in NAFLD was significantly reduced by metformin and BBR. It could be inferred that inhibition of CCL19 may be an effective treatment for NAFLD.

Radix Cyathula officinalis Kuan inhibits arterial remodeling in spontaneously hypertensive rats.

There is still no resolution for arterial remodeling related with hypertension, though hypertension treatment has access to a number of pharmacological agents. The present study aimed at investigating the prevention of Cyathula officinalis Kuan's roots (C. officinalis Kuan) against in arterial remodeling in vitro. Spontaneously hypertensive rats (SHRs) were intragastrically administered 3, 6 or 12 g/kg C. officinalis Kuan or normal saline or enalapril (2.5 mg/kg) once a day for 8 weeks. Hematoxylin and eosin were used to measure blood pressure and stain carotid and arota. The serum concentration of nitric oxide (NO) was measured by NO assay kit (nitrate reductase method). The endothelin-1 transcriptional level, endothelial NO synthase of endothelium as well as angiotensin II receptor type 1 (AT1R) of aorta and carotid was tested by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and the protein level in aorta was also measured by western blotting. The blood pressure in SHR+enalapril, SHR+3 g/kg, SHR+6 g/kg and SHR+12 g/kg C. officinalis Kuan groups was significantly decreased at 4, 6 and 8 weeks post-treatment compared with SHR group. Different doses of C. officinalis Kuan and enalapril treatment showed aortic wall thinness and strengthened NO serum level, but made no impact on the transcriptional level of AT1R in aorta or endothelial NO synthase in carotid. It is suggested by such results that therapy by C. officinalis Kuan is able to fight against arterial remodeling, thus may provide a new means to treat arterial remodeling caused by hypertension.

Supramolecular chirality of amphiphilic block copolymer films made through two steps: self-assembling first, and then solution coating.

Supramolecular chirality is achieved in amphiphilic block copolymer films made through two-step fabrication: self-assembling first and then solution coating. The amphiphilic block copolymer is composed of poly(N-isopropyl acrylamide) (pNIPAM) as hydrophilic segments and poly(methyl methacrylate) with chiral side groups as hydrophobic segments. The films fabricated by two steps show sensible circular dichroism (CD) signals around a wavelength of 200 nm. However, CD signals cannot be detected from films made by directly coating the solution of copolymers on the quartz surface. The CD signal at about 200 nm is from supramolecular arrangement of benzene units connected to the chiral group in the hydrophobic segment. This result is thought to be originated from the aggregation of the copolymer during the first step of the film forming process, and the corresponding investigation into factors affecting this process has been performed in this work. It is also found that the films fabricated by two steps can adsorb chiral small molecules enantioselectively, while the films obtained by coating the solution of copolymers directly have no such enatioselective adsorption ability.

Enantioselective assembly of amphipathic chiral polymer and racemic chiral small molecules during preparation of micro-scale polymer vesicles.

Enantioselective assembly is observed during preparation of vesicles from a solution mixture of an amphipathic block copolymer bearing pendent chiral L- or D-phenylalanine groups in hydrophobic segments and racemic chiral small molecules. Primary experimental results reveal that racemic chiral small molecules have been enantioselectively encapsulated into the hydrophobic shells of assembled vesicles with homochiral bilayer membrane structure, showing reverse CD signals compared with the original vesicles. A further study shows that the enantiomeric excess obtained through the enantioselective assembly is directly dependent on the molecular weight of the hydrophobic chiral chain segments, implying both the hydrophobic interaction and chirality are key points during the assembly of vesicles. Other factors, such as hydrogen-bonding interactions and π-π stacking interaction, are also found to be responsible for the enantioselective assembly phenomenon during the formation of the vesicles.

[Eco-physiological responses and related adjustment mechanisms of Artemisia ordosica and Caragana korshinskii under different configuration modes to precipitation variation].

This paper studied the community characteristics of two sand-fixing plants (Artemisia ordosica and Caragana korshinskii) under different configuration modes (1 m x 1 m and 2 m x 2 m) in the Shapotou region of Northwest China as well as the water relation, gas exchange, and their adjustment mechanisms of the plants under natural and artificial precipitation conditions. With the variation of soil water content, the physiological water consumption and growth characteristics of A. ordosica differed from those of C. korshinskii. A. ordosica presented obvious fluctuation in the stomatal conductance, water potential, transpiration rate, photosynthetic rate, and rapid growth, and had higher water consumption than C. korshinskii. However, the variations of the above-mentioned indices of C. korshinskii were relatively slow and more constant. The C. korshinskii had a lower photosynthetic rate but a very high accumulated biomass over years than A. ordosica. The response procedures and adjustment mechanisms of the two plants under water stress differed, with a water-conserving mechanism for A. ordosica and a water-saving mechanism for C. korshinskii. In extremely drought years, the C. korshinskii had stronger capabilities of water-saving and stress tolerance than A. ordosica. It was suggested that the selection of sand-fixing plants should have a view to the benefits in water saving and sand fixation, and also, to the stability of sand-fixing forest.