Amphiphilic brush polymers produced using the RAFT polymerisation method stabilise and reduce the cell cytotoxicity of lipid lyotropic liquid crystalline nanoparticles.

Self-assembled lipid lyotropic liquid crystalline nanoparticles such as hexosomes and cubosomes contain internal anisotropic and isotropic nanostructures, respectively. Despite the remarkable potential of such nanoparticles in various biomedical applications, the stabilisers used in formulating the nanoparticles are often limited to commercially available polymers such as the Pluronic block copolymers. This study explored the potential of using Reversible Addition-Fragmentation chain Transfer (RAFT) technology to design amphiphilic brush-type polymers for the purpose of stabilising phytantriol and monoolein-based lipid dispersions. The synthesised brush-type polymers consisted of a hydrophobic C12 short chain and a hydrophilic poly(ethylene glycol)methyl ether acrylate (PEGA) long chain with multiple 9-unit poly(ethylene oxide) (PEO) brushes with various molecular weights. It was observed that increasing the PEO brush density and thus the length of the hydrophilic component improved the stabilisation effectiveness for phytantriol and monoolein-based cubosomes. Synchrotron small-angle X-ray scattering (SAXS) experiments confirmed that the RAFT polymer-stabilised cubosomes had an internal double-diamond cubic phase with tunable water channel sizes. These properties were dependent on the molecular weight of the polymers, which were considered in some cases to be anisotropically distributed within the cubosomes. The in vitro toxicity of the cubosomes was assessed by cell viability of two human adenocarcinoma cell lines and haemolytic activities to mouse erythrocytes. The results showed that phytantriol cubosomes stabilised by the RAFT polymers were less toxic compared to their Pluronic F127-stabilised analogues. This study provides valuable insight into designing non-linear amphiphilic polymers for the effective stabilisation and cellular toxicity improvement of self-assembled lipid lyotropic liquid crystalline nanoparticles.

miR-149 reverses cisplatin resistance of gastric cancer SGC7901/DDP cells by targeting FoxM1.

Drug resistance remains a major unresolved obstacle for gastric cancer (GC) treatment. Recently, increasing studies have showen that microRNAs (miRNAs) are involved in cancer chemotherapeutic resistance and can potentially be applied to reverse drug resistance in cancers. The relationship between miRNA-149 expression and cisplatin (DDP) resistance in GC cells is still unknown. Here, we detected miR-149 expression by using RT-PCR and found that expression of miR-149 was downregulated in SGC7901/DDP cells compared with SGC7901cells, indicating a role of miR-149 in determining cisplatin-resistance of GC cells. Then, SGC7901/DDP cells were tansfected with miR-149 mimics, MTT assay was performed to determine SGC7901/DDP cell viability, and showed that overexpression of miR-149 inhibited the cell viability after cisplatin treatment, suggesting that up-regulation of miR-149 enhanced SGC7901/DDP cell sensitivity to cisplatin. Furthermore, we confirmed that Forkhead box M1 (FoxM1) is a direct target of miR-149 in SGC7901/DDP cells by using luciferase reporter assay. Besides, we also demonstrated that miR-149 enhances SGC7901/DDP cell sensitivity to cisplatin by downregulating FoxM1 expression. In summary, our data provide new insights that miR-149 plays an important role in determining sensitivity of cisplatin-resistant GC cells by targeting FoxM1 and suggest that miR-149 could be a potential target for reversing drug resistance in GC.

Recurrent PROC and novel PROS1 mutations in Vietnamese patients diagnosed with idiopathic deep venous thrombosis.

INTRODUCTION: Genetic mutations of PROC and PROS1 are well-known risk factors for deep venous thrombosis (DVT) in the Asian population. However, the genetic profile of Vietnamese patients with DVT remains elusive. This study aimed to investigate the spectrum of genetic mutations of these two genes in Vietnamese patients diagnosed with idiopathic DVT. MATERIALS AND METHODS: A total of 50 Vietnamese patients diagnosed with idiopathic DVT were recruited in this study. The entire coding regions of the protein C and protein S genes were amplified and directly sequenced to determine genetic alterations. RESULTS: Four and six genetic mutations were detected in protein C and protein S genes, respectively, in 24 Vietnamese DVT patients. PROC c.565C > T (p.R189W) was the most common mutation found in 13 out of 50 patients, while the mutations of PROS1 comprised three missense and three nonsense variants which diffuse along the gene. CONCLUSIONS: This study shows that mutations of protein C and protein S genes are prevalent in Vietnamese patients diagnosed with idiopathic DVT, and PROC c.565C > T (p.R189W) was the most common genetic alteration.

Long non-coding RNA MIAT promotes gastric cancer proliferation and metastasis via modulating the miR-331-3p/RAB5B pathway.

Gastric cancer (GC) remains a threat to the health of the global population. The present study investigated the effects and mechanisms of the long non-coding RNA myocardial infarction associated transcript (MIAT) on the proliferation, apoptosis and metastasis of GC (HGC-27 and AGS) cells. The expression levels of MIAT, micoRNA (miR)-331-3p and RAB5B mRNA were analyzed using reverse transcription-quantitative PCR analysis. Cell growth, apoptosis, migration and invasion were measured using 5-ethynyl-2'-deoxyuridine, flow cytometry, wound healing and Transwell assays, respectively. A luciferase assay was used to determine whether miR-331-3p targeted MIAT and RAB5B. The results indicated that MIAT levels were significantly upregulated in GC tissues and cells, correlated with RAB5B levels and inversely associated with miR-331-3p levels. MIAT overexpression promoted proliferation and metastasis, and inhibited the apoptosis of GC cells. MIAT knockdown had the opposite effect on GC cells. The rescue experiments revealed that the effects of MIAT knockdown on the biological behaviour of GC cells were attenuated by RAB5B overexpression. These data suggest that MIAT promotes GC progression via modulating miR-331-3p/RAB5B pathway.

α-Glucosidase inhibitors from the leaves of Embelia ribes.

A novel and rare 1,4-dehydrated ceramide, embelamide (1), and a new C-glycoalkaloid which is based on a ß-carboline ring system, 1-(2'-deoxy-α-d-ribopyranosyl)-ß-carboline (4), were isolated from the CHCl3 soluble fraction of the leaves of Embelia ribes (Myrsinaceae), together with thirteen known compounds (2-3, 5-15). Their structures were elucidated on the basis of spectroscopic data. Compounds 1, and 5-12 possessed significant α-glucosidase inhibitory activity in a concentration-dependent manner, and showed more potent inhibitory activity, with IC50 values ranging from 1.3 to 155.0 µM, than that of a positive control acarbose (IC50, 214.5 µM).

Preparation and helical folding of aromatic polyamides.

Long aromatic polyamide chains are prepared from the corresponding monomers. The resultant polymer adopts a hollow helical conformation that is stabilized by intramolecular H-bonding interaction between side chains.