Mild Acid-Responsive "Nanoenzyme Capsule" Remodeling of the Tumor Microenvironment to Increase Tumor Penetration.

Dense extracellular matrix (ECM) severely impedes the spread of drugs in solid tumors and induces hypoxia, reducing chemotherapy efficiency. Different proteolytic enzymes, such as collagenase (Col) or bromelain, can directly attach to the surface of nanoparticles and improve their diffusion, but the method of ligation may also impair the enzymatic activity due to conformational changes or blockage of the active site. Herein, a "nanoenzyme capsule" was constructed by combining collagenase nanocapsules (Col-nc) with heavy-chain ferritin (HFn) nanocages encapsulating the chemotherapy drug doxorubicin (DOX) to enhance tumor penetration of the nanoparticles by hydrolyzing collagen from the ECM. Col-nc could protect the activity of the enzyme before reaching the site of action while being degraded under mildly acidic conditions in tumors, and the released proteolytic enzyme could digest collagen. In addition, HFn as a carrier could effectively load DOX and had a self-targeting ability, enabling the nanoparticles to internalize into cancer cells more effectively. From in vivo and in vitro studies, we found that collagen was effectively degraded by Col-nc/HFn(DOX) to increase the accumulation and penetration of nanoparticles in the solid tumor site and could alleviate hypoxia inside the tumor to enhance the antitumor effects of DOX. Therefore, the strategy of increasing nanoparticle penetration in this system is expected to provide a potential approach for the clinical treatment of solid tumors.

Differential effects of Chinese high-fat dietary habits on lipid metabolism: mechanisms and health implications.

BACKGROUND: The traditional Chinese diet blends lard with vegetable oil, keeping the fatty acid balance intake ratio of saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids at nearly 1:1:1. However, the effects of a mixture of lard and vegetable oil on lipid metabolism have never been researched. In the present study, by simulating Chinese high-fat dietary habits, we explored the effects of a mixture of lard and vegetable oil on lipid metabolism. METHODS: We randomly assigned 50 male C57BL/6 J mice to 5 groups (10 in each group) and fed them lard, sunflower oil (SFO), soybean oil (SBO), lard blended with sunflower oil (L-SFO), or lard blended with soybean oil (L-SBO) for 12 weeks. RESULTS: We found that the final body weights of mice in the lard group were significantly higher than those of mice in the SFO and SBO groups. Body fat rate and volume of fat cell of the lard group were significantly higher than those of the SFO, SBO, and L-SBO groups. Liver triglyceride level of the lard group increased significantly compared to the other groups. Although body fat rate and liver triglyceride level in the SBO and SFO groups decreased compared to those in the other groups, the high-density lipoprotein cholesterol/low-density lipoprotein cholesterol ratio were also significantly decreased in the SBO and SFO groups. CONCLUSIONS: We found that a lard diet induced accumulation of body fat, liver and serum lipids, which can increase the risk of obesity, non-alcoholic fatty acid liver disease, and atherosclerosis. The vegetable oil diet resulted in cholesterol metabolism disorders even though it did not lead to obesity. The mixed oil diet induced body fat accumulation, but did not cause lipid accumulation in the liver and serum. Thus, differential oil/fat diets have an impact on differential aspects in mouse lipid metabolism.

The complete chloroplast genome of Codonopsis tsinglingensis (Campanulaceae), an endemic Chinese medicine species in Qinling mountains.

Codonopsis tsinglingensis, belonging to the Campanulaceae family, is a perennial medicinal herb highly valued in Chinese traditional medicine. The complete chloroplast genome of C. tsinglingensis was sequenced using the Illumina Hiseq 4000 platform. The size of the C. tsinglingensis chloroplast genome is 170,253 bp, with an average GC content of 38.3%. This circular molecule has a typical quadripartite structure containing a large single copy (LSC) region of 85,408 bp, a small single copy (SSC) region of 8179 bp, and two inverted (IRs) repeat regions of 38,333 bp. The genome contains 138 genes, including 92 protein-coding genes, 38 transfer RNA genes (tRNA), 8 ribosomal RNA genes (rRNA). Phylogenetic analysis based on complete chloroplast genome sequences of 14 species indicates that C. tsinglingensisis closely related to Codonopsis minima in the Campanulaceae family.

Characterization of the complete chloroplast genome of sunflower family species Aster Flaccidus (Compositae).

Aster flaccidus is a perennial medicinal plant belong the sunflower family Compositae, which is widely distributed in China and some other Asian countries. The complete chloroplast genome sequence of A. flaccidus was sequenced using the Illumina Hiseq 4000 platform. The size of the A. flaccidus chloroplast genome is 151,329 bp, with an average GC content of 37.5%. This circular molecule has a typical quadripartite structure containing a large single copy (LSC) region of 83,480 bp, a small single copy (SSC) region of 18,149 bp, and two inverted (IRs) repeat regions of 24,850 bp. A total of 132 genes were successfully annotated containing 87 protein-coding genes, 37 tRNA genes, 8 rRNA genes. A maximum likelihood (ML) phylogenetic tree supported that the chloroplast genome of A. flaccidus is closely related to that of Aster indicus.

Anti-obesity effect of a traditional Chinese dietary habit-blending lard with vegetable oil while cooking.

Obesity, which is associated with dietary habits, has become a global social problem and causes many metabolic diseases. In China, both percentages of adult obesity and overweight are far lower compared to western countries. It was designed to increase the two levels of daily intake in human, namely 3.8% and 6.5%, which are recommendatory intake (25 g/d) and Chinese citizens' practical intake (41.4 g/d), respectively. The mice were respectively fed with feeds added with soybean oil, lard or the oil blended by both for 12 weeks. In the mice fed with diet containing 3.8% of the three oils or 6.5% blended oil, their body weight, body fat rate, cross-sectional area of adipocytes, adipogenesis and lipogenesis in adipose were decreased, whereas hydrolysis of triglyserides in adipose was increased. This study demonstrated that the oil mixture containing lard and soybean oil had a remarkable anti-obesity effect. It suggests that the traditional Chinese dietary habits using oils blended with lard and soybean oil, might be one of the factors of lower percentages of overweight and obesity in China, and that the increasing of dietary oil intake and the changing of its component resulted in the increasing of obesity rate in China over the past decades.

Rapid and sensitive detection of point mutation by DNA ligase-based electrochemiluminescence assay.

The identification of single-base mutations in particular genes plays an increasingly important role in medical diagnosis and prognosis of genetic-based diseases. Here we report a new method for the analysis of point mutations in genomic DNA through the integration of allele-specific oligonucleotide ligation assay (OLA) with magnetic beads-based electrochemiluminescence (ECL) detection scheme. In this assay, the tris(bipyridine) ruthenium (TBR) labeled probe and the biotinylated probe are designed to perfectly complementary to the mutant target; thus a ligation can be generated between those two probes by Taq DNA Ligase in the presence of mutant target. If there is an allele mismatch, the ligation does not take place. The ligation products are then captured onto streptavidin-coated paramagnetic beads, and detected by measuring the ECL signal of the TBR label. Results showed that the new method held a low detection limit down to 10 fmol and was successfully applied in the identification of point mutations from ASTC-alpha-1 cell line, PANC-1 cell line and blood cell in codon 273 of TP53 oncogene. In summary, this method provides a sensitive, cost-effective and easy operation approach for point mutation detection.