Comparative analysis of the gut microbiota of wild adult rats from nine district areas in Hainan, China.

BACKGROUND: Wild rats have the potential to hold zoonotic infectious agents that can spread to humans and cause disease. AIM: To better understand the composition of gut bacterial communities in rats is essential for preventing and treating such diseases. As a tropical island located in the south of China, Hainan province has abundant rat species. Here, we examined the gut bacterial composition in wild adult rats from Hainan province. METHODS: Fresh fecal samples were collected from 162 wild adult rats, including three species (Rattus norvegicus, Leopoldamys edwardsi, and Rattus losea), from nine regions of Hainan province between 2017-2018. RESULTS: We analyzed the composition of gut microbiota using the 16S rRNA gene amplicon sequencing. We identified 4903 bacterial operational taxonomic units (30 phyla, 175 families, and 498 genera), which vary between samples of different rat species in various habitats at various times of the year. In general, Firmicutes were the most abundant phyla, followed by Bacteroidetes (15.55%), Proteobacteria (6.13%), and Actinobacteria (4.02%). The genus Lactobacillus (20.08%), unidentified_Clostridiales (5.16%), Romboutsia (4.33%), unidentified_Ruminococcaceae (3.83%), Bacteroides (3.66%), Helicobacter (2.40%) and Streptococcus (2.37%) were dominant. CONCLUSION: The composition and abundance of the gut microbial communities varied between rat species and locations. This work provides fundamental information to identify microbial communities useful for disease control in Hainan province.

Effect of CUL4A on the metastatic potential of lung adenocarcinoma to the bone.

Cullin 4A (CUL4A) is a member of the cullin family of proteins and has been demonstrated to be abnormally expressed in various types of malignancies. However, the function of CUL4A in metastasis of lung adenocarcinoma to the bone has rarely been reported. The aim of present of the study was to explore the biological functions and potential underlying molecular mechanisms of CUL4A in lung adenocarcinoma, highlighting a novel therapeutic target for the diagnosis and treatment of patients with lung adenocarcinoma. A549­CUL4A, H1299­CUL4A and H460­shCUL4A cells were created using lentiviral infection. The efficiency of knockdown or overexpression was assessed using reverse transcription­quantitative PCR and western blotting. The effects of CUL4A on proliferation, migration and invasion of lung adenocarcinoma cells in vitro and metastasis to the bone in vivo were determined using an MTT assay, colony formation assay, wound­healing assay, Transwell assay and a mouse model of bone metastasis. The relationship between CUL4A and the EMT­activator zinc finger E­box binding homeobox 1 (ZEB1) were detected by western blotting. The results showed that overexpression of CUL4A in lung adenocarcinoma cells increased proliferation, migration and invasion, and increased metastasis of A549 to the bones in vivo. Silencing of CUL4A expression in lung adenocarcinoma cells reduced proliferation, migration and invasion in vitro. Mechanistically, CUL4A transcriptionally upregulated expression of ZEB1 which resulted in epithelial­mesenchymal transition, which in turn promoted metastasis of lung adenocarcinoma to the bones. Taken together, these results suggest that CUL4A may serve an important regulatory role in the development of metastasis of lung adenocarcinoma to the bone.

Computed Tomography Imaging-Guided Tandem Catalysis-Enhanced Photodynamic Therapy with Gold Nanoparticle Functional Covalent Organic Polymers.

Tandem catalysis from hydrogen peroxide (H2O2) to oxygen (O2) and then to singlet oxygen (1O2) is a convenient way to overcome the hypoxic environment of the tumor for efficient cancer therapy. In this work, meso-tetrakis(4-carboxyl)-21H,23H-porphine (TCPP) and ß-cyclodextrin (ß-CD) functional gold nanoparticles (CD-AuNPs) are integrated together with a brushy covalent organic polymer (COP-8) to form COP@Au@TCPP nanocomposites. The brushy red emissive COP-8 was prepared with 9,9-dioctyl-2,7-diaminofluorene and 2,4,6-triformylphloroglucinol through a simple Schiff base reaction and acts as a sensor to monitor the material transfer and location in tumor cells. The n-octyl groups on the surface of COP-8 act as hooks to load CD-AuNPs via hydrophobic interaction, while the ß-CD improves the biocompatibility of the whole COP@Au@TCPP. The COP@Au@TCPP nanocomposites aggregate efficiently in the tumor site through enhanced permeability and retention effect. The CD-AuNPs act as catalyzers to decompose H2O2 into O2 in tumor cells. Then, TCPPs on COP@Au@TCPP sensitize O2 to form 1O2 under 655 nm radiation for efficient photodynamic therapy (PDT). In combination with the X-ray computed tomography (CT) imaging capacity of CD-AuNPs, the CT-imaging-guided PDT system was successfully prepared. The imaging information, in turn, shows the tandem catalysis PDT efficiency of the COP@Au@TCPP. This work paves the way for the preparation of an imaging-guided therapy system with COP as a matrix to ingrate various biocompatibility components.

Targeted imaging and targeted therapy of breast cancer cells via fluorescent double template-imprinted polymer coated silicon nanoparticles by an epitope approach.

Targeting is vital for precise positioning and efficient therapy, and integrated platforms for diagnosis and therapy have attracted more and more attention. Herein, we established dual-template molecularly imprinted polymer (MIP) coated fluorescent silicon nanoparticles (Si NPs) by using the linear peptide of the extracellular region of human epidermal growth factor receptor-2 (HER2) and adopting doxorubicin (DOX) as templates for targeted imaging and targeted therapy. Benefiting from the epitope imprinting approach, the imprinted sites generated by peptides on the MIP surface can be employed for recognizing the corresponding protein, which allowed the MIP to specifically and actively target HER2-positive breast cancer cells. Because of its ability to identify breast cancer cells, the MIP was applied for targeted fluorescence imaging by taking advantage of the excellent fluorescence properties of Si NPs, and the DOX-loaded MIP (MIP@DOX) can act as a therapeutic probe to effectively target and kill breast cancer cells. In fluorescence images, the targeting of the MIP promoted more uptake of the nanoparticles by cells than the non-imprinted polymer (NIP), so HER2-positive breast cancer cells incubated with the MIP exhibited stronger fluorescence, and there was no significant difference in fluorescence when HER2-negative cells and normal cells were respectively hatched with the MIP and NIP. Importantly, the cell viability was evaluated to demonstrate targeted accumulation and therapy of MIP@DOX for breast cancer cells. The nanoplatform for diagnosis and therapy combined the high sensitivity of fluorescence with the high selectivity of the molecular imprinting technique, which holds vital potential in targeted imaging and targeted therapy in vitro.

GSH-activated MRI-guided enhanced photodynamic- and chemo-combination therapy with a MnO2-coated porphyrin metal organic framework.

Glutathione (GSH) in tumors consumes 1O2 and seriously inhibits the PDT effect. MnO2-coated porphyrin metal-organic frameworks are developed to realize the oxidation of GSH by MnO2 for enhanced PDT, activated MR imaging, and controllable release of DOX as magnetic resonance imaging guided drug-PDT dual-therapy.

The role of GDF15 in bone metastasis of lung adenocarcinoma cells.

Lung cancer is the most common malignant tumor in China. It often metastasizes to bone, thereby significantly shortening the lives of patients, and reducing their quality of life. However, the efficacy of treatment for bone metastasis of lung cancer at this stage is very limited. The development and clinical application of molecular­targeted drugs for the effective targeted therapy of bone metastasis of lung cancer are urgently required. The growth differentiation factor 15 (GDF15) gene which may be associated with bone metastasis of lung cancer, was screened out by whole­genome sequencing. In the present study, we used a recombinant GDF15 lentivirus technique to upregulate the expression of GDF15 in lung adenocarcinoma A549 cells, and the results revealed that GDF15 could inhibit the proliferation, migration and invasion, while promoting apoptosis of A549 cells. In addition, GDF15 significantly decreased the number and sites of lung metastases and bone metastases in vivo compared to the control group. Finally, it was revealed that Smad2 and phospho­Smad2 protein expression was lower in the GDF15­overexpressing A549 cells. This result indicated that the tumor suppressive effect of GDF15 may be related to the TGF­ß/Smad signaling pathway, although more studies are still required for confirmation. In summary, GDF15 inhibited the growth and bone metastasis of lung adenocarcinoma A549 cells, and this effect may be achieved through the TGF­ß/Smad signaling pathway.

Glycerophosphate-based chitosan thermosensitive hydrogels and their biomedical applications.

Chitosan is non-toxic, biocompatible and biodegradable polysaccharide composed of glucosamine and derived by deacetylation of chitin. Chitosan thermosensitive hydrogel has been developed to form a gel in situ, precluding the need for surgical implantation. In this review, the recent advances in chitosan thermosensitive hydrogels based on different glycerophosphate are summarized. The hydrogel is prepared with chitosan and ß-glycerophosphate or αß-glycerophosphate which is liquid at room temperature and transits into gel as temperature increases. The gelation mechanism may involve multiple interactions between chitosan, glycerophosphate, and water. The solution behavior, rheological and physicochemical properties, and gelation process of the hydrogel are affected not only by the molecule weight, deacetylation degree, and concentration of chitosan, but also by the kind and concentration of glycerophosphate. The properties and the three-dimensional networks of the hydrogel offer them wide applications in biomedical field including local drug delivery and tissue engineering.

Astin B, a cyclic pentapeptide from Aster tataricus, induces apoptosis and autophagy in human hepatic L-02 cells.

Astins (including astin B) are a class of halogenated cyclic pentapeptides isolated from the medicinal herb of Aster tataricus. However, our previous works showed that the herbal medicine was hepatotoxic in vivo, and a toxicity-guided isolation method led to the identification of a cyclopeptide astin B. Astin B is structurally similar to cyclochlorotine, a well-known hepatotoxic mycotoxin. Thus, the aim of this study was to determine the potential cytotoxic effects and the underlying mechanism of astin B on human normal liver L-02 cells. We found that astin B has hepatotoxic effects in vitro and in vivo and that hepatic injury was primarily mediated by apoptosis in a mitochondria/caspase-dependent manner. Astin B provoked oxidative stress-associated inflammation in hepatocytes as evidenced by increased levels of reactive oxygen species (ROS), reduced contents of intracellular glutathione (GSH), and enhanced phosphorylation of c-Jun N-terminal kinase (JNK). Furthermore, the mitochondria-dependent apoptosis was evidenced by the depolarization of the mitochondrial membrane potential, the release of cytochrome c into cytosol, the increased ratio of Bax/Bcl-2, and the increased activities of caspases-9 and -3. Interestingly, astin B treatment also induces autophagy in L-02 cells, characterized by acidic-vesicle fluorescence, increased LC3-II and decreased p62 expression. Autophagy is a protective mechanism that is used to protect cells from apoptosis. The presence of autophagy is further supported by the increased cytotoxicity and the enhanced cleaved caspase-3 after co-treatment of cells with an autophagy inhibitor, also by increased LC3-II and decreased p62 after co-treatment with a caspase inhibitor. Taken together, astin B, most likely together with other members of astins, is the substance that is primarily responsible for the hepatotoxicity of A.tataricus.

[Effects of aquatic plants during their decay and decomposition on water quality].

Taking 6 aquatic plant species as test objects, a 64-day decomposition experiment was conducted to study the temporal variation patterns of nutrient concentration in water body during the process of the aquatic plant decomposition. There existed greater differences in the decomposition rates between the 6 species. Floating-leaved plants had the highest decomposition rate, followed by submerged plants, and emerged plants. The effects of the aquatic plant species during their decomposition on water quality differed, which was related to the plant biomass density. During the decomposition of Phragmites australis, water body had the lowest concentrations of chemical oxygen demand, total nitrogen, and total phosphorus. In the late decomposition period of Zizania latifolia, the concentrations of water body chemical oxygen demand and total nitrogen increased, resulting in the deterioration of water quality. In the decomposition processes of Nymphoides peltatum and Nelumbo nucifera, the concentrations of water body chemical oxygen demand and total nitrogen were higher than those during the decomposition of other test plants. In contrast, during the decomposition of Potamogeton crispus and Myriophyllum verticillatum, water body had the highest concentrations of ammonium, nitrate, and total phosphorus. For a given plant species, the main water quality indices had the similar variation trends under different biomass densities. It was suggested that the existence of moderate plant residues could effectively promote the nitrogen and phosphorus cycles in water body, reduce its nitrate concentration to some extent, and decrease the water body nitrogen load.

Antidiabetic effect of oleanolic acid: a promising use of a traditional pharmacological agent.

Diabetes mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia. Although the clear mechanisms of DM and insulin resistance are still to be cleared, it has been well documented that reactive oxygen species (ROS) play a pivotal role in DM and multiple types of insulin resistance. For the past few years, natural substances have been shown to have the potential to treatment DM. Attention has been especially focused on plants rich in triterpenoids, which generally show antioxidant and antiglycation effect. In our previous studies, it was shown that oleanolic acid (OA), a natural triterpenoid and an aglycone of many saponins, is a potent antioxidant acting as not only a free radical-scavenger through direct chemical reactions but also as a biological molecule, which may enhance the antioxidant defenses. The present study aimed to investigate the potential antidiabetic effect of OA. Oleanolic acid showed a significant blood glucose-lowering and weight-losing effect in diabetic animals induced by streptozotocin (STZ). In the insulin resistant model, it was also shown that OA may promote insulin signal transduction and inhibit oxidative stress-induced hepatic insulin resistance and gluconeogenesis, in which process the phosphorylation of ERK and the protective effect on mitochondrial function may be involved. These findings may significantly better the understanding of the pharmacological actions of OA and advance therapeutic approaches to DM.