Anticancer Effect of Active Component of Astragalus Membranaceus Combined with Olaparib on Ovarian Cancer Predicted by Network-Based Pharmacology.

In China, a traditional Chinese medicine formulation called astragalus membranaceus (AM) has been utilised for more than 20 years to treat tumors with extraordinary effectiveness. The fundamental mechanisms, nevertheless, are still not well understood. The aim of this study is identifying its possible therapeutic targets and to evaluate the effects of AM in combination with a PARP inhibitor (olaparib) in the treatment of BRCA wild-type ovarian cancer. Significant genes were collected from Therapeutic Target Database and Database of Gene-Disease Associations. The components of AM were analyzed using the Traditional Chinese Medicine System Pharmacology (TCMSP) database to screen the active ingredients of AM based on their oral bioavailability and drug similarity index. In order to find intersection targets, Venn diagrams and STRING website diagrams were employed. STRING was also used to create a protein-protein interaction network. In order to create the ingredient-target network, Cytoscape 3.8.0 was used. DAVID database was utilized to carry out enrichment and pathway analyses. The binding ability of the active compounds of AM to the core targets of AM-OC was verified with molecular docking using AutoDock software. Experimental validations, including cell scratch, cell transwell, cloning experiment, were conducted to verify the effects of AM on OC cells. A total of 14 active ingredients of AM and 28 AM-OC-related targets were screened by network pharmacology analysis. The ten most significant Gene Ontology (GO) biological function analyses, as well as the 20 foremost Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathways were selected. Moreover, molecular docking results showed that bioactive compound (quercetin) demonstrated a good binding ability with tumor protein p53 (TP53), MYC, vascular endothelial growth factor A (VEGFA), phosphatase and tensin homolog (PTEN), AKT serine/threonine kinase 1 (AKT1) and cyclin D1 (CCND1) oncogenes. According to experimental methods, in vitro OC cell proliferation and migration appeared to be inhibited by quercetin, which also increased apoptosis. In addition, the combination with olaparib further enhanced the effect of quercetin on OC. Based on network pharmacology, molecular docking, and experimental validation, the combination of PARP inhibitor and quercetin enhanced the anti-proliferative activity in BRCA wild-type ovarian cancer cells, which supplies the theoretical groundwork for additional pharmacological investigation.

Comparison of fecal microbiota of SPF and non-SPF Beagle dogs.

Microbial colonization of animal intestine impacts host metabolism and immunity. The study was aimed to investigate the diversity of the intestinal microflora in specific pathogen free (SPF) and non-SPF Beagle dogs of different ages by direct sequencing analysis of the 16S rRNA gene. Stool samples were collected from four non-SPF and four SPF healthy Beagle dogs. From a total of 792 analyzed Operation taxonomic units, four predominant bacterial phyla were identified: Firmicutes (75.23%), Actinobacteria (10.98%), Bacteroidetes (9.33%), and Proteobacteria (4.13%). At the genus level, Streptococcus, Lactobacillus, and Bifidobacterium were dominated. Among which, Alloprevotella, Prevotella_9, and Faecalibacterium were presented exclusively in non-SPF beagles, with potentially anti-inflammatory capability, which could protect non-SPF beagles from complex microbial environment. The number and diversity of intestinal flora for non-SPF Beagle dogs were the highest at birth and gradually decreased with growth, whereas the results for the SPF beagle samples were the opposite, with the number and diversity of intestinal microbiota gradually increases as beagles grow. In a nutshell, the microbial complexity of the rearing environment can enrich the gut microbiota of beagles, many of which are anti-inflammatory microbiota with the potential to increase the adaptability of the animal to the environment. However, the gut microbiota of SPF beagles was more sensitive to environmental changes than that of non-SPF beagles. This study is of great significance for understanding the bionomics of intestinal microflora in non-SPF and SPF beagles, improving the experimental accuracy in scientific research.

Towards two-dimensional color tunability of all-solid-state electrochromic devices using carbon dots.

Electrochromic devices (ECDs) that display multicolor patterns have gradually attracted widespread attention. Considering the complexity in the integration of various electrochromic materials and multi-electrode configurations, the design of multicolor patterned ECDs based on simple approaches is still a big challenge. Herein, it is demonstrated vivid ECDs with broadened color hues via introducing carbon dots (CDs) into the ion electrolyte layer. Benefiting from the synergistic effect of electrodes and electrolytes, the resultant ECDs presented a rich color change. Significantly, the fabricated ECDs can still maintain a stable and reversible color change even in high temperature environments where operating temperatures are constantly changing from RT to 70°C. These findings represent a novel strategy for fabricating multicolor electrochromic displays and are expected to advance the development of intelligent and portable electronics.

Golgi-localized calcium/manganese transporters FgGdt1 and FgPmr1 regulate fungal development and virulence by maintaining Ca2+ and Mn2+ homeostasis in Fusarium graminearum.

Calcium and manganese transporters play important roles in regulating Ca2+ and Mn2+ homeostasis in cells, which is necessary for the normal physiological activities of eukaryotes. Gdt1 and Pmr1 function as calcium/manganese transporters in the Golgi apparatus. However, the functions of Gdt1 and Pmr1 have not been previously characterized in the plant pathogenic fungus Fusarium graminearum. Here, we identified and characterized the biological functions of FgGdt1 and FgPmr1 in F. graminearum. Our study shows that FgGdt1 and FgPmr1 are both localized to the cis- and medial-Golgi. Disruption of FgGdt1 or FgPmr1 in F. graminearum caused serious defects in vegetative growth, conidiation, sexual development and significantly decreased virulence in wheat but increased deoxynivalenol (DON) production. Importantly, FgGdt1 is involved in Ca2+ and Mn2+ homeostasis and the severe phenotypic defects of the ΔFggdt1 mutant were largely due to loss of FgGdt1 function in Mn2+ transportation. FgGdt1-mCherry colocalizes with FgPmr1-GFP at the Golgi, and FgGDT1 exerts its biological function upstream of FgPMR1. Taken together, our results collectively demonstrate that the cis- and medial-Golgi-localized proteins FgGdt1 and FgPmr1 regulate Ca2+ and Mn2+ homeostasis of the Golgi apparatus, and this function is important in modulating the growth, development, DON biosynthesis and pathogenicity of F. graminearum.

Sorting nexin (MoVps17) is required for fungal development and plant infection by regulating endosome dynamics in the rice blast fungus.

Vps17 is a sorting nexin (SNX) and a component of the retromer, a protein complex mediating retrograde vesicle transport between endosomes and the trans-Golgi network. However, its role in the development and pathogenicity of filamentous fungi such as the rice blast fungus (Magnaporthe oryzae) remains unclear. We investigate the functional relationship between the SNX and the cargo-selective complex (CSC) of the fungal retromer by genetic analysis, live cell imaging and immunological assay. Our data show that the MoVps17 null mutation causes defects in growth, development and pathogenicity in M. oryzae. MoVps17 is localized to endosomes depending on the activity of phosphatidylinositol 3-kinase (PI3K), a key enzyme for fungal development and infection. Both PX and BAR domains of MoVps17 are essential for its endosomal localization and function. Furthermore, our yeast two-hybrid assays show that MoVps17 and MoVps5 can interact. Lastly, live cell imaging suggests that MoVps17 can regulate early endosome fusion and budding as well as endocytosis. Taken together, our results suggest that MoVps17 specifically functions as a retromer component with CSC and also plays a distinct role in the regulation of endosome dynamics during fungal development and plant infection.

Effects of polysaccharide on chicks co-infected with Bordetella avium and Avian leukosis virus.

Chicks' co-infection with immunosuppressive virus and bacteria seriously threaten the development of the poultry industry. In this study, a model was established in which chicks were injected with either subgroup B ALV (ALV-B)+Bordetella avium (B. avium), or ALV-B+B. avium+Taishan Pinus massoniana pollen polysaccharide (TPPPS), or B. avium only, or B. avium+TPPPS. The data showed that the group injected with ALV-B and B. avium exhibited significant inhibition of the immune function and therefore increased pathogenicity compared with the group injected with B. avium-only. Application of TPPPS effectively alleviated immunosuppression, and body weights increased sharply in the TPPPS groups compared with non-TPPPS groups. To some extent, TPPPS may reduce the proliferation of ALV-B. These results suggest that Pinus pollen polysaccharides are beneficial treating co-infections with immunosuppressive virus and bacteria and therefore have potential for development into safe and effective immunoregulator.

Immunoregulatory effects of Taishan Pinus massoniana pollen polysaccharide on chicks co-infected with avian leukosis virus and Bordetella avium early in ovo.

In recent years, co-infection of chicken embryos with immunosuppressive viruses and bacteria occurs with an annually increasing frequency. Consequently, studies on new and safe immunoregulators, especially plant polysaccharides, have become a popular topic in the poultry industry. In the present study, we selected 300 specific pathogen free embryonated eggs, which were injected with subgroup B avian leukosis virus (ALV-B) and Bordetella avium (B. avium) to establish an artificial co-infection model. The chicks that hatched from these co-infected embryonated eggs were treated with Taishan Pinus massoniana pollen polysaccharide (TPPPS). Results indicated that relevant indices in the co-infection group were significantly lower than that in B. avium-only group. Furthermore, pathogenicity of B. avium was exacerbated, with the chicks exhibiting decreased body weights. The TPPPS groups exhibited gradual improvements in immune function and developmental status. Therefore, in terms of improving immunologic function and production performance, TPPPS could be used as immunoregulator for immune responses.

Positive inductive effect of swine interleukin-4 on immune responses elicited by modified live porcine reproductive and respiratory syndrome virus (PRRSV) vaccine.

Porcine reproductive and respiratory syndrome (PRRS) has become one of the most economically important diseases to the global pork industry. Currently, the efficacies of available commercial vaccines remain questionable: the modified live-PRRSV vaccines (MLVs) were generally effective but variable in sufficient protection, and the outcomes of inactivated-PRRSV vaccines (IVs) in the field were not very promising. In the present study, we investigated the effect of swine interleukin 4 (IL-4) on the development of virus-specific immune responses elicited by an MLV. The antibody titer against PRRSV membrane proteins in pigs elicited by MLV plus recombinant plasmid encoding IL-4 (group 3) was significantly higher than those elicited by MLV alone (group 1) and MLV plus empty plasmid (group 2) from 35 days post-inoculation (dpi). Similarly, the neutralizing efficacy of sera from group 3 was markedly enhanced compared with group 1 and group 2. In cellular immunity, the ratio of CD3⁺CD4⁺/CD3⁺CD8⁺ T lymphocyte subpopulations from group 3 monitored by flow cytometry (FCM) was significantly higher than those from group 1 and group 2 from 42 dpi to 21 days post-challenge (dpc). After viral challenge, pigs in group 3 showed significantly lower virus loads in peripheral blood measured by a real-time quantitative PCR (RT-qPCR), as compared with those in group 1 and group 2. Pigs in group 1 and group 2 had a low fever and displayed mild inappetence, lethargy, rough hair coats, and no lung lesions, while those in group 3 showed almost no clinical signs, no lung lesions. The scores of clinical signs of pigs in group 3 were significantly lower than those in both group 1 and group 2. Interestingly, the scores of lung lesions showed no significant differences among the three groups. Our results indicate that swine IL-4 markedly enhanced the protective immune response of pigs and improved the efficacy of the MLV in preventing PRRS disease.