Effect of Azelaic Acid on Psoriasis Progression Investigated Based on Phosphatidylinositol 3-Kinase (PI3K)/Protein Kinase B (AKT) Signaling Pathway.

Objective: To probe into the effect of azelaic acid on psoriasis based on the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Methods: Psoriasis gene expression data were downloaded from the GEO database for differential expression analysis to identify differentially expressed genes (DEGs). KEGG and GSEA analyses were performed to identify important signaling pathways that may be involved in psoriasis progression for subsequent validation. Thirty-six C57BL/6 mice aged 8 weeks old were randomly assigned into the blank control group (n = 9), negative control group (n = 9), psoriasis model group (n = 9), and azelaic acid treat group (n = 9). Mice models of psoriasis were prepared with imiquimod (IMQ) in the latter two groups, and azelaic acid ointment was applied in azelaic acid treat group. Then, hematoxylin-eosin (HE) staining was carried out to detect the effect of azelaic acid on the pathological damage of mice models of psoriasis in each group. HaCaT cells cultured in vitro were divided into blank control group, negative control group (addition of azelaic acid), IL-17 group (20 ng/mL) and IL-17+azelaic acid group, with 3 replicates for each group. Immunofluorescence assay and Western blotting were used to detect the protein expression of PI3K/AKT signaling pathway related molecules. Results: KEGG analysis showed that DEGs were significantly enriched in PI3K-AKT signaling pathway. GSEA analysis showed that PI3K and MTOR signaling pathways were up-regulated in psoriasis, while AUTOPHAGY signaling pathway was down-regulated. HE staining showed that azelaic acid could significantly inhibit the local skin injury in mice caused by IMQ-induced psoriasis. Moreover, azelaic acid can inhibit the expression of PI3K/AKT signaling pathway related proteins phosphorylated (p)-PI3K, p-AKT, p-mammalian target of rapamycin (mTOR), vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), angiogenin-1 and hypoxia-inducible factor-1α (HIF-1α). These results imply that azelaic acid may inhibit the activation of PI3K/AKT signaling pathway and angiogenesis, thereby improving the symptoms of psoriasis. Conclusion: Azelaic acid may inhibit the activation of PI3K/AKT signaling pathway and angiogenesis, thereby improving the symptoms of psoriasis.

Draft Genome Sequence of NRRL 5109, an Ex-Type Isolate of Aspergillus neoellipticus.

We report here a draft genome sequence of an ex-type strain of Aspergillus neoellipticus, NRRL 5109, which was isolated from pus of a case of chronic emphysema. The final assembly consists of 160 scaffolds totaling 27.55 Mbp (G+C content, 49.96%) and 8,858 predicted genes.

Metabolic Phenotype Characterization of Botrytis cinerea, the Causal Agent of Gray Mold.

Botrytis cinerea, which causes gray mold, is an important pathogen in four important economic crops, tomato, tobacco, cucumber and strawberry, in China and worldwide. Metabolic phenomics data on B. cinerea isolates from these four crops were characterized and compared for 950 phenotypes with a BIOLOG Phenotype MicroArray (PM). The results showed that the metabolic fingerprints of the four B. cinerea isolates were similar to each other with minimal differences. B. cinerea isolates all metabolized more than 17% of the tested carbon sources, 63% of the amino acid nitrogen substrates, 80% of the peptide nitrogen substrates, 93% of the phosphorus substrates, and 97% of the sulfur substrates. Carbon substrates of organic acids and carbohydrates, and nitrogen substrates of amino acids and peptides were the significant utilization patterns for B. cinerea. Each B. cinerea isolate contained 94 biosynthetic pathways. These isolates showed a large range of adaptabilities and were still able to metabolize substrates in the presence of the osmolytes, including up to 6% potassium chloride, 10% sodium chloride, 5% sodium sulfate, 6% sodium formate, 20% ethylene glycol, and 3% urea. These isolates all showed active metabolism in environments with pH values from 3.5 to 8.5 and exhibited decarboxylase activities. These characterizations provide a theoretical basis for the study of B. cinerea in biochemistry and metabolic phenomics and provide valuable clues to finding potential new ways to manage gray mold.

Metabolic activities of five botryticides against Botrytis cinerea examined using the Biolog FF MicroPlate.

Tobacco grey mold caused by Botrytis cinerea is an important fungal disease worldwide. Boscalid, carbendazim, iprodione, pyrimethanil and propiconazole are representative botryticides for grey mold management. This research investigated the sensitivities of B. cinerea from tobacco to these chemicals using the Biolog FF Microplate. All five chemicals showed inhibitory activity, with average EC50 values of 0.94, 0.05, 0.50, 0.61 and 0.31 µg ml(-1), respectively. B. cinerea metabolized 96.8% of tested carbon sources, including 29 effectively and 33 moderately, but the metabolic fingerprints differed under pressures imposed by these botryticides. For boscalid, B. cinerea was unable to metabolize many substrates related to tricarboxylic acid cycle. For carbendazim, carbon sources related to glycolysis were not metabolized. For iprodione, use of most carbon substrates was weakly inhibited, and the metabolic profile was similar to that of the control. For propiconazole, no carbon substrates were metabolized and the physiological and biochemical functions of the pathogen were totally inhibited. These findings provide useful information on metabolic activities of these botryticides, and may lead to future applications of the Biolog FF Microplate for examining metabolic effects of other fungicides on other fungi, as well as providing a metabolic fingerprint of B. cinerea that could be useful for identification.