Bldesin,the first functionally characterized pathogenic fungus defensin with Kv1.3 channel and chymotrypsin inhibitory activities

Fungus defensin is a kind of important natural peptide resource, such as plectasin from the soil fungus Pseudoplectania nigrella with potential application in the antimicrobial peptide lead drug discovery. Here, a fungus defensin named Bldesin with Kv1.3 channel and serine protease inhibitory activities was first explored. By GST‐Bldesin fusion expression and enterokinase cleaving strategy, recombinant Bldesin was obtained successfully. Antimicrobial assays showed that Bldesin had potent activity against Gram‐positive Staphylococcus aureus, but had no effect on Gram‐negative Escherichia coli. Electrophysiological experiments showed that Bldesin had Kv1.3 channel inhibitory activity. Serine protease inhibitory associated experiments showed that Bldesin had unique chymotrypsin protease inhibitory, elastase protease inhibitory, and serine protease‐associated coagulation inhibitory activities. To the best of our knowledge, Bldesin is the first functionally characterized pathogenic fungus defensin with Kv1.3 channel and chymotrypsin inhibitory activities and highlighted novel pharmacological effects of fungus‐derived defensin peptides.     

From Bench to Humans: Formulation Development of a Poorly Water Soluble Drug to Mitigate Food Effect

This study presents a formulation approach that was shown to mitigate the dramatic food effect observed for a BCS Class II drug. In vitro (dissolution), in vivo (dog), and in silico (GastroPlus®) models were developed to understand the food effect and design strategies to mitigate it. The results showed that such models can be used successfully to mimic the clinically observed food effect. GastroPlus® modeling showed that food effect was primarily due to the extensive solubilization of the drug into the dietary lipid content of the meal. Several formulations were screened for dissolution rate using the biorelevant dissolution tests. Surfactant type and binder amount were found to play a significant role in the dissolution rate of the tablet prototypes that were manufactured using a high-shear wet granulation process. The performance of the lead prototypes (exhibiting best in vitro dissolution performance) was tested in dogs and human subjects. A new formulation approach, where vitamin E TPGS was included in the tablet formulation, was found to mitigate the food effect in humans.     

Isolation and characterization of culturable halophilic microorganisms of salt ponds in Lianyungang,China

The Lianyungang salt ponds are an extreme saline environment, and their microbial communities have not been characterized. A typical extreme halophilic archaeon strain designated as HBCC-2 (GenBank accession number: EF687739) was isolated from the salt ponds of Lianyungang in Jiangsu Province, P. R. China, using conventional microbial culture methods. The other halotolerant bacterial strain designated as HBCC-3 (GenBank accession number: EU377478) was isolated from the same sampling sites. The morphological and physiological characteristics of HBCC-2 and HBCC-3 were observed and examined. G+C content of HBCC-2 and HBCC-3 were determined using high-performance liquid chromatography. The cellular phospholipid fatty acids were analyzed using gas chromatography-mass spectrometry. The 16S rRNA gene sequences of the strains HBCC-2 and HBCC-3 were amplified by PCR using archaeal primers and bacterial primers, respectively. Homology of 16S rRNA gene sequences of the strains HBCC-2 and HBCC-3 were compared with the other similar sequences obtained from GenBank using the BLAST program. Phylogenetic analysis was performed using the software MEGA 4.0 after multiple alignments of sequence data using software CLUSTALW 1.8. The evolutional distances (by Kimura’s model) were calculated and the clusters were performed with the neighbor-joining method. The results showed that the 16S rRNA gene sequences of the strains HBCC-2 and HBCC-3 are related to the genera Halorubrum and Alkalibacillus, respectively. Two phylogenetic trees were constructed by phylogenetic analysis based on the 16S rRNA gene sequence. Based on the above results, the strains HBCC-2 and HBCC-3 were finally identified. The discovery of the two species provides an opportunity to further study these halophilic microorganisms in the Lianyungang salt ponds.     

High Soil Available Phosphorus Favors Carbon Metabolism in Cotton Leaves in Pot Trials

Journal of Plant Growth Regulation - Phosphorus (P) is an essential macronutrient for plant growth and its metabolism. Because reproductive growth could be influenced by carbon metabolism of the...