Cocktail hepatocarcinoma therapy by a super-assembled nano-pill targeting XPO1 and ATR synergistically / 药物分析学报

Intensive cancer treatment with drug combination is widely exploited in the clinic but suffers from inconsistent pharmacokinetics among different therapeutic agents.To overcome it,the emerging nanomedicine offers an unparalleled opportunity for encapsulating multiple drugs in a nano-carrier.Herein,a two-step super-assembled strategy was performed to unify the pharmacokinetics of a pep-tide and a small molecular compound.In this proof-of-concept study,the bioinformatics analysis firstly revealed the potential synergies towards hepatoma therapy for the associative inhibition of exportin 1(XPO1)and ataxia telangiectasia mutated-Rad3-related(ATR),and then a super-assembled nano-pill(gold nano drug carrier loaded AZD6738 and 97-110 amino acids of apoptin(AP)(AA@G))was con-structed through camouflaging AZD6738(ATR small-molecule inhibitor)-binding human serum albumin onto the AP-Au supramolecular nanoparticle.As expected,both in vitro and in vivo experiment results verified that the AA@G possessed extraordinary biocompatibility and enhanced therapeutic effect through inducing cell cycle arrest,promoting DNA damage and inhibiting DNA repair of hepatoma cell.This work not only provides a co-delivery strategy for intensive liver cancer treatment with the clinical translational potential,but develops a common approach to unify the pharmacokinetics of peptide and small-molecular compounds,thereby extending the scope of drugs for developing the advanced com-bination therapy.

Improving the freeze-drying survival rate of Lactobacillus plantarum LIP-1 by increasing biofilm formation based on adjusting the composition of buffer salts in medium.

Lactic acid bacteria can improve their resistance to adverse environments through the formation of biofilm. This study found that adding different buffer salts in culture medium had a great impact on the freeze-drying survival rate of the Lactobacillus plantarum LIP-1, which could be linked to biofilm formation. Transcriptome data showed that potassium ions in buffer salt increased the expression of the luxS gene in the LuxS/autoinducer-2 (AI-2) quorum sensing system and increase synthesis of the quorum sensing signal AI-2. The AI-2 signal molecules up-regulated the cysE gene, which helps to promote biofilm formation. By adding a biofilm inhibitor, d-galactose, and performing a real-time quantitative polymerase chain reaction experiment, we found that d-galactose could down-regulated the luxS and cysE genes, reduced biofilm formation, and decreased the freeze-drying survival rate. The results of this study showed that promoting biofilm formation using appropriate buffer salts may lead to better freeze-drying survival rates.

Effects of buffer salts on the freeze-drying survival rate of Lactobacillus plantarum LIP-1 based on transcriptome and proteome analyses.

Buffer salts are often added to culture medium to promote bacterial growth. However, we found that buffer salts can improve the freeze-drying survival rate. In this experiment, the mechanisms for the effects of different buffer salts on the survival rate of freeze-dried strains were examined. The results showed that buffer salts had important effects on the freeze-drying survival rate of L. plantarum LIP-1 that were related to changes in fatty acid composition. Different buffer salts affected the expression of fatty acid metabolic genes. A new gene cluster that regulates fatty acid metabolism and synthesis was discovered. Potassium ions in buffer salts upregulated the trkA gene and lysR-type transcription factor, and then upregulated the expression of fatty acid synthesis-related acc and fab family genes. These genes help to extend the fatty acid carbon chain and promote the unsaturated fatty acids content, which improves cell membrane fluidity and improves resistance to freeze-drying.

The CT features of gastrointestinal tract diospyrobezoar and its complications / 实用放射学杂志

Objective To explore the CT features of gastrointestinal tract diospyrobezoar and its complications,to improve the recognition. Methods The plain CT scan of 36 patients with gastrointestinal tract diospyrobezoar confirmed by gastroscope and surgery were analyzed retrospectively.Results The number and location of diospyrobezoar showed by CT were consistent with the results of gastroscope and surgery.There were 1 1 cases of stomach diospyrobezoar,1 9 cases of small intestine diospyrobezoar,and 6 cases of stomach and small intestine diospyrobezoar.32 cases were solitary lesion,and 4 cases were multiple lesions.A total of 41 diospyrobezoars were removed, most of which were wel-l defined ovoid mass.3 1 lesions presented mottled internal gas bubbles with high-density encapsulating wall.6 lesions showed mottled gas pattern without encapsulating wall.4 lesions showed uneven high density.Over time,1 lesion moved in the digestive tract and the boundary and density were changed.Complications:gastric and duodenal diospyrobezoar accompanied by gastric retention,which manifested as a significant expansion of the gastric cavity effusion.Small intestine diospyrobezoar was accompanied by small bowel obstruction,which showed that the proximal intestinal tube of the diospyrobezoar was obviously dilated,and the distal intestine was suddenly collapsed.There was a focal transition zone between them.Conclusion Gastrointestinal tract diospyrobezoar has a variety of CT manifestations,of which oval shape,clear boundary,uneven mass composed of gas and soft tissue are common.