Advances in drug delivery strategies against Helicobacter pylori / 药学学报

italic>Helicobacter pylori (H. pylori) can cause a variety of digestive tract diseases, the serious may develop into gastric cancer. Nowadays, H. pylori infection rate exceeds 50%, and its eradication rate is declining due to the continuous increase of drug resistance, leading to the occurrence of plenty of stubborn infections, which seriously threaten human health. At present, it is difficult to achieve satisfactory curative effect by increasing the types of antibiotics combination or increasing their dose. In this review, the clinical treatments of H. pylori were introduced. Proceed from the characteristics and pathological background of H. pylori infection that makes H. pylori difficult to eradicate, the research advances of drug delivery strategies for improving H. pylori eradication rate were reviewed, such as strategies that could increase drug concentration in stomach (e.g. drug delivery systems with gastric acid-stabilized ability), increase drug concentration in H. pylori colonization sites (e.g. drug delivery systems with gastric retention or H. pylori targeted abilities), overcome H. pylori resistance (metal nanoparticles, anti-biofilm delivery systems), enhance host immune response (vaccine preparation) and so on. Novel drug delivery systems, such as cell membrane coating technology and phage therapy, are comparatively rare in the field of anti-H. pylori, but have broad application prospects. This review would provide reference for the development and application of therapeutic strategies to improve H. pylori eradication rate.

Lrrc34 Is Highly Expressed in SSCs and Is Necessary for SSC Expansion In Vitro / 中国医学科学杂志(英文版)

Objective To discover critical genes contributing to the stemness and maintenance of spermatogonial stem cells (SSCs) and provide new insights into the function of the leucine-rich repeat (LRR) family member Lrrc34 (leucine-rich repeat-containing 34) in SSCs from mice. Methods Bioinformatic methods, including differentially expressed gene (DEG), gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, were used to uncover latent pluripotency-related genes. Reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence analyses were utilized to verify the mRNA and protein expression levels, respectively. RNA interference of Lrrc34 using siRNA was performed to detect its transient impact on SSCs. Results Eight DEGs between ID4-EGFP+ (G) and ID4-EGFP+/TSPAN8High (TH), eight DEGs between G and ID4-EGFP+/TSPAN8Low (TL) and eleven DEGs between TH and TL were discovered, and eleven protein-protein interaction (PPI) modules were found to be significant in the PPI network of DEGs. One of the DEGs, Lrrc34, was selected as a potential pluripotency-related gene due to its differential expression among ID4-EGFP+ spermatogonia subsets and its interaction with fibroblast growth factor 2 in the fifth module. Immunofluorescence experiments exhibited specific expression of Lrrc34 in a subpopulation of undifferentiated spermatogonia marked by LIN28A, and RT-PCR experiments confirmed the high expression of Lrrc34 in SSCs from P7 and adult mice. The transient knockdown of Lrrc34 in SSCs resulted in reduced colony sizes and significant changes in the transcriptome and apoptotic pathways. Conclusion Lrrc34 is highly expressed in mouse SSCs and is required for SSC proliferation in vitro through effects on transcriptome and signaling transduction pathways.

[Laboratory design and practice for undergraduates: Using RNAi to modulate gene expression].

RNA interference is a gene silencing phenomenon mediated by short double-stranded RNAs, which has become a widely used research technology for reverse genetics. In order to make students understand the technology better, the students were required to select target genes, to design small interfering RNAs (siRNAs) and primers, and then to test the effect of gene silencing mediated by siRNAs. Taking the fifth group in 2018 as an example, Mus musculus acyl-CoA synthetase long-chain family member 1 (Acsl1) was selected as the target gene, two pairs of siRNAs targeting Acsl1 mRNA were designed and transfected into 3T3-L1 by electroporation, then the total RNAs were extracted and synthesized to cDNA, and the expression levels of mRNAs were finally tested by relative quantitative PCR. The results showed that both pairs of siRNAs had more than 60% silencing effects. In the past three years, about 83% of the students completed all the experiments successfully and screened out at least a pair of effective siRNA. This teaching practice for undergraduates enhances students' understanding of RNA interference principle and technology, and exercises students' lab experience and scientific research ability.

An in vitro method for preliminarily screening competing agents to enhance drug permeation in cyclodextrin inclusion complexes / 药学学报

Cyclodextrin can increase the solubility of poorly soluble drugs, but also decrease the permeability of poorly soluble drugs in inclusion complexes simultaneously, which partially or completely counteracts the contribution of improvement in solubility to the oral absorption of poorly soluble drugs. If a competing agent is added to the system to compete binding sites of cyclodextrins with drugs, drug permeability can be improved by increasing the concentration of free drugs in the inclusion complex system. In this paper, a rapid in vitro screening method for competing agents of cyclodextrin inclusion complex is proposed based on the principle that good drug permeability is in accord with good cell uptake. The equilibrium constants between drugs and hydroxypropyl-beta-cyclodextrin (HPCD) were determined by phase equilibrium solubility method. Cinnarizine (CN) with a high equilibrium constant was selected as a competing agent, coumarin 6 (C6) and 9-octadecyl berberine (BD) with smaller equilibrium constants were selected as model drugs. Both changes of solubility and uptake by Caco-2 and A549 cells of C6 and BD were investigated different concentrations of CN to the HPCD solution of C6 and BD. The results showed that the uptake of C6 and BD increased in a CN concentration-dependent manner, and the solubility of C6 and BD in HPCD solution decreased with the prolongation of equilibrium time. It might be due to increased free drug concentrations that resulted from the competition of CN for drug binding sites with HPCD. In our study, in vitro cell uptake method was firstly used to validate the ability of CN as a competing agent to increase drug permeability (cell uptake). This method can be used for preliminarily screening of competing agents for drug-cyclodextrin inclusion complexes.

Bacterial biofilms: characteristics and combat strategies / 药学学报

Eighty percent of bacterial infections are related to the formation of bacterial biofilm. Compared with planktonic bacteria, bacterial biofilm is 10-1 000 times more resistant to antibiotics, which is the main cause of current bacterial drug resistance. A comprehensive understanding of the characteristics and resistance mechanisms of bacteria biofilm will help us treat the stubborn infections caused by the bacterial biofilm better and solve the problem of bacterial drug resistance. In this review, the composition and quorum sensing of bacterial biofilm, two major patterns of biofilm formation and drug resistance mechanisms were presented. Furthermore, representative compounds with anti-biofilm activity and compounds synergistic with antibiotics in anti-biofilm actions were introduced. Nano drug delivery strategies used for anti-biofilm in recent years as well as a novel drug delivery system-molecularly imprinted polymer was also introduced.

Application of triple rule-out with 64-slice spiral CT in the diagnosis of acute chest pain / 中华放射学杂志

Objective To investigate the performance of triple rule-out with(M-slice spiral CT in the combined examination of pulmonary artery,thoracic aorta and coronary artery for patients with acute chest pain.Methods Seventy patients who presented with acute chest pain were included in the study.All of the patients underwent retrospective ECG-gated 64-slice computed tomography triple rule-out examination to evaluate the pulmonary arteries,thoracic aorta and coronary arteries.Multi-planar reconstruction(MPR), maximum intensity projection(MIP),curved-planar reconstruction(CPR)and volume rendering(VR) were used to display pulmonary arteries,thoracic aorta and coronary arteries.We evaluated the image quality of coronary artery and the enhancement of the pulmonary artery and thoracic aorta to estimate if the examination can fulfill the clinical demand for the differential diagnosis of acute chest pain.Results The mean scan time was(8.5?1.0)s,and the dose of contrast medium injected was 100 ml.There were 95.7%(67/70)of patients whose CT values detected in the pulmonary artery and thoracic aorta after enhancement were ≥200 HU.The image quality of 85.8%(720/839)coronary segments was classified as excellent,8.6%(72/839)as good,and 5.6%(47/839)as poor.There were 20 cases with coronary stenoses≥50%,2 cases with pulmonary embolism,and 2 cases with aortic dissection.Conclusion The triple ride-out examination with 64-slice spiral CT could depict pulmonary artery,thoracic aorta,and coronary artery in 8 s with good image quality.It has great potential in the etiological diagnosis for the patients with acute chest pain.