Therapeutic effect of demethylated hydroxylated phillygenin derivative on Helicobacter pylori infection.

Modifying and transforming natural antibacterial products is a novel idea for developing new efficacious compounds. Phillygenin has an inhibitory effect on H. pylori. The aim of the present study was to prepare a phillygenin derivative (PHI-Der) through demethylation and hydroxylation. The minimum inhibitory concentration of 18 strains of H. pylori from different sources was 8-32 µg/mL in vitro, and the activity increased 2-8 times than that of phillygenin. PHI-Der could significantly inhibit the colonization of H. pylori in vivo, reduce the inflammatory response, and promote the repair of inflammatory damage. Further, we used SwissTargetPrediction to predict that its main targets are ALOX5, MCL1, and SLC6A4, and find that it can inhibit bacterial biofilm formation and reduce bacterial infection of cells. It can enhance the intracellular oxidative capacity of H. pylori to inhibit H. pylori growth. Further, it could prevent the oxidation of H. pylori-infected cells and reduce the inflammatory response, which plays a role in protection. In conclusion, compared to phillygenin, PHI-Der had better antibacterial activity and was more effective in treating H. pylori infection. It has characteristics of high safety, specificity, resistance to drug resistance and better antibacterial activity than phillygenin, it's a good antioxidant for host cells.

Phillygenin Inhibits Helicobacter pylori by Preventing Biofilm Formation and Inducing ATP Leakage.

With the widespread use and abuse of antibiotics, Helicobacter pylori (H. pylori) has become seriously drug resistant. The development of new antibiotics is an important way to solve H. pylori's drug resistance. Screening antibacterial ingredients from natural products is a convenient way to develop new antibiotics. Phillygenin, an effective antibacterial component, was selected from the natural product, forsythia, in this study. Its minimal inhibitory concentration (MIC) for 18 H. pylori strains was 16-32 µg/ml. The minimum bactericidal concentration (MBC) of H. pylori G27 was 128 µg/ml; the higher the drug concentration and the longer the time, the better the sterilization effect. It was non-toxic to gastric epithelial cell (GES)-1 and BGC823 cells at the concentration of 100 µg/ml. It presented a better antibacterial effect on H. pylori in an acidic environment, and after 24 days of induction on H. pylori with 1/4 MIC of phillygenin, no change was found in the MIC of H. pylori. In the mechanism of action, phillygenin could cause ATP leakage and inhibit the biofilm formation; the latter was associated with the regulation of spoT and Hp1174 genes. In addition, phillygenin could regulate the genes of Nhac, caggamma, MATE, MdoB, flagellinA, and lptB, leading to the weakening of H. pylori's acid resistance and virulence, the diminishing of H. pylori's capacity for drug efflux, H. pylori's DNA methylation, the initiation of human immune response, and the ATP leakage of H. pylori, thus accelerating the death of H. pylori. In conclusion, phillygenin was a main ingredient inhibiting H. pylori in Forsythia suspensa, with a good antibacterial activity, high safety, strong specificity, better antibacterial effect under acidic conditions, and low risk of resistance development by H. pylori. Its mechanism of action was mainly associated with inhibiting the biofilm formation and resulting in ATP leakage. In addition, phillygenin was shown to be able to reduce the acid resistance and virulence of H. pylori.

Early genetic diagnosis of clarithromycin resistance in Helicobacter pylori.

BACKGROUND: The drug resistance rate of clinical Helicobacter pylori (H. pylori) isolates has increased. However, the mechanism of drug resistance remains unclear. In this study, drug-resistant H. pylori strains were isolated from different areas and different populations of Chinese for genomic analysis. AIM: To investigate drug-resistant genes in H. pylori and find the genes for the early diagnosis of clarithromycin resistance. METHODS: Three drug-resistant H. pylori strains were isolated from patients with gastritis in Bama County, China. Minimal inhibitory concentrations of clarithromycin, metronidazole, and levofloxacin were determined and complete genome sequencing was performed with annotation. Hp1181 and hp1184 genes were found in these strains and then detected by reverse transcription polymerase chain reaction. The relationships between hp1181 or hp1184 and clarithromycin resistance were ascertained with gene mutant and drug-resistant strains. The homology of the strains with hp26695 was assessed through complete genome detection and identification. Differences in genome sequences, gene quantity, and gene characteristics were detected amongst the three strains. Prediction and analysis of the function of drug-resistant genes indicated that the RNA expression of hp1181 and hp1184 increased in the three strains, which was the same in the artificially induced clarithromycin-resistant bacteria. After gene knockout, the drug sensitivity of the strains was assessed. RESULTS: The strains showing a high degree of homology with hp26695, hp1181, and hp1184 genes were found in these strains; the expression of the genes hp1184 and hp1181 was associated with clarithromycin resistance. CONCLUSION: Hp1181 and hp1184 mutations may be the earliest and most persistent response to clarithromycin resistance, and they may be the potential target genes for the diagnosis, prevention, and treatment of clarithromycin resistance.

Application of traditional Chinese medicine in treatment of Helicobacter pylori infection.

Helicobacter pylori (H. pylori) has a high rate of infection and antibiotic resistance and poses a serious threat to human life. One of the main strategies to overcome drug resistance is to develop new treatment plans. Traditional Chinese medicine (TCM) that is commonly used to treat many diseases in China can reduce drug resistance and increase the eradication rate of H. pylori. In this paper, we review the research progress on TCM in the treatment of H. pylori infection. The mechanism of action of TCM is reviewed and research and applications of TCM in the treatment of H. pylori are demonstrated. Finally, we discuss problems confronting the use of TCM for the treatment of H. pylori infection and propose possible solutions. In addition, the plans of TCM in H. pylori treatment were also screened: Dampness-heat syndrome in the spleen and stomach, deficiency of spleen and stomach, and cold-heat complicated syndrome, and the effective components therein are studied. The antibacterial effect of TCM is relatively slow; for rapid improvement of the treatment effect of refractory H. pylori gastritis, we provide an appropriate treatment regime combining TCM and Western medicine with immune-regulatory and synergistic antibacterial effects.

Comparison of Standards of Intellectual Impairment in China Using ICF / 中国康复理论与实践

Objective:To compare the standards of intellectual impairment in China based on ICF to provide evidences for standardization of identification and services of intellectual impairment. Methods:The national standards of intellectual impairment or injury from Standard of Identification of Work Capacity: Identification Classification of DisabilityCaused by Work-related Injuries, Occupational Diseases and Classification of Impairment Related to Injury and China Insurance Disability Standard and Code were compared under the framework, terminology, coding and evaluation of ICF. Results:These three standards covered ICF three components, including body structure, body function, activity and participation, but not contextual factors. The terminology and coding system of China Insurance Disability Standard and Code came from ICF. However, there was no standardized terminology and coding system among sectors. The classification and evaluation for intellectual impairment were different among these three standards, that made it difficult to compare the outcome directly. Conclusion:It is proposed to adopt the ICF framework and approach to standardize the definition, terms, coding, and evaluation of intellectual impairment in disability standards in China to promote data exchange of evaluation and service among sectors.

Individualized Services and Support Plan for People with Intellectual Disability Based on ICF / 中国康复理论与实践

Objective To analyze the unmet needs of services and support, and design structured, standardrized and individualized service and support plans for people with intellectual disability using ICF framework.Methods In respective of intellectual function and adaptive behavior, a structured, standardrized and individualized service and support plan had been constructed according to process of individualized plan using ICF.Results Based on ICF model of functioning and disability, the structured and standardized service and support plan had been constructed, including functional diagnosis and service needs reporting, and individualized services protocols.Conclusion With the analysis of functioning and reporting of unmet needs of service using ICF, the structured, standardrised and individualized service and support plan can be developed to promote the total rehabilitation for people with intellectual disabilities.

[Experimental Conditions and Reliability Analysis of Results of COD components].

The present study attempts to use SF( OUR(max)/OUR(en)) instead of S(0)/X(0) as an index of optimal initial conditions for determination of COD components by means of respirometry, thereby simplifying the measuring process and the operation can be automated. Further, the ratio of COD consumed by the growth of biomass can be used for the reliability assessment of results. Experimental results show that, experimental conditions for obtaining good results as follows: (1) for samples that composed of a large amount of easily biodegradable components (e. g., synthetic wastewater made by sodium acetate), SF should be in the range of 2.8 to 5.3, and the ratio of COD consumed by growth of biomass should be less than 30%; (2) for samples that composed of both readily biodegradable and slowly biodegradable components (i. e., typical domestic wastewater), SF should be in the range of 5.8 to 6.4, and the ratio of COD consumed by growth of biomass should be less than 30%; (3) and for samples that composed of a large amount of slowly biodegradable industrial wastewater (i. e., landfill leachate), SF should be 15 or less, and the ratio of COD consumed by growth of biomass should be approximately 40%. Therefore, when respirometry is used for the determination of COD components, the optimal conditions in terms of SF increase with the complexity of carbon source.

Inhibition of Pim-1 attenuates the proliferation and migration in nasopharyngeal carcinoma cells.

OBJECTIVE: To explore the role of proto-oncogene Pim-1 in the proliferation and migration of nasopharyngeal carcinoma (NPC) cells. METHODS: Pim-1 expressions in NPC cell lines CNE1, CNE1-GL, CNE-2Z and C666-1 were examined by RT-PCR, western blotting and immunoflucesence, respectively. After CNE1, CNE1-GL and C666-1 cells were treated with different concentrations of Pim-1 special inhibitor, quercetagetin, the cell viability, colony formation rate and migration ability were analyzed. RESULTS: Pim-1 expression was negative in well-differentiated CNE1 cells, whereas expressed weakly positive in poor-differentiated CNE-2Z cells and strongly positive in undifferentiated C666-1 cells. Interestingly, CNE1-GL cells that derived from CNE1 transfected with an Epstein Barr virus latent membrane protein-1 over-expression plasmid displayed stronger expression of Pim-1. Treatment of CNE1-GL and C666-1 cells with quercetagetin significantly decreased the cell viability, colony formation rate and migration ability but not the CNE1 cells. CONCLUSIONS: These findings suggest that Pim-1 overexpression contributes to NPC proliferation and migration, and targeting Pim-1 may be a potential treatment for anti-Pim-1-expressed NPCs.