Evaluation of the key active ingredients of 'Radix Astragali and Rehmanniae Radix Mixture' and related signaling pathways involved in ameliorating diabetic foot ulcers from the perspective of TCM-related theories.

BACKGROUND AND OBJECTIVE: Traditional Chinese Medicine is more inclined to holistic thinking than most modern pharmacological research. The multiple components and targets of traditional Chinese medicine have become a stumbling block in the study of drug action mechanisms in the life sciences. The current study aimed to reveal the active ingredients of "Radix Astragali and Rehmanniae Radix Mixture (RA-RRM)" involved in ameliorating diabetic foot ulcers and to analyze the related signaling pathways. METHOD: The Traditional Chinese Medicine Systems Pharmacology Data base and Analysis Platform (TCMSP) was used to screen the active ingredients in RA-RRM based on the evaluation of the molecular weight (MW), bioavailability (OB), and transport of these active ingredients across intestinal epithelial cells (Caco-2) and the blood-brain barrier (BBB). The PubChem database was used to illustrate the structural formula and SMILES of these active ingredients in RA-RRM. The Swiss Target Prediction Database, DrugBank, Genecards, and CTD were used to predict the targets that were correlated with RA-RRM-based treatment of diabetic foot ulcers. Cytoscape 3.7.0 software was used to construct the protein/gene interaction network diagram, compound target interaction network diagram, and target pathway network diagram for these active ingredients in the amelioration of diabetic foot ulcers in RA-RRM. Topological parameter calculations of target information using Cytoscape 3.7.0 software yielded drug-disease targets were used to reveal the relationship between key active ingredients in RA-RMM and targets of interest for the treatment of diabetic foot. The disease targets of drug action were imported into the David database (GO and KEGG analysis) to analyze the enriched pathways and biological processes. RESULTS: The following results were obtained using the abovementioned screening and analysis. Fourteen key active ingredients in RA-RRM and 309 targets were found; among them, 85 targets were found to be related to diabetic foot ulcers using TCMSP. Twenty-three biological processes, 7 cell components and 14 molecular functions were found to ameliorate diabetic foot ulcers using GO analysis. In addition, 29 signaling pathways were found to be involved in RA-RRM-induced amelioration, including the NF-κB, TNF, TGF-ß, VEGF, and HIF-1 signaling pathways, using KEGG analysis. CONCLUSIONS: Based on current available evidence obtained from the abovementioned data/information databases and based on the perspective of TCM-related theories, the present study revealed the key active ingredients in RA-RRM and related signaling pathways in the treatment of diabetic foot ulcers, promoting further studies on and clinical applications of RA-RRM.

The global prevalence ptxP3 lineage of Bordetella pertussis was rare in young children with the co-purified aPV vaccination: a 5 years retrospective study.

BACKGROUND: The global prevalent ptxP3 strains varies from about 10% to about 50% of circulating B. pertussis population in different areas of China. METHODS: To investigate the difference of vaccination status between different genotypes in the circulating B. pertussis after 10 years of acellular pertussis vaccine (aPV) used in China. The nasopharyngeal swabs and isolates of B. pertussis from these patients were used to perform genotyping of antigen genes. We use antibiotic susceptibility test against erythromycin and sequencing methods for site 2047 of 23S rRNA to determine the resistance status. RESULTS: The ptxP1 allele with erythromycin resistant (ER) B. pertussis infection (total of 449 subjects) consisted of 84.70 to 96.70% from 2012 to 2016 in this study. Vaccinated with co-purified aPV was found in 133(133/403,33.0%), 1(1/9,11.1%) and 2(2/21,9.5%) in ptxP1/fhaB3-ER, ptxP1/fhaB2-ES and ptxP3/fhaB2-ES B. pertussis infected children each, which showed a significant difference (χ2 = 6.87, P = 0.032). CONCLUSIONS: The ptxP3-ES B. pertussis was rare while the ptxP1-ER B. pertussis was steadily increased in Xi'an, China from 2012 to 2016, where co-purified aPV was prevalent used. This pose a hypothesis that the co-purified aPV might protect against ptxP3 strains more efficient, which generated a rare chance for ptxP3 strains to be under the antibiotic pressure and further developed to be erythromycin resistance. A further cohort study and the mechanisms of the additional antigen proteins of co-purified aPV protected against B. pertussis should be consideration.

Cross reactivity of Neisseria meningitidis crgA diagnostic PCR primers with nontypeable haemophilus influenzae.

BACKGROUND: CrgA based PCR are usually used for diagnosis of Neisseria meningitidis while the crgA gene was observed in the genomes of Haemophilus influenzae. In this study, we aimed to evaluate whether the crgA primers routinely used in the diagnosis of N. meningitidis could cross react with H. influenzae isolates. METHODS: A diagnostic test study analysis of sixty-two H. influenzae isolates from oropharyngeal swabs of healthy individuals aged 9 to 11 years between 2011 and 2012, using commonly used crgA primers for diagnostic analysis of N. meningitidis. RESULTS: It revealed that 19.3% nontypable H. influenzae isolates were positive for the crgA gene. All the biotype IV H. influenzae isolates were crgA PCR positive. CONCLUSIONS: Our study has shown a significant finding of crgA gene especially in bitotype IV nontypable H. influenzae by N. meningitidis crgA diagnostic PCR primers. It is necessary to further evaluate the prevalence of the crgA gene in more non-typable H. influenzae strains, particularly invasive strains.

High-fluence low-power laser irradiation promotes odontogenesis and inflammation resolution in periodontitis by enhancing stem cell proliferation and differentiation.

Periodontitis can exert a severe impact on the life of patients, and the use of stem cell therapy for this disease is promising. The inflammatory response consequent to periodontitis can promote stem cell proliferation. Activated inflammation triggers inhibitory cytokine secretion, thus reducing inflammation subsequent to stem cell activation. High­fluence low­power laser irradiation (HF­LPLI) has the ability to regulate stem cell function through its effect on inflammation. Thus, the aim of the present study was to examine whether HF­LPLI is able to activate stem cells to promote regeneration in periodontitis by promoting inflammation resolution, as well as to evaluate the underlying mechanism of action if an effect is observed. Stem cells were treated with HF­LPLI following inflammation activation. Reverse transcription­quantitative polymerase chain reaction and EdU assay were used to evaluate cell proliferation and differentiation. Flow cytometry and immunofluorescence were also used to detect the ability of HF­LPLI to regulate the surrounding inflammatory environment. Animal models of periodontal disease were treated with stem cells and HF­LPLI, and regeneration was detected by hematoxylin and eosin staining and in vivo imaging. It was observed that HF­LPLI promoted inflammation resolution by reducing the excessive inflammatory response, and finally stimulated stem cell proliferation and differentiation. Furthermore, in vivo results revealed that stem cells treated with HF­LPLI induced bone regeneration. HF­LPLI stimulated stem cell proliferation and differentiation by promoting inflammation resolution subsequent to stem cell activation, providing a new strategy for the clinical treatment of periodontitis.

Comparison of long-term immunogenicity (23 years) of 10 µg and 20 µg doses of hepatitis B vaccine in healthy children.

To compare the long-term immunogenicity and seroprotection rates in healthy children following 23 years of vaccination with 10 µg or 20 µg doses of plasma-derived hepatitis B vaccine, we revisited all participants from our previous randomized controlled trial. At year 23, 81 participants were tested for HBV serological markers and HBV-DNA, and a booster dose was given to those with anti-HBs titer < 10 mIU/mL. After eliminating the interference of a Year 11 booster dose and vaccines received outside of the trial, around 50% of participants still maintained anti-HBs titers ≥ 10 mIU/mL in both 10 µg and 20 µg groups (p > 0.05). The peak immune response of vaccination (anti-HBs antibody levels at 12 mo after 1st vaccine dose) and Year 11 anti-HBs levels were significantly associated with Year 23 seroprotection rates. Most of the participants in both groups, regardless of their prior immune status, developed a rapid and robust anamnestic antibody response after the booster dose at year 23. No case of clinically significant HBV infection was observed during the entire study period of 23 y with only one transient HBsAg seroconversion in 10 µg vaccine group. We concluded that seroprotection provided by 10µg or 20 µg doses of hepatitis B vaccine persists for 23 years in more than half of vaccinated individuals in highly HBV-endemic areas, irrespective of 10 µg or 20 µg vaccine doses. Future studies with larger sample sizes comparing long-term efficacy of various doses of plasma-derived and recombinant HBV vaccines are recommended.