[Activity of Codonopsis canescens against rheumatoid arthritis based on TLRs/MAPKs/NF-κB signaling pathways and its mechanism].

This paper aims to explore the activity of Codonopsis canescens extract against rheumatoid arthritis(RA) based on the Toll-like receptors(TLRs)/mitogen-activated protein kinases(MAPKs)/nuclear factor kappa B(NF-κB) signaling pathways and its mechanism. The ultra-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry(UPLC-Q-TOF-MS) was used to identify the components of C. canescens extract. Forty-eight male SD rats were randomly divided into six groups, namely the normal group, the model group, the methotrexate(MTX) tablet group, and the low, medium, and high-dose C. canescens extract(ZDS-L, ZDS-M, and ZDS-H) groups, with 8 rats in each group. The model of collagen-induced arthritis in rats was induced by injection of bovine type Ⅱ collagen emulsion. MTX(2.5 mg·kg~(-1)), ZDS-L, ZDS-M, and ZDS-H(0.3 g·kg~(-1), 0.6 g·kg~(-1), and 1.2 g·kg~(-1)) were administrated by gavage. Rats in the normal group and the model group received distilled water. MTX was given once every three days for 28 days, and the rest medicines were given once daily for 28 days. Body weight, degree of foot swelling, arthritis index, immune organ index, synovial histopathological changes, and serum levels of tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß), and interleukin-6(IL-6) were observed. Protein expressions of TLR2, TLR4, NF-κB p65, p38 MAPK, and p-p38 MAPK in rats were determined by Western blot. Thirty-four main components were identified by UPLC-Q-TOF-MS, including 15 flavonoids, 7 phenylpropanoids, 4 terpenoids, 4 organic acids, 2 esters, and 2 polyalkynes. As compared with the normal group, the body weight of the model group was significantly decreased(P<0.01), and foot swelling(P<0.05, P<0.01), arthritis index(P<0.01), and the immune organ index(P<0.01) were significantly increased. The synovial histopathological injury was obviously observed in the model group. The serum levels of inflammatory factors TNF-α, IL-1ß, and IL-6 were significantly increased(P<0.01), and the protein expression levels of TLR2, TLR4, NF-κB p65, p-p38 MAPK/p38 MAPK in the synovial tissue were significantly increased(P<0.01) in the model group. As compared with the model group, the body weights of the ZDS dose groups were increased(P<0.01), and the degree of foot swelling(P<0.01) and the arthritis index were decreased(P<0.05, P<0.01). The immune organ index was decreased(P<0.01) in the ZDS dose groups, and the synovial tissue hyperplasia and inflammatory cell infiltration were alleviated. The serum levels of TNF-α, IL-1ß, and IL-6 were significantly decreased(P<0.05, P<0.01), and the protein expression levels of TLR2, TLR4, NF-κB p65, p-p38 MAPK/p38 MAPK were decreased(P<0.05, P<0.01) in the ZDS dose groups. C. canescens extract containing apigenin, tricin, chlorogenic acid, aesculin, ferulic acid, caffeic acid, and oleanolic acid has a good anti-RA effect, and the mechanism may be related to the inhibition of TLRs/MAPKs/NF-κB signaling pathways.

Simulation Insight into the Synergic Role of Citrate and Polyaspartic Peptide in Biomineralization.

Hydroxyapatite (HAP) is one of the most important inorganic components in biological minerals such as bones and teeth. More than 90% of the total citrate is accumulated in human bones and other biomineralized tissues. In addition, mineralizing proteins are enriched in glutamate and aspartate residues, which are important for their mineral-regulating properties. However, how citrate ions (CITs) and/or acidic amino acids regulate the formation of HAP is still unclear. In this work, molecular dynamics simulations were performed to study how CIT regulates the adsorption behavior of polyaspartic acid (PASP) on the HAP surface in the calcium phosphate solution. The simulation results indicate that PASP can be used as an ion chelator to complex Ca2+ and can serve as templates for HAP mineralization by templating the distribution of Ca2+ on its surface, which are attributed to the -COO- and α-helix structure. Most importantly, the orientation distributions of PASP in all systems are narrower with the help of CIT, thereby PASP can be adsorbed on the HAP surface stably with a "lying-down" orientation. This indicates that CIT can be used as a bridging agent to bond the acidic peptide to the HAP surface in biomineralization. Thus, the synergic role of CIT and the acidic peptide on the HAP surface were revealed in this work, which can provide new insights into the interfacial phenomena during the biomineralization.

Falcarindiol and dichloromethane fraction are bioactive components in Oplopanax elatus: Colorectal cancer chemoprevention via induction of apoptosis and G2/M cell cycle arrest mediated by cyclin A upregulation.

Oplopanax elatus (Nakai) Nakai has a long history of use as an ethnomedicine by the people living in eastern Asia. However, its bioactive constituents and cancer chemopreventive mechanisms are largely unknown. The aim of this study was to prepare O. elatus extracts, fractions, and single compounds and to investigate the herb's antiproliferative effects on colon cancer cells and the involved mechanisms of action. Two polyyne compounds were isolated from O. elatus, falcarindiol and oplopandiol. Based on our HPLC analysis, falcarindiol and oplopandiol are major constituents in the dichloromethane (CH2Cl2) fraction. For the HCT-116 cell line, the dichloromethane fraction showed significant effects. Furthermore, the IC50 for falcarindiol and oplopandiol was 1.7 µM and 15.5 µM, respectively. In the mechanistic study, after treatment with 5 µg/ml for 48 h, dichloromethane fraction induced cancer cell apoptosis by 36.5% (p < 0.01% vs. control of 3.9%). Under the same treatment condition, dichloromethane fraction caused cell cycle arrest at the G2/M phase by 32.6% (p < 0.01% vs. control of 23.4%), supported by upregulation of key cell cycle regulator cyclin A to 21.6% (p < 0.01% vs. control of 8.6%). Similar trends were observed by using cell line HT-29. Data from this study filled the gap between phytochemical components and the cancer chemoprevention of O. elatus. The dichloromethane fraction is a bioactive fraction, and falcarindiol is identified as an active constituent. The mechanisms involved in cancer chemoprevention by O. elatus were apoptosis induction and G2/M cell cycle arrest mediated by a key cell cycle regulator cyclin A.

[Herbal textual research on Chuanxiong Rhizoma in Chinese classical prescriptions].

Fourteen classical prescriptions in the Catalog of 100 Ancient Classical Prescriptions(First Batch) promulgated in 2018 contain Chuanxiong Rhizoma, which reveals the high medicinal value and wide application of Chuanxiong Rhizoma. This paper systematically reviews the ancient herbal books and modern literature to explore the name, origin, genuine producing area, medicinal part, harvesting, and processing of Chuanxiong Rhizoma, thus facilitating the development of classical prescriptions containing Chuan-xiong Rhizoma. It is confirmed that Chuanxiong Rhizoma, formerly known as "Xiongqiong" in Chinese, was first called "Chuanxiong" in late Tang Dynasty, which has been gradually accepted as its official name due to the rise of the status of Chuanxiong Rhizoma produced in Sichuan. The main original plant of Chuanxiong Rhizoma in past dynasties has always been deemed to be Ligusticum chuan-xiong(Umbellifera), whose rhizome serves as the medicinal part. In general, it is best harvested in summer but the harvesting time can vary with different growth environments. Since the Song Dynasty, Sichuan province has been recognized as the genuine producing area of Chuanxiong Rhizoma in light of the high yield and good quality. It is suggested that Chuanxiong Rhizoma from Sichuan be used preferentially in the development of classical prescriptions. There are multiple processing methods of Chuanxiong Rhizoma recorded in ancient medical classics, and the raw(after purifying and slicing) or wine-processed or stir-fried Chuanxiong Rhizoma is still in use today. In the development of classical prescriptions containing Chuanxiong Rhizoma, Chuanxiong Rhizoma is advised to be processed in accordance with current processing standards if the specific processing method is described in the medical classics. If not, the raw Chuanxiong Rhizoma is preferred and then processed following the processing standards of Chuanxiong Rhizoma decoction pieces in Chinese Pharmacopoeia.

Human intestinal microbiota derived metabolism signature from a North American native botanical Oplopanax horridus with UPLC/Q-TOF-MS analysis.

Oplopanax horridus, widely distributed in North America, is an herbal medicine traditionally used by Pacific indigenous peoples for various medical conditions. After oral ingestion, constituents in O. horridus extract (OhE) could be converted to their metabolites by the enteric microbiome before absorption. In this study, in order to mimic gut environment, the OhE was biotransformed using the enteric microbiome of healthy human subjects. For accurate and reliable data collection with optimized approaches in sample preparation and analytical conditions, ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry were used to characterize parent constituents and their metabolites. In the extract, 20 parent compounds were identified including polyynes, sesquiterpenes, monoterpeondids, phenylpropanoids and phenolic acids. After the biotransformation, a total of 78 metabolites were identified, of which 37 belonged to polyynes metabolites. The common biotransformation pathways are hydroxylation, acetylization, methylation and demethylation. Based on the pathway distributions, the metabolism signature of OhE has been explored. The metabolism pathways of OhE compounds are dependent on their structural classifications and hydrophilic/hydrophobic properties. In summary, with comprehensive analysis, we systematically investigated human microbiome-derived OhE metabolites. The enteric microbial metabolism signature provides novel information for future effective use of O. horridus.

Gallic acid activates hippocampal BDNF-Akt-mTOR signaling in chronic mild stress.

Gallic acid (3,4,5-trihydroxybenzoic acid) is a naturally occurring polyphenolic compound. Previous study has shown that gallic acid possessed significant antidepressant-like activity in mice, which was partly mediated by increasing serotonin and catecholamine levels. The main aim of the present study is to investigate the possible effects of gallic acid on brain-derived neurotrophic factor (BDNF) signaling activation. Mice were exposed to chronic mild stress (CMS) and orally administrated with gallic acid for four weeks. The behavioral results showed that gallic acid not only reversed the decreased sucrose preference, but also attenuated the increased immobility time. In addition, gallic acid promoted both the BDNF and p-TrkB levels in the hippocampus induced by CMS. Moreover, the results also demonstrated that the inactivated Akt-mTOR signaling pathway, as well as its downstream effectors induced by CMS was activated again by gallic acid. Last, immunofluorescence detection indicated that gallic acid reversed the newborn neurons inhibition in the dentate gyrus by CMS. In conclusion, these results show that the activation of the hippocampal BDNF-Akt-mTOR signaling is involved in the antidepressant-like effects of gallic acid.

[Research on XOD captured components in Lagotis brevituba based on UPLC-Q-TOF-MS and molecular docking technology].

Potential xanthine oxidase (XOD) inhibitors in Lagotis brevituba were captured by using affinity and ultrafiltration. The structures of the captured components were identified by ultra-performance liquid chromatography coupled with Q-TOF mass spectrometry (UPLC-Q-TOF-MS). The binding intensity and binding mechanism between the captured components and XOD were analyzed by using molecular docking software Autodock 4.2. A total of 17 compounds were identified, including 9 flavonoids, 5 phenolic acids and 3 triterpenes. Molecular docking results showed that all the captured components could be spontaneously bound with XOD mainly via hydrogen bond, Van der Waals' force and hydrophobic interaction. From the perspective of binding energy and scoring function, the collected fractions all had potential prospects for XOD inhibitors, and the flavonoid luteolin-3',7 glucuronide had the best effect. The results also showed that affinity and ultrafiltration, ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and molecular docking technology can provide a powerful tool for the analysis of XOD inhibitor components in natural products.

[Fast identification of constituents of Lagotis brevituba by using UPLC-Q-TOF-MS/MS method].

The chemical constituents of Lagotis brevituba were rapidly determined and analyzed by using ultra performance liquid chromatography tandem quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS/MS) method, providing material basis for the clinical application of L. brevituba. The separation was performed on UPLC YMC-Triart C18 (2.1 mm×100 mm, 1.9 µm) column, with acetonitrile-water containing 0.2% formic acid as mobile phase for gradient elution. The flow rate was 0.4 mL•min-1 gradient elution and column temperature was 40 ℃, the injection volume was 2 µL. ESI ion source was used to ensure the data collected in a negative ion mode. The chemical components of L. brevituba were identified through retention time, exact relative molecular mass, cleavage fragments of MS/MS and reported data. The results showed that a total of 22 compounds were identified, including 11 flavones, 6 phenylethanoid glycosides, 1 iridoid glucosides, and 4 organic acid. The UPLC-Q-TOF-MS/MS method could fast identify the chemical components of L. brevituba, providing valuable information about L. brevituba for its clinical application.

[Chemical Constitutes from Seeds of Plantago asiatica].

OBJECTIVE: To study the chemical constituents of Plantago asiatica seeds. METHODS: The constituents were isolated from the seeds of Plantago asiatica by column chromatography over silica gel, MCI gel, macroporous resin HP-20, Sephadex LH-20, Polyamide and by preparative HPLC. Their structures were elucidated by analysis of physical and chemical properties and spectral data. RESULTS: Five compounds were isolated and their structures were identified as acteoside (1), isoacteoside (2), decaffeoylacteoside (3), tetradecanoic acid (4), and bis (2-ethythexyl) benzene-1,2-dicarboxylate (5). CONCLUSION: Compound 5 is isolated from Plantaginaceae for the first time. Compounds 3 and 4 are firstly characterized in Plantago asiatica.

[Study on genetic polymorphism of Platycodon grandiflorum based on barcoding of ITS2].

OBJECTIVE: ITS2 of DNA barcoding was used to study genetic polymorphism of Platycodon grandiflorum. METHOD: Total genomic DNA was isolated from P. grandiflorum. PCR was used to amplified the region of internal transcribed spacer 2 (ITS2), and PCR products were sequenced. The sequences of ITS2 were analyzed and compared by Clustal. The intraspecies genetic distance was calculated based on Kimura 2-parameter model by using MEGA 5.05. The ITS2 sequence of Codonopsis pilosula was used as the outreach value for plants of the genus, and the phylogenic tree used constructed by Neighbor-Joining (NJ) method. RESULT: The K2-P's genetic distance of all samples were ranged from 0 to 0.930. The K2-P's genetic distance of samples at the same area were ranged from 0 to 0.178. The K2-P's genetic distance of samples at different areas were ranged from 0.735 to 0.930. The analytical result showed that the degree of genetic variation were heavy in intraspecies of P. grandiflorum and significantly correlated with geographical location. CONCLUSION: The DNA barcoding of ITS2 can applied to study the intraspecific genetic diversity, it provides a reference for further development of DNA barcoding technology applications.

Comparative pharmacokinetics of five primary constituents in Huai-hua powder: a study on normal rats and rats with ulcerative colitis.

OBJECTIVES: The goal of this research was to develop a fast, reliable, and sensitive method to simultaneously quantify five key components of Huai-hua Powder (HHP) in rat plasma with genistein served as the internal standard. Furthermore, the established method was used to perform a comparative evaluation of the pharmacokinetic properties of HHP in normal rats and rats with ulcerative colitis (UC). METHODS: Chromatographic separation was conducted using an ACQUITY HSS T3 column held at a constant temperature of 35°C, with acetonitrile and a 0.1% formic acid solution in water employed as the mobile phases. Multiple-reaction monitoring facilitated MS operation in positive-negative-ion-switching mode. The method's validation demonstrated exceptional linearity (with a correlation coefficient of r ≥ 0.9970), and the validation tests, encompassing precision within and between days, accuracy, recovery, matrix effect, and stability; all met the predefined acceptable criteria. KEY FINDINGS: The results revealed significant variations in the pharmacokinetic characteristics of the five components between normal and UC rats, suggesting altered drug metabolism rates and extents in the latter group. CONCLUSIONS: These findings offer crucial scientific insights into the potential clinical application of HHP, particularly in the context of treating UC.

Emergence and ongoing outbreak of ST80 vancomycin-resistant Enterococcus faecium in Guangdong province, China from 2021 to 2023: a multicenter, time-series and genomic epidemiological study.

BACKGROUND: Surveillance systems revealed that the prevalence of vancomycin-resistant Enterococcus faecium (VREfm) has increased. We aim to investigate the epidemiological and genomic characteristics of VREfm in China. METHODS: We collected 20,747 non-redundant E. faecium isolates from inpatients across 19 hospitals in six provinces between January 2018 and June 2023. VREfm was confirmed by antimicrobial susceptibility testing. The prevalence was analyzed using changepoint package in R. Genomic characteristics were explored by whole-genome sequencing. RESULTS: 5.59% (1159/20,747) of E. faecium isolates were resistant to vancomycin. The prevalence of VREfm increased in Guangdong province from 5% before 2021 to 20-50% in 2023 (p < 0.0001), but not in the other five provinces. Two predominant clones before 2021, ST17 and ST78, were substituted by an emerging clone, ST80, from 2021 to 2023 (88.63%, 195/220). All ST80 VREfm from Guangdong formed a single lineage (SC11) and were genetically distant from the ST80 VREfm from other countries, suggesting a regional outbreak. All ST80 VREfm in SC11 carried a new type of plasmid harbouring a vanA cassette, which was embedded in a Tn1546-like structure flanked by IS1678 and ISL3. However, no conjugation-related gene was detected and no transconjugant was obtained in conjugation experiment, indicating that the outbreak of ST80 VREfm could be attributed to clonal transmission. CONCLUSIONS: We revealed an ongoing outbreak of ST80 VREfm with a new vanA-harbouring plasmid in Guangdong, China. This clone has also been identified in other provinces and countries, foreboding a risk of wider spreading shortly. Continuous surveillance is needed to inform public health interventions.

[HPLC fingerprint and chemical pattern recognition of liposoluble chemical components for euodiae fructus].

OBJECTIVE: To establish a method of HPLC fingerprint and chemical pattern recognition of liposoluble chemical components for quality evaluation of Euodiae Fructus. METHODS: The HPLC chromatographic separation was performed on a C18 column (250 mm x 4.6 mm, 5 microm). The mobile phase was a mixture of acetonitrile-0.5% acetic acid in gradient elution with flow rate of 1 mL/min. The detection wavelength was set at 249 nm, and the column temperature was 30 degrees C. RESULTS: There were 9 common peaks in the HPLC fingerprint of 34 batches of Euodiae Fructus samples. The results of cluster analysis and principal component analysis showed that the liposoluble chemical components of Euodia rutaecarpa (Juss.) Benth. var. officinalis (Dode) Huang and Euodia rutaecarpa (Juss.) Benth. var. bodinieri (Dode) Huang were more similar than that of Euodia rutaecarpa (Juss.) Benth. CONCLUSION: The results provide new experimental and theoretical basis for quality control and evaluation of Euodiae Fructus.

[Study on the liver-protective and choleretic effect of zhizi baipi soup and its disassembled prescription].

OBJECTIVE: To investigate the effect of Zhizi Baipi soup and its disassembled prescription on protecting liver and improving choleresis and explore the regularity of Zhizi Baipi soup composition. METHODS: The model of mouse liver injury induced by carbon tetraehlofide (CCl4) was used to observe the effects of Zhizi Baipi soup and its disassembled prescription by oral adminstration, the bile volume was determinied by common bile duct drainage. RESULTS: Zhizi Baipi soup and each treatment group with gardenia could significantly inhibit the increased serum ATL and AST activities, reduce liver MDA level, and significantly promote the bile flow and bilirubin in bile in normal rats. CONCLUSION: Zhizi Baipi soup has effects on protecting liver and increasing bile secretion, its monarch drug, gardenia plays an important role in the decoction, the effect of eliminating dampness and heat are mainly ascribed to the synergic effect of gardenia and phellodendron.

Thermal Insulation Properties and Simulation Analysis of Foam Concrete Regulated by Mechanical and Chemical Foaming.

To address, mitigate, or prevent thermal environmental issues arising from the heat dissipation of high-temperature surrounding rocks in deep hot tunnels, a research proposal is put forward based on previous studies and the team's initial experiments. The proposal involves using mechanical and chemical foaming to enhance the thermal insulation properties of foamed concrete, and this will be tested through engineering verification. Different proportions of cementitious materials, latex powder, polypropylene fiber, and self-made composite foam materials were designed using an orthogonal approach for testing the macroperformance and microstructure of foamed concrete. The pore structure of foamed concrete was quantitatively analyzed by Image-Pro Plus 6.0 software, and a fitting expression was established between thermal conductivity and the number of pores (1-2 mm). Characteristics of heat transfer inside the foam concrete were simulated and analyzed using COMSOL software, and the transmission path of heat streamline was found to be ″concave-convex form″, illustrating the blocking effect of foam concrete on heat. A thermal insulation engineering model was created using Fluent software to investigate the effects of thermal insulation layer thickness, water gushing heat release, seasonal factors, and other working conditions on the airflow temperature in the roadway before and after the application of foam concrete. The simulation results demonstrate that foam concrete can effectively reduce the airflow temperature in the roadway and weaken the surrounding rock heat dissipation. Additionally, it is found that the decreasing rate of heat dissipation of surrounding rock increases with the increase of insulation layer thickness, proving the engineering applicability of foam concrete for roadway insulation. The research results provide a theoretical basis and practical guidance for heat damage control of deep mining roadway.

Effective materials and mechanisms study of Tibetan herbal medicine Lagotis integra W. W. Smith treating DSS-induced ulcerative colitis based on network pharmacology, molecular docking and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Lagotis integra W. W. Smith (L. integra W. W. Smith) is an important origin plant of the famous Tibetan medicine HERBA LAGOTIS. It was documented to treat "Chi Ba" disease clinically, the symptoms of which are similar to ulcerative colitis (UC). AIMS OF THIS STUDY: To screen out the active components and study the mechanisms of L. integra W. W. Smith treating UC. MATERIALS AND METHODS: The components of L. integra W. W. Smith were comprehensively analyzed using UHPLC-Q-TOF/MS method. The mechanisms were investigated using network pharmacology method including target prediction, protein-protein interaction network analysis and gene enrichment analysis. Then, the mechanisms were verified using Dextran Sulfate Sodium (DSS)-induced UC model. Finally, the core active components were further screened out through molecular docking. RESULTS: The results showed that 32 major components were identified including 8 flavonoids, 9 phenylpropanoid glycosides, 13 iridoid glycosides and 1 phenolic acid. 76 potential core therapeutic targets and top 5 key targets, which were AKT serine/threonine kinase 1 (AKT1), vascular endothelial growth factor (VEGFA), tumor necrosis factor-α (TNF-α), epidermal growth factor receptor (EGFR) and caspase-3 (CASP3), were screened out according to network pharmacology analysis. Animal experiments confirmed that those compounds could downregulate the expression levels of the 5 key target proteins in colonic tissue of mice to exert excellent anti-UC effect. Molecular docking results showed that the main active components were echinacoside, hemiphroside B, plantamajoside, plantainoside D, 10-O-trans-isoferuloyl catalpol and scutellarioside II. CONCLUSIONS: For the first time, our study provides insights into the effective materials and molecular mechanisms of L. integra W. W. Smith treating UC, which contributes to the understanding of its pharmacodynamics.

The activities and mechanisms of intestinal microbiota metabolites of TCM herbal ingredients could be illustrated by a strategy integrating spectrum-effects, network pharmacology, metabolomics and molecular docking analysis: Platycodin D as an example.

BACKGROUND: The intestinal microbiota plays a key role in understanding the mechanism of traditional Chinese medicine (TCM), as it could transform the herbal ingredients to metabolites with higher bioavailability and activity comparing to their prototypes. Nevertheless, the study of the activity and mechanism of microbiota metabolites reported by the published literature still lacks viable ways. Hence a new strategy is proposed to solve this issue. PURPOSE: A new strategy to study the activity and mechanism of intestinal microbiota metabolites of TCM herbal ingredients by integrating spectrum-effect relationship, network pharmacology, metabolomics analysis and molecular docking together was developed and proposed. METHOD: Platycodin D (PD) and its microbiota metabolites with antitussive and expectorant effect were selected as an example for demonstration. First, the PD and its microbiota metabolites with important contribution to antitussive and/or expectorant effects were screened through spectrum-effect relationship analysis. Second, network pharmacology and metabolomics analysis were integrated to identify the upstream key targets of PD and its microbiota metabolites as well as the downstream endogenous metabolites. Finally, the active forms of PD were further confirmed by molecular docking. RESULTS: Results showed that PD was an active ingredient with antitussive and/or expectorant effects, and the active forms of PD were its microbiota metabolites: 3-O-ß-d-glucopyranosyl platycodigenin, 3-O-ß-d-glucopyranosyl isoplatycodigenin, 7­hydroxyl-3-O-ß-d-glucopyranosyl platycodigenin, platycodigenin and isoplatycodigenin. In addition, those microbiota metabolites could bind the key targets of PAH, PLA2G2A, ALOX5, CYP2C9 and CYP2D6 to exert antitussive effects by regulating four metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, glycerophospholipid metabolism and linoleic acid metabolism. Similarly, they could also bind the key targets of PLA2G1B, ALOX5, CYP2C9 and CYP2D6 to exert expectorant effect by regulating two pathways of glycerophospholipid metabolism and linoleic acid metabolism. CONCLUSION: The proposed strategy paves a new way for the illustration of the activities and mechanisms of TCM herbal ingredients, which is very important to reconcile the conundrums of TCM herbal ingredients with low oral bioavailability but high activity.

Molecular epidemiology and genomic dynamics of Pseudomonas aeruginosa isolates causing relapse infections.

Pseudomonas aeruginosa (P. aeruginosa) is one of the leading causes of chronic infections, including reinfection, relapse, and persistent infection, especially in cystic fibrosis patients. Relapse P. aeruginosa infections are more harmful because of repeated hospitalization and undertreatment of antimicrobials. However, relapse P. aeruginosa infection in China remains largely unknown. Herein, we performed a 3-year retrospective study from 2019 to 2022 in a tertiary hospital, which included 442 P. aeruginosa isolates from 196 patients. Relapse infection was identified by screening clinical records and whole-genome sequencing (WGS). We found that 31.6% (62/196) of patients had relapsed infections. The relapse incidence of carbapenem-resistant P. aeruginosa infection (51.4%) is significantly higher than that of carbapenem-susceptible P. aeruginosa infection (20.2%, P < 0.0001). These isolates were assigned to 50 distinct sequence types and sporadically distributed in phylogeny, indicating that relapsed infections were not caused by certain lineages. Fast adaptation and evolution of P. aeruginosa isolates were reflected by dynamic changes of antimicrobial resistance, gene loss and acquisition, and single-nucleotide polymorphisms during relapse episodes. Remarkably, a convergent non-synonymous mutation that occurs in a pyochelin-associated virulence gene fptA (T1056C, M252T) could be a considerable target for the diagnosis and treatment of relapse P. aeruginosa infection. These findings suggest that integrated utilization of WGS and medical records provides opportunities for improved diagnostics of relapsed infections. Continued surveillance of the genomic dynamics of relapse P. aeruginosa infection will generate further knowledge for optimizing treatment and prevention in the future.IMPORTANCEPseudomonas aeruginosa is a predominant pathogen that causes various chronic infections. Relapse infections promote the adaptation and evolution of antimicrobial resistance and virulence of P. aeruginosa, which obscure evolutionary trends and complicate infection management. We observed a high incidence of relapse P. aeruginosa infection in this study. Whole-genome sequencing (WGS) revealed that relapse infections were not caused by certain lineages of P. aeruginosa isolates. Genomic dynamics of relapse P. aeruginosa among early and later stages reflected a plasticity scattered through the entire genome and fast adaptation and genomic evolution in different ways. Remarkably, a convergent evolution was found in a significant virulence gene fptA, which could be a considerable target for diagnosis and treatment. Taken together, our findings highlight the importance of longitudinal surveillance of relapse P. aeruginosa infection in China since cystic fibrosis is rare in Chinese. Integrated utilization of WGS and medical records provides opportunities for improved diagnostics of relapse infections.

[Comprehensive chemical pattern recognition of pantagirus semen].

OBJECTIVE: To establish a method of comprehensive chemical pattern recognition of plantain seed via HPLC fingerprint, principal component analysis (PCA) and cluster analysis. METHOD: The chromatographic separation was performed on a C18 column (4.6 mm x 250 mm, 5 microm). The mobile phase was a mixture of acetonitrile-0.5% acetic acid aqueous solution in gradient elution. The HPLC fingerprint of ethyl acetate fraction of 24 batches Plantaginis Semen from different habits and varieties was set up and 10 common peaks were obtained. RESULT: The result of the principal component analysis (PCA) and cluster analysis is similar but there is disparity between them. CONCLUSION: The method could be used for the quality control and comprehensive evaluation of Plantaginis Semen.

Preliminary screening of the potential active ingredients in traditional Chinese medicines using the Ussing chamber model combined with HPLC-PDA-MS.

An in vitro intestinal absorption model combined with high-performance liquid chromatography-photo diode array-tandem mass spectrometry (HPLC-PDA-MS) was used for preliminary screening of potential active ingredients from complex multi-component traditional Chinese medicine (TCM) system. Oral administration is one of the main administration methods for TCMs. Only the ingredients that could be absorbed have the opportunity to play a role. Thus, these were defined as potential active ingredients. Studying of intestinal absorption can provide a theoretical basis for the mechanism of TCMs. The Caco-2 cell model, the everted rat gut sac model, and the Ussing chamber model were established for TCMs. The degree of anastomosis between the in vitro intestinal model and the actual intestinal absorption of TCMs were evaluated by the gavage method in rats. The Ussing chamber model was best fit for oral experiments in rats and was selected as the research means to preliminarily screen potential active ingredients from eight TCMs, including Salvia miltiorrhiza Bunge, Astragalus propinquus Schischkin, Plantago asiatica L, Fallopia multiflora (Thunb.) Harald, Epimedium brevicornu Maxim, Moutan Cortex, Citrus reticulata Blanco, and Panax notoginseng (Burkill) F. H. Chen ex C. H. Chow. A total of 44 components were absorbed and screened as the potential active ingredients from the 80 components identified in eight TCMs by HPLC-PDA-MS.