This study aims to explore the pharmacodynamic material basis of Jinbei Oral Liquid(JBOL) against idiopathic pulmonary fibrosis(IPF) based on serum pharmacochemistry and network pharmacology. The ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) technology was employed to analyze and identify the components absorbed into rat blood after oral administration of JBOL. Combined with network pharmacology, the study explored the pharmacodynamic material basis and potential mechanism of JBOL against IPF through protein-protein interaction(PPI) network construction, "component-target-pathway" analysis, Gene Ontology(GO) functional enrichment, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. First, a total of 114 compounds were rapidly identified in JBOL extract according to the exact relative molecular mass, fragment ions, and other information of the compounds with the use of reference substances and a self-built compound database. Second, on this basis, 70 prototype components in blood were recognized by comparing blank serum with drug-containing serum samples, including 28 flavonoids, 25 organic acids, 4 saponins, 4 alkaloids, and 9 others. Finally, using these components absorbed into blood as candidates, the study obtained 212 potential targets of JBOL against IPF. The anti-IPF mechanism might involve the action of active ingredients such as glycyrrhetinic acid, cryptotanshinone, salvianolic acid B, and forsythoside A on core targets like AKT1, TNF, and ALB and thereby the regulation of multiple signaling pathways including PI3K/AKT, HIF-1, and TNF. In conclusion, JBOL exerts the anti-IPF effect through multiple components, targets, and pathways. The results would provide a reference for further study on pharmacodynamic material basis and pharmacological mechanism of JBOL.
Drugs, Chinese Herbal/pharmacokinetics* ; Animals ; Tandem Mass Spectrometry ; Network Pharmacology ; Rats ; Chromatography, High Pressure Liquid ; Rats, Sprague-Dawley ; Male ; Idiopathic Pulmonary Fibrosis/metabolism* ; Humans ; Administration, Oral ; Protein Interaction Maps/drug effects* ; Signal Transduction/drug effects*

In order to support the implementation of the Opinions on Improving the Quality of Traditional Chinese Medicine and Promoting the High-Quality Development of the Traditional Chinese Medicine Industry and fundamentally promote the high-quality development of Chinese materia medica(CMM) industry, this article analyzed the quality and safety issues arising during the transition of CMM from wild harvesting to cultivation. Root causes of these issues were identified, including changes in the habitats of medicinal plants caused by inappropriate field cultivation patterns, excessive use of chemical inputs such as fertilizers and pesticides, and shortened cultivation periods due to rising economic costs. To address the above issues, the following countermeasures and suggestions were proposed to advance the high-quality development of CMM:(1) comprehensively adjust the cultivation patterns, vigorously promote ecological cultivation of CMM, and ensure production quality and safety of CMM from the source;(2) strengthen the breeding of high-quality, stress-resistant CMM varieties, improve cultivation techniques to reduce the use of fertilizers and pesticides, and improve the quality and efficiency of ecological cultivation of CMM;(3) systematically design the production, operation, and supervision models for ecological cultivation of CMM, carry out demonstrations of "high quality with fair price", and ensure the sustainable development of ecological cultivation of CMM.
Drugs, Chinese Herbal/standards* ; Quality Control ; Plants, Medicinal/chemistry* ; Plant Roots/chemistry* ; China ; Fertilizers/analysis* ; Materia Medica/standards* ; Medicine, Chinese Traditional/standards*

Benzylisoquinoline alkaloids (BIAs) are a structurally diverse group of plant metabolites renowned for their pharmacological properties. However, sustainable sources for these compounds remain limited. Consequently, researchers are focusing on elucidating BIA biosynthetic pathways and genes to explore alternative sources using synthetic biology approaches. CYP80B, a family of cytochrome P450 (CYP450) enzymes, plays a crucial role in BIA biosynthesis. Previously reported CYP80Bs are known to catalyze the 3'-hydroxylation of (S)-N-methylcoclaurine, with the N-methyl group essential for catalytic activity. In this study, we successfully cloned a full-length CYP80B gene (StCYP80B) from Stephania tetrandra (S. tetrandra) and identified its function using a yeast heterologous expression system. Both in vivo yeast feeding and in vitro enzyme analysis demonstrated that StCYP80B could catalyze N-methylcoclaurine and coclaurine into their respective 3'-hydroxylated products. Notably, StCYP80B exhibited an expanded substrate selectivity compared to previously reported wild-type CYP80Bs, as it did not require an N-methyl group for hydroxylase activity. Furthermore, StCYP80B displayed a clear preference for the (S)-configuration. Co-expression of StCYP80B with the CYP450 reductases (CPRs, StCPR1, and StCPR2), also cloned from S. tetrandra, significantly enhanced the catalytic activity towards (S)-coclaurine. Site-directed mutagenesis of StCYP80B revealed that the residue H205 is crucial for coclaurine catalysis. Additionally, StCYP80B exhibited tissue-specific expression in plants. This study provides new genetic resources for the biosynthesis of BIAs and further elucidates their synthetic pathway in natural plant systems.
Cytochrome P-450 Enzyme System/chemistry* ; Benzylisoquinolines/chemistry* ; Hydroxylation ; Plant Proteins/chemistry* ; Alkaloids/metabolism* ; Stephania tetrandra/genetics*

Objective To specifically extract and analyze nascent proteins synthesized by bone marrow mesenchymal stem cells(BMSCs)after transplantation into ischemic hearts using a technique employing mutant methionyl-tRNA synthetase(MetRSL247G)for nascent protein labeling,in order to explore the potential mechanisms of action in BMSCs post-transplantation.Methods Point mutation at position 274 of the MetRS gene in BMSCs was induced via lentiviral infection to enable azidonorleucine(ANL)-mediated labeling of nascent proteins in BMSCs.The labeling efficiency was verified by means of fluorescent non-canonical amino-acid tagging(FUNCAT).Thirty healthy female C57BL/6J mice(8-10 weeks old)were divided into control and experimental groups,with 15 mice in each group.The acute myocardial infarction model was constructed by ligating the left anterior descending coronary artery in experimental group,while control mice underwent only thoracotomy without coronary ligation.After modeling,both groups received intramyocardial injections of MetRSL247G-modified BMSCs(MetRSL247G-BMSCs)at 3 different sites in the peri-infarct ischemic region.Mice were intraperitoneally injected with ANL every 6 hours for 4 times on postoperative days 0,2,and 6(n=5 for each time point)respectively,euthanized 24 h after the last injection,and cardiac tissues were isolated.The newly synthesized and labeled proteins produced by BMSCs after transplantation into the myocardium of experimental and control groups were collected,using an enrichment technique for ANL-tagged proteins and liquid chromatography-tandem mass spectrometry(LC-MS)analysis.Gene ontology(GO)analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis,protein-protein interaction(PPI)analysis,and heatmap visualization analysis were performed to identify differentially expressed proteins at the 3 time points and screen key pathways and genes.Results Under fluorescence microscopy,the MetRSL247G lentivirus-infected BMSCs were observed to be labelled with mCherry signals,confirming the successful construction of the MetRSL247G-BMSCs cell line.Green fluorescent signals were detected only in nascent proteins in culture medium containing both MetRSL247G-BMSCs and ANL,validating the sensitivity and specificity of the labeling method.GO analysis revealed that differentially expressed proteins were primarily involved in basic cellular biological processes such as extracellular exosome formation,extracellular matrix organization,and focal adhesion.KEGG and PPI analyses indicated that the differential proteins were mainly involved in complement and coagulation cascade pathway,actin cytoskeleton regulation pathway,and apoptosis pathway.Heatmap analysis showed significantly upregulated expression of anti-apoptosis and cell adhesion-related factors in experimental group on day 1(P＜0.05),upregulated anti-apoptotic factors,pro-apoptotic factors,and cell adhesion-related factors on day 3(P＜0.05),and upregulated anti-apoptotic factors,cell differentiation-related factors,and cell adhesion-related factors on day 7(P＜0.05)compared with control group.Expression of apoptosis-inducing factor 1 was significantly downregulated on days 1 and 7(P＜0.05).On day 3,most differentially expressed proteins,including anti-apoptosis factors(Protein S100-A11,Clusterin,Gelsolin),pro-apoptosis factor(Cathepsin B),cell differentiation-related factor(Transgelin-2),and cell adhesion-related factors(Cofilin-1,Periostin,Fibronectin)were significantly upregulated(P＜0.05).Conclusions The MetRSL247G mutation enables BMSCs to incorporate ANL and synthesize labeled proteins,confirming the feasibility of this nascent protein labeling technique.Nascent proteins of BMSCs in ischemic myocardium primarily contribute to extracellular exosome secretion and extracellular matrix organization.BMSCs may adapt to and respond to ischemic and hypoxic environments by influencing complement and coagulation cascades,activating inflammatory factors,regulating actin cytoskeleton structure,and modulating apoptosis,thereby maintaining the survival of BMSCs.

OBJECTIVE To analyze the chemical constituents from classical prescription Xiehuang San(XHS)standard decoc-tion by UPLC-Q-TOF-MS technology,and classify the chemical composition and analyze the representative components.METHODS Acquity HSS T3 column(2.1 mm×100 mm,1.8 μm)was used as the chromatographic column,with 0.1%formic acid solution-0.1%formic acid acetonitrile as the mobile phase for gradient elution.The volume flow rate was 0.4 mL·min-1 and the column tem-perature was 40℃.Mass spectrometry data of XHS were collected in positive and negative ion modes.The chemical constituents from classical prescription XHS were analyzed and identified by Masslynx 4.1 software comparison with reference materials,mass spectrome-try data analysis and reference to relevant literature.RESULTS A total of 107 compounds were analyzed and identified from XHS,including 45 flavonoids,27 triterpenoids,11 monoterpenoids,10 phenylpropanoids,6 chromogenic ketones,5 alkaloids and 3 other other compounds.CONCLUSION The study provides an experimental basis for the further research on the substance basis and qual-ity control of XHS.

Objective: To investigate which types of environmental exposure during pregnancy are risk and protective factors for cleft lip with or without cleft palate (CL/P). Methods: This case-control study included 278 orthodontic patients with CL/P (CL/P group) and 51 without CL/P (non-CL/P group). Demographic and environmental exposure data were collected using questionnaires completed by the parents. Statistical analyses were performed to identify the potential risk and protective factors for CL/P. Results The two groups did not show significant difference in (1) body weight at birth and number of previous births;(2) fathers’ ages at birth and occupation; (3) parents’ chronic diseases, alcohol consumption, and exposure to harmful substances; and (4) mothers’ smoking, secondhand smoking, and vitamin and calcium intake. Most patients with CL/ P were born at normal term (≥ 37 weeks, 93.2%) with normal body weight (2.9–3.7 kg, 63.7%) and as either the first or second child (90.3%). In the CL/ P group, the percentages of mothers who were very young or old (≤ 19 years, ≥ 40 years) and with physical labor in their occupation were low (1.8% and 2.2%, respectively). Compared with the non-CL/P group, the CL/P group showed a lower percentage of maternal folic acid intake (68.6% vs. 20.9%, odds ratio [OR] = 0.121; P < 0.001) and higher percentages of mothers’ drug intake and fathers’ smoking habits (3.9% vs. 16.2%, OR = 4.73, P < 0.05; 39.2% vs. 61.2%, OR = 2.44, P < 0.01). Conclusions: The findings of this study may explain the association between environmental factors and CL/P risk.

Objective: To investigate which types of environmental exposure during pregnancy are risk and protective factors for cleft lip with or without cleft palate (CL/P). Methods: This case-control study included 278 orthodontic patients with CL/P (CL/P group) and 51 without CL/P (non-CL/P group). Demographic and environmental exposure data were collected using questionnaires completed by the parents. Statistical analyses were performed to identify the potential risk and protective factors for CL/P. Results The two groups did not show significant difference in (1) body weight at birth and number of previous births;(2) fathers’ ages at birth and occupation; (3) parents’ chronic diseases, alcohol consumption, and exposure to harmful substances; and (4) mothers’ smoking, secondhand smoking, and vitamin and calcium intake. Most patients with CL/ P were born at normal term (≥ 37 weeks, 93.2%) with normal body weight (2.9–3.7 kg, 63.7%) and as either the first or second child (90.3%). In the CL/ P group, the percentages of mothers who were very young or old (≤ 19 years, ≥ 40 years) and with physical labor in their occupation were low (1.8% and 2.2%, respectively). Compared with the non-CL/P group, the CL/P group showed a lower percentage of maternal folic acid intake (68.6% vs. 20.9%, odds ratio [OR] = 0.121; P < 0.001) and higher percentages of mothers’ drug intake and fathers’ smoking habits (3.9% vs. 16.2%, OR = 4.73, P < 0.05; 39.2% vs. 61.2%, OR = 2.44, P < 0.01). Conclusions: The findings of this study may explain the association between environmental factors and CL/P risk.

Objective: To investigate which types of environmental exposure during pregnancy are risk and protective factors for cleft lip with or without cleft palate (CL/P). Methods: This case-control study included 278 orthodontic patients with CL/P (CL/P group) and 51 without CL/P (non-CL/P group). Demographic and environmental exposure data were collected using questionnaires completed by the parents. Statistical analyses were performed to identify the potential risk and protective factors for CL/P. Results The two groups did not show significant difference in (1) body weight at birth and number of previous births;(2) fathers’ ages at birth and occupation; (3) parents’ chronic diseases, alcohol consumption, and exposure to harmful substances; and (4) mothers’ smoking, secondhand smoking, and vitamin and calcium intake. Most patients with CL/ P were born at normal term (≥ 37 weeks, 93.2%) with normal body weight (2.9–3.7 kg, 63.7%) and as either the first or second child (90.3%). In the CL/ P group, the percentages of mothers who were very young or old (≤ 19 years, ≥ 40 years) and with physical labor in their occupation were low (1.8% and 2.2%, respectively). Compared with the non-CL/P group, the CL/P group showed a lower percentage of maternal folic acid intake (68.6% vs. 20.9%, odds ratio [OR] = 0.121; P < 0.001) and higher percentages of mothers’ drug intake and fathers’ smoking habits (3.9% vs. 16.2%, OR = 4.73, P < 0.05; 39.2% vs. 61.2%, OR = 2.44, P < 0.01). Conclusions: The findings of this study may explain the association between environmental factors and CL/P risk.

Objective: To investigate which types of environmental exposure during pregnancy are risk and protective factors for cleft lip with or without cleft palate (CL/P). Methods: This case-control study included 278 orthodontic patients with CL/P (CL/P group) and 51 without CL/P (non-CL/P group). Demographic and environmental exposure data were collected using questionnaires completed by the parents. Statistical analyses were performed to identify the potential risk and protective factors for CL/P. Results The two groups did not show significant difference in (1) body weight at birth and number of previous births;(2) fathers’ ages at birth and occupation; (3) parents’ chronic diseases, alcohol consumption, and exposure to harmful substances; and (4) mothers’ smoking, secondhand smoking, and vitamin and calcium intake. Most patients with CL/ P were born at normal term (≥ 37 weeks, 93.2%) with normal body weight (2.9–3.7 kg, 63.7%) and as either the first or second child (90.3%). In the CL/ P group, the percentages of mothers who were very young or old (≤ 19 years, ≥ 40 years) and with physical labor in their occupation were low (1.8% and 2.2%, respectively). Compared with the non-CL/P group, the CL/P group showed a lower percentage of maternal folic acid intake (68.6% vs. 20.9%, odds ratio [OR] = 0.121; P < 0.001) and higher percentages of mothers’ drug intake and fathers’ smoking habits (3.9% vs. 16.2%, OR = 4.73, P < 0.05; 39.2% vs. 61.2%, OR = 2.44, P < 0.01). Conclusions: The findings of this study may explain the association between environmental factors and CL/P risk.

Objective: To investigate which types of environmental exposure during pregnancy are risk and protective factors for cleft lip with or without cleft palate (CL/P). Methods: This case-control study included 278 orthodontic patients with CL/P (CL/P group) and 51 without CL/P (non-CL/P group). Demographic and environmental exposure data were collected using questionnaires completed by the parents. Statistical analyses were performed to identify the potential risk and protective factors for CL/P. Results The two groups did not show significant difference in (1) body weight at birth and number of previous births;(2) fathers’ ages at birth and occupation; (3) parents’ chronic diseases, alcohol consumption, and exposure to harmful substances; and (4) mothers’ smoking, secondhand smoking, and vitamin and calcium intake. Most patients with CL/ P were born at normal term (≥ 37 weeks, 93.2%) with normal body weight (2.9–3.7 kg, 63.7%) and as either the first or second child (90.3%). In the CL/ P group, the percentages of mothers who were very young or old (≤ 19 years, ≥ 40 years) and with physical labor in their occupation were low (1.8% and 2.2%, respectively). Compared with the non-CL/P group, the CL/P group showed a lower percentage of maternal folic acid intake (68.6% vs. 20.9%, odds ratio [OR] = 0.121; P < 0.001) and higher percentages of mothers’ drug intake and fathers’ smoking habits (3.9% vs. 16.2%, OR = 4.73, P < 0.05; 39.2% vs. 61.2%, OR = 2.44, P < 0.01). Conclusions: The findings of this study may explain the association between environmental factors and CL/P risk.