1.The therapeutic effect of Qingjie Huagong decoction on acute lung injury in rats with severe acute pancreatitis model and its mechanism
Min-Chao FENG ; Fang LUO ; Xi-Ping TANG ; Kai LI ; Xiao-Dong ZHU ; Bing-Yu ZHANG ; Guo-Zhong CHEN
Chinese Pharmacological Bulletin 2024;40(5):975-983
Aim To investigate the possible mechanism of action of Qingjie Huagong decoction(QJHGD)on acute lung injury(ALI)associated with severe acute pancreatitis(SAP)using network pharmacology,and to verify it by animal experiments.Methods The TC-MSP,BATMAN-TCM,ETCM,and SwissTargetPredic-tion databases were searched to obtain the action tar-gets of the blood-entering active ingredients of each drug in the QJHGD.The GeneCard database was searched to obtain SAP-ALI disease targets.The drug targets and disease targets were intersected to obtain common targets.Subsequently,the common targets were analyzed by STRING database and Cytoscape 3.7.1 software for protein interaction network analysis.GO and KEGG enrichment analysis was performed with the help of DAVID database.Finally,the key signa-ling pathways were verified by animal experiments.Results A total of 28 active ingredients were screened out for the treatment of SAP-ALI with 42 common tar-gets.PPI network analysis showed that STAT3,IL-6,and TGFB1 might be core targets;GO and KEGG en-richment analysis mainly involved cell proliferation,PI3K/AKT signaling pathways,etc.Animal experi-ments confirmed that QJHGD could improve the pathol-ogy of pancreas and lung tissues in SAP-ALI rat mod-el,down-regulate the expression levels of α-amylase,lipase,IL-1 β,IL-6,and TNF-α in serum,and down-regulate the expression levels of proteins and mRNAs related to PI3K/AKT1 signaling pathway in lung tis-sues.Conclusion QJHGD synergistically treats SAP-ALI through multi-component,multi-target,and multi-pathway,with a mechanism that may be related to the inhibition of PI3K/AKT signaling pathway activation.
2.Exploration of the Mechanism of Toddalia asiatica in the Treatment of Ischemic Stroke:Based on Network Pharmacology and Experimental Validation
Jian-Hong GAO ; Dan YANG ; Gang WANG ; Tian-Ying SONG ; Fang-Yu ZHAO ; Xian-Bing CHEN
Chinese Pharmacological Bulletin 2024;40(7):1375-1383
Aim This study aims to investigate the therapeutic effect and underlying mechanism of Todda-lia asiatica in the treatment of ischemic stroke(IS),utilizing network pharmacology,molecular docking technology,and animal experiments.Methods To screen the chemical components of Toddalia asiatica and its targets related to IS,a database was utilized.A protein-protein interaction(PPI)network was con-structed,followed by KEGG pathway enrichment anal-ysis.Molecular docking was performed to investigate the interaction between the components and target pro-teins.Finally,the effects of the drug on the PI3K/AKT/mTOR pathway and autophagy were validated through animal experiments.We established a middle cerebral artery occlusion(MCAO)rat model and di-vided the rats into the model group,Donepezil hydro-chloride group,Toddalia asiatica group,and sham op-eration group randomly.Observed the pathological changes in neurons of the rat hippocampal and cortical regions induced by the drug,performed immunohisto-chemical analysis to detect and localize mTOR expres-sion,and used Western blot to assess the expression levels of PI3K,p-PI3K,AKT,p-AKT,mTOR,as well as autophagy markers(LC3-Ⅱ and p62).Re-sults A total of 22 active ingredients from Toddalia asiatica,including AKT1 and MAPK3,were identified through screening.Additionally,194 signaling path-ways,such as PI3K/AKT and MAPK,were analyzed.The active compounds in Toddalia asiatica demonstra-ted stable binding affinity with targets associated with ischemic stroke.The results of the animal experiment indicated that,compared to the sham-operated group,the neuronal distribution in the hippocampal and corti-cal regions of the model group rats became sparser and more disorganized.There was a decrease in the number of Nissl bodies and cytoplasmic vacuolization.The ex-pression of mTOR-positive cells in the hippocampal and cortical regions was reduced.Additionally,the ex-pression levels of p-PI3K,p-AKT,mTOR,and p62 in the rat hippocampal tissue decreased(P<0.05,P<0.01),while the expression of LC3-Ⅱ increased(P<0.01).Compared with the model group,the rats in the Toddalia asiatica and the Donepezil hydrochloride groups effectively improved the aforementioned indica-tors in rats.Conclusions Network pharmacology a-nalysis has revealed the promising potential of Toddalia asiatica in treating ischemic stroke,attributed to its di-verse components,targets,and pathways.The animal experiment showed that Toddalia asiatica can protect the neuronal structure in the hippocampal and cortical regions,which may be related to the inhibition of ex-cessive autophagy mediated by the PI3 K/AKT/mTOR pathway.
3.Research progress on mechanism of interaction between traditional Chinese medicine and intestinal flora
Jing WU ; Wei-Yi TIAN ; Kun CAI ; Su-Fang ZHOU ; Yao-Feng LI ; Xiang-Yun CHEN ; Hai-Bing QIAN ; Sha-Sha YANG
Chinese Pharmacological Bulletin 2024;40(10):1823-1829
Modern Chinese medicine studies have confirmed that the interaction between traditional Chinese medicine(TCM)and intestinal flora is the key to the treatment of diseases with tradi-tional Chinese medicine.This interplay includes such activities as:traditional Chinese medicine can be metabolized by intestinal flora into effective components with different biological activities from its precursors;TCM chemicals improve the composition of gut microbiota,consequently ameliorating its dysfunction as well as associated pathological conditions;and gut microbiota mediate the interactions between the multiple chemicals in TCM.There-fore,it becomes an important way to understand the modern sci-entific connotation of traditional Chinese medicine theory to study the pharmacological mechanism of the efficacy of traditional Chi-nese medicine by targeting Gut microbiota.
4.Total saponins from Trillium tschonoskii maxim alleviates cerebral ischemia-reperfusion injury by inhibiting ferroptosis through Keap-1/Nrf2/HO-1 and Nrf2/SLC7A11/GPX4 pathways
Jian-Hong GAO ; Tian-Ying SONG ; Chao-Xi TIAN ; Fang-Yu ZHAO ; Yi-Duo HE ; Xin LIU ; Xian-Bing CHEN
Chinese Pharmacological Bulletin 2024;40(10):1850-1857
Aim To examine the neuroprotective im-pacts of total saponins from Trillium tschonoskii maxim(TST)on cerebral ischemia-reperfusion injury(CIRI)in rats and delve into the mechanisms of ferroptosis.Methods The CIRI model was prepared by dividing male SD rats into the model group,TST(0.1 g·kg-1)group,Donepezil hydrochloride(0.45 mg·kg-1)group,and sham group.The cognitive functions of rats in each group were assessed through the Morris water maze test,the changes in neurological function were evaluated using the Zea-Longa method,the infarct area was observed via TTC staining,and the pathologi-cal alterations in brain tissue were analysed using HE and Nissl staining.To further investigate the underly-ing mechanism,the mitochondrial structural changes were examined using transmission electron microscopy,and the levels of GSH-PX,MDA,and SOD were ana-lyzed.Additionally,the expressions of GPX4 and Nrf2 proteins were evaluated through immunohistochemistry and immunofluorescence.Furthermore,the protein lev-els of Keap1/Nrf2/HO-1 and Nrf2/SLC7A11/GPX4 pathways in rats were examined using Western blot-ting.Results The rats in the model group displayed diminished learning and memory capabilities in com-parison to those in the sham group,as well as a signifi-cantly increased cerebral infarction area and higher neurological function scores(P<0.01),significantly increased cerebral infarct area,disordered and loosely arranged neurons,and reduced Nissl bodies.Addition-ally,mitochondria showed typical signs of ferroptosis.Changes related to ferroptosis included decreased activ-ities of SOD and GSH-PX(P<0.01)and increased MDA levels(P<0.01).The expression of GPX4 and Nrf2-positive cells was significantly reduced,along with decreased fluorescence intensity of GPX4.Further-more,the protein expression of Keap1,Nrf2,HO-1,GPX4,SLC7A11 in the hippocampus decreased(P<0.05,P<0.01).Following the administration of TST,these effects showed improvement.Conclusions TST has neuroprotective effects,enhancing learning and memory abilities while reducing oxidative stress levels.The mechanism may involve the inhibition of ferroptosis through the Keap-1/Nrf2/HO-1 and Nrf2/SLC7 A11/GPX4 pathways.
5.Key points and standard status of quality evaluation of oromucosal drug delivery preparations
Liuliu YANG ; Mingyan LI ; Junqi ZHANG ; Bing WANG ; Yue SHANG ; Fang CHEN
Drug Standards of China 2024;25(3):220-226
Oromucosal drug delivery preparations offer advantages such as convenient administration,suitability for patients with dysphagia,rapid onset of action,and avoidance of first-pass metabolism in the liver.The 2020 edition of the Chinese Pharmacopoeia,EP11.0,BP2022,USP44-NF39,and JP18 all include relevant standards for the quality control of different oromucosal drug delivery systems.This article compares the differences in general re-quirements for oromucosal formulations among different countries and provides an overview of inspection items for marketed oral mucosal formulations and those documented in pharmacopoeias both domestically and internationally.Foreign pharmacopoeias include a wide range of oromucosal drug delivery formulations,with more refined quality control measures for systemic action.These findings can serve as a reference for the improvement and enhancement of standards for oromucosal drug delivery systems in China.
6.Effect of long non-coding RNA FGD5-AS1 on high glucose-induced myocardial cell injury through regulation of the miR-195-5p/PIM1 axis
Bing TAN ; Lingyan FANG ; Minghua CHEN ; Qiaoli ZENG ; Runmin GUO
Journal of China Medical University 2024;53(6):487-494
Objective To investigate the effect of the long non-coding RNA FGD5 antisense RNA1(lncRNA FGD5-AS1)on myocar-dial cell injury induced by high glucose levels through regulation of the miR-195-5p/Pim-1 proto-oncogene(PIM1)axis.Methods The rat myocardial cell line H9c2 and human myocardial cells were randomly allocated to the control,model,lncRNA FGD5-AS1 overex-pression,miR-195-5p inhibitor,negative control,and lncRNA FGD5-AS1 overexpression+miR-195-5p mimic groups to determine the expression of lncRNA FGD5-AS1,miR-195-5p,and PIM1.In addition,cell proliferation,apoptosis,and pro-inflammatory cytokine levels of the cells in each group were analyzed.Results Compared with the control group,the protein and mRNA expressions of lncRNA FGD5-AS1 and PIM1 and the survival and proliferation rates in H9c2 and human myocardial cells in the model group decreased(P<0.05),and the expression of miR-195-5p,apoptosis rate,and production levels of tumor necrosis factorα(TNF-α)and interleukin-6(IL-6)increased(P<0.05).Overexpression of the lncRNA FGD5-AS1 reversed these pathological changes in model group cells,whereas upregulation of miR-195-5p could weaken the effects of overexpression of lncRNA FGD5-AS1.Conclusion Overexpression of lncRNA FGD5-AS1 enhances the expression of PIM1 by downregulating miR-195-5p,thereby inhibiting high glucose-induced myocyte inflamma-tion,promoting survival and growth,and alleviating apoptotic injury.
7.Environmental hygiene and healthcare-associated infection:a time-series study based on generalized additive model
Kai LIN ; Kun CHEN ; Jian-Bing WANG ; Fang-Hua FAN ; Hui LIANG ; Fang CHEN ; Kai-Ling JIN ; Wen-Jie CHU ; Wei-Guo CHEN ; Huan SHAN
Chinese Journal of Infection Control 2024;23(7):798-805
Objective To quantitatively analyze the impact of environmental hygiene on the occurrence of health-care-associated infections(HAI).Methods Monitoring data of HAI and environmental hygiene from a tertiary first-class hospital from January 2018 to December 2022 were collected,and the impact of environmental bacterial colony forming unit(CFU)on the occurrence of HAI was analyzed by a time-series generalized additive model.Results The single-contamination model showed a significant positive correlation between HAI and staff's hand bacterial CFU(β1=0.009,P=0.012).For an increase of 1 interquartile range(IQR)in the monthly mean CFU per dish(MCFU/Dish)of staffs'hand,the incidence of HAI increased by 13.28%(95%CI:2.82%-24.81%).Subgroup and lag effect analysis showed that when the monthly MCFU/Dish(after hand disinfection)of staffs'hand in-creased by one IQR,the excess risk(ER)of HAI for the month(lag0)was 16.26%(95%CI:15.45%-17.09%).In the multi-contamination model,the correlation between surface contamination and HAI was also statistically sig-nificant.Conclusion There is a significant correlation between hospital environmental hygiene and the occurrence of HAI.
8.Hua Xian Fang alleviates radiation-induced pulmonary fibrosis by upregulating the level of IFN-γ in blood and tissues
Junyang CHEN ; Pingjin ZOU ; Zengyi FANG ; Cuicui GONG ; Jie YIN ; Meihua CHEN ; Bing LIN ; Jinyi LANG
Chinese Journal of Radiation Oncology 2024;33(6):554-561
Objective:To investigate the therapeutic efficacy and underlying mechanisms of the traditional Chinese medicine formula "Hua Xian Fang" (HXF) in the treatment of radiation-induced pulmonary fibrosis (RIPF).Methods:In vivo experiment, 36 male specific pathogen free (SPF)-grade C57BL/6 mice aged 6-8 weeks were randomly divided into the control, irradiation (17 Gy thoracic irradiation), and irradiation+HXF groups (17 Gy thoracic irradiation+HXF). After 16 weeks, lung coefficient, HE staining and Masson staining were used to evaluate the degree of pulmonary inflammation and fibrosis. Immunohistochemistry was performed to measure the expression levels of α-smooth muscle actin (α-SMA) in lung tissues. Quantitative real-time PCR (qPCR) was performed to detect the mRNA expression levels of interferon-γ (IFN-γ). Enzyme linked immunosorbent assay (ELISA) was conducted to determine the levels of IFN-γ in serum and bronchoalveolar lavage fluid (BALF). During in vitro experiment, NIH/3T3 fibroblasts were stimulated with IFN-γ after 6 Gy irradiation, followed by 48 hours of culture. qPCR, immunofluorescence staining, and Western blot were used to assess the expression of α-SMA and collagen Ⅰ at the transcription and protein levels. One way ANOVA was used for multiple group comparisons, and Tukey test was used for inter group multiple comparisons. Results:Compared to the control group, mice in the irradiation group showed significant increases in lung coefficient, Szapiel score, Ashcroft score, and α-SMA expression in lung tissues (all P<0.001). Compared to the irradiation group, the irradiation+HXF group exhibited significant decreases in the above indicators (all P<0.001). qPCR demonstrated that the mRNA expression levels of IFN-γ were significantly higher in the irradiation+HXF group than that in the irradiation group ( P=0.001). ELISA results showed that the levels of IFN-γ in serum and BALF were significantly elevated in the irradiation+HXF group compared to those in the irradiation group ( P=0.032, 0.037). In vitro experiment revealed that after irradiation, the expression levels of α-SMA and collagen Ⅰ mRNA and protein in NIH/3T3 cells were significantly increased, while decreased after IFN-γ stimulation. Conclusion:HXF effectively alleviates RIPF, probably by the upregulation of IFN-γ in blood and tissues and inhibition of fibroblast activation.
9.A Precise and Portable Detection System for Infectious Pathogens Based on CRISPR/Cas Technology
Yi-Chen LIU ; Ru-Jian ZHAO ; Bai-Yang LYU ; De-Feng SONG ; Yi-Dan TANG ; Yan-Fang JIANG ; Bing-Ling LI
Chinese Journal of Analytical Chemistry 2024;52(2):187-197
Nucleic acid-based molecular diagnostic methods are considered the gold standard for detecting infectious pathogens.However,when applied to portable or on-site rapid diagnostics,they still face various limitations and challenges,such as poor specificity,cumbersome operation,and portability difficulties.The CRISPR(Clustered regularly interspaced short palindromic repeats)/CRISPR-associated protein(Cas)-fluorescence detection method holds the potential to significantly enhance the specificity and signal-to-noise ratio of nucleic acid detection.In this study,we developed a portable grayscale reader detection system based on loop-mediated isothermal amplification(LAMP)-CRISPR/Cas.On one hand,in the presence of CRISPR RNA(crRNA),the CRISPR/Cas12a system was employed to achieve precise fluorescent detection of self-designed LAMP amplification reactions for influenza A and influenza B viruses.This further validated the high selectivity and versatility of the CRISPR/Cas system.On the other hand,the accompanying independently developed portable grayscale reader allowed for low-cost collection of fluorescence signals and high-reliability visual interpretation.At the end of the detection process,it directly provided positive or negative results.Practical sample analyses using this detection system have verified its reliability and utility,demonstrating that this system can achieve highly sensitive and highly specific portable analysis of influenza viruses.
10.Research on three-dimensional ordered porous carbon-based materials prepared from Acanthopanax senticosus traditional Chinese medicine residues and their drug loading performance
De-sheng WANG ; Jia-xin FAN ; Ri-qing CHENG ; Shi-kui WU ; Lai-bing WANG ; Jia-hao SHI ; Ting-ting CHEN ; Qin-fang HE ; Chang-jin XU ; Hui-qing GUO
Acta Pharmaceutica Sinica 2024;59(10):2857-2863
Three-dimensional ordered porous carbon materials exhibit potential application prospects as excellent drug supports in drug delivery systems due to their high specific surface area, tunable pore structure, and excellent biocompatibility. In this study, three-dimensional ordered porous carbon materials were prepared using

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