1.Network Pharmacology and Experimental Verification Unraveled The Mechanism of Pachymic Acid in The Treatment of Neuroblastoma
Hang LIU ; Yu-Xin ZHU ; Si-Lin GUO ; Xin-Yun PAN ; Yuan-Jie XIE ; Si-Cong LIAO ; Xin-Wen DAI ; Ping SHEN ; Yu-Bo XIAO
Progress in Biochemistry and Biophysics 2025;52(9):2376-2392
ObjectiveTraditional Chinese medicine (TCM) constitutes a valuable cultural heritage and an important source of antitumor compounds. Poria (Poria cocos (Schw.) Wolf), the dried sclerotium of a polyporaceae fungus, was first documented in Shennong’s Classic of Materia Medica and has been used therapeutically and dietarily in China for millennia. Traditionally recognized for its diuretic, spleen-tonifying, and sedative properties, modern pharmacological studies confirm that Poria exhibits antioxidant, anti-inflammatory, antibacterial, and antitumor activities. Pachymic acid (PA; a triterpenoid with the chemical structure 3β-acetyloxy-16α-hydroxy-lanosta-8,24(31)-dien-21-oic acid), isolated from Poria, is a principal bioactive constituent. Emerging evidence indicates PA exerts antitumor effects through multiple mechanisms, though these remain incompletely characterized. Neuroblastoma (NB), a highly malignant pediatric extracranial solid tumor accounting for 15% of childhood cancer deaths, urgently requires safer therapeutics due to the limitations of current treatments. Although PA shows multi-mechanistic antitumor potential, its efficacy against NB remains uncharacterized. This study systematically investigated the potential molecular targets and mechanisms underlying the anti-NB effects of PA by integrating network pharmacology-based target prediction with experimental validation of multi-target interactions through molecular docking, dynamic simulations, and in vitro assays, aimed to establish a novel perspective on PA’s antitumor activity and explore its potential clinical implications for NB treatment by integrating computational predictions with biological assays. MethodsThis study employed network pharmacology to identify potential targets of PA in NB, followed by validation using molecular docking, molecular dynamics (MD) simulations, MM/PBSA free energy analysis, RT-qPCR and Western blot experiments. Network pharmacology analysis included target screening via TCMSP, GeneCards, DisGeNET, SwissTargetPrediction, SuperPred, and PharmMapper. Subsequently, potential targets were predicted by intersecting the results from these databases via Venn analysis. Following target prediction, topological analysis was performed to identify key targets using Cytoscape software. Molecular docking was conducted using AutoDock Vina, with the binding pocket defined based on crystal structures. MD simulations were performed for 100 ns using GROMACS, and RMSD, RMSF, SASA, and hydrogen bonding dynamics were analyzed. MM/PBSA calculations were carried out to estimate the binding free energy of each protein-ligand complex. In vitro validation included RT-qPCR and Western blot, with GAPDH used as an internal control. ResultsThe CCK-8 assay demonstrated a concentration-dependent inhibitory effect of PA on NB cell viability. GO analysis suggested that the anti-NB activity of PA might involve cellular response to chemical stress, vesicle lumen, and protein tyrosine kinase activity. KEGG pathway enrichment analysis suggested that the anti-NB activity of PA might involve the PI3K/AKT, MAPK, and Ras signaling pathways. Molecular docking and MD simulations revealed stable binding interactions between PA and the core target proteins AKT1, EGFR, SRC, and HSP90AA1. RT-qPCR and Western blot analyses further confirmed that PA treatment significantly decreased the mRNA and protein expression of AKT1, EGFR, and SRC while increasing the HSP90AA1 mRNA and protein levels. ConclusionIt was suggested that PA may exert its anti-NB effects by inhibiting AKT1, EGFR, and SRC expression, potentially modulating the PI3K/AKT signaling pathway. These findings provide crucial evidence supporting PA’s development as a therapeutic candidate for NB.
2.Application and research progress of artificial intelligence in the assessment of subsolid nodules
Fei LI ; Zhen BAI ; Jin-Long LIU ; Dan-Yang SU ; Shen-Yu YANG ; Yuan-Bo MA ; Ya-Man LI ; Yu-Fang DU ; Xiao-Peng YANG
Medical Journal of Chinese People's Liberation Army 2025;50(10):1243-1249
Lung cancer has the highest incidence and mortality among malignant tumors in China.Persistent subsolid nodules(SSNs)are closely associated with early-stage lung adenocarcinoma.Artificial intelligence(AI),as an emerging technology,is capable of performing in-depth analysis of large-scale imaging data through autonomous learning and possesses the ability to predict outcomes from new data,demonstrating great potential and application prospects in the assessment of SSNs.AI can not only effectively assist radiologists in diagnosis and treatment,but also improve work efficiency while reducing misdiagnosis and missed diagnosis rates.This review summarizes the recent applications and research progress of AI in the assessment of SSNs,to provide new insights for the diagnosis and treatment of SSNs.
3.Regulatory effect of polygonatum odoratum extract on inflammatory factor tumor necrosis factor-α in Alzheimer's disease cells
Ping SHEN ; Hang LIU ; Zhao-Ming ZENG ; Yu-Bo XIAO ; Ling-Yan DENG ; Lan-Yu LI ; Zhong-Cheng MO
Acta Anatomica Sinica 2025;56(5):548-556
Objective To investigate the potential mechanism of action of polygonatum odoratum in treating Alzheimer's disease through the utilization of network pharmacology and molecular docking techniques.Methods The methods employed include target screening,Gene Ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,and molecular docking simulations to assess the binding interactions between the active compounds in polygonatum odoratum(POD)and the key target proteins associated with Alzheimer's disease.Subsequently,lipopolysaccharide(LPS)was used to induce an inflammatory cell model in BV2 microglial cells.After treating the cell model with POD extract for 24 hours,the cells were collected,and the expression of the target genes were detected by Real-time PCR.Results Eight active ingredients and 172 targets of POD were screened.The biological processes such as protein phosphorylation and signal transduction,protein binding and ATP binding were obtained by GO functional analysis.KEGG enrichment yielded PI3K/Akt,cAMP and other signaling pathways.The molecular docking result showed that the active ingredient of POD had well binding activity with epidermal growth factor receptor(EGFR),proto-oncogene tyrosine-protein kinase Src(SRC),tumor necrosis factor(TNF),STAT3.Through Real-time PCR experiments,the gene expressions of inducible nitric oxide synthase(iNOS),prostaglandin G/H synthase 2(PTGS2),interleukin(IL)-6,and IL-1β in the LPS-induced inflammatory cell model were significantly upregulated.After treating the inflammatory model with POD extract for 24 hours,the expression of TNF-α was significantly reduced,the expression of STAT3 was upregulated,there were no significant changes in the expressions of SRC and EGFR.Conclusion Network pharmacology suggests polygonatum odoratum's potential anti-Alzheimer's effects may be mediated through its interaction with targets such as EGFR,TNF,SRC,and STAT3.The experimental results suggest that polygonatum odoratum exerts an anti-inflammatory effect by acting on TNF-α,which may further alleviate the symptoms of Alzheimer's disease.
5.Primary Study of Video-assisted Thoracoscopic Surgery Without Chest Tube Drainage for Infants With Congenital Pulmonary Airway Malformation
Xiao LI ; Chun CAI ; Bin ZHOU ; Lei LOU ; Linghui SHEN ; Gang ZHANG ; Xiaotong ZHOU ; Gang YU
Chinese Journal of Minimally Invasive Surgery 2025;25(2):65-69
Objective To evaluate the technical feasibility and safety of video-assisted thoracoscopic surgery(VATS)without chest tube placement for infants with congenital pulmonary airway malformation(CPAM).Methods Clinical data of 145 infants with CPAM treated by VATS from May 2019 to August 2022 were retrospectively analyzed.Six cases had a chest tube placement at the end of the surgery,while 139 cases did not.Among them,there were 99 segmental lobectomies,36 lobectomies,and 4 lobectomies and segmental lobectomies.Clinical efficacy and postoperative complications were observed.Results All the 145 patients underwent resection by VATS without conversion to thoracotomy.There was no mortality during the perioperative period.In the 139 cases without chest tube placement at the end of surgery,the operation time was(42.0±16.6)min,and the intraoperative blood loss was(2.7±2.0)ml.The were 6 cases who were given indwelling drainage tube for pneumothorax or pleural effusion after surgery,the rate of re-catheterization being 4.3%.The remaining 133 cases had chest X-ray review on the third day after routine surgery.Among them,8 cases had mild pneumothorax(lung compression<20%)on the surgical side,which did not require further treatment.Before discharge,chest X-ray re-examination showed that pneumothorax was basically absorbed.All the patients were discharged with uneventful recovery,and the hospital stay was(6.6±1.3)d.Conclusion VATS without chest tube placement is a safe and feasible surgical procedure for some selective infants with congenital pulmonary airway malformation.
6.Research Progress on Detection Methods for Cytokeratin 19 Fragment Antigen 21-1
Jia-Hui DONG ; Li-Yue SHEN ; Ji-Hao SI ; Xiao-Ping YU ; Tao PENG
Chinese Journal of Analytical Chemistry 2025;53(3):328-337
Cytokeratin 19 fragment antigen 21-1(CYFRA21-1)is a new biomarker which has received much attention in recent years for cancer screening,and has shown great potentials for screening and diagnosis of various cancers,especially non-small cell lung cancer.CYFRA21-1 level in human serum has important clinical significance in the diagnosis,prognosis and treatment of lung cancer.Recently,a variety of detection techniques have been established to effectively enrich the detection technology system of CYFRA21-1,such as enzyme-linked immunosorbent assay,chemiluminescence,fluorescence,immunochromatography,electrochemical method,and surface enhanced Raman spectroscopy,etc.These techniques provide technical support for early diagnosis of lung cancer.However,the research progress of CYFRA21-1 detection methods is rarely reported.In this paper,CYFRA21-1 and its clinical significance were briefly introduced,and the progress of detection technology in recent ten years was reviewed,which was expected to provide reference for developing more sensitive,accurate,fast and convenient detection methods.
7.Synthesis and Application of Benzimidazole-Carbazole-based Fluorescent Probe for Detection of Phosgene
Guang-Mei XU ; Ze-Yu SONG ; Qin-Qin TIAN ; Xiao-Hong ZHU ; Jin-Chao SHEN ; Wei HE
Chinese Journal of Analytical Chemistry 2025;53(10):1705-1713,中插37-中插41
Phosgene is a highly reactive chemical substance and a prevalent chemical warfare agent,and it is vitally important for rapid and accurate detection of phosgene to counteract terrorist threats and industrial accidents.In this work,a phosgene probe,designated as SX-Pho,which incorporated benzimidazole and hydroxyl groups as recognition motifs,was prepared through Suzuki coupling and Debus-Radziszewski methodologies to incorporate an electron-donating carbazole moiety.This probe exhibited a large Stokes shift(Approximately 130 nm).Upon exposure to triphosgene/triethylamine conditions(in situ phosgene generation),the fluorescence emission of probe at 470 nm underwent significant quenching,with a 20-fold reduction in intensity,while the fluorescence lifetime decreased from 3.30 ns to 3.06 ns.Concentration titration experiments demonstrated that SX-Pho achieved a lower detection limit of 57.8 nmol/L with high specificity and interference resistance.Preton nuclear magnetic resonance spectroscopy(1H NMR),high-resolution mass spectrometry,and density functional theory(DFT)calculations confirmed the cyclization reaction between hydroxyl groups,imines,and phosgene.The extent of overlap between the highest occupied molecular orbital(HOMO)and the lowest unoccupied molecular orbital(LUMO)was notably decreased,leading to the suppression of radiative transitions.The energy gap underwent a reduction of 0.43 eV,while the non-radiative transition was augmented,resulting in fluorescence quenching and achieving rapid detection of phosgene.Based on this,probe-loaded test strips were prepared.The color change under 365 nm illumination allowed visual discrimination of phosgene at concentrations below 20 μL/L.Furthermore,using a smartphone's built-in RGB application to measure the intensity of the blue(B)channel after the test strips were exposed to phosgene enabled both qualitative and quantitative detection.The detection range was 1.82-50 μL/L,with a limit of detection(LOD)of 1.814 μL/L.
8.Ursodeoxycholic acid inhibits the uptake of cystine through SLC7A11 and impairs de novo synthesis of glutathione
Fu'an XIE ; Yujia NIU ; Xiaobing CHEN ; Xu KONG ; Guangting YAN ; Aobo ZHUANG ; Xi LI ; Lanlan LIAN ; Dongmei QIN ; Quan ZHANG ; Ruyi ZHANG ; Kunrong YANG ; Xiaogang XIA ; Kun CHEN ; Mengmeng XIAO ; Chunkang YANG ; Ting WU ; Ye SHEN ; Chundong YU ; Chenghua LUO ; Shu-Hai LIN ; Wengang LI
Journal of Pharmaceutical Analysis 2025;15(1):189-207
Ursodeoxycholic acid(UDCA)is a naturally occurring,low-toxicity,and hydrophilic bile acid(BA)in the human body that is converted by intestinal flora using primary BA.Solute carrier family 7 member 11(SLC7A11)functions to uptake extracellular cystine in exchange for glutamate,and is highly expressed in a variety of human cancers.Retroperitoneal liposarcoma(RLPS)refers to liposarcoma originating from the retroperitoneal area.Lipidomics analysis revealed that UDCA was one of the most significantly down-regulated metabolites in sera of RIPS patients compared with healthy subjects.The augmentation of UDCA concentration(≥25 μg/mL)demonstrated a suppressive effect on the proliferation of liposarcoma cells.[15N2]-cystine and[13Cs]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione(GSH)synthesis.Mechanistically,UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis,leading to reactive oxygen species(ROS)accumulation and mitochondrial oxidative damage.Furthermore,UDCA can promote the anti-cancer effects of ferroptosis inducers(Erastin,RSL3),the murine double minute 2(MDM2)inhibitors(Nutlin 3a,RG7112),cyclin dependent kinase 4(CDK4)inhibitor(Abemaciclib),and glutaminase inhibitor(CB839).Together,UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity,and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA.More importantly,in combination with other antitumor chemotherapy or physiotherapy treatments,UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.
9.Research progress of renin-angiotensin system in hypertensive depression
Lu-fan SHEN ; Xiao-ke WANG ; Hong WANG ; Ling-na ZHANG ; Jia-wei LI ; Yu-yuan LU ; Jiao TIAN ; Wan-rong KANG ; A-ni YANG ; Lin YI
Chinese Pharmacological Bulletin 2025;41(9):1629-1635
With the establishment of bio-psycho-social medical model,both social and psychological factors play an important role in the occurrence,development and treatment of diseases.Hypertension is a common chronic multiple disease in China,and patients are often complicated with depression and other e-motional disorders.The interaction between hypertension and depression significantly increases the risk of poor prognosis.Current studies have shown a bidirectional promoting relationship between hypertension and depression,and they have some com-mon pathogenesis.However,the specific mechanism of their co-morbidity has not been fully elucidated.Renin-angiotensin sys-tem(RAS)plays an important role in the regulation of hyperten-sion and depression and other emotions.It is composed of two antagonistic pathways.The balance is maintained by angioten-sin-converting enzyme 2(ACE2).Therefore,this article reviews the relationship and mechanism of RAS in hypertension,depres-sion and comorbid states,in order to provide new treatment ide-as for hypertension and depression.
10.Study on the Correlation between Sleep Disorder and Postoperative Pain,Inflammation Stress Response,and Cognitive Function in Patients with Primary Liver Cancer Undergoing TACE Operative
Xiao-ming GU ; Yu WANG ; Cui-cui ZHANG ; Min SHEN
Progress in Modern Biomedicine 2025;25(10):1676-1684
Objective:To observe the correlation between sleep disorder and postoperative pain,inflammation stress response,and cognitive function in patients with primary liver cancer undergoing transcatheter arterial chemoembolization(TACE)operative.Methods:80 patients with primary liver cancer who were treated in Shandong Provincial Third Hospital from July 2022 to July 2024 were selected,all patients underwent TACE operative.The patients were divided into non sleep disorder group and sleep disorder group according to the pittsburgh sleep quality index(PSQI)score 1 month postoperative.The visual analog scale(VAS),postoperative inflammatory mediators[serum interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-8(IL-8)],postoperative stress response[superoxide dismutase(SOD),malondialdehyde(MDA)],and mini-mental state examination(MMSE)scores between sleep disorder group and non sleep disorder group were compared.Pearson correlation analysis was used to investigate the correlation between sleep disorder and postoperative pain,inflammation stress response,and cognitive function in patients underwent TACE.Results:VAS score,IFN-γ,TNF-α,IL-1β,IL-8,and MDA in the sleep disorder group were higher than those in non sleep disorder group(P<0.05).SOD and MMSE score in sleep disorder group were lower than those in non sleep disorder group(P<0.05).Pearson correlation analysis results showed that,sleep disorder were negatively correlated with SOD and MMSE,while positively correlated with VAS score,IFN-γ,TNF-α,IL-1β,IL-8,and MDA(P<0.05).Conclusion:The incidence of sleep disorder is higher in patients with primary liver cancer TACE postoperative,and sleep disorder can exacerbate postoperative pain and inflammation stress response in patients undergoing TACE operative,and affect cognitive function.

Result Analysis
Print
Save
E-mail