1.Research on compaction behavior of traditional Chinese medicine compound extract powders based on unsupervised learning
Ying FANG ; Yan-long HONG ; Xiao LIN ; Lan SHEN ; Li-jie ZHAO
Acta Pharmaceutica Sinica 2025;60(2):506-513
Direct compression is an ideal method for tablet preparation, but it requires the powder's high functional properties. The functional properties of the powder during compression directly affect the quality of the tablet. 15 parameters such as Py, FES-8KN,
2.Terms Related to The Study of Biomacromolecular Condensates
Ke RUAN ; Xiao-Feng FANG ; Dan LI ; Pi-Long LI ; Yi LIN ; Zheng WANG ; Yun-Yu SHI ; Ming-Jie ZHANG ; Hong ZHANG ; Cong LIU
Progress in Biochemistry and Biophysics 2025;52(4):1027-1035
Biomolecular condensates are formed through phase separation of biomacromolecules such as proteins and RNAs. These condensates exhibit liquid-like properties that can futher transition into more stable material states. They form complex internal structures via multivalent weak interactions, enabling precise spatiotemporal regulations. However, the use of inconsistent and non-standardized terminology has become increasingly problematic, hindering academic exchange and the dissemination of scientific knowledge. Therefore, it is necessary to discuss the terminology related to biomolecular condensates in order to clarify concepts, promote interdisciplinary cooperation, enhance research efficiency, and support the healthy development of this field.
3.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.
4.Determination of tamoxifen and its active metabolite Endoxifen in human plasma by UPLC-MS/MS and its application
Xiao-Dong LIN ; Zhe WANG ; Yao-Yao DONG ; Rui-Jie CHEN ; Guang-Hui ZHU
The Chinese Journal of Clinical Pharmacology 2024;40(1):112-116
Objective To establish a rapid and convenient UPLC-MS/MS method for the determination of tamoxifen and its active metabolite endoxifen in plasma of patients with breast cancer.Methods With diazepam as the internal standard,the plasma sample was precipitated with acetonitrile and methanol-acetonitrile was used as mobile phase.The samples were separated by chromatographic column ZORBAX Eclipse plus C18(18 μm,2.1 mm x50 mm)and scanned by electrospray ion source and positive ion multiple reaction monitoring mode.The ion channels were detected as tamoxifen m/z 372.0→72.1,endoxifen m/z 374.0→58.2 and diazepam m/z 285→192.9.Results The linearity of tamoxifen and endoxifen were good in the concentration range of 1-500 ng·mL-1(R2=0.999 5)and 0.5-250 ng·mL-1,respectively(R2=0.999 9).The intra-day and inter-day precision of low,medium and high quality control concentrations were all less than 10%.Tamoxifen and endoxifen were stable at low temperature and stable after repeated freeze-thaw.Conclusion The experimental results show that the method meets the requirements of biological sample analysis,and the sample treatment is simple,specific,and can be used for the accurate and rapid determination of tamoxifen and indoloxifen in human plasma.
5.Clinical trial of Morinda officinalis oligosaccharides in the continuation treatment of adults with mild and moderate depression
Shu-Zhe ZHOU ; Zu-Cheng HAN ; Xiu-Zhen WANG ; Yan-Qing CHEN ; Ya-Ling HU ; Xue-Qin YU ; Bin-Hong WANG ; Guo-Zhen FAN ; Hong SANG ; Ying HAI ; Zhi-Jie JIA ; Zhan-Min WANG ; Yan WEI ; Jian-Guo ZHU ; Xue-Qin SONG ; Zhi-Dong LIU ; Li KUANG ; Hong-Ming WANG ; Feng TIAN ; Yu-Xin LI ; Ling ZHANG ; Hai LIN ; Bin WU ; Chao-Ying WANG ; Chang LIU ; Jia-Fan SUN ; Shao-Xiao YAN ; Jun LIU ; Shou-Fu XIE ; Mao-Sheng FANG ; Wei-Feng MI ; Hong-Yan ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(6):815-819
Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P<0.05).After continuation treatment,the remission rate was 54.59%(202 cases/370 cases),and the recurrence rate was 6.49%(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35%(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.
6.Medullary differentiation-2 mediates obesity-induced myocardial injury by regulating adenosine AMPK
Cheng-Ke HUANG ; Ling-Li ZHOU ; Wei SUN ; Xiao-Dong LIN ; Rui-Jie CHEN
The Chinese Journal of Clinical Pharmacology 2024;40(10):1458-1462
Objective To investigate the effects of medullary differentiation-2(MD-2)in obesity-induced myocardial injury by regulating adenosine 5'-monophosphate-activated protein kinase(AMPK)activity.Methods The obese mice model was established by feeding high-fat feed.The wild-type and MD-2 gene knockout mice were randomly divided into wild-type(WT)-control group(fed normally),WT-model group(fed with high-fat diet),knockout(KO)-control group(fed normally)and KO-model group(fed with high-fat diet)with 8 mice in each group.At week 16,creatine kinase-MB(CK-MB)and lactate dehydrogenase(LDH)were measured by reagent kits;the left ventricular ejection fraction(LVEF)and left ventricular fraction shortening(LVFS)were measured with ultrasonic apparatus;the pathological changes in myocardial tissue were observed by hematoxylin and eosin(HE)staining and Masson staining;the protein expression of phosphorylation AMPK(p-AMPK)was measured by Western blot.Results HE staining and Masson staining results revealed significant necrosis and fibrosis of the myocardial tissue in WT-model group,while the degrees of necrosis and fibrosis in KO-model group were significantly reduced.The LVEF values of the WT-control group,WT-model group,KO-control group and KO-model group were(83.98±7.58)%,(52.03±4.91)%,(76.42±3.89)%and(73.71±4.22)%,respectively;the LVFS values of each group were(53.61±8.51)%,(24.56±3.76)%,(48.14±5.00)%and(44.07±3.74)%,respectively;the CK-MB values of each group were(49.83±15.49),(83.75±11.90),(54.03±18.66)and(66.85±12.98)U·L-1,respectively;the LDH values of each group were(12.24±3.20),(27.90±6.10),(13.55±3.55)and(15.53±2.58)U·L-1,respectively;the relative expression levels of p-AMPK in each group were 221.31±88.76,46.29±10.07,148.66±32.02 and 161.49±78.11.Compared with WT-control group,the above indicators in WT-model group,compared with WT-model group,the above indicators in KO-model group,the differences were statistically significant(all P<0.05).Conclusion MD-2 mediates high-fat feed induced myocardial injury in obese mice by inhibiting AMPK activity.
7.Pan-cancer analysis revealed the correlation between SPP1 and clinical prognosis of multiple tumors
Jie CHEN ; Mo ZHANG ; Zhan-Yu MEN ; Lin CHEN ; Lu WANG ; Xiao-Cong PANG
The Chinese Journal of Clinical Pharmacology 2024;40(12):1827-1831
Objective This study utilized bioinformatics to investigate the role of secreted phosphoprotein 1(SPP1)in tumors and assess its differential expression and prognostic significance across human cancers.Method Cancer sample data was sourced from the Cancer Genome Atlas(TCGA)and Genotype-tissue Expression(GTEx)database.Analysis of gene expression differences in pan-cancer involving SPP1 utilized the CPTAC database,correlations between SPP1 and patient survival outcomes were assessed using GEPIA2,and alterations in gene mutations for SPP1 across 32 cancers were appraised via the CbioPortal tool.Results Across 32 tumor types,SPP1 mRNA disparity is observed in eight cancer types,decreasing only in clear cell renal carcinoma while increasing in other malignancies.Expression in tumor stage is specific;SPP1 mRNA negatively correlates with patient overall survival(OS)and disease-free survival(DFS);low methylation associated with SPP1 gene activity promotes oncogene activation,impacting tumor cell generation,apoptosis,and proliferation,thereby influencing cancer progression;SPP1 primarily exhibits missense mutations that correlate with poor prognoses in prostate and stomach cancer patients.Conclusion Through pan-cancer studies,SPP1's selective expression in human malignancies was validated and found to be strongly correlated with clinical prognosis.This suggests that SPP1 is a viable target for cancer prognostic precision.
8.Immunoinfiltration correlation analysis of secreted phosphoprotein SPP1 in multiple tumors
Jie CHEN ; Lin CHEN ; Yan-Lun GU ; Mo ZHANG ; Zhan-Yu MEN ; Lu WANG ; Xiao-Cong PANG
The Chinese Journal of Clinical Pharmacology 2024;40(13):1968-1971
Objective To utilize bioinformatic approaches to elucidate the correlation between secreted phosphoprotein 1(SPP1)and immune infiltration in various malignancies,elucidating the mechanism of gene function in cancer-immune cell interplay.Methods Cancer samples were derived from the Cancer Genome Atlas(TCGA)and Genotype-tissue Expression(GTEx)database,examining SPP1 expression difference between tumors and normal tissues using Gene Expression Profiling Interactive Analysis(GEPIA2),and its correlation with different immune cells in extracellular matrix via TIMER2 Database.SPP1's association with interacting molecules was scrutinized on the STRING website,followed by assessment of its distinct functional state across various cancers from Cancer Single-cell State Atlas Database(Cancer SEA).Results In 32 tumor types,SPP1 mRNA is significantly elevated in 23 types of cancers and correlates heavily with fibroblast,integrin family,and CD44.Furthermore,the SPP1 gene exhibits profound specificity in tumor functions such as vascular invasion,metastasis,DNA damage,and repair.Conclusion Specific expression of SPP1 in tumors signifies a significant correlation with tumor immune cells in the extracellular matrix,promoting tumor progression and invasion.This suggests that targeted monitoring of SPP1 could serve as a prospective cancer diagnostics/therapeutics biomarker.
9.Effects of matrine on the proliferation,migration,and invasion of neuroblastoma cells
Nan-Jing LIU ; Dong-Juan WANG ; Fang-Jie LIU ; Wen-Xia HUANG ; Lin ZOU ; Xiao-Yan HE
The Chinese Journal of Clinical Pharmacology 2024;40(14):2048-2052
Objective To observe the effects of matrine on the proliferation,migration,and invasion of human neuroblastoma cells,and to investigate its potential mechanism.Methods This study was divided into AS experimental group(SK-N-AS cells treated with IC50 concentration of matrine),AS blank group(SK-N-AS cells cultured under normal conditions),AS control group(SK-N-AS cells treated with an equal amount of dimethyl sulfoxide),DZ experimental group(SK-N-DZ cells treated with IC50 concentration of matrine),DZ blank group(SK-N-DZ cells cultured under normal conditions),and DZ control group(SK-N-DZ cells treated with an equal amount of dimethyl sulfoxide).Scratch assay and Transwell chamber were used to measure the effect of matrine on the migration and invasion.The expression of E-cadherin,N-cadherin and Vimentin were tested by Western blot.Results After different intervention,the migration percentages of AS blank group,AS control group,AS experimental group,DZ blank group,DZ control group and DZ experimental group were(66.32±3.12)%,(65.27±3.44)%,(23.73±0.79)%,(46.25±4.68)%,(44.15±5.60)%and(16.77±3.52)%,respectively;the number of invasive cells were 870.45±19.32,865.32±23.39,492.74±16.81,1 198.10±43.71,1 203.03±71.91 and 891.69±42.62,respectively;the expression levels of E-cadherin protein were(100.00±11.72)%,(105.65±13.11)%,(477.20±29.71)%,(100.00±12.54)%,(97.78±12.77)%and(240.53±12.23)%,respectively;the expression levels of N-cadherin protein were(100.00±15.44)%,(103.90±10.76)%,(43.52±9.96)%,(100.00±10.12)%,(104.95±10.49)%and(38.39±8.70)%,respectively;Vimentin protein expression levels were(100.00±9.51)%,(97.39±11.33)%,(59.13±10.25)%,(100.00±13.20)%,(96.27±11.01)%and(47.67±9.48)%,respectively.There were statistically significant differences in the above indexes between the AS group and the AS blank group(P<0.01,P<0.001),and there were statistically significant differences between the above indexes in the DZ group and the DZ blank group(P<0.01,P<0.001).Conclusion Matrine inhibits the proliferation,migration,and invasion of neuroblastoma SK-N-AS and SK-N-DZ cells,potentially through suppressing epithelial-mesenchymal transition.
10.Polysaccharide of Alocasia cucullata Exerts Antitumor Effect by Regulating Bcl-2, Caspase-3 and ERK1/2 Expressions during Long-Time Administration.
Qi-Chun ZHOU ; Shi-Lin XIAO ; Ru-Kun LIN ; Chan LI ; Zhi-Jie CHEN ; Yi-Fei CHEN ; Chao-Hua LUO ; Zhi-Xian MO ; Ying-Bo LIN
Chinese journal of integrative medicine 2024;30(1):52-61
OBJECTIVE:
To study the in vitro and in vivo antitumor effects of the polysaccharide of Alocasia cucullata (PAC) and the underlying mechanism.
METHODS:
B16F10 and 4T1 cells were cultured with PAC of 40 µg/mL, and PAC was withdrawn after 40 days of administration. The cell viability was detected by cell counting kit-8. The expression of Bcl-2 and Caspase-3 proteins were detected by Western blot and the expressions of ERK1/2 mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). A mouse melanoma model was established to study the effect of PAC during long-time administration. Mice were divided into 3 treatment groups: control group treated with saline water, positive control group (LNT group) treated with lentinan at 100 mg/(kg·d), and PAC group treated with PAC at 120 mg/(kg·d). The pathological changes of tumor tissues were observed by hematoxylin-eosin staining. The apoptosis of tumor tissues was detected by TUNEL staining. Bcl-2 and Caspase-3 protein expressions were detected by immunohistochemistry, and the expressions of ERK1/2, JNK1 and p38 mRNA were detected by qRT-PCR.
RESULTS:
In vitro, no strong inhibitory effects of PAC were found in various tumor cells after 48 or 72 h of administration. Interestingly however, after 40 days of cultivation under PAC, an inhibitory effect on B16F10 cells was found. Correspondingly, the long-time administration of PAC led to downregulation of Bcl-2 protein (P<0.05), up-regulation of Caspase-3 protein (P<0.05) and ERK1 mRNA (P<0.05) in B16F10 cells. The above results were verified by in vivo experiments. In addition, viability of B16F10 cells under long-time administration culture in vitro decreased after drug withdrawal, and similar results were also observed in 4T1 cells.
CONCLUSIONS
Long-time administration of PAC can significantly inhibit viability and promote apoptosis of tumor cells, and had obvious antitumor effect in tumor-bearing mice.
Mice
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Animals
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Alocasia/metabolism*
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MAP Kinase Signaling System
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Caspase 3/metabolism*
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Apoptosis
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RNA, Messenger/metabolism*

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