OBJECTIVE: To help researchers learn and utilize drug target database for new drug research, and to provide important information for the management and construction of Drug Target Database.

OBJECTIVEIn this study, we aimed to investigate the expressions of adhesion molecules on human bronchial epithelial cells and neutrophils in co-culture system, assess the effects of puerarin on suppressing these adhesion molecules expressions, and explore the roles of two crucial signal-transduction elements p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor kappa B (NF-κB) in modulating adhesion molecules expressions.

METHODSNeutrophils and BEAS-2B cells (one human bronchial epithelial cell line) were co-cultured, and adhesion molecules expressions on cell surface were detected using flow cytometry. The mRNA levels of adhesion molecules were assessed by real-time quantitative polymerase chain reaction (real-time qPCR). Phosphorylated p38 MAPK and inhibitor κB were analyzed by Western blot.

RESULTSIn co-culture system, adhesion molecules expressions on BEAS-2B cells and neutrophils were enhanced significantly (P<0.05). Correspondingly, the mRNA levels of adhesion molecules were also increased greatly. Moreover, the pretreatment of peurarin obviously suppressed adhesion molecules expressions on cell surface. Furthermore, phosphorylated p38 MAPK and inhibitor κB in BEAS-2B cells and neutrophils were elevated in co-culture system, but decreased significantly after upon the treatment of peurarin (P<0.05).

CONCLUSIONSCoculture boosted the interactions between human bronchial epithelial cells and neutrophils mimicking airway inflflammation, whereas peurarin decreased the expression of adhesion molecules on cell surface by suppressing the activities of p38 MAPK and NF-κB pathways, and exhibiting its anti-inflflammation activity.

Animals ; Base Sequence ; Bronchi ; cytology ; enzymology ; metabolism ; Cattle ; Cell Adhesion Molecules ; metabolism ; Cell Line ; Coculture Techniques ; DNA Primers ; Down-Regulation ; drug effects ; Epithelial Cells ; enzymology ; metabolism ; Isoflavones ; pharmacology ; NF-kappa B ; metabolism ; Neutrophils ; enzymology ; metabolism ; Phosphorylation ; Real-Time Polymerase Chain Reaction ; p38 Mitogen-Activated Protein Kinases ; metabolism

OBJECTIVE To clarify out the network pharmacology mechanism of Polygala tenuifolia against Alzheimer disease(AD).METHODS Firstly,we collected the chemical constituents from Polyg-ala tenuifolia and key targets toward AD.Machine learning algorithms were applied to construct classifi-ers for predicting the effective constituents. Secondly, docking models were utilized for further evalua-tion.Finally,we built constituent-target,target-target network and target-biology pathway network.RE-SULTS 104 chemical constituents Polygala tenuifolia from were collected.Through prediction of blood-brain penetration and validation,36 chemical constituents were selected among 100 chemical constitu-ents,their action targets mainly focused on AChE,COX-2,TNF-α,insulin-degrading enzyme and APP. Their main structure types include Polygala saponins, Polygala glycosides, Polygala shrubby ketones, polygala xanthones and sterols,which acted on AchE,APP,M-TAU,GSK3β and 5HT1A with high fre-quency.Gene-Ontology and KEGG enrichment analysis showed that the main pathways of these con-stituents involve in neurotransmitter release,synaptic conduction and synaptic plasticity,apoptosis reg-ulation,phosphorylation pathway,Ca2+signaling pathway,and so on.CONCLUSION This study uncov-ered a network mechanism of Polygala tenuifolia against Alzheimer disease,which may provide impor-tant information for the further study and new drug development.

OBJECTIVE Using bioinformatics methods, to establish Xiao-Xu-Ming decoction (XX-MD)"compound-vasoconstriction G Protein-Coupled Receptors(GPCR)targets"network,and analyze the vasoconstriction regulatory effective components and the potential targets of XXMD. METHODS Ac-cording to the XXMD herb sources,we retrieved the chemical structures from the national scientific da-ta sharing platform for population and health pharmaceutical information center,TCMSP database and the latest research literature.The chemical molecular library was established after class prediction and screening for medicinal and metabolic properties.Five kinds of vasoconstriction GPCR crystal structure including 5-HT receptors(5-HT1AR,5-HT1BR),AT1R,β2-AR,hUTR and ETB were retrieved from Bank Pro-tein Data Bank database or homology modeling using Discovery Studio 4.1 built-in modeling tools.After virtual screening by Libdock molecular docking,the highest rated 50 compounds of each target were col-lected and analyzed. The collected data were further used to construct and analyze the network. RE-SULTS 859 single compound structures information in XXMD were generalized following the screen-ing of obtained 2043 compounds.The complicated compound-vasoconstriction GPCR targets network of XXMD was then constructed and analyzed by molecular docking with the above five kinds of GPCR target receptors. Most of the chemical composition effects were associated with different vasoconstric-tion GPCR targets,while a few effective components can be applied to multiple GPCR targets at the same time,therefore forming synergies.CONCLUSION Vasorelaxant effects of XXMD may not only result from the collaborative interaction between a variety of active ingredients in Chinese medicine and multi-ple targets,but also from the interaction between some effective component and multiple targets.

OBJECTIVE To find a promising candidate for anti- Alzheimer disease (AD) with multiple targets in multiple pathways. METHODS A series of classifiers were constructed for predicting the active compounds against 51 key targets toward Alzheimer disease (AD) using the multitarget-quantitative structure- activity relationships (mt- QSAR) method. While drug screening assays were established to evaluate the predicted active molecules. In addition, various cellular models and animal models related with AD were set up to further study the effects of the active compounds. RESULTS A system for the discovery of Multitarget-Directed Ligands against AD was set up and applied, the predicted active compounds were validated by the drug screening assays, and several active compounds with multiple targets were discovered. Among them, DL0410 exerted high activity on H3R, α7nAChR, AChE and ERα, also displayed the most significant effect in improving the ability of memory and learning in several AD animal models. The study on its action mechanisms showed that it's effect may partially through increasing neurotransmitter, inhibiting oxidative emergency, inhibiting the expression of APP, and promoting long- term potentiation. Besides, DL0410 is of more safety than the first- line clinical medicines. CONCLUSION DL0410 is a promising candidate for further development for AD treatment.

OBJECTIVETo evaluate the efficacy of the monotherapy of 15 agents in treating essential hypertension.

METHODSAfter 2-week wash-out, a total of 370 patients with seated diastolic blood pressure 95-114 mmHg and seated systolic blood pressure < 180 mmHg were randomized to different therapeutic groups. 24-hour ambulatory blood pressure monitoring was performed before medication and at the end of 8 weeks.

RESULTAll the agents significantly reduced the 24 hour mean blood pressures after treatment except doxazosin, terazosin, and torasemide.

CONCLUSIONThe result suggested that the angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers and long-acting calcium antagonists were effective in treating essential hypertension, while the low-dose doxazosin, terazosin and torasemide can be used for combination therapy but not for monotherapy.

Adrenergic beta-Antagonists ; therapeutic use ; Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Antihypertensive Agents ; classification ; therapeutic use ; Blood Pressure Monitoring, Ambulatory ; Calcium Channel Blockers ; therapeutic use ; Doxazosin ; therapeutic use ; Drug Therapy, Combination ; Humans ; Hypertension ; drug therapy ; Prazosin ; analogs & derivatives ; therapeutic use ; Sulfonamides ; therapeutic use ; Treatment Outcome

Objective To determine the proportion of heroin use among patients who were involved in community-based methadone maintenance treatment (MMT) program and to identify the risk factors associated with heroin use. Methods This study was conducted in 9 MMT clinics within 3 provinces. Thirteen hundred and one patients who met the study criteria were selected from each of the five groups with different dosages of methadone users. An administrative questionnaire was applied to explore the demographics,drug abuse-related behaviors and MMT services received by the clients,etc. The prevalence of depression and anxiety among the clients were also collected by SAS and SDS. Urine samples were collected as a biological marker to indicate if heroin had been used. Results Of the 1301 patients,76.2% were males. The mean age was (34.6±6.5) years while 71.7% had an education level of primary school or below. The average daily dosage of methadone was (48.1±29.4) mg and self-satisfied evaluation score on treatment was 8.6. On average,27.7% urine samples showed positive opiate evidence. Marital status,employment status,treatment retention,self-satisfied evaluation score on dosage and dropout history were found to be significantly associatedwith heroin use,while gender,education level and dosage had no significant association with heroin use. It seemed that risk factors that associated with heroin use were different from areas to areas. Conclusion High quality MMT clinic services,high self-satisfied score,longer treatment retention and low dropout rate seemed to have the effects of reducing the risk of ongoing heroin abuse under the methadone maintenance treatment program.

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.

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.

Lipids,including fats(triglycerides)and lipoids(phospholipids and sterols),not only serve as an energy source for the body but also play a pivotal role throughout the reproductive process,particularly in the establishment and maintenance of early pregnancy.This encompasses the regulate of early embryonic development and uterine tolerance,and the facilitation of embryo implantation.Given the diversity of lipids,this review focuses on extensively studied lipid mediators such as polyunsaturated fatty acids,endocannabinoids,prostaglandins,lysophosphatidic acid,sphingolipids and steroid hormones.It systematically elaborates on the regulatory effects of fatty acid,phospholipid,and cholesterol metabolism on the formation of endometrial receptivity and embryo implantation,as well as the potential underlying mechanisms.The review aims to provide new insights and feasible intervention approaches for predicting and improving the outcomes of natural pregnancy and/or assisted reproductive technology.