Analgesic Effect and Mechanism of Osteoking on Dorsal Root Ganglion Compression Model Rats / 中国实验方剂学杂志

ObjectiveTo investigate the analgesic effect and mechanism of Osteoking （OK） on nerve compression in lumbar disc herniation. MethodThe rat model of chronic compression of dorsal root ganglion （CCD） was established to simulate clinical lumbar disc herniation. The CCD rats were randomly divided into model group， low， medium， and high dose OK groups （1.31， 2.63， 5.25 mL·kg-1·d-1）， and pregabalin group （5 mg·kg-1）， with eight rats in each group. Another eight SD rats were taken as the blank group， and the same volume of normal saline was given by gavage. Behavioral tests， side effect evaluation， network analysis， Western blot， immunofluorescence， and antagonist application were used to explore the effect. ResultCompared with the blank group， the mechanical hyperalgesia threshold， thermal hyperalgesia threshold， and the expression of inflammatory factors in the spinal dorsal horn of the model group are significantly increased （P<0.01）， and the related indicators of the affected foot footprints are significantly down-regulated （P<0.01）. The expression of signal transducer and activator of transcription 3 （STAT3）， vascular endothelial growth factor A （VEGFA）， and phosphorylated extracellular regulated protein kinase （p-ERK） in microglia in the spinal dorsal horn is significantly increased in the model group （P<0.01）. Compared with the model group， low， medium， and high dose OK groups can increase the mechanical hyperalgesia and thermal hyperalgesia thresholds of CCD rats （P<0.05， P<0.01） in a dose-dependent manner， improve the gait of CCD rats （P<0.05， P<0.01）， and reduce the expression of inflammatory factors in the spinal dorsal horn （P<0.05， P<0.01）. The expression of STAT3， VEGFA， and p-ERK in the spinal dorsal horn microglia of CCD rats is significantly decreased （P<0.05， P<0.01）， and the acetic acid-induced nociceptive response in rats is effectively reduced （P<0.05， P<0.01）. In addition， there is no tolerance. The results of the body mass test， organ index， forced swimming， and rotation show that OK has no obvious toxic or side effects. Further antagonist experiments show that MRS1523 and RS127445 can reverse the transient analgesic effect of OK compared with the high dose OK group （P<0.01）. ConclusionOK has a good analgesic effect on the CCD model without obvious toxic side effects， and its mechanism may be related to the activation of ADORA3 and HTR2B and the inhibition of STAT3， VEGFA， p-ERK， and other elements in microglia.

New avenues for systematically inferring cell-cell communication: through single-cell transcriptomics data

For multicellular organisms, cell-cell communication is essential to numerous biological processes. Drawing upon the latest development of single-cell RNA-sequencing (scRNA-seq), high-resolution transcriptomic data have deepened our understanding of cellular phenotype heterogeneity and composition of complex tissues, which enables systematic cell-cell communication studies at a single-cell level. We first summarize a common workflow of cell-cell communication study using scRNA-seq data, which often includes data preparation, construction of communication networks, and result validation. Two common strategies taken to uncover cell-cell communications are reviewed, e.g., physically vicinal structure-based and ligand-receptor interaction-based one. To conclude, challenges and current applications of cell-cell communication studies at a single-cell resolution are discussed in details and future perspectives are proposed.

The role of B cell osteoimmunity in periodontitis / 口腔疾病防治

@#As the most important pathological feature of periodontitis, alveolar bone resorption also results in tooth loss and oral dysfunction. According to recent research, the host immune response is the major factor leading to alveolar bone resorption. Antibodies, immune cells and inflammatory cytokines involved in this procedure cause an imbalance of bone formation and destruction, which is called osteoimmunity. Given the importance of adaptive humoral immunity during periodontitis, B cells are considered crucial in the development of periodontitis. Therefore, establishing B cell osteoimmunity is an effective way for us to deeply assess the start, development and prognosis of periodontitis. It has been proven that the development process of B cells is accompanied by changes in bone density or morphology. We have reviewed previous literature to understand the role of B cell bone immunity in the pathological process of periodontitis, and the results showed that B cells regulate the development of bone cell lines through transcription factors (such as RANKL, PU.1, E2A, etc.). In addition, various cytokines expressed by B cells (such as IFN-γ, IL-17, IL-10, TGF-β, etc.) can participate in the regulation of bone cells.

Research on mechanism of Sini Powder in treatment of depression based on network pharmacology / 中草药

Objective: To investigate the mechanism of depression by Sini Powder. Methods: The chemical composition and targets of Bupleuri Radix, Paeonia Radix Alba, Aurantii Fructus Immaturus, and Glycyrrhizae Radix et Rhizoma were searched by the analysis of traditional Chinese medicine system pharmacology platform (TCMSP). Depression related genes were screened from OMIM, TDD, Drugbank, and Digsee multiple databases. The target corresponding genes were searched through UniProt, GeneCards, and PubMed database query and then Cytoscape 3.2.1 was used to build compound-targets (genes) networks, protein interaction (PPI) filter core targe; At last, the enrichment of gene ontology (GO) function analysis by DAVID based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was carried out, and the mechanism of its action research was predicted. Results: The compound-target network contained 121 compounds and the corresponding 259 targets, and the key targets involved PTGS2, CALM1, ESR1, HSP90AA1, AR, etc. The PPI core network contained 15 proteins, key proteins involved in CASP3, CHRM2, CYP3A4, and etc. The function enrichment analysis of GO was 375 (P < 0.05), of which there were 307 biological processes (BP), and 37 related items of cell composition (CC), and 31 molecular function (MF) items. 37 related items of cell composition (CC), and 31 molecular function (MF) items. There were 37 signal pathways (P < 0.05) in KEGG pathway enrichment screening, involving neuroactive ligand-receptor interaction, dopaminergic synapse, IL-17 signaling pathway and so on. Conclusion: The active components in Sini Powder play an antidepressant role by acting on 15 key targets such as CASP3, CHRM2, DRD1 to regulate multiple signaling pathways.

Mechanistic ligand-receptor interaction model: operational model of agonism

This tutorial explains the basic principles of mechanistic ligand-receptor interaction model, which is an operational model of agonism. A growing number of agonist drugs, especially immune oncology drugs, is currently being developed. In this tutorial, time-dependent ordinary differential equation for simple E(max) operational model of agonism was derived step by step. The differential equation could be applied in a pharmacodynamic modeling software, such as NONMEM, for use in non-steady state experiments, in which experimental data are generated while the interaction between ligand and receptor changes over time. Making the most of the non-steady state experimental data would simplify the experimental processes, and furthermore allow us to identify more detailed kinetics of a potential drug. The operational model of agonism could be useful to predict the optimal dose for agonistic drugs from in vitro and in vivo animal pharmacology experiments at the very early phase of drug development.

Bioinformatics analysis of microarray data to reveal the pathogenesis of diffuse intrinsic pontine glioma

BACKGROUND: Diffuse intrinsic pontine glioma (DIPG) is the main cause of pediatric brain tumor death. This study was designed to identify key genes associated with DIPG. METHODS: The gene expression profile GSE50021, which consisted of 35 pediatric DIPG samples and 10 normal brain samples, was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified by limma package. Functional and pathway enrichment analyses were performed by the DAVID tool. Protein-protein interaction (PPI) network, and transcription factor (TF)-microRNA (miRNA)-target gene network were constructed using Cytoscape. Moreover, the expression levels of several genes were validated in human glioma cell line U251 and normal glia HEB cells through real-time polymerase chain reaction (PCR). RESULTS: A total of 378 DEGs were screened (74 up-regulated and 304 down-regulated genes). In the PPI network, GRM1, HTR2A, GRM7 and GRM2 had higher degrees. Besides, GRM1 and HTR2A were significantly enriched in the neuroactive ligand-receptor interaction pathway, and calcium signaling pathway. In addition, TFAP2C was a significant down-regulated functional gene and hsa-miR-26b-5p had a higher degree in the TF-miRNA-target gene network. PCR analysis revealed that GRM7 and HTR2A were significantly downregulated while TFAP2C was upregulated in U251 cells compared with that in HEB cells (p < 0.001). GRM2 was not detected in cells. CONCLUSIONS: GRM1 and HTR2A might function in DIPG through the neuroactive ligand-receptor interaction pathway and the calcium signaling pathway. Furthermore, the TFAP2C and hsa-miR-26b-5p might play important roles in the development and progression mechanisms of DIPG.

Progress in targeting-delivery systems for curcumin / 中国药学杂志

By a targeting-delivery system, drugs are delivered and concentrated in a local district such as target tissues, organs, cells or a special district of cells to avoid harm to healthy tissues. Curcumin has various pharmacological activities, but the clinical application of curcumin is severely limited by its main drawbacks including instability, low solubility and poor bioavailability. Recently curcurnin-targeting dosage forms which improved the curcumin bioavailability surged. In this article, the new targeting-delivery systems and their use in curcumin delivery mainly including liposomes, ligand-receptors, magnetic iron oxides and other systems are reviewed in design methodologies and bioactive effects. Advantages and disadvantages for the target-delivery systems are discussed.

Stress Sensitive Signal Pathway Osteoprotegerin/Receptor Activator of Nuclear Factor-κB ligand/Receptor Activator of Nuclear Factor-κB and Osteoporosis (review) / 中国康复理论与实践

@#Exercise is benefic for osteoporosis, without clear molecular biology mechanism. The osteoprotegerin/receptor activator of nuclear factor-κB ligand/receptor activator of nuclear factor-κB (OPG/RANKL/RANK) signal pathway contributes to osteoporosis, which can be mediated by mechanical force. Research progress on osteoporosis and the stress sensitive signal pathway OPG/RANKL/RANK were reviewed in this paper.

Research progress in receptor binding assay by mass spectrometry / 中国药学杂志

OBJECTIVE: To explain that receptor-ligand binding assay is an important drug screening method, which can quickly and inexpensively study the interactions between the targeted receptor and the potential ligands in vitro and provide information about the relative binding affinity of ligand-receptor. METHODS: The correlative literature and abroad were collected and analyzed. RESULTS AND CONCLUSION: The concept of MS binding assay based on mass spectrometric quantification of nonlabeled markers represents a promising alternative to conventional radioligands binding without inherent drawbacks. The technique will play an important role in the design and screening of receptor-targeting pharmaceuticals.

Apoptosis and upregulation of TNF-alpha and TRAIL receptor 1 (DR4) in the pathogenesis of food protein-induced enterocolitis syndrome / 소아과

PURPOSE: Expression levels of tumor necrosis factor (TNF)-alpha expression on the mucosa of the small intestine is increased in patients with villous atrophy in food protein-induced enterocolitis syndrome (FPIES). TNF-alpha has been reported to induce apoptotic cell death in the epithelial cells. We studied the TNF family and TNF-receptor family apoptosis on the duodenal mucosa to investigate their roles in the pathogenesis of FPIES. METHODS: Fifteen infants diagnosed as having FPIES using standard oral challenge test and 5 controls were included. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining was performed to identify the apoptotic cell death bodies. Immunohistochemical staining of TNF-alpha, Fas ligand (FasL) for TNF family and TNF-related apoptosis-including ligand (TRAIL) receptor 1 (DR4), TRAIL receptor 2 (DR5), and Fas for TNF-receptor family were performed to determine the apoptotic mechanisms. RESULTS: TUNEL+ was significantly more highly expressed in the duodenal mucosa of FPIES patients than in controls (P=0.043). TNF-alpha (P=0.0001) and DR4 (P=0.003) were significantly more highly expressed in FPIES patients than in controls. Expression levels of FasL, Fas, and DR5 were low in both groups and were not significantly different between the 2 groups. CONCLUSION: These results suggest that FPIES pathogenesis is induced by apoptosis, and that TNF-alpha expression and DR4 pathway may have an important role in apoptosis.

Gene Expression of Cytokine Pathway,Jak-Stat Signal Pathway and Neuroactive Ligand-receptor Pathway in Patients with Primary Sjgren′s Syndrome / 医学研究杂志

Objective This study is to investigate cytokine pathway,Jak-Stat signal pathway,neuroactive ligand-receptor pathway gene expression pattern of peripheral blood mononuclear cell(PBMC) of primary sjgren syndrome patients.Methods The PBMC sample of 3 patients with sjgren syndrome and 3 healthy volunteers with consistent age were collected.The total RNAs was extracted from the PBMC samples,and reverse transcripted in vitro transcription(IVT),labeled with Cy5/Cy3 and hybridized on the gene chips.After scanning and data extraction with LuxScan 3.0,differentially expressed genes were analyzed with SAM method.The online tool of molecule analysis system(MAS) was used for biological knowledge mining.Results Statistical difference was calculated between the patient and control group in the following three pathways: cytokine pathway,Jak-Stat signal pathway,neuroactive ligand-receptor pathway.Among these,genes of IL-2RA,IL-10 were up-regulated and genes of PF4,GZMA were down-regulated.Conclusion Understanding of differently expressed genes should help us disclose the potential molecular mechanism underlying the development process of pathogenesis of primary Sjgren′s syndrome.And the research may provide new target therapy for SS.

Combination therapy of Docetaxel with radiation increases apoptosis of human Hela cell line and expressions of TRAIL and its receptors / 医学研究生学报

Objective: Docetaxel as a newly semi-synthesized anti-tumor drug,exhibits significant cyrotoxic activity and enhanced sensitivity for radiotherapy.The aim of this study was to investigate the correlation of the apoptosis of human Hela cell line with the expressions of TRAIL and its receptors induced by the combination therapy of Docetaxel with radiation.Methods: We treated the Hela line by Docetaxel,radiation,and combination therapy of Docetaxel with radiation,respectively,detected the apoptosis of the Hela cells using Hoechst 33342 staining and the TUNEL method,and observed the changes in the mRNA expressions of TRAIL and its receptors TRAIL-R in the three groups by RT-PCR.Results: Compared with the Docetaxel and the radiation groups,the apoptosis of the Hela cells was increased significantly in the combination therapy group,and so were the mRNA expressions of TRAIL and its receptors TRIAL-R1 and TRAIL-R2.Conclusion: The combination therapy of Docetaxel with radiation increased the apoptosis of the Hela cell line,which might be mediated by the up-regulation of mRNA expressions of TRAIL and its receptors TRAIL-R1 and TRAIL-R2.

Expression and Significance of Tumor Necorisis Factor Related Apoptosis Induced Ligand Receptor(TRAILR) in Human Craniopharyngioma / 实用儿科临床杂志

Objective To investigate the expression and significance of tumor necorisis factor related apoptosis induled ligand receptor(TRAILR) in human craniopharyngioma.Methods The expression of TRAILR was determined by immunohistochemistry and in situ hybridization in 24 samples of craniopharyngioma and 16 samples of normal brain tissue.Results With low decoy receptor(DcR) expression in partial craniopharyngioma cells and low death receptor(DR) expression in partial normal brain cells,DR was expressed highly in all craniopharyngioma samples while DcR in most normal brain tissue. High DR expression and low DcR expression in craniopharyngioma tissue differed from low DR expression and high DcR expression in normal brain tissue(P

INVESTIGATION OF RELATIONSHIP BETWEEN EXPRESSION OF MANNOSE-LIGAND RECEPTOR ON CAPACITATED HUMAN SPERM IN VITRO AND ACROSOME REACTION INDUCED BY SOLUBILIZED MOUSE ZONA PELLUCIDA / 解剖学报

Objective To study the correlation between expression of mannose-ligand receptor(MR) on capacitated human sperm in vitro and acrosome reaction induced by zona pellucida(ZP). Methods The swimming-up sperms were incubated in capacitating medium BWW for 6 hours at 37℃, and then treated with solubilized mouse zona pellucida(mZPS).After an hour, the percentages of spermatozoa labeled with FITC-DMA were counted and used to show the expression of MR; the percentages of acrosome-reacted sperm visualized with fluoresceinated Pisum sativum agglutinin(PSA) were recorded. Results There is no correlation between expression of MR on capacitated human sperm in vitro and acrosome reaction induced by mZPS.Conclusion Expression of MR on capacitated human sperm in vitro might not be the essence of capacitation.;