AIM:To explore the protective effects of salidroside on endothelial progenitor cells (EPCs) dam-aged by radiation and its mechanisms.METHODS:EPCs from normal peripheral blood were cultured in fibronectin-coated flasks with endothelial progenitor medium.The effects of salidroside on the viability, migration, adhesion and apoptosis of radiation-damaged EPCs were detected.The viability, apoptosis and migration of the cells were assayed by CCK-8 assay, flow cytometry and Transwell chamber experiment, respectively.The cell adhesion assay was performed by re-plating the cells on fibronectin-coated dishes, and then the adherent cells were counted.The expression of Akt protein in the cells was assessed by Western blotting.RESULTS:Salidroside improved the viability, and migratory and adhesive capacities of the EPCs, and decreased the apoptosis after radiation.Salidroside also increased the protein level of phosphorylated Akt.How-ever, the effects of salidroside on radiation-damaged EPCs were inhibited by phosphatidylinositol 3-kinase inhibitor LY294002.CONCLUSION: Salidroside protects EPCs from radiation damages and its mechanism is associated with en-hancing phosphatidylinositol 3-kinase/Akt signaling pathway.

Objective To investigate the protective effect of 1,25-(OH) 2D3 on radiation-induced bone marrow microenvironment injury and to explore the related molecular mechanism.Methods Sixty 7-week old male BALB/c mice were randomly divided into control group without any treatment; radiation group exposed to 6.0 Gy 60Co γ-rays with DMSO,and 1,25-(OH)2 D3 + radiation group treated with 1,25-(OH)2D32.5 μg/kg dissolved in DMSO each day and 6 Gy of γ-rays.The body weight and peripheral white blood cells,femur bone marrow histology,and the proportion of adipocyte area were measured.The expression of peroxisome proliferator-activated receptor-gamma (PPARγ) was detected immunohistochemistrically at 8 d after irradiation.Results After irradiation,the number of white blood cells and the body weight decreased obviously,and the percentage of adipocyte area was increased significantly.Compared with radiation group,1,25-(OH)2D3 reduced the decrease rate of body weight (t =-2.23,-2.34,P ＜ 0.05),partly recovered the number of white blood cells at 4 or 8 d after irradiation(t =-4.99,-4.46,P ＜ 0.05),and reduced the proportion of adipocyte area (t =-3.75,-2.10,P ＜ 0.05).With immunohistochemistrical assay,it was found that 1,25-(OH) 2D3 inhibited adipogenesis by reducing the expression of PPARγ.Conclusions 1,25-(OH) 2 D3 decreases radiationinduced adipogenesis and hence protects the bone marrow microenvironment from radiation damage.

Objective To investigate the potential and underlying molecular mechanism of salidroside in ameliorating radiation-induced bone marrow adipogenesis and stimulating hematopoiesis.Methods The female BALB/c mice aged 6-7 weeks were randomly divided into normal control group,radiation group and salidroside group.The radiation group and salidroside group were irradiated with 6.0 Gy of 60Co γ-rays.The salidroside group was intraperitoneally injected with 30 mg· kg-1 · d-1 salidroside at 12 h and then every day until 8th d after radiation.The normal control group and radiation group were treated with equal volume of saline as control of salidroside.At 14 d after radiation,the mice weight,peripheral blood count,femur bone marrow histology,and the proportion of adipocyte area were measured,and the expressions of PPAR-γ and FABP4 were detected by q-PCR.Results After irradiation,the numbers of white blood cells,hemoglobin and platelet in peripheral blood were reduced obviously,and the percentage of adipocyte area was increased significantly.Compared with mice in the radiation group,salidroside inhibited adipogenesis and reduced the proportion of adipocyte area (t =13.31,P ＜ 0.05) by reducing the expressions of PPAR-γ and FABP4 (t =8.64,13.19,P ＜ 0.05).The number of white blood cells was partly recovered at 7 d after irradiation (t =5.80,P ＜ 0.05).Both white blood cells and hemoglobinin in peripheral blood of the salidroside group were higher than those in the radiation group at 14 d after irradiation.Conclusions Salidroside could inhibit radiation-induced bone marrow adipogenesis and regulate bone marrow microenvironment,thereby promotes hematopoietic recovery in mice after radiation injury.

[ABSTRACT]AIM:ToinvestigatetheeffectofmiR-155-specificsiRNAaloneorincombinationwithcytosinear-abinoside (Ara-C) on the growth and apoptosis of Burkitt lymphoma Raji cells .METHODS: miR-155-specific siRNA and/or Ara-C were used to treat the cells .Quantitative real-time polymerase chain reaction was used to detect the expres-sion of miR-155.The growth of the cells was analyzed by CKK-8 assay.The cell apoptosis was determined by flow cytome-try.RESULTS:The miR-155 expression level of the cells transfected with miR-155 siRNA was significantly lower than that in the 2 control groups .Ara-C or miR-155 siRNA alone inhibited the growth of Raji cells in a dose-depend manner . miR-155 siRNA combined with Ara-C produced more inhibition of cell proliferation (P<0.05).After treatment for 48 h, the apoptotic rate of Raji cells in miR-155 siRNA+Ara-C group [(38.4 ±1.4)%] was higher than that in Ara-C group [(16.5 ±0.3)%] and miR-155 siRNA group [(14.6 ±0.3)%], with statistically significant difference (P<0.05). The expression of caspase-3 in Ara-C+miR-155 siRNA group was increased significantly as compared with Ara-C group and miR-155 siRNA group.CONCLUSION:miR-155-specific siRNA enhances the chemosensitivity of Raji cells to Ara-C by inducing apoptosis through the caspase-3 pathway .

AIM: To investigate whether salidroside has influence on the activities of endothelial progenitor cells (EPCs) and its mechanism.METHODS:Mononuclear cells from normal human peripheral blood were cultured in fi-bronectin coated flasks in endothelial progenitor medium .After 7 d, EPCs were characterized as adherent cells with acLDL-DiI uptaking and lectin binding by direct fluorescent staining .The proliferation and migration of EPCs were analyzed by MTT assay and Transwell chamber assay , respectively.The EPCs adhesion assay was performed by re-plating the cells on fibronectin-coated dishes , and then adherent cells were counted .NO and Akt protein were also detected .RESULTS:Sali-droside promoted EPCs proliferative , migratory and adhesive capacities in a concentration dependent manner .Salidroside also increased NO secretion , and the level of phosphorylated Akt protein .However , the effects of salidroside on EPCs were inhibited by phosphoinositide 3-kinase inhibitor LY294002.CONCLUSION:Salidroside regulates the activity of EPCs by phosphoinositide 3-kinase/Akt signaling pathway .

Objectives: To elucidate the potential mechanisms of electroacupuncture (EA) in restoring detrusor-bladder neck dyssynergia (DBND) following suprasacral spinal cord injury (SSCI). Methods: A total of 52 specific pathogen-free (SPF) grade famale Sprague-Dawley (SD) rats (10 – 12 weeks, 250 – 280 g) were randomly assigned to either a sham group (n = 12) or a spinal cord injury model group (n = 40). In the model group, DBND was induced through Hassan Shaker spinal cord transection at T10 level, with 24 rats meeting inclusion criteria and subsequently randomized into DBND group (n = 12) and EA intervention group (DBND + EA group, n = 12). After spinal shock recovery (day 19 after modeling), DBND + EA group received EA treatment at Ciliao (BL32), Zhongji (RN3), and Sanyinjiao (SP6) acupoints for 20 min per session at 10/50 Hz frequencies, once daily for 10 d. Sham and DBND groups received anesthesia only without EA intervention. On day 29 post-modeling, all rats underwent urodynamic assessments, followed by hematoxylin and eosin (HE) staining, tandem mass tag (TMT) proteomics, and Western blot (WB) analysis of detrusor and bladder neck tissues. Differentially expressed proteins (DEPs) were defined as proteins with P < 0.05, unique peptides ≥ 2, and fold change > 1.2 or < 0.83. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed using KOBAS 3.0 (P < 0.01), and protein-protein interaction (PPI) networks were analyzed using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) 11.5 and Cytoscape 3.9.1. Results: Compared with sham group, DBND group showed significantly elevated leak point pressure (LPP) and maximum cystometric capacity (MCC) (both P < 0.01). EA treatment significantly reduced both LPP and MCC compared with DBND group (P < 0.01 and P < 0.05, respectively). HE staining revealed that EA reduced detrusor fibrosis and improved bladder neck inflammation. TMT proteomics identified 30 overlapping DEPs in detrusor and 59 overlapping DEPs in bladder neck when comparing DBND + EA/DBND groups with sham group. In detrusor tissue, KEGG analysis revealed 10 significantly enriched pathways (P < 0.01), including mitogen-activated protein kinase (MAPK) signaling pathway. PPI analysis showed 22 of 30 DEPs were interconnected. In bladder neck tissue, 14 pathways were significantly enriched (P < 0.01), including relaxin signaling pathway, with 51 of 59 DEPs showing interconnections. Both TMT and WB validations demonstrated that compared with sham controls, DBND rats exhibited upregulated collagen type IV alpha 2 chain (Col4a2) and downregulated guanine nucleotide-binding protein G(z) subunit alpha (Gnaz) in detrusor tissue, while EA treatment normalized both proteins (both P < 0.05). In bladder neck tissue, DBND rats showed decreased expression of smoothelin (Smtn) and calcium-activated potassium channel subunit beta-1 (Kcnmb1) compared with sham controls (both P < 0.01), which were both upregulated following EA treatment (P < 0.01 and P < 0.05, respectively). Conclusion EA restores detrusor-bladder neck coordination in DBND through dual-target mechanisms. In detrusor tissue, EA modulates contraction via extracellular matrix remodeling, cyclic adenosine monophosphate (cAMP) signaling pathway regulation, and enhanced adenosine triphosphate (ATP) biosynthesis mediated by neurotransmitters. In bladder neck tissue, EA promotes relaxation by maintaining contractile phenotypes, reducing fibrosis, suppressing smooth muscle excitation, and regulating presynaptic neurotransmitter release. These findings provide mechanistic insights into EA's therapeutic role in managing DBND.

The crystal form of solid substance had intrinsic correlation with its three dimensional crystal morphology. Based on the characterization of the three dimensional crystal morphology of clopidogrel bisulfate, this research is to establish a model based on the three dimensional morphological parameters. The granular samples composed of polymorphs of clopidogrel bisulfate and microcrystalline cellulose (MCC) were scanned by synchrotron radiation X-ray microscopic CT technology (SR-microCT) and the three dimensional structural models for which were constructed. Seven groups of three dimensional morphological parameters were calculated. Finally, the mathematical model was established with the multi-layer perception (MLP) artificial neutral network methods to identify and predict the polymorphs of clopidogrel bisulfate. The success rate of the model prediction for the polymorphs of clopidogrel bisulfate was 92.7% and the area under the ROC curve was 96.2%. The polymorphs of drugs could be identified and predicted through the numerical description of the three dimensional morphology. The volume, number of the vertices and the surface area were the major determinants for the identification of the polymorphs of clopidogrel bisulfate.