OBJECTIVETo explore the effect of total flavonoids of Herba Epimedium (FHE) on BMP-2/RunX2/OSX signaling pathway in promoting osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs).

METHODSPassage 3 BMSCs were randomly divided into the control group, the experimental group, and the inhibitor group. BMSCs in the control group were cultured in 0.2% dimethyl sulfoxide + Osteogenuxic Supplement (OS) fluid + DMEM/F12 culture media. BMSCs in the experimental group were intervened by 20 microg/mL FHE. BMSCs in the inhibitor group were intervened by 20 microg/mL FHE and 1 microg/mL NOGGIN recombinant protein. At day 9 alkaline phosphatase (ALP) activity was measured. Calcium nodules were stained by alizarin red staining and the density was observed. The transcription expression of osteogenic differentiation-related proteins (type I collagen, osteocalcin, and osteopontin) and related factors of BMP-2/RunX2/OSX signaling pathway was assayed by RT-PCR.

RESULTSCompared with the control group, ALP activities were enhanced and the density of calcium nodules significantly increased; type I collagen, osteocalcin, and osteopontin expression levels were increased in the experimental group. The expression of osteogenesis-related transcription factor was also increased in the experimental group. Noggin recombinant protein inhibited FHE promoting BMSCs osteogenesis in the inhibitor group. Compared with the experimental group, ALP activity decreased (P < 0.05), the density of calcium nodules was lowered, expression levels of type I collagen, osteocalcin, osteopontin significantly decreased (P < 0.05) in the inhibitor group.

CONCLUSION20 microg/mL FHE promoted osteogenic differentiation process of BMSCs by BMP-2/RunX2/OSX signaling pathway.

Bone Morphogenetic Protein 2 ; metabolism ; Cell Differentiation ; drug effects ; Cells, Cultured ; Collagen Type I ; metabolism ; Core Binding Factor Alpha 1 Subunit ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Epimedium ; chemistry ; Flavonoids ; pharmacology ; Humans ; Mesenchymal Stromal Cells ; cytology ; drug effects ; Osteocalcin ; metabolism ; Osteogenesis ; drug effects ; Osteopontin ; metabolism ; Signal Transduction ; Sp7 Transcription Factor ; Transcription Factors ; metabolism

Poly(ADP-ribose)polymerase-1 (PARP-1) plays a significant role in the DNA repair process by catalyzing the transfer of ADP-ribose from NAD+ to its receptors. It is a promising anticancer drug target and many PARP-1 inhibitors have been developed and used in the clinical trial. In this work, a series of 3-(2-oxo-2-substituted acetamido)benzamides have been synthesized and their inhibitory activities against PARP-1 were evaluated. Of all the tested compounds, six compounds displayed inhibitory activities with IC50 values ranging from 0.23 to 5.78 µmol.L-1 . The binding pose of compound 5a was predicted using molecular docking to facilitate further structural modification.
Antineoplastic Agents ; Benzamides ; chemistry ; DNA Repair ; Drug Design ; Humans ; Molecular Docking Simulation ; Poly(ADP-ribose) Polymerase Inhibitors ; chemical synthesis ; chemistry ; Poly(ADP-ribose) Polymerases

One new neolignan identified as 2, 3-( trans) -dihydro-2-(4-hydroxy-3-methoxyphenyl) -3-[(beta-D-glucopyranosyloxy) methyl]-7-methoxybenzofuran-5-propenoic acid (1) and five known steroidal glycosides namely torvoside A(2), torvoside C(3), torvoside H(4), solanolactoside A (5), (25S)-6alpha-hydroxy-5alpha-spirostan-3-one-6-0-[alpha-L-rhamnopyranosyl-(1-->3-beta3)-beta-D-D-quinovopyr-anoside] (6) were isolated from the fruits of Solanum torvum. Their structures were elucidated on the basis of 1D, 2D NMR and MS spectroscopic analysis.
Fruit ; chemistry ; Isomerism ; Lignans ; chemistry ; isolation & purification ; Solanum ; chemistry

0.05), but the level of albumin dropped significantly(P

Background Normal adult optic disc rim width follows inferior ≥ superior ≥ nasal ≥ temporal (ISNT) rule.Analysis of the optic disc structural parameters with Heidelberg retina tomograph (HRT) can understand whether ISNT principle is suitable to other optic disc structure parameters.Objective This study was to investigate the characteristics of optic nerve head structure parameters in normal Chinese adults.Methods The parents of twins who participated Guangzhou Twin Eye Study were enrolled in Zhongshan Ophthalmic Center from 2006 June to 2011 August.All subjects received the routine eye examinations,including visual acuity,slit lamp microscope,direct ophthalmoscope examination,auto-refraction examination and HRT Ⅲ examination.All data from the right eyes were collected and analyzed.HRT values from different quadrants of optical nerve head were compared with one-way analysis of variance,and the multiple comparison between quadrants was carried out by Bonferroni test.The differences of optical nerve head parameters in different gender were analyzed using independent sample t test and Bland-Altman test.Results In this study,1672 eyes of 1672 subjects were included,with the 759 male and 913 female persons and average age of (41.8±5.3)years.No significant differences were seen in the disc area (DA)between the superior and inferior,as well as the nasal and temporal quadrants among the subjects (P＞0.05).In addition,there were not significantly different in the rim area (RA) between the superior and nasal disc as well as the rim volume (RV) among the inferior,superior and nasal disc (P＞O.05).However,significant differences were found in the cup area (CA),cup/disk area ratio (C/DAR),cup volume (CV),mean cupdepth (MCD),maximum cup depth (MxCD),height variation contour (HVC),cup shape measure (CSM),mean retinal nerve fiber layer thickness (mRNFLT) and retinal nerve fiber layer cross section area (RNFLcsa) among the different quadrants (P＜0.001).The local differences from only DA and RA complied with an ordination of the ISNT rule.The values of DA,CA,C/DAR,CV,MCD,MxCD from male individuals were higher,but those of the RV,HVC,mRNFLT RNFLcsa were lower in comparison with female individuals.Nevertheless,all the differences were ＜ 0.1 with a maximal mean difference in DA and CA (both 0.07 mm2).Conclusions The optical nerve head configurations measured by HRT have different distributing characteristics in four quadrants in normal adults.Most parameters show the higher values in the inferior and superior than those in nasal and temporal of disc,but DA and RA meet ISNT rule.The differences of most parameters between male and female subjects can be ignored.

Background Heidelberg Retinal Tomograph (HRT) has been widely used in clinical diagnosis of glaucomatous optic neuropathy,importantly,the measurement results of HRT may be affected by myopia.Therefore,studying the effect of different refractive status and axial length on structural parameters of the optic disc is important.Objective This study was to evaluate the influence of refractive error and axial length to optic nerve head parameter measured by HRT.Methods The parents who participate in Guangzhou Twin Study were enrolled in this investigation from July 2006 to August 2011.The regular eye examinations,including visual acuity,slit lamp,fundus,auto-refraction,HRT-Ⅲ and intraocular lens (IOL) Master,were performed on all the subjects.Thc data from right eyes of subjects were collected and analyzed.The linear correlation analysis and multiple linear regression analysis were applied to analyze the correlation between HRT optic papilla configuration parameter and equivalent sphere and ocular axis length.Results A pilot prospective series cases observational study was designed.1748subjects were enrolled in this study.The disc area (DA) (P=0.021),rim area (RA) (P＜0.001),rim volume (RV) (P＜0.001),mean retinal nerve fiber layer thickness (mRNFLt) (P＜0.001) and retinal nerve fiber layer cross section area (RNFLcsa) in the high myopia were greater than those of the emmetropic group,with significant difference between the two groups (P＜0.001).However,the cup area (CA),cup/disk area ratio (C/DAR) and cup volume (CV) were less in the high myopic group than those of the emmetropic group (P=0.004,P＜0.001 and P＜O.001),respectively.In the mild-moderatc myopic group,the RV,mRNFLt and RNFLcsa were greater than those of the emmetropic group (all of the P value less than 0.001),but the numbers of DA,CA,C/DAR,and CV were less than those of the emmetropic group,the differences were significant and their P valuables were 0.038,＜ 0.001,＜0.001 and 0.001 respectively.The differences of structure parameters between the hyperopia group and the emmetropic group were not statistically significant (P＞0.05).The DA,CA,RA,C/DAR,CV,RV,mean cup depth (MCD),maximum cup depth (MxCD),cup shape measure (CSM),mRNFLt and RNTLcsa were (2.04±0.43) mm2,(0.49±0.34) mm2,(1.55 ± 0.34) mm2,0.23-0.13,(0.11 ± 0.12) mm3,(0.45 ± 0.19) mm3,(0.21 ± 0.09) mm,(0.60±0.21) mm,-0.21 ± 0.07,(0.29 ± 0.07) mm and (1.46 ± 0.36)mm2,respectively,in the 1748 eyes of 1748 subjects.No significant correlation was found between the DA value with SE (r=-0.032,P =0.186).However,weaker positive correlations were seen between the CA,C/DAR,CV,MCD,MxCD with SE (r=0.139,0.163,0.130,0.004,0.054,P＜ 0.05) and negative correlation between RA,RV,mRNFLt and RNFLcsa with SE (r =-0.178,-0.331,0.241,-0.239,P＜0.001).With the increase of the ocular axial length,the DA,RA,RV,mRNFLt and RNFLcsa values were enlarged,and the CV value was smaller.With the increase of CA,the RA,C/DAR,CV,RV,MCD,MxCD,CSM and RNFLcsa values elevated,but mRNFLt value was decreased.Conclusions Refractive error is not associated with DA,but the measuring results are different among various refractive groups.Refractive error,ocular axial length and DA affect the measuring result of HRT.

The shape and structure of granules are controlled by the granulation process, which is one of the main factors to determine the nature of the solid dosage forms. In this article, three kinds of granules of a traditional Chinese medicine for improving appetite and promoting digestion, namely, Jianwei Granules, were prepared using granulation technologies as pendular granulation, high speed stirring granulation, and fluidized bed granulation and the powder properties of them were investigated. Meanwhile, synchrotron radiation X-ray computed micro tomography (SR-µCT) was applied to quantitatively determine the irregular internal structures of the granules. The three-dimensional (3D) structure models were obtained by 3D reconstruction, which were more accurately to characterize the three-dimensional structures of the particles through the quantitative data. The models were also used to quantitatively compare the structural differences of granules prepared by different granulation processes with the same formula, so as to characterize how the production process plays a role in the pharmaceutical behaviors of the granules. To focus on the irregularity of the particle structure, the box counting method was used to calculate the fractal dimensions of the granules. The results showed that the fractal dimension is more sensitive to reflect the minor differences in the structure features than the conventional parameters, and capable to specifically distinct granules in structure. It is proved that the fractal dimension could quantitatively characterize the structural information of irregular granules. It is the first time suggested by our research that the fractal dimension difference (Df,c) between two fractal dimension parameters, namely, the volume matrix fractal dimension and the surface matrix fractal dimension, is a new index to characterize granules with irregular structures and evaluate the effects of production processes on the structures of granules as a new indicator for the granulating process control and optimization.
Drugs, Chinese Herbal ; analysis ; Fractals ; Medicine, Chinese Traditional ; Powders ; Quantitative Structure-Activity Relationship ; Synchrotrons ; Technology, Pharmaceutical ; Tomography, X-Ray Computed

Mesoporous silica nanoparticles as drug carrier have become the new hot point in the field of biomedical application in recent years. This review focuses on the more recent developments and achievements on experimental design aspect of mesoporous silica nanoparticles with cancer diagnosis and therapy. The key advances of functionalization strategies of mesoporous silica nanoparticles with controlled release, tumor targeting and overcoming multidrug resistance are discussed in particular. Mesoporous silica nanoparticles as unique delivery systems have the potential to provide significantly a sound platform for cancer theranostic application.
Animals ; Antineoplastic Agents ; administration & dosage ; therapeutic use ; Delayed-Action Preparations ; Drug Carriers ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Humans ; Nanoparticles ; Neoplasms ; diagnosis ; therapy ; Porosity ; Silicon Dioxide

Fifty-six patients with Graves' ophthalmopathy(GO)were treated with antithyroid drug and oral prednisone for three months,TSH receptor antibody(TRAb)level was reduced,GO activity and severity of some patients were ameliorated but still positively associated with TRAb.It suggests that TRAb not only triggers off GO but also plays a possible role in the maintenance of the autoimmune process in GO.