Objective To explore the possible mechanism of Dipsaci Radix in the treatment of osteoporosis based on systems pharmacology method. Methods The drug components of Dipsaci Radix were obtained from TCMSP database to screen active ingredients and predict target protein. The target protein of osteoporosis was searched in the TTD and CTD database in order to build Drug-Target protein-Disease interaction Network. Then, the analysis on the role of core target protein pathways were performed by DAVID tool. The protein interaction network of primary signal pathways was built in String database. Results Seven active ingredients of Dipsaci Radix and their 63 target proteins were obtained, 118 targets of osteoporosis were selected, and 118 cross-acting proteins between Dipsaci Radix and osteoporosis were obtained. Then 24 signaling pathways related to cell proliferation and differentiation and immune function were enriched, wherein PI3K-AKT signaling pathway contained the largest number of related genes. String database analysis showed that AKT1, MAPK1, and MAPK3 protein appeared frequently in signal pathways. Conclusion Dipsaci Radix may affect the PI3K-AKT signaling pathway mainly through AKT1, MAPK1, and MAPK3 for the treatment of osteoporosis. This study provides a new idea for the further mechanism study on the treatment of osteoporosis of Dipsaci Radix.

Objective To investigate the atypical appearances of small hepatocellular carcinoma(SHCC) with triple-phase spiral CT enhanced scan, and its correlation with the histopathology .Methods The atypical CT signs in triple-phase and histopathologic changes of SHCC confirmed pathologically in 30 cases (32 lesions) were analysed.Results 32 atypical lesions were found in 30 patients,of them,14 lesions were hypodense in hepatic arterial phase(HAP),portal venous phase(PVP) and delayed phase(DP).10 lesions enhanced markedly in the AP,while these lesions became isodense or slight hyperdense in the PVP and DP.8 lesions were enhanced as ring like or punctual shape in the AP,and constant enhancement in PVP and DP.Conclusion The atypical appearances are present in triple- phase spiral CT scan in SHCC,the pattern of blood supply and the base of histopathology are usually the cause of these findings .

OBJECTIVE: To investigate the regulatory role of the long non-coding RNA LINC00926 in pyroptosis of hypoxia-induced human umbilical vein vascular endothelial cells (HUVECs) and explore the molecular mechanism. METHODS: HUVECs were transfected with a LINC00926-overexpressing plasmid (OE-LINC00926), a siRNA targeting ELAVL1, or both, followed by exposure to hypoxia (5% O2) or normoxia. The expression of LINC00926 and ELAVL1 in hypoxia-treated HUVECs was detected using real-time quantitative PCR (RT-qPCR) and Western blotting. Cell proliferation was detected using Cell Counting Kit-8 (CCK-8), and the levels of IL-1β in the cell cultures was determined with ELISA. The protein expression levels of pyroptosis-related proteins (caspase-1, cleaved caspase-1 and NLRP3) in the treated cells were analyzed using Western blotting, and the binding between LINC00926 and ELAVL1 was verified with RNA immunoprecipitation (RIP) assay. RESULTS: Exposure to hypoxia obviously up-regulated the mRNA expression of LINC00926 and the protein expression of ELAVL1 in HUVECs, but did not affect the mRNA expression of ELAVL1. LINC00926 overexpression in the cells significantly inhibited cell proliferation, increased IL-1β level and enhanced the expressions of pyroptosis-related proteins (all P < 0.05). LINC00926 overexpression further up-regulated the protein expression of ELAVL1 in hypoxia-exposed HUVECs. The results of RIP assay confirmed the binding between LINC00926 and ELAVL1. ELAVL1 knockdown significantly decreased IL-1β level and the expressions of pyroptosis-related proteins in hypoxia-exposed HUVECs (P < 0.05), while LINC00926 overexpression partially reversed the effects of ELAVL1 knockdown. CONCLUSION LINC00926 promotes pyroptosis of hypoxia-induced HUVECs by recruiting ELAVL1.
Humans ; Caspase 1 ; ELAV-Like Protein 1 ; Human Umbilical Vein Endothelial Cells ; Pyroptosis ; RNA, Messenger ; RNA, Long Noncoding/genetics* ; Cell Hypoxia

Objective : To study the effect and mechanism of action of Silibinin on the differentiation of 3T3-F442A preadipocytes in murine． Methods : The effects of 0－400 μmol / L Silibinin on the proliferation of 3T3-F442A adi- pocytes at 24，48 and 72 h were detected by 3-(4，5-dimethylthiazol-2) -2，5-diphenyltetrazolium bromide ( MTT) assay，and the effects of Silibinin on the adipogenesis of 3T3-F442A adipocytes were visualized by Oil Red O stai- ning ; RT-qPCR , Western blot and ELISA assays were used to detect the effects of Silibinin on 3T3-F442A adipo- cyte differentiation-associated transcription factor CCAAT / enhancer binding protein ( C / EBP) α , C / EBP β , per- oxisome proliferator-activated receptor γ cular endothelial growth factor (VEGF) -α and VEGF receptor 2 (VEGFR-2) ，matrix metalloproteinase (MMP) -2 and MMP-9，mitogen-activated protein kinase (MEK) and phosphorylated MEK (p-MEK) ，and extracellular regu- lated protein kinase (ERK) and phosphorylated ERK (p-ERK) expression. (PPARγ) ，adipocyte protein 2 (aP2) ，adipose generation-associated vas Results : MTT assay showed that the cell proliferation rate of 3T3-F442A preadipocytes decreased after 100，200，and 400 μmol /L Silibinin treatment compared with the control group (P＜0. 001) ; Oil Red O staining assay showed that the accumulation of red lipid droplets of the cells in the 160 μmol /L Silibinin assay group significantly decreased ; RT-qPCR assay showed that mRNA expression of C/EBPα , C/EBPβ , PPARγ , aP2，VEGF-α , VEGFR-2，MMP-2，and MMP-9 was down-reg- ulated in 3T3-F442A adipocytes treated with 160 μmol /L Silibinin compared with the control group (P＜0. 001) ; Western blot assay showed that protein expression of C /EBPα , C /EBPβ , PPARγ and aP2 was down-regulated in 3T3-F442A adipocytes treated with 160 μmol /L Silibinin (P＜0. 001) ，and the phosphorylation level of p-MEK/ MEK and p-ERK/ ERK proteins was down-regulated compared with the control group (P ＜0. 001) ; ELISA assay showed that the protein concentrations of MMP-2 and MMP-9 in the cell supernatant were down-regulated (P < 0. 001) in 3T3-F442A adipocytes treated with 160 μmol /L Silibinin． Conclusion Silibinin inhibited 3T3-F442A adipocyte differentiation and adipogenesis through inhibition of the MEK/ ERK pathway and matrix metalloproteinase activity.

Objective: To provide a scientific standard of left ventricular Tei index for healthy people from various region of China, and to lay a reliable foundation for the evaluation of left ventricular diastolic and systolic function. Methods: The correlation and principal component analysis were used to explore the left ventricular Tei index, which based on the data of 3 562 samples from 50 regions of China by means of literature retrieval. hTe nine geographical factors were longitude(X1), latitude(X2), altitude(X3), annual sunshine hours (X4), the annual average temperature (X5), annual average relative humidity (X6), annual precipitation (X7), annual temperature range (X8) and annual average wind speed (X9). ArcGIS sotfware was applied to calculate the spatial distribution regularities of letf ventricular Tei index. Results: hTere is a signiifcant correlation between the healthy people’s letf ventricular Tei index and geographical factors, and the correlationcoeffcients were 0.107 (r1), 0.301 (r2), 0.029 (r3), 0.277 (r4),?0.256(r5),?0.289(r6),?0.320(r7), 0.310 (r8) and 0.117 (r9), respectively. A linear equation between the Tei index and the geographical factor was obtained by regression analysis based on the three extracting principal components. hTe geographical distribution tendency chart for healthy people’s letf Tei index was iftted out by the ArcGIS spatial interpolation analysis. Conclusion: hTe geographical distribution for letf ventricular Tei index in China follows certain pattern. hTe reference value in North is higher than that in South, while the value in East is higher than that in West.

BACKGROUNDThe cholesterol-lowering statin drugs have some non-lipid-lowering effects, such as inhibiting myocardial remodeling. However, the underlying mechanism is still unclear.

METHODSThe left anterior descending coronary artery was ligated to establish a rat model of heart failure, and the rats were divided into a sham operation (SO) group, myocardial infarction model (MI) group, and MI-atorvastatin group. Changes in hemodynamic parameters were recorded after the final drug administration. Histological diagnosis was made by reviewing hematoxylin and eosin (HE) stained tissue. Real-time quantitative polymerase chain reaction (PCR) was performed to determine the expressions of type I and type III collagen, matrix metalloproteinase-2 (MMP-2), and tissue matrix metalloproteinase inhibitor-2 (TIMP-2). Further, primary rat cardiac fibroblasts were cultured and the MTT assay was performed to determine the effect of atorvastatin on cardiac fibroblast proliferation.

RESULTSThe model of heart failure was established and the results of HE staining and Masson's trichrome staining revealed that the rats in the heart failure group showed obvious hyperplasia of fibrotic tissue, which was significantly reduced in the atorvastatin group. Real-time quantitative PCR showed that the MI group showed a significantly increased expression of type I and type III collagen, MMP-2, and TIMP-2, but a significantly reduced MMP-2/TIMP-2 ratio. Compared with the MI group, the atorvastatin group showed significantly reduced expression of type I and III collagen, unchanged expression of MMP-2, significantly reduced expression of TIMP-2, and an increased MMP-2/TIMP-2 ratio. We further found that atorvastatin significantly inhibited the Ang II-induced fibroblast proliferation and the expression of type I and type III collagen in cardiac fibroblasts while increasing the MMP-2/TIMP-2 ratio.

CONCLUSIONSThese data suggest that atorvastatin can inhibit cardiac fibroblast proliferation and enhance collagen degradation by increasing the MMP-2/TIMP-2 ratio, thereby inhibiting the formation of myocardial fibrosis in rats with heart failure after myocardial infarction.

Animals ; Atorvastatin Calcium ; Collagen ; biosynthesis ; Disease Models, Animal ; Female ; Fibrosis ; Heart Failure ; drug therapy ; pathology ; Heptanoic Acids ; pharmacology ; therapeutic use ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; pharmacology ; Matrix Metalloproteinase 2 ; genetics ; Myocardial Infarction ; complications ; Myocardium ; pathology ; Pyrroles ; pharmacology ; therapeutic use ; Rats ; Rats, Wistar ; Tissue Inhibitor of Metalloproteinase-2 ; genetics ; Ventricular Remodeling ; drug effects

OBJECTIVETo observe the effect of NL-608 (a nutlin analog) on apoptosis induction in human breast cancer MCF-7 cells in vitro, and investigate the relevant molecular mechanism.

METHODSThe effect of NL-608 on proliferation of MCF-7 cells was determined by MTT assay. The apoptosis in MCF-7 cells was determined by flow cytometry with annexin V-FITC and PI. The activity of caspase 3, caspase 8 and caspase 9 was determined with caspase activity assay kit and Western blot, and the proteins of Fas and FasL were determined by Western blot.

RESULTSNL-608 showed a dose-dependent inhibitory effect on the proliferation of MCF-7 cells. It induced apoptosis in MCF-7 cells in a dose-dependent manner. The activity of caspase 3 and caspase 8 in MCF-7 cells was increased with the increasing concentration of NL-608, but caspase 9 had no changes. The proteins of Fas and FasL were increased in a dose-dependent manner.

CONCLUSIONNL-608 induces apoptosis in MCF-7 cells in vitro through inducing caspase 3 activity and death receptor-mediated signal pathway.

Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Caspase 8 ; metabolism ; Caspase 9 ; metabolism ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; Fas Ligand Protein ; metabolism ; Humans ; Imidazoles ; pharmacology ; MCF-7 Cells ; Piperazines ; pharmacology ; fas Receptor ; metabolism

OBJECTIVETo assess the regional left ventricular systolic function of children with Kawasaki disease before and after treatment by vector myocardial strain and strain rate imaging (VSI) technology.

METHODSThe regional left ventricular systolic function was assessed using VSI technology in 32 children with Kawasaki disease before treatment and one month after treatment and in 30 age-matched normal children.

RESULTSNine segments of the left ventricular in the Kawasaki disease group before treatment had decreased longitudinal peak systolic strain rate (LSRs) compared with the normal control group. After treatment, the LSRs in 9 segments in the Kawasaki disease group increased, but 6 segments had decreased LSRs compared with the normal control group. The radial peak systolic strain rate (RSRs) of 8 segments in the Kawasaki disease group before treatment was lower than that in the control group. After treatment, only one segment had decreased RSRs compared with the control normal group and 5 segments had increased RSRs compared with that before treatment. The circumferential peak systolic velocity (CVs) of 6 segments in the Kawasaki disease group before treatment group was lower than that in the control normal group. After treatment, only one segment had decreased CVs in the Kawasaki disease group compared with the control normal group and 3 segments had increased CVs compared with that before treatment.

CONCLUSIONSThe regional left ventricular systolic function in children with Kawasaki disease before and after treatment can be accurately assessed using VSI technology, which shows the clinical significance of this technology in assessment of treatment outcome in children with Kawasaki disease.

Child, Preschool ; Female ; Humans ; Image Interpretation, Computer-Assisted ; Infant ; Male ; Mucocutaneous Lymph Node Syndrome ; physiopathology ; Stress, Mechanical ; Systole ; physiology ; Ventricular Function, Left ; physiology