BACKGROUND:The development of tissues and organs in the body is a precise and autonomously regulated process,and the function of biomechanical factors at this macroscale is a basic scientific question worth exploring. OBJECTIVE:To investigate the roles of cell mechanics in morphogenesis of the lobular organoid of 3D Madin-Darby canine kidney(MDCK). METHODS:The formation of MDCK lobular organoid was visualized by fluorescence resonance energy transfer technology,and the influence of different cellular mechanical signals and extracellular matrix environment on lobular organoid formation and corresponding changes in extracellular regulated protein kinases(ERK)activity were examined. RESULTS AND CONCLUSION:(1)Inhibition of ERK signaling pathway can inhibit the growth of MDCK lobular organoid.(2)Inhibition of cell contractile force signals such as ROCK pathway and Myosin Ⅱ activity,reduced ERK activity and lobular organoid size.(3)Selective inhibition of calcium channels in plasma membrane and endoplasmic reticulum led to reduced ERK activity and lobular organoid growth.(4)By inhibiting the mechanically-sensitive receptor Piezo ion channel or integrin signal on the cell membrane,the lobular organoid became smaller or MDCK cells could not generate tissue morphology.(5)Extracellular matrix compositions affected the morphogenesis of lobular organoid.The addition of type I collagen in Matrigel changed the lobular organoid to elongated shape.(6)The results of this study preliminarily show that mechanical signals in the cells and extracellular matrix environment play an important role in culturing MDCK lobular organoid,and provides certain molecular mechanisms.

This study aims to explore the mechanism of Qingkailing(QKL) Oral Preparation's heat-clearing, detoxifying, mind-tranquilizing effects based on "component-target-efficacy" network. To be specific, the potential targets of the 23 major components in QKL Oral Preparation were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The target genes were obtained based on UniProt. OmicsBean and STRING 10 were used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the targets. Cytoscape 3.8.2 was employed for visualization and construction of "component-target-pathway-pharmacological effect-efficacy" network, followed by molecular docking between the 23 main active components and 15 key targets. Finally, the lipopolysaccharide(LPS)-induced RAW264.7 cells were adopted to verify the anti-inflammatory effect of six monomer components in QKL Oral Preparation. It was found that the 23 compounds affected 33 key signaling pathways through 236 related targets, such as arachidonic acid metabolism, tumor necrosis factor α(TNF-α) signaling pathway, inflammatory mediator regulation of TRP channels, cAMP signaling pathway, cGMP-PKG signaling pathway, Th17 cell differentiation, interleukin-17(IL-17) signaling pathway, neuroactive ligand-receptor intera-ction, calcium signaling pathway, and GABAergic synapse. They were involved in the anti-inflammation, immune regulation, antipyretic effect, and anti-convulsion of the prescription. The "component-target-pathway-pharmacological effect-efficacy" network of QKL Oral Preparation was constructed. Molecular docking showed that the main active components had high binding affinity to the key targets. In vitro cell experiment indicated that the six components in the prescription(hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide) can reduce the expression of nitric oxide(NO), TNF-α, and interleukin-6(IL-6) in cell supernatant(P<0.05). Thus, the above six components may be the key pharmacodynamic substances of QKL Oral Preparation. The major components in QKL Oral Prescription, including hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide, cholic acid, isochlorogenic acid A, and γ-aminobutyric acid, may interfere with multiple biological processes related to inflammation, immune regulation, fever, and convulsion by acting on the key protein targets such as IL-6, TNF, prostaglandin-endoperoxide synthase 2(PTGS2), arachidonate 5-lipoxygenase(ALOX5), vascular cell adhesion molecule 1(VCAM1), nitric oxide synthase 2(NOS2), prostaglandin E2 receptor EP2 subtype(PTGER2), gamma-aminobutyric acid receptor subunit alpha(GABRA), gamma-aminobutyric acid type B receptor subunit 1(GABBR1), and 4-aminobutyrate aminotransferase(ABAT). This study reveals the effective components and mechanism of QKL Oral Prescription.
Chlorogenic Acid ; Drugs, Chinese Herbal/pharmacology* ; gamma-Aminobutyric Acid ; Interleukin-6 ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Tumor Necrosis Factor-alpha/genetics* ; Animals ; Mice ; RAW 264.7 Cells

Objective To determine the biomechanical parameters of left ventricular by using velocity vector imaging (VVI),and to indirectly assess the coronary artery stenosis with VVI in the patients with coronary artery disease (CAD).Methods 52 patients who had one coronary artery lesions at least diagnosed by coronary angiography (CAG)were divided into coronary artery mild stenosis group and severe stenosis group;2 1 patients in mild stenosis group had one coronary stenosis <75%;31 patients in severe stenosis group had one coronary artery stenosis ≥75% at least.At the same time,20 cases of normal people without coronary artery stenosis showed by CAG were selected as normal control group. VVI was used to detect the left ventricular wall segments of the overall longitudinal strain (GLS ), the overall circumferential strain (GCS ) and the overall radial strain (GRS ). Results The absolute values of GLS,GRS,GCS of the patients in mild and severe coronary artery stenosis groups were significantly decreased than those in normal control group(P<0.05),and the strain parameters in severe stenosis group were decreased more significantly, there were significant differences compared mild stenosis group (P<0.05 ). The distribution of the segments with decreased longitudinal strain matched the LV myocardial segment with the coronary stenosis rate ≥ 75%,and GLS had the most sensitivity.The GLS in normal control group,mild stenosis group and severe stenosis group were negatively correlated to left ventricular ejection fraction (LVEF)(r=-0.58,P<0.05;r=-0.51,P<0.05;r=-0.43,P<0.05).GLS-16.14 % was used to assess the severe coronary artery stenosis with requiring the implementation of PTCA treatment as the diagnostic cut-off point with sensitivity 96.8%, specificity of 70%, the highest Yuedden index 0.668. Conclusion The decreasing of left ventricular strain could be detected by VVI, which suggests that severe coronary artery stenosis exists in coronary artery;the distribution of the segments with significantly decreased strains can be used to assess the coronary lesions and stenosis degrees.

BACKGROUND:Umbilical cord blood-derived mesenchymal stem cel s are multipotential stem cel s in the mesoderm in early development stage, and have been paid great attention due to its properties of multi-directional differentiation. OBJECTIVE:To summarize the potential of induced differentiation of umbilical cord blood-derived mesenchymal stem cel s. METHODS:We retrieved PubMed Database for articles concerning the differentiation potential of umbilical cord blood-derived mesenchymal stem cel s published from January 1999 to December 2012. In titles and abstracts, the key words were“umblical cord blood, mesenchymal stem cel s, potential, differentiation”. Total y, 52 articles addressing the differentiation potential of umbilical cord blood-derived mesenchymal stem cel s were reviewed. RESULTS AND CONCLUSION:Numerous studies have confirmed that human umbilical cord blood-derived mesenchymal stem cel s can successful y differentiate into multiple kinds of cel lines, but their understanding remains minor. If we can master the characteristics of the differentiation potential of umbilical cord blood-derived mesenchymal stem cel s, it would be used to repair bone and myocardium detects. Present studies remain in a starting stage. Isolation and purification, regulation of differentiation direction, in vitro amplification and immunogenicity require further investigations.