A Bioinspired Dynamical Vertical Climbing Robot

This paper describes the inspiration, design, analysis, implementation of and experimentation with the first dynamical vertical climbing robot. Biologists have proposed a pendulous climbing model that abstracts remarkable similarities in dynamic wall scaling behavior exhibited by radically different animal species. We study numerically a version of that pendulous climbing template dynamically re-scaled for applicability to utilitarian payloads with conventional electronics and actuation. This simulation study reveals that the incorporation of passive compliance can compensate for an artifact’s poorer power density and scale disadvantages relative to biology. However the introduction of additional dynamical elements raises new concerns about stability regarding both the power stroke and limb coordination that we allay via mathematical analysis of further simplified models. Combining these numerical and analytical insights into a series of design prototypes, we document the correspondence of the various models to the variously scaled platforms and report that our approximately two kilogram platform climbs dynamically at vertical speeds up to 1.5 bodylengths per second. In particular, the final 2.6 kg final prototype climbs at an average steady state speed of 0.66 m/s against gravity on a carpeted vertical wall, in rough agreement with our various models’ predictions

Elevated circulating level of P2X7 receptor is related to severity of coronary artery stenosis and prognosis of acute myocardial infarction

Background: Acute myocardial infarction (AMI) is a severely life-threatening cardiovascular disease. Previous research has identified an association between the P2X7 receptor (P2X7R) and the development of atherosclerosis. However, the correlation of its expression with the clinical prognosis of patients with AMI remains unclear. The present study aimed to investigate the potential role of P2X7R in Chinese patients with AMI. Methods: Seventy-nine patients with AMI and 48 controls were consecutively enrolled in this prospective observational study. Circulating P2X7R mRNA expression levels and other clinical variables were determined upon admission to the hospital. Patients were followed up for 360 days, and the end-point was considered as the occurrence of major adverse cardiovascular events (MACE). Results: Circulating P2X7R mRNA expression level in peripheral blood mononuclear cells of patients with AMI were significantly higher than those in controls and had promising diagnostic ability of AMI with an area under the curve of 0.928. Furthermore, P2X7R was demonstrated to be correlated positively with the severity of coronary artery stenosis. Additionally, this is the first study to indicate that higher P2X7R mRNA expression is associated with a higher rate of MACE within 360 days after AMI. Conclusions: The present study showed that the circulating level of P2X7R was elevated in AMI patients and was closely associated with the severity of coronary artery stenosis and prognosis of AMI

MicroRNA roles in beta-catenin pathway

β-catenin, a key factor in the Wnt signaling pathway, has essential functions in the regulation of cell growth and differentiation. Aberrant β-catenin signaling has been linked to various disease pathologies, including an important role in tumorigenesis. Here, we review the regulation of the Wnt signaling pathway as it relates to β-catenin signaling in tumorigenesis, with particular focus on the role of microRNAs. Finally, we discuss the potential of β-catenin targeted therapeutics for cancer treatment

MicroRNA-221 and microRNA-222 regulate gastric carcinoma cell proliferation and radioresistance by targeting PTEN

<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs) can function as either oncogenes or tumor suppressor genes via regulation of cell proliferation and/or apoptosis. MiR-221 and miR-222 were discovered to induce cell growth and cell cycle progression via direct targeting of p27 and p57 in various human malignancies. However, the roles of miR-221 and miR-222 have not been reported in human gastric cancer. In this study, we examined the impact of miR-221 and miR-222 on human gastric cancer cells, and identified target genes for miR-221 and miR-222 that might mediate their biology.</p> <p>Methods</p> <p>The human gastric cancer cell line SGC7901 was transfected with AS-miR-221/222 or transduced with pMSCV-miR-221/222 to knockdown or restore expression of miR-221 and miR-222, respectively. The effects of miR-221 and miR-222 were then assessed by cell viability, cell cycle analysis, apoptosis, transwell, and clonogenic assay. Potential target genes were identified by Western blot and luciferase reporter assay.</p> <p>Results</p> <p>Upregulation of miR-221 and miR-222 induced the malignant phenotype of SGC7901 cells, whereas knockdown of miR-221 and miR-222 reversed this phenotype via induction of PTEN expression. In addition, knockdonwn of miR-221 and miR-222 inhibited cell growth and invasion and increased the radiosensitivity of SGC7901 cells. Notably, the seed sequence of miR-221 and miR-222 matched the 3'UTR of PTEN, and introducing a PTEN cDNA without the 3'UTR into SGC7901 cells abrogated the miR-221 and miR-222-induced malignant phenotype. PTEN-3'UTR luciferase reporter assay confirmed PTEN as a direct target of miR-221 and miR-222.</p> <p>Conclusion</p> <p>These results demonstrate that miR-221 and miR-222 regulate radiosensitivity, and cell growth and invasion of SGC7901 cells, possibly via direct modulation of PTEN expression. Our study suggests that inhibition of miR-221 and miR-222 might form a novel therapeutic strategy for human gastric cancer.</p

MicroRNA-21 inhibitor sensitizes human glioblastoma cells U251 (PTEN-mutant) and LN229 (PTEN-wild type) to taxol

<p>Abstract</p> <p>Background</p> <p>Substantial data indicate that the oncogene microRNA 21 (miR-21) is significantly elevated in glioblastoma multiforme (GBM) and regulates multiple genes associated with cancer cell proliferation, apoptosis, and invasiveness. Thus, miR-21 can theoretically become a target to enhance the chemotherapeutic effect in cancer therapy. So far, the effect of downregulating miR-21 to enhance the chemotherapeutic effect to taxol has not been studied in human GBM.</p> <p>Methods</p> <p>Human glioblastoma U251 (PTEN-mutant) and LN229 (PTEN wild-type) cells were treated with taxol and the miR-21 inhibitor (in a poly (amidoamine) (PAMAM) dendrimer), alone or in combination. The 50% inhibitory concentration and cell viability were determined by the MTT assay. The mechanism between the miR-21 inhibitor and the anticancer drug taxol was analyzed using the Zheng-Jun Jin method. Annexin V/PI staining was performed, and apoptosis and the cell cycle were evaluated by flow cytometry analysis. Expression of miR-21 was investigated by RT-PCR, and western blotting was performed to evaluate malignancy related protein alteration.</p> <p>Results</p> <p>IC(50) values were dramatically decreased in cells treated with miR-21 inhibitor combine with taxol, to a greater extent than those treated with taxol alone. Furthermore, the miR-21 inhibitor significantly enhanced apoptosis in both U251 cells and LN229 cells, and cell invasiveness was obviously weakened. Interestingly, the above data suggested that in both the PTEN mutant and the wild-type GBM cells, miR-21 blockage increased the chemosensitivity to taxol. It is worth noting that the miR-21 inhibitor additively interacted with taxol on U251cells and synergistically on LN229 cells. Thus, the miR-21 inhibitor might interrupt the activity of EGFR pathways, independently of PTEN status. Meanwhile, the expression of STAT3 and p-STAT3 decreased to relatively low levels after miR-21 inhibitor and taxol treatment. The data strongly suggested that a regulatory loop between miR-21 and STAT3 might provide an insight into the mechanism of modulating EGFR/STAT3 signaling.</p> <p>Conclusions</p> <p>Taken together, the miR-21 inhibitor could enhance the chemo-sensitivity of human glioblastoma cells to taxol. A combination of miR-21 inhibitor and taxol could be an effective therapeutic strategy for controlling the growth of GBM by inhibiting STAT3 expression and phosphorylation.</p

MiR-221 and miR-222 target PUMA to induce cell survival in glioblastoma

<p>Abstract</p> <p>Background</p> <p>MiR-221 and miR-222 (miR-221/222) are frequently up-regulated in various types of human malignancy including glioblastoma. Recent studies have reported that miR-221/222 regulate cell growth and cell cycle progression by targeting p27 and p57. However the underlying mechanism involved in cell survival modulation of miR-221/222 remains elusive.</p> <p>Results</p> <p>Here we showed that miR-221/222 inhibited cell apoptosis by targeting pro-apoptotic gene PUMA in human glioma cells. Enforced expression of miR-22/222 induced cell survival whereas knockdown of miR-221/222 rendered cells to apoptosis. Further, miR-221/222 reduced PUMA protein levels by targeting PUMA-3'UTR. Introducing PUMA cDNA without 3'UTR abrogated miR-221/222-induced cell survival. Notably, knockdown of miR-221/222 induces PUMA expression and cell apoptosis and considerably decreases tumor growth in xenograft model. Finally, there was an inverse relationship between PUMA and miR-221/222 expression in glioma tissues.</p> <p>Conclusion</p> <p>To our knowledge, these data indicate for the first time that miR-221/222 directly regulate apoptosis by targeting PUMA in glioblastoma and that miR-221/222 could be potential therapeutic targets for glioblastoma intervention.</p

Epimorphin Regulates Bile Duct Formation via Effects on Mitosis Orientation in Rat Liver Epithelial Stem-Like Cells

Understanding how hepatic precursor cells can generate differentiated bile ducts is crucial for studies on epithelial morphogenesis and for development of cell therapies for hepatobiliary diseases. Epimorphin (EPM) is a key morphogen for duct morphogenesis in various epithelial organs. The role of EPM in bile duct formation (DF) from hepatic precursor cells, however, is not known. To address this issue, we used WB-F344 rat epithelial stem-like cells as model for bile duct formation. A micropattern and a uniaxial static stretch device was used to investigate the effects of EPM and stress fiber bundles on the mitosis orientation (MO) of WB cells. Immunohistochemistry of liver tissue sections demonstrated high EPM expression around bile ducts in vivo. In vitro, recombinant EPM selectively induced DF through upregulation of CK19 expression and suppression of HNF3α and HNF6, with no effects on other hepatocytic genes investigated. Our data provide evidence that EPM guides MO of WB-F344 cells via effects on stress fiber bundles and focal adhesion assembly, as supported by blockade EPM, β1 integrin, and F-actin assembly. These blockers can also inhibit EPM-induced DF. These results demonstrate a new biophysical action of EPM in bile duct formation, during which determination of MO plays a crucial role