ABSTRACT
Anoikis is a form of apoptosis induced upon cell detachment from extracellular matrix.It has been determined that acquisition of resistance to anoikis is a critical step for tumor cell metastasis.MiR-21,the most prominent oncomiR,plays an important role in tumor progression.In this study,we revealed that up-regulation of miR-21 in human esophageal adenocarcinoma (EA) is associated with lymph node metastasis and poor survival rate.Because of the established anti-apoptosis effect of miR-21,it is tempting to speculate that miR-21 might contribute to tumor metastasis by regulating anoikis,qRT-PCR analysis demonstrated that miR-21 expression in OE33/AR cells (subpopulation of human EA OE33 cells that acquired resistance to anoikis) was significantly increased.Also,transfection of miR-21 mimics provided OE33 cells resisting to anoikis.By luciferase assays,we verified that PDCD4 and PTEN were the functional targets of miR-21.In mouse model,via tail vein injection experiment,we showed that the metastasis formation of OE33 cells in vivo could be mediated by changing the miR-21 expression pattern.Taken together,our findings suggested that miR-21 was involved in the regulation of anoikis in human EA cells.Targeting miR-21 may provide a novel strategy to prevent metastasis.
ABSTRACT
Anoikis is a form of apoptosis induced upon cell detachment from extracellular matrix.It has been determined that acquisition of resistance to anoikis is a critical step for tumor cell metastasis.MiR-21,the most prominent oncomiR,plays an important role in tumor progression.In this study,we revealed that up-regulation of miR-21 in human esophageal adenocarcinoma (EA) is associated with lymph node metastasis and poor survival rate.Because of the established anti-apoptosis effect of miR-21,it is tempting to speculate that miR-21 might contribute to tumor metastasis by regulating anoikis,qRT-PCR analysis demonstrated that miR-21 expression in OE33/AR cells (subpopulation of human EA OE33 cells that acquired resistance to anoikis) was significantly increased.Also,transfection of miR-21 mimics provided OE33 cells resisting to anoikis.By luciferase assays,we verified that PDCD4 and PTEN were the functional targets of miR-21.In mouse model,via tail vein injection experiment,we showed that the metastasis formation of OE33 cells in vivo could be mediated by changing the miR-21 expression pattern.Taken together,our findings suggested that miR-21 was involved in the regulation of anoikis in human EA cells.Targeting miR-21 may provide a novel strategy to prevent metastasis.
ABSTRACT
Objective To analyze the influence of microporous parameters on mechanical behavior of bone tissue engineered-scaffolds, and provide references for optimizing the microporous structure design. Methods The finite element models of scaffolds with microporous structures were established by using ANYSYS software. The relationships between porosity and maximum equivalent stress as well as maximum total deformation were calculated. The effects of microporous spacing and diameter on maximum equivalent stress, maximum total deformation and internal strain were compared and analyzed. Results The influence rule of microporous spacing in x and y direction was consistent. With the increase of microporous spacing from 0.6 mm to 2.0 mm, the maximum equivalent stress reduced from 63.1 MPa to 46.3 MPa, the maximum total deformation reduced from 23.8 μm to 21.8 μm, and the proportion of the best strain range increased from 80% to 84%. However, with the increase of microporous spacing in z direction, the maximum equivalent stress increased from 38.3 MPa to 47.8 MPa, the maximum total deformation increased from 20. 8 μm to 22.8 μm, and the proportion of the best strain range fluctuated within the range of 82%-85%. With the increase of microporous diameter in x and y direction from 0.1 mm to 1.0 mm, the maximum equivalent stress increased from 32.4 MPa to 78.4 MPa, the maximum total deformation increased from 19.9 μm to 38.2 μm, and the proportion of the best strain range reduced from 90% to 53%. With the increase of microporous diameter in z direction, the maximum equivalent stress reduced from 58.8 MPa to 37.9 MPa, the maximum total deformation increased from 23.3 μm to 25.9 μm, and the proportion of the best strain range increased from 82% to 87%. Conclusions The greater the porosity and the proportion of the best strain range, the smaller maximum equivalent stress and maximum total deformation would be, the scaffolds would have the better biological and mechanical properties. These results have reference values for design and optimization of scaffold structure.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the correlation between different Chinese medicine (CM) syndromes and variations in microcirculation in septic shock patients.</p><p><b>METHODS</b>seventy Septic shock patients were divided into four groups: heat damaging qi-yin group (HDQY, 23 cases); yin exhaustion and yang collapse group (YEYC, 26 cases); excessive heat in Fu organ group (EHFO, 10 cases); and heat damaging nutrient-blood group (HDNB, 11 cases). Sublingual microcirculation parameters were observed by sidestream dark-field (SDF) imaging and scored by Acute Physiology and Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure Assessment (SOFA), and parameters of microcirculation perfusion variations and prognoses were analyzed.</p><p><b>RESULTS</b>Compared with those with qi-yin heat damage, perfused vessel density (PVD) in other groups decreased dramatically (P<0.05), and APACHE II scores increased significantly (P<0.05). In addition, the recovery time was prolonged substantially (P<0.05), and the mixed venous oxygen saturation (SVO2) decreased (P<0.05). Blood lactic acid increased significantly (P<0.05), and the mixed SVO decreased (P<0.05), in the YEYC group. Compared with the thermal injury camp blood group, sublingual microcirculation parameter variations showed no obvious difference in the YEYC and EHFO groups (P>0.05). There were significant positive correlations between CM syndromes and APACHE II scoring in different groups (r=0.512, P<0.05). There were negative correlations between PVD and APACHE II scoring (r=-0.378, P=0.043), the proportion of perfused vessels (PPV) and APACHE II scoring (r=-0.472, P=0.008), as well as between the microvascular flow index (MFI) and APACHE II scoring (r=-0.424, P=0.023) in different patients.</p><p><b>CONCLUSION</b>Sublingual microcirculation may serve as a clinical diagnostic parameter of the patient condition, as well as being a prognostic indicator.</p>