Objective To investigate the antitumor effects on ovarian cancer using recombinant adenoviruses expressing autocatalytic caspase-3 driven by amplified human telomerase reverse transcriptase promoter (AdHTVP2G5-rev-casp3) combined with flavopiridol. Methods Following the treatment with AdHTVP2G5-rev-casp3 combined with flavopiridol, cell survival rate was measured by cell counting kit 8;cell apoptotic rate and cell cycle distribution were detected by flow cytometry. Western blot was performed to observe the expression of p17, the active subunit of caspase-3, and p85, the cleavage segment of substrate of caspase-3, in AO cells. The mice survival rates were measured for abdominally metastatic tumor models and the volume of tumor nodules were determined for subcutaneous tumor models following the treatments of AdHTVP2G5-rev-casp3 combined with flavopiridol. HE staining was used to detect the histopathological changes of various organs, and the serum level of alanine transaminase (ALT) and aspartate aminotransferase (AST) were measured to monitor liver damages following the intraperitoneal administration of AdHTVP2G5-rev-casp3 and flavopiridol. Results There was no significant cell-killing effects or apoptosis in AO cells following treatments with AdHTVP2G5-rev-casp3 or flavopiridol at low dosage alone (apoptotic rate all < 11% ), whereas significant synergism of their sequential combination was observed in AO cells. This sequential treatment of AdHTVP2G5-rev-casp3 [multiplicity of infection (MOI) was 20]infection for 72 hours, followed by flavopiridol ( 300 nmol/L) for 48 hours, could result in the most substantial cell death, and AO cells survival rate and apoptotic rate were 73. 5% and 11.6%, respectively.Following treatments with AdHTVP2G5-rev-casp3 at low doses ( MOI = 10), there was a significant increase in cell number with S-phase content ( 62. 5% ), which resulted in the most marked apoptosis induced by sequential treatments with flavopiridol. The sequential combination could induce significantly higher levels of p17 and p85 expression than that when their applications alone. Combined AdHTVP2G5-rev-casp3 and flavopiridol treatment prolonged mouse survival [ mean survival time of ( 286 ± 6) days ] and suppressed tumor growth significantly (tumor growth suppression rate of 81% ), when compared with treatment using either alone. The levels of serum ALT and AST were not significantly elevated and no obvious lesions were found in any organs in treatments with AdHTVP2G5-rev-casp3 of low doses combined with flavopiridol.Conclusions AdHTVP2G5-rev-casp3 at low doses results in a significant increase in cell number with Sphase content, which significantly enhanced the sensitivity of cells to flavopiridol. Treatments of autocatalytic caspase-3 combined at low doses with flavopiridol result in significant synergistic antitumor effects,significant tumor growth suppression and prolonged survival of mice. When compared with normal dose flavopiridol alone, the combination could resulted in minimal liver toxicity.
Key words:
Ovarian neoplasms; Caspase 3; Cyclin-dependent kinases; Flavonoids; Piperidines
3 kinds of quinazoline derivatives and 5 kinds pyrrolo[3,2- d ]pyrimidine derivatives targeting TLR7 were synthesized. The antiviral efficacy of these compounds was evaluated in vitro and in vivo .
With the emergence of RISC-V architecture in embedded devices, its inherent low-power features have propelled its extensive adoption across various industrial settings. Displacement sensors leveraging Hall sensors and magnetic flux measurement present notable benefits including cost-effectiveness and compact design. This study undertakes the porting of Hall sensors onto RISC-V architecture embedded devices, validating their functionality within displacement sensors. Empirical investigations substantiate that the ported system consistently delivers comparable outcomes to those obtained from x86 architecture systems employing PM-MFM methods, affirming its reliability and performance in practical applications.
Objective
To study the clinical value of intraoperative epicardial echocardiography (IEE) in assessing graft-left anterior descending artery (LAD) of off-pump coronary artery bypass grafting (OPCABG).
Methods
IEE was used to detecte graft vessels anastomosis in 53 patients with OPCABG-LAD. Two-dimensional grey ultrasound and color Doppler ultrasound was used to show whether there was abnormal echo in proximal and distal lumen, measuring diameter and rate of stenosis. Pulse Doppler ultrasound was used to observe the blood flow spectrum. Intraoperative transient blood flow meter (TTFM) was employed to measure the pulsatility index and flow volume.
Results
Among the 53 patients with OPCABG-LAD, 38 cases were left internal mammary artery graft (LIMA), 15 cases were saphenous vein graft (GSV). Pulsatility index and flow volume showed normal by TTFM. The detection rates of graft vessels-LAD anastomosis in proximal and distal segment were 100% using IEE, including 10 cases anastomotic plaques and 10 cases proximal plaques. Comparison of blood flow parameter of graft by IEE and TTFM in operation, there was no significant difference in LIMA grafts (P=0.091), but the correlation was statistically significant (r=0.809, P<0.001); the difference in GSV grafts had no statistical significance (P=0.821), but the correlation was statistically significant (r=0.684, P=0.005).
Conclusions
IEE clearly displays the lumen of graft vessel and LAD, and measures the hemodynamic indexes. It provides an intuitive, accurate and convenient method for detecting the patency of the graft vessels during OPCABG.
Key words:
Echocardiography; Coronary artery bypass, off-pump; Left anterior descending artery; Graft vessel
Objective To assess regional left ventricular systolic function in patients with hypertrophic cardiomyopathy (HCM) using real-time three-dimensional echocardiography (RT-3DE).Methods Twenty-five patients with HCM which was asymmetric septal hypertrophy,and twenty healthy subjects were enrolled in the study.The apical four-chamber view of left ventricular was acquired by RT-3DE.The left ventricular volume-time curves were analyzed quantitatively with Tomtec 4D LV-Analysis 3.0,and regional end-diastolic volume and end-systolic volume of left ventricular (rEDV,rESV),the time to minimum systolic volume (rESVT),regional stroke volume (rSV),regional ejection fraction (rEF),regional-global ejection fraction (rgEF) and the parameters of left ventricular dyssynchrony were measured.Results In the HCM group,the values of Tmsv16-Dif,Tmsv16-SD,Tmsv16-Dif%,Tmsv16-SD% were significantly lower compared with the control group (P < 0.01),and rEDV,rSV,rEF and rgEF in hypertrophic segments were lower than those in non-thickening and mild-thickening segments (P <0.05).In the control group,there were no significant difference of those parameters among all segments (P >0.05).The values of rEDV,rSV and rgEF in hypertrophic segments decreased in the HCM group (P <0.05),at the basal level,rEF in hypertrophic segments decreased,at the apical level,it increased,but the differences at the mid-ventricular level between the two groups were not significant;the values of rEF and rgEF in non-thickening and mild-thickening segments increased (P <0.05).Conclusions RT-3DE could sensitively detect left ventricular dyssynchrony and accurately assess regional left ventricular volume and function of different segments in patients with HCM.
Key words:
Echocardiography, real-time three-dimensional; Cardiomyopathy, hypertrophic; Ventricular function, left
Abstract Previous studies have shown that four and a half LIM domain protein 2 (FHL2) plays an essential role in the regulation of follicular development in mammals. Although the FHL2 genes of human and mouse have been well characterized, the expression and location of FHL2 in ovary and the biological functions of FHL2 on granulosa cells (GCs) of ovine are still not clear. In this study, full‐length complementary DNA (cDNA) of FHL2 from ovine follicular GCs was amplified by real‐time PCR (RT‐PCR). The expression and location of FHL2 in ovary and GCs of ovine were studied by immunohistochemistry and immunofluorescence, and the biological effects of FHL2 on the cell proliferation, cell apoptosis, cell cycles and expression level of related genes of ovine GCs were also explored by overexpression or knockdown of FHL2. The results indicated that FHL2 was expressed in ovine follicular GCs and the sequence of the FHL2 cDNA was consistent with that predicted in GenBank, which did not cause an amino acid change. According to the results, FHL2 was expressed in ovine ovary and mainly located in the cytoplasm and nucleus of GCs. In addition, overexpression of FHL2 significantly reduced the cell viability, promoted the cell apoptosis and decreased the percentage of G0/G1 and S phase cells. RT‐PCR showed that overexpression of FHL2 significantly increased the mRNA expression level of Bax and decreased the expression of Bcl‐2 and the Bcl‐2/Bax mRNA ratio compared with the control group. Besides, the knockdown of FHL2 gene in ovine GCs significantly improved the cell viability, suppressed the cell apoptosis, decreased the mRNA expression level of Caspase‐3 gene, increased the Bcl‐2/Bax mRNA ratio and increased the percentage of S and G2/M phase cells. Our results suggest that FHL2 may play an important role in the biological functions of GCs in ovine.