Adenosine induces cell cycle arrest and apoptosis via cyclinD1/Cdk4 and Bcl-2/Bax pathways in human ovarian cancer cell line OVCAR-3

Adenosine is a regulatory molecule with widespread physiological effects in almost every cells and acts as a potent regulator of cell growth. Adenosine has been shown to inhibit cell growth and induce apoptosis in the several cancer cells via caspase activation and Bcl-2/Bax pathway. The present study was designed to understand the mechanism underlying adenosine-induced apoptosis in the OVCAR-3 human ovarian cancer cells. MTT viability, BrdU and cell counting assays were used to study the cell proliferation effect of adenosine in presence of adenosine deaminase inhibitor and the nucleoside transporter inhibitor. Cell cycle analysis, propidium iodide and annexin V staining, caspase-3 activity assay, cyclinD1, Cdk4, Bcl-2 and Bax protein expressions were assessed to detect apoptosis. Adenosine significantly inhibited cell proliferation in a concentration-dependent manner in OVCAR-3 cell line. Adenosine induced cell cycle arrest in G0/G1 phase via Cdk4/cyclinD1-mediated pathway. Adenosine induced apoptosis, which was determined by Annexin V-FITC staining and increased sub-G1 population. Moreover, down-regulation of Bcl-2 protein expression, up-regulation of Bax protein expression and activation of caspase-3 were observed in response to adenosine treatment. The results of this study suggest that extracellular adenosine induced G1 cell cycle arrest and apoptosis in ovarian cancer cells via cyclinD1/ Cdk4 and Bcl-2/Bax pathways and caspase-3 activation. These data might suggest that adenosine could be used as an agent for the treatment of ovarian cancer.     

Pulmonary arterial pressure detects functional mitral stenosis after annuloplasty for primary mitral regurgitation: An exercise stress echocardiographic study

Introduction

The restrictive mitral valve annuloplasty (RMA) is the treatment of choice for degenerative mitral regurgitation (MR), but postoperative functional mitral stenosis remains a matter of debate. In this study, we sought to determine the impact of mitral stenosis on the functional capacity of patients.

Methods

In a cross‐sectional study, 32 patients with degenerative MR who underwent RMA using a complete ring were evaluated. All participants performed treadmill exercise test and underwent echocardiographic examinations before and after exercise.

Results

The patients’ mean age was 50.1 ± 12.5 years. After a mean follow‐up of 14.1 ± 5.9 months (6–32 months), the number of patients with a mitral valve peak gradient >7.5 mm Hg, a mitral valve mean gradient >3 mm Hg, and a pulmonary arterial pressure (PAP) ≥25 mm Hg at rest were 50%, 40.6%, and 62.5%, respectively. 13 patients (40.6%) had incomplete treadmill exercise test. All hemodynamic parameters were higher at peak exercise compared with at rest levels (all P < .05). The PAP at rest and at peak exercise as well as peak transmitral gradient at peak exercise were higher in patients with incomplete exercise compared with complete exercise test (all P < .05). The PAP at rest (a sensitivity and a specificity of 84.6% and 52.6%, respectively; area under the curve [AUC] = .755) and at peak exercise (a sensitivity and a specificity of 100% and 47.4%, respectively; AUC = .755) discriminated incomplete exercise test.

Conclusion

The RMA for degenerative MR was associated with a functional stenosis and the PAP at rest and at peak exercise discriminated low exercise capacity.     

Hemodynamic parameters and reproductive outcome after intracytoplasmic sperm injection and fresh embryo transfer in patients undergoing oocyte retrieval with general anesthesia using fentanyl,remifentanil or alfentanil – A randomized clinical trial

ObjectiveAnesthesia for assisted reproductive technology is very important to provide less stressful and painful environment for patients, with minimal side effects on oocytes. In the present study, we aimed to evaluate hemodynamic parameters, recovery time and intracytoplasmic sperm injection (ICSI) outcome among patients underwent anesthesia with fentanyl, remifentanil or alfentanil.Material and methodsThis randomized double-blinded clinical trial was conducted in patients undergoing anesthesia for transvaginal ultrasound guided oocyte retrieval (TUGOR). Patients were randomly allocated to alfentanil (A; 15 μg/kg), fentanyl (F; 1.5 μg/kg) or remifentanil (R; 1.5 μg/kg) groups.ResultsThree hundred forty patients were assessed for eligibility and randomized for transvaginal oocyte retrieval following general anesthesia and 105 were lost to follow up. No statistically significant differences were noted among groups regarding basic characteristics. Although, time to respond to verbal command was significantly different among groups (A: 1.99 ± 1.64, F: 2.56 ± 1.72, R: 1.78 ± 1.34, P = 0.014). There were no significant differences among groups with respect to the first and second postoperative pain intensity, patient satisfaction, pre-induction and post-induction systolic and diastolic blood pressure (BP). Terminal systolic (A: 101.61 ± 9.15, F: 105.29 ± 12.61, R: 102 ± 12.91, P = 0.01) and diastolic (A: 59.97 ± 9, F: 65.63 ± 9.13, R: 63.69 ± 11.01, P = 0.003) BP was significantly different among groups. The fertilization rate was significantly different among groups (A: 51.6%, F: 54.4%, R: 62.2%, P = 0.018). Implantation rate, biochemical and clinical pregnancy rate was similar among groups.ConclusionsThe results of present study demonstrated that all three opioids have the same efficiency, in regards to patient satisfaction and pregnancy outcome. However, Anesthesia with alfentanil compared with fentanyl and remifentanil, seems to be inferior for TUGOR due to higher effect on fertilization rate and less hemodynamic stability.Registration numberIRCT201410258677N4.     

Interleukin-6-174 Promoter Polymorphism and Susceptibility to Hepatitis B Virus Infection as a Risk Factor for Hepatocellular Carcinoma in Iran

Background: Hepatitis B virus (HBV) is a major risk factor for hepatocellular carcinoma (HCC). Cytokines play an important role in the regulation of immune responses and defense against viral infections. Human interleukin 6 (IL6) is a multifunctional cytokine that participates in these processes. Objective: The aim of this study was to assess the IL6-174 gene polymorphism in patients with chronic hepatitis B virus (HBV) infection as compared with healthy controls in an Iranian population. Materials and Methods: Totals of 297 HBV patients and 368 control individuals were evaluated. Genomic DNA was extracted from peripheral blood and the SSP-PCR (sequence specific primer-polymerase chain reaction) method was applied for genotyping. Results: The frequencies of genotypes C/C, G/G and C/G in HBV cases were 4.7%, 34.3%, 60.9% and in controls were 12.8%, 39.7% and 47.6%, respectively. The frequencies of G and C allele in patients and controls were 78.1%, 21.9% and 67.4%, 32.6 % respectively. There was a significant difference in the frequencies of G/G genotype (CI=1.8-7.1, OR=3.47, P=0.00001) and G allele (CI=1.34-2.23, OR=1.72, P=0.0001) between HBV patients and the control group. Conclusions: These findings suggest that the IL6-174 C/G genotype and the G allele are strongly associated with susceptibility to HBV infection. Demographic information showed that most of the subjects were male (74.4%). According to high frequency of G/G genotype in male participants (63.1%) men probably are more susceptible to hepatitis than women.     

Step-by-step full mouth rehabilitation of a nasopharyngeal carcinoma patient with tooth and implant-supported prostheses: A clinical report

This clinical report presents a 46-year-old man diagnosed with nasopharyngeal carcinoma with the chief complaint of masticatory and speech deficiency because of radiation therapy. After a period of controlling post radiation caries, the patient was rehabilitated with tooth and implant supported metal ceramic restorations following surgical and endodontic intervention.     

Alu repeat discovery and characterization within human genomes

Human genomes are now being rapidly sequenced, but not all forms of genetic variation are routinely characterized. In this study, we focus on Alu retrotransposition events and seek to characterize differences in the pattern of mobile insertion between individuals based on the analysis of eight human genomes sequenced using next-generation sequencing. Applying a rapid read-pair analysis algorithm, we discover 4342 Alu insertions not found in the human reference genome and show that 98% of a selected subset (63/64) experimentally validate. Of these new insertions, 89% correspond to AluY elements, suggesting that they arose by retrotransposition. Eighty percent of the Alu insertions have not been previously reported and more novel events were detected in Africans when compared with non-African samples (76% vs. 69%). Using these data, we develop an experimental and computational screen to identify ancestry informative Alu retrotransposition events among different human populations.     

Polymerization behavior and thermal characteristics of two new composites at five temperatures: refrigeration to preheating

PURPOSE

Heat of composite polymerization (HP) indicates setting efficacy and temperature increase of composite in clinical procedures. The purpose of this in vitro experimental study was to evaluate the effects of 5 temperatures on HP of two new composites.

MATERIALS AND METHODS

From each material (Core Max II [CM] and King Dental [KD]), 5 groups of 5 specimens each were prepared and their total HPs (J/gr) were measured and recorded, at one of the constant temperatures 0℃, 15℃, 23℃, 37℃ and 60℃ (2 × 5 × 5 specimens) using a differential scanning calorimetry (DSC) analyzer. The data were analyzed using a two-way ANOVA, a Tukey''s test, an independent-samples t-test, and a linear regression analysis (α=0.05).

RESULTS

No polymerization reactions occurred at 0℃; then this temperature was excluded from statistical analyses. The mean HP of the remaining 20 KD specimens was 20.5 ± 14.9 J/gr, while it was 40.7 ± 12.9 J/gr for CM. The independent-samples t-test showed that there were significant differences between the HP of the two materials at the temperatures 15℃ (P=.0001), 23℃ (P=.0163), 37℃ (P=.0039), and 60℃ (P=.0106). Linear regression analysis showed statistically significant correlations between environment temperatures and HP of CM (R²=0.777).

CONCLUSION

Using CM is advantageous over conventional composite because of its better polymerization capacity. However due to its high HP, further studies should assess its temperature increase in vivo. Preheating KD is recommended. Refrigerating composites can negatively affect their polymerization potential.     

Role of corvids in epidemiology of west Nile virus in southern California

The invasion of different southern California landscapes by West Nile virus (WNV) and its subsequent amplification to epidemic levels during 2004 enabled us to study the impact of differing corvid populations in three biomes: the hot Colorado desert with few corvids (Coachella Valley), the southern San Joaquin Valley (Kern County) with large western scrub-jay but small American crow populations, and the cool maritime coast (Los Angeles) with a large clustered American crow population. Similar surveillance programs in all three areas monitored infection rates in mosquitoes, seroconversion rates in sentinel chickens, seroprevalence in wild birds, numbers of dead birds reported by the public, and the occurrence of human cases. Infection rates in Culex tarsalis Coquillett and sentinel chicken seroconversion rates were statistically similar among all three areas, indicating that highly competent mosquito hosts were capable of maintaining enzootic WNV transmission among less competent and widely distributed avian hosts, most likely house sparrows and house finches. In contrast, infection rates in Culex pipiens quinquefasciatus Say were statistically higher in Kern and Los Angeles counties with elevated corvid populations than in Coachella Valley with few corvids. Spatial analyses of dead corvids showed significant clusters near known American crow roosts in Los Angeles that were congruent with clusters of human cases. In this area, the incidence of human and Cx. p. quinquefasciatus infection was significantly greater within corvid clusters than without, indicating their importance in virus amplification and as a risk factor for human infection. In contrast the uniform dispersion by territorial western scrub-jays resulted in a high, but evenly distributed, incidence of human disease in Kern County.