To investigate whether the day of embryo transfer (day 2 or day 3) affects clinical pregnancy outcomes in poor responder patients.We retrospectively analyzed the pregnancy rates of 265 initial fresh cycles of in vitro fertilization-embryo transfer (IVF-ET), all transferred on day 2 (n = 169) or day 3 (n = 96) irrespective of quality because of an extremely low number of available embryos.Among the poor responders aged < 35 years, a higher rate of clinical pregnancy was achieved in the day-3 than in the day-2 group (50% vs 32.43% ; RR = 0.65, 95% CI: 0.43 - 0.99), and among those aged years, the two groups showed similar pregnancy outcomes.Shortening the time of embryo culture has no obvious benefit for the pregnancy outcome. For the poor responders under 35 years of age, day-3 embryo transfer may afford an even higher rate of clinical pregnancy.
Human papillomaviruses (HPVs) have important roles in the development and progression of cervical cancer, but the underlying mechanisms are yet to be fully elucidated. MicroRNA‑130a (miR‑130a) has previously been reported to promote cervical cancer growth. However, the underlying molecular mechanisms by which miR‑130a promotes cervical cancer progression have remained largely elusive. In the present study, polymerase chain reaction and western blot analyses were performed to examine the expression levels of miR‑130a and associated proteins. A wound healing assay and a Transwell assay were applied to study cell migration and invasion. A luciferase reporter gene assay was performed to confirm the targeting associations of miR‑130a. It was observed that miR‑130a was significantly upregulated in cervical cancer tissues compared with that in adjacent non‑tumorous tissues. High expression of miR‑130a was significantly associated with lymph node metastasis and an advanced clinical stage of cervical cancer. Furthermore, the expression of miR‑130a was also higher in HPV(+) cervical cancer cell lines compared with that in HPV(‑) cells. Knockdown of HPV18 E6 significantly inhibited the expression of miR‑130a in HeLa cervical cancer cells. Furthermore, knockdown of miR‑130a reduced the migration and invasion of HeLa cells. Tissue inhibitor of metalloproteinase 2 (TIMP2), an antagonist of matrix metalloproteinase 2 (MMP2), was identified as a novel, direct target gene of miR‑130a. The expression of TIMP2 was negatively mediated by miR‑130a, and HPV18 E6 inhibited the expression of TIMP2 in HeLa cells. Furthermore, knockdown of TIMP2 rescued the suppressive effects of miR‑130a downregulation on the migration and invasion of HeLa cells. In summary, the present study suggests that HPV18 E6 promotes the expression of miR‑130a, which further inhibits the expression of TIMP2 and promotes cervical cancer cell invasion. Therefore, HPV/miR‑130a/TIMP2 signaling may be a potential target for the prevention of cervical cancer metastasis.
The particle fabrication technique was used to fabricate monodisperse size and shape specific poly (lactide-co-glycolide) particles loaded with the silybin. Response surface methodology (RSM) using the central composite rotatable design (CCRD) model was used to optimize formulations of silybin nanoparticles. Further the optimized nanoparticles are characterized for particle size, zeta potential, surface morphology, entrapment efficiency, in-vitro drug release, silybin availability for tumor, plasma, lung, spleen, liver were determined. The significant findings were the optimal formulation of PLGA concentration 10 mg, PVA concentration 2000 and PET width of 6 gave rise to the EE of 88%, mean diameter of 223 nm and zeta potential of 25-mV. Release studies were investigated at pH 1.2 and pH 6.8. It was studied that lower the pH, faster the release of sylibin. The nanoparticles had~15-fold higher plasma exposure as measured by AUC contrasted to pure silybin. The nanoparticles had a 60% increase altogether tumor silybin presentation contrasted with pure silybin. Nanoparticles had higher silybin presentation in the spleen and liver contrasted with pure silybin suspension as expected for a nanoparticle formulation. The lung silybin presentation for the nanoparticle was additionally 2-fold higher than that of the pure silybin suspension. The results of pharmacokinetic parameters and oral bioavailability data exhibited that drug-nanoparticle complex could enhance the oral absorption of silybin and as well as the use of particles with smaller feature size may be preferred to decrease clearance by organs of the mononuclear phagocyte system.
To investigate the effects and molecular mechanism of downregulated histone deacetylase 2 (HDAC2) expression on cell proliferation and cell cycle in cervical cancer Hela cells.HDAC2 small interfering (si)RNA and control siRNA were transfected into cervical cancer Hela cells. A cell proliferation assay using a cell counting kit-8 was applied to analyze the change in cell proliferation before and after transfection. Flow cytometry was used to detect the change in cell cycle distribution before and after transfection. Finally, Western blot was used to detect changes in the expression of cell proliferation and cell cycle-related proteins.HDAC2 siRNA significantly downregulated the expression of HDAC2 proteins in cervical cancer cells, markedly inhibiting their proliferation. In addition, the percentage of Hela cells in the G0/G1 phase in the HDAC2 siRNA group was 63.3±2.0%, significantly higher than those in the untreated group (29.3±1.7%) or the control siRNA group (29.4±1.7%) (F=354.181, p=0.000). Furthermore, Western blot analyses demonstrated that downregulated HDAC2 expression inhibited the expression of cyclin D1, cyclin E, and cdk2 proteins but elevated the expression of p21 protein.The proliferation inhibition and cell cycle arrest mediated by downregulated HDAC2 expression may be tightly associated with the decrease of cyclin D1, cyclin E, and cdk2 proteins expression and the increase in p21 protein expression.
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