Developmental Potential of Abnormally Fertilized Oocytes and the Associated Clinical Outcomes.

This study aims to investigate the embryo development potential of extending the culture of abnormally fertilized zygotes with no pronuclear (0PN), monopronuclear (1PN), and poor-quality day 3 embryos and to determine the associated clinical outcomes. This is a retrospective study performed between January 2014 and May 2018 at Jinhua People's Hospital. The normal developed embryos and the abnormal 0PN, 1PN, and poor-quality day 3 embryos were cultured to day 5 or 6 for embryo transfer. Clinical outcomes resulting from abnormal embryos and normally developed embryos were compared. A total of 6466 embryos (1542 0PN, 852 1PN, and 4072 poor-quality day 3 embryos) from 831 treatment cycles were cultured to the blastocyst stage. The total blastulation rate was 17.3% (1121/6466) with 18.2% in 0PN, 26.1% in 1PN, and 15.2% in poor-quality day 3 embryos. The rate for good-quality blastocyst formation was 9.5% (616/6466) with 11.2% in 0PN group, 14.8% in 1PN group, and 7.8% in poor-quality day 3 embryos, respectively. Blastulation rates of 0PN and 1PN derived from intracytoplasmic sperm injection (ICSI) were significantly lower compared with the in vitro fertilization group. A total of 243 cycles were transferred with blastocysts originating from abnormal embryos, resulting in 109 (44.9%) clinical pregnancies and 19 (17.4%) miscarriages; in the control group, a total of 350 cycles resulted in 214 (61.1%) clinical pregnancies and 18 (8.4%) miscarriages. The live birth rate was significantly lower in the abnormal embryo group than that in the control group. Collectively, conventional in vitro fertilization derived 0PN and 1PN zygotes, not ICSI, together with day 3 embryos with poor quality, that were able to reach the blastocyst stage and produce a fair pregnancy rate and live birth rate.

MicroRNA-21 promotes proliferation, migration, and invasion of colorectal cancer, and tumor growth associated with down-regulation of sec23a expression.

BACKGROUND: MicroRNA-21 (miR-21) is up-regulated in many cancers, including colorectal cancer (CRC). Nevertheless, the function of miR-21 in CRC and the mechanism underlying that function is still unclear. METHODS: After analyzing the expression of miR-21 and Sec23A in CRC cell lines, we transfected the highest miR-21 expressing cell line, SW-480, with a plasmid containing an miR-21 inhibitor and the lowest miR-21 expressing cell line, DLD-1, with a plasmid containing an miR-21 mimic and measured the effects on the expression of Sec23A and on cell proliferation, migration, and invasion. We also evaluated the effect of knocking down Sec23A on miR-21 expression and its effects on cell proliferation, migration, and invasion. Finally, we assessed the effect of miR-21 in a xenograft tumor model in mice. Tumor tissues from these mice were subjected to immunohistochemical staining to detect the expression of Sec23A. RESULTS: Genetic deletion of miR-21 suppressed the proliferation, migration, and invasion of SW-480 cells, while over-expression of miR-21 promoted proliferation, migration, and invasion of DLD-1 cells. Inhibition of miR-21 increased the expression of Sec23A protein in SW-480 cells while over-expression of miR-21 significantly suppressed the expression of Sec23A protein and Sec23A mRNA in DLD-1 cells. Knockdown of Sec23A increased the expression of miR-21 in SW480 and DLD-1 cells and their proliferation (DLD-1 only), migration, and invasion. Over-expression of miR-21 promoted tumor growth in BALB/c nude mice and suppressed tumor expression of Sec23A. CONCLUSION: These findings provide novel insight into the molecular functions of miR-21 in CRC, which may serve as a potential interesting target.

Methylglyoxal suppresses human colon cancer cell lines and tumor growth in a mouse model by impairing glycolytic metabolism of cancer cells associated with down-regulation of c-Myc expression.

Methylglyoxal (MG) is a highly reactive dicarbonyl compound exhibiting anti-tumor activity. The anti-tumor effects of MG have been demonstrated in some types of cancer, but its role in colon cancer and the mechanisms underlying this activity remain largely unknown. We investigated its role in human colon cancer and the underlying mechanism using human colon cancer cells and animal model. Viability, proliferation, and apoptosis were quantified in DLD-1 and SW480 colon cancer cells by using the Cell Counting Kit-8, plate colony formation assay, and flow cytometry, respectively. Cell migration and invasion were assessed by wound healing and transwell assays. Glucose consumption, lactate production, and intracellular ATP production also were assayed. The levels of c-Myc protein and mRNA were quantitated by western blot and qRT-PCR. The anti-tumor role of MG in vivo was investigated in a DLD-1 xenograft tumor model in nude mice. We demonstrated that MG inhibited viability, proliferation, migration, and invasion and induced apoptosis of DLD-1 and SW480 colon cancer cells. Treatment with MG reduced glucose consumption, lactate production, and ATP production and decreased c-Myc protein levels in these cells. Moreover, MG significantly suppressed tumor growth and c-Myc expression in vivo. Our findings suggest that MG plays an anti-tumor role in colon cancer. It inhibits cancer cell growth by altering the glycolytic pathway associated with downregulation of c-Myc protein. MG has therapeutic potential in colon cancer by interrupting cancer metabolism.

Metformin inhibits prostate cancer cell proliferation, migration, and tumor growth through upregulation of PEDF expression.

Metformin has been reported to inhibit the growth of various types of cancers, including prostate cancer. Yet the mode of anti-cancer action of metformin and the underlying mechanisms remain not fully elucidated. We hypothesized that the antitumorigenic effects of metformin are mediated through upregulation of pigment epithelium-derived factor (PEDF) expression in prostate cancer cells. In this report, metformin treatment significantly inhibited the proliferation and colony formation of prostate cancer cells, in a dose- and time-dependent manner. Meanwhile, Metformin markedly suppressed migration and invasion and induced apoptosis of both LNCaP and PC3 cancer cells. Metformin also reduced PC3 tumor growth in BALB/c nude mice in vivo. Furthermore, metformin treatment was associated with higher PEDF expression in both prostate cancer cells and tumor tissue. Taken together, metformin inhibits prostate cancer cell proliferation, migration, invasion and tumor growth, and these activities are mediated by upregulation of PEDF expression. These findings provide a novel insight into the molecular functions of metformin as an anticancer agent.