Seung-Chul Kim

Clinical significance of preoperative neutrophil-lymphocyte versus platelet-lymphocyte ratio in patients with operable colorectal cancer

The objective of this study was to clarify whether the neutrophil-lymphocyte ratio (NLR) and the platelet-lymphocyte ratio (PLR) are significant prognostic markers in patients with resectable colorectal cancer (CRC). A total of 200 patients who underwent curative resection for CRC were enrolled. The NLR and PLR were positively correlated (p < 0.001). Both the NLR and PLR were shown to be good prognostic biomarkers of overall survival (OS) (p = 0.002 and p = 0.001, respectively). The PLR was an independent prognostic factor of OS based on multivariate analysis (hazard ratio, 1.971; 95% confidence interval, 1.102–3.335; p = 0.021).

Role of leptin in improvement of oocyte quality by regulation of ovarian angiogenesis.

Ovarian angiogenesis plays an important role in folliculogenesis. An active blood supply via ovarian angiogenesis seems to be essential for the induction of oocytes with good quality. Leptin is an angiogenic factor which regulates VEGF expression. This study was aimed to investigate whether leptin administration during superovulation influences ovarian response, oocyte quality and VEGF expression in the ovary using different aged mice model. C57BL inbred female mice of two age groups (18-21, and 29-31 weeks) were superovulated by intraperitoneal co-injection with 5IU of pregnant mares serum gonadotropin (PMSG) supplemented with recombinant mouse leptin at various doses (0.01, 0.1, 1 microg), followed by injection with 5IU of human chorionic gonadotropin (hCG) approximately 48 h later. Then, the mice were immediately paired with an individual male. The control group was superovulated with PMSG and hCG without leptin. After 18 h, one-cell embryos were flushed and cultured for 4 days. Proteins were extracted from ovaries removed just after the retrieval of one-cell embryos and VEGF expression was examined by Western blot. Treatment of 0.1 microg and 1 microg leptin significantly increased the number and embryo development rate of one-cell embryos retrieved compared to the control group. This positive effect of leptin was more significant with advancing female age. Ovarian VEGF expression was also significantly increased in 0.1 and 1 microg leptin-treated groups compared to the control group in both age groups (P<0.05). Our present study showed that leptin administration with gonadotropins during superovulation in aged mice increased the ovarian response, developmental competence of oocytes and ovarian VEGF expression. This research may have potential clinical implications in the treatment of age-related decline of fertility.

Decreased expressions of vascular endothelial growth factor and visfatin in the placental bed of pregnancies complicated by preeclampsia

Aim:  The aim of the present study was to examine the expression of vascular endothelial growth factor (VEGF) and visfatin in the third trimester placental bed of pregnancies with and without preeclampsia (PE).

The adverse effect of 4-tert-octylphenol on fat metabolism in pregnant rats via regulation of lipogenic proteins

Alkylphenols such as 4-tert-octylphenol (OP), nonylphenol, and bisphenol A are classified as endocrine-disrupting chemicals (EDCs). Digestion and metabolism of food are controlled by many endocrine factors, including insulin, glucagon, and estrogen. These factors are differentially regulated during pregnancy. The alteration of nutritional intake and fat metabolism may affect the maintenance of pregnancy and supplementation of nutrients to the fetus, and therefore can cause severe metabolic diseases such as ketosis, marasmus and diabetes mellitus in pregnant individuals. In this study, we examined the effects of OP on fat metabolism in pregnant rats. Ethinyl estradiol (EE) was also administered as an estrogenic positive control. In our results, rats treated with OP showed significantly reduced body weights compared to the control group. In addition, histological analysis showed that the amount of fat deposited in adipocytes was reduced by OP treatment. To study the mechanism of action of OP in fat metabolism, we examined the expression levels of fat metabolism-associated genes in rat adipose tissue and liver by real-time PCR. OP and EE negatively regulated the expression of lipogenic enzymes, including FAS (fatty acid synthase), ACC-1 (acetyl-CoA carboxylase-1), and SCD-1 (stearoyl-CoA desaturase-1). The levels of lipogenic enzyme-associated transcription factors such as C/EBP-α (CAAT enhancer binding protein alpha) and SREBP-1c (sterol regulatory element binding protein-1c) were also reduced in both liver and adipose tissue. In summary, these findings suggest that OP has adverse effects on fat metabolism in pregnant rats and inhibits fat deposition via regulating lipogenic genes in the liver and adipose tissue. The altered fat metabolism by OP may affect the nutrition balance during pregnancy and can cause metabolism-related diseases.

Effects of 17β‐estradiol on the release of monocyte chemotactic protein‐1 and MAPK activity in monocytes stimulated with peritoneal fluid from endometriosis patients

Aim:  Hormones and inflammation have been implicated in the pathological process of endometriosis; therefore, we investigated the combined effects of 17β‐estradiol (E2) and peritoneal fluid obtained from patients with endometriosis (ePF) or a control peritoneal fluid (cPF) obtained from patients without endometriosis on the release of monocyte chemotactic protein‐1 (MCP‐1) by monocytes and the role of signaling pathways.

Crucial role of HMGA1 in the self-renewal and drug resistance of ovarian cancer stem cells

Cancer stem cells are a subpopulation of cancer cells characterized by self-renewal ability, tumorigenesis and drug resistance. The aim of this study was to investigate the role of HMGA1, a chromatin remodeling factor abundantly expressed in many different cancers, in the regulation of cancer stem cells in ovarian cancer. Spheroid-forming cancer stem cells were isolated from A2780, SKOV3 and PA1 ovarian cancer cells by three-dimensional spheroid culture. Elevated expression of HMGA1 was observed in spheroid cells along with increased expression of stemness-related genes, such as SOX2, KLF4, ALDH, ABCB1 and ABCG2. Furthermore, spheroid A2780 cells, compared with adherent cells, showed higher resistance to chemotherapeutic agents such as paclitaxel and doxorubicin. HMGA1 knockdown in spheroid cells reduced the proliferative advantage and spheroid-forming efficiency of the cells and the expression of stemness-related genes. HMGA1 overexpression in adherent A2780 cells increased cancer stem cell properties, including proliferation, spheroid-forming efficiency and the expression of stemness-related genes. In addition, HMGA1 regulated ABCG2 promoter activity through HMGA1-binding sites. Knockdown of HMGA1 in spheroid cells reduced resistance to chemotherapeutic agents, whereas the overexpression of HMGA1 in adherent ovarian cancer cells increased resistance to chemotherapeutic agents in vitro. Furthermore, HMGA1-overexpressing A2780 cells showed a significant survival advantage after chemotherapeutic agent treatment in a xenograft tumorigenicity assay. Together, our results provide novel insights regarding the critical role of HMGA1 in the regulation of the cancer stem cell characteristics of ovarian cancer cells, thus suggesting that HMGA1 may be an important target in the development of therapeutics for ovarian cancer patients.

Estrogen administration during superovulation increases oocyte quality and expressions of vascular endothelial growth factor and nitric oxide synthase in the ovary

Aims:  This study investigated whether estrogen administration during superovulation enhances oocyte quality using a mice model. We also investigated whether this estrogen treatment regulates the expressions of angiogenic factors, such as vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS), in the ovary.

Effect of vitamin D3 on production of progesterone in porcine granulosa cells by regulation of steroidogenic enzymes

Abstract 1,25-dihydroxyvitamin D3 (VD3), an active form of Vitamin D, is photosynthesized in the skin of vertebrates in response to solar ultraviolet B radiation (UV-B). VD3 deficiency can cause health problems such as immune disease, metabolic disease, and bone disorders. It has also been demonstrated that VD3 is involved in reproductive functions. Female sex hormones such as estrogen and progesterone are biosynthesized mainly in ovarian granulosa cells as the ovarian follicle develops. The functions of sex hormones include regulation of the estrus cycle and puberty as well as maintenance of pregnancy in females. In this study, we isolated granulosa cells from porcine ovaries and cultured them for experiments. To examine the effects of VD3 on ovarian granulosa cells, the mRNA and protein levels of genes were analyzed by Real-time PCR and Western blotting assay. Production of progesterone from granulosa cells was also measured by ELISA assay. As a result, transcriptional and translational regulation of progesterone biosynthesis-related genes in granulosa cells was significantly altered by VD3. Furthermore, progesterone concentrations in porcine granulosa cell-cultured media decreased in response to VD3. These results show that VD3 was a strong regulator of sex steroid hormone production in porcine granulosa cells, suggesting that vitamin D deficiency may result in inappropriate sexual development of industrial animals and eventually economic loss.

Differential expressions of stromal cell-derived factor-1α and vascular endothelial growth factor in the placental bed of pregnancies complicated by preeclampsia.

Objective: The aim of this study is to examine the differential expression of stromal cell-derived factor-1α (SDF-1α)/CXCR4 and vascular endothelial growth factor (VEGF) in the third trimester placental bed of normotensive controls and preeclamptic patients. Methods: Placental bed tissues were collected from 15 patients with preeclampsia (PE) and 15 gestational-matched normotensive controls at the time of their cesarean delivery. Placental bed expressions of SDF-1α, CXCR4 and VEGF were evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR), real-time PCR and immunohistochemical staining. Results: No statistical difference was found between the PE and the normotensive control group with respect to their age and parity, gravidity and body mass index. The placental bed expressions of SDF-1α/CXCR4 and VEGF were significantly decreased in the PE group compared with the normotensive control group. Conclusions: This study showed decreased expressions of SDF-1α/CXCR4 and VEGF in the third trimester placental bed of pregnancies with PE. This result suggests that decreased expressions of SDF-1α/CXCR4 and VEGF in the placental bed could be associated with the pathogenesis of PE.

Mussel-inspired surface functionalization of porous carbon nanosheets using polydopamine and Fe3+/tannic acid layers for high-performance electrochemical capacitors

A facile mussel-inspired surface modification of interconnected porous carbon nanosheet (IPCN) electrodes is demonstrated through the formation of a polydopamine coating and the subsequent layer-by-layer deposition of ferric ions (Fe3+) and tannic acid, with the aim of developing high-performance electrochemical capacitors. After the deposition of the polydopamine coating, the specific capacitance increases by ∼40% as compared to that of an unmodified IPCN electrode. This increase in the capacitance can be explained based on the pseudocapacitance induced by the catechol groups of polydopamine. Furthermore, the electrodes coated with both polydopamine and layers of Fe3+ and tannic acid exhibit an additional increase in the capacitance to ∼244 F g−1 at 5 mV s−1, which is ∼83% higher than that of the unmodified IPCN electrode. This is attributable to the presence of many redox moieties, which are introduced by polydopamine and tannic acid. Furthermore, the strong interactions between the Fe3+ ions and the catechol groups result in improved capacitance retention even after 1000 cycles. The mussel-inspired surface modification of IPCN electrodes demonstrated in this work can potentially be exploited for developing novel pseudocapacitive electrode materials with excellent performances.