Pathogenetic factors involved in recurrent pregnancy loss from multiple aspects

Recurrent pregnancy loss (RPL) is a common complication in obstetrics, affecting about 5% of women of childbearing age. An increase in the number of abortions results in escalation in the risk of miscarriage. Although concentrated research has identified numerous causes for RPL, about 50% of them remain unexplained. Pregnancy is a complex process, comprising fertilization, implantation, organ and tissue differentiation, and fetal growth, which is effectively controlled by a number of both maternal and fetal factors. An example is the immune response, in which T cells and natural killer cells participate, and inflammation mediated by tumor necrosis factor or colony-stimulating factor, which hinders embryo implantation. Furthermore, vitamin D affects glucose metabolism and inhibits embryonic development, whereas microRNA has a negative effect on the gene expression of embryo implantation and development. This review examines the causes of RPL from multiple perspectives, and focuses on the numerous factors that may result in RPL.

Lipopolysaccharide-binding protein plasma levels as a biomarker of obesity-related insulin resistance in adolescents / 소아과

PURPOSE: Lipopolysaccharide-binding protein (LBP) is a 65-kDa acute phase protein, derived from the liver, which is present in high concentrations in plasma. Data regarding the association between circulating plasma LBP levels and obesity-related biomarkers in the pediatric population are scarce. We aimed to determine whether there was a difference in plasma LBP levels between overweight/obese and normal-weight adolescents and to assess the correlation of circulating LBP levels with anthropometric measures and obesity-related biomarkers, including insulin resistance, liver enzyme levels, and lipid profiles. METHODS: The study included 87 adolescents aged 12-13 years; 44 were overweight/obese and 43 were of normal-weight. We assessed anthropometric and laboratory measures, including body mass index (BMI), blood pressure, insulin resistance, liver enzyme levels, and lipid profiles. Plasma LBP levels were measured using an enzyme-linked immunosorbent assay. RESULTS: The mean age of the participants was 12.9±0.3 years. Circulating plasma LBP levels were significantly increased in overweight/obese participants compared with those in normal-weight participants (7.8±1.9 µg/mL vs. 6.0±1.6 µg/mL, P<0.001). LBP levels were significantly and positively associated with BMI, systolic blood pressure, aspartate aminotransferase, alanine aminotransferase, total cholesterol, low density lipoprotein-cholesterol, fasting glucose and insulin, and insulin resistance as indicated by the homeostatic model assessment of insulin resistance (HOMA-IR) (all P<0.05). In multivariate linear regression analysis, BMI and HOMA-IR were independently and positively associated with plasma LBP levels. CONCLUSION: LBP is an inflammatory biomarker associated with BMI and obesity-related insulin resistance in adolescents. The positive correlation between these parameters suggests a potentially relevant pathophysiological mechanism linking LBP to obesity-related insulin resistance in adolescents.

Systematic Analysis of the Anticancer Agent Taxol-Producing Capacity in Colletotrichum Species and Use of the Species for Taxol Production

Paclitaxel (taxol) has long been used as a potent anticancer agent for the treatment of many cancers. Ever since the fungal species Taxomyces andreanae was first shown to produce taxol in 1993, many endophytic fungal species have been recognized as taxol accumulators. In this study, we analyzed the taxol-producing capacity of different Colletotrichum spp. to determine the distribution of a taxol biosynthetic gene within this genus. Distribution of the taxadiene synthase (TS) gene, which cyclizes geranylgeranyl diphosphate to produce taxadiene, was analyzed in 12 Colletotrichum spp., of which 8 were found to contain the unique skeletal core structure of paclitaxel. However, distribution of the gene was not limited to closely related species. The production of taxol by Colletotrichum dematium, which causes pepper anthracnose, depended on the method in which the fungus was stored, with the highest production being in samples stored under mineral oil. Based on its distribution among Colletotrichum spp., the TS gene was either integrated into or deleted from the bacterial genome in a species-specific manner. In addition to their taxol-producing capacity, the simple genome structure and easy gene manipulation of these endophytic fungal species make them valuable resources for identifying genes in the taxol biosynthetic pathway.

Antioxidant, lipid peroxidation inhibition and free radical scavenging efficacy of a diterpenoid compound sugiol isolated from Metasequoia glyptostroboides

OBJECTIVE@#To investigate the antioxidant efficacy of a biologically active diterpenoid compound sugiol isolated from Metasequoia glyptostroboides (M. glyptostroboides) in various antioxidant models.@*METHODS@#An abietane type diterpenoid sugiol, isolated from ethyl acetate extract of M. glyptostroboides cones, was analyzed for its antioxidant efficacy as reducing power ability and lipid peroxidation inhibition as well as its ability to scavenge free radicals such as 1,1-diphenyl-2-picryl hydrazyl, nitric oxide, superoxide and hydroxyl radicals.@*RESULTS@#The sugiol showed significant and concentration-dependent antioxidant and free radical scavenging activities. Consequently, the sugiol exerted lipid peroxidation inhibitory effect by 76.5% as compared to α-tocopherol (80.13%) and butylated hydroxyanisole (76.59%). In addition, the sugiol had significant scavenging activities of 1,1-diphenyl-2-picryl hydrazyl, nitric oxide, superoxide and hydroxyl free radicals in a concentration-dependent manner by 78.83%, 72.42%, 72.99% and 85.04%, when compared to the standard compound ascorbic acid (81.69%, 74.62%, 73.00% and 73.79%) and α-tocopherol/butylated hydroxyanisole (84.09%, 78.61%, 74.45% and 70.02%), respectively.@*CONCLUSIONS@#These findings justify the biological and traditional uses of M. glyptostroboides or its secondary metabolites as confirmed by its promising antioxidant efficacy.

Correlation of AR, EGFR, and HER2 Expression Levels in Prostate Cancer: Immunohistochemical Analysis and Chromogenic In Situ Hybridization / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The androgen receptor (AR) plays a central role in prostate cancer. Evidence from several groups indicates that epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) may enhance AR activity in prostate cancer cell lines. This study was designed to investigate the protein expression of AR, EGFR, and HER2 and to determine whether the EGFR and HER2 genes are amplified in prostate cancer tissues. MATERIALS AND METHODS: The protein expression levels of AR, EGFR, and HER2 in a tissue microarray block of 66 prostate cancer samples were investigated by immunohistochemical analysis and chromogenic in situ hybridization was used to determine whether the EGFR and HER2 genes were amplified in these tissues. RESULTS: The AR and EGFR proteins were expressed in 59.1% and 40.9% of prostate cancers, respectively, but their expression levels were not significantly associated with clinicopathologic factors. Of the cases in which tissues were negative for EGFR protein expression, 69.2% were positive for AR protein expression; however, AR protein expression was significantly reduced (44.4%) in tissues in which EGFR protein was expressed. HER2 expression was detected in only 1 case (1.5%). No amplification of the EGFR or HER2 genes was found in prostate cancer specimens. CONCLUSION: This study was limited by small number of subjects, but it can still be inferred that the expression levels of the AR and EGFR proteins are inversely correlated in prostate cancer patients. The potential utility of EGFR and HER2 as prognostic factors or therapeutic targets warrants further study.

Mitochondrial DNA Copy Number in the Patients of Korean Polycystic Ovary Syndrome (PCOS) / 대한불임학회지

OBJECTIVE: We analyzed quantification of mitochondria DNA (mtDNA) to investigate the relationship of mitochondria and pathogenesis of PCOS. MATERIALS AND METHODS: Peripheral blood samples were collected from 28 patients with PCOS who were under the inclusion criteria for PCOS and from 28 healthy controls. Genomic DNA was used to analyze real-time PCR for mtDNA copy number quantification. The mtDNA copy number was compared between the control and PCOS groups. All data was expressed as mean +/- SD. Statistical analysis was assessed by t-test. RESULTS: In this study, the mtDNA CT was 11.67+/-0.422 in PCOS patients and 11.51+/-0.722 in control group, respectively. The mtDNA copy number was 1726410.71+/-407858.591 the patients of in PCOS and 2167887.51+/-252459.28 in control group (p=0.08), respectively. CONCLUSION: In our study, using real-time PCR, there was a tendency of lower mtDNA copy number in the patients of PCOS when comparing to the control group even though statistical difference was not significant. However, more extensive analysis is required to clarity relationship between mtDNA copy number and pathogenesis of PCOS.

HIDE, a Testis Specific Deubiquitinating Enzyme, Interacts with HSP90 / 대한불임학회지

No abstract available.

Regulation of Insulin Signaling through Protein Degradation / 대한내분비학회지

No abstract available.

Effect of Metformin Treatment and Insulin Resistance in Patients with Polycystic Ovary Syndrome / 대한산부인과학회잡지

OBJECTIVE: This study was performed to investigate the effect of metformin treatment and insulin resistance in the patients with polycystic ovary syndrome. METHODS: Twenty three patients with polycystic ovary syndrome were included at Seoul National University Hospital from September 2001 to September 2003. Metformin was administered at daily 1,500 mg for 3 months to these patients. Then restoration of regular menstruation or recovery of ovulation was evaluated and insulin resistance was compared between the responder and the non-responder before and after metformin treatment. RESULTS: Eleven patients (47.8%) showed a significant improvement in menstrual or ovulation cyclicity whereas twelve patients had no change. There was no statistically significant difference in the insulin resistance between the responder and the non-responder before and after metformin treatment. CONCLUSION: In non-obese patients with polycystic ovary syndrome, metformin treatment seems to be effective to improvement of menstrual or ovulation cyclicity irrespective of insulin resistance expressed as glucose-to- insulin ratio and HOMA.

The Study of 5,10-Methylenetetrahydrofolate Reductase Variation (MTHFR C677T) in Infertile Females with Polycystic Ovarian Syndrome (PCOS) in Korea / 대한불임학회지

OBJECTIVE: To investigate the association of genetic background between MTHFR C677T genotype and infertile females with polycystic ovarian syndrome. MATERIALS AND METHODS: We compared 86 infertile females with polycystic ovarian syndrome (PCOS) with 100 healthy fertile females with one or more offspring. Pyrosequencing analysis for MTHFR C677T variation was performed on polymerase chain reaction (PCR) product of study group. To validate pyrosequencing data of C677T variation for randomly selected 50 samples, we compared the pyrosequencing result with the PCR-RFLP (Restriction Fragment Length Polymorphism) result of MTHFR C677T genotype. RESULTS: The prevalence of the C677T mutant homozygous (TT) was significantly lower (p=0.0085) in females with PCOS (8.14%) than in fertile females (21.00%). MTHFR 677 TT genotype had a decreased risk (3.7-fold) of PCOS compared with wild type (MTHFR 677 CC). CONCLUSION: Our data support a role for MTHFR mutant homozygous (677 TT) genotype in reducing risk in Korean infertile females with Polycystic ovarian syndrome.

Expression of Immunosuppression-Related Genes in Fetal Chorionic Villi Derived from Recurrent Spontaneous Abortion Patients / 대한불임학회지

No abstract available.

Conjugation and deconjugation of ubiquitin regulating the destiny of proteins

The homeostasis for a number of cellular proteins is regulated by not only phosphorylation and dephosphorylation, but also ubiquitination and deubiquitination. A number of proteins involved in the degradation of polypeptides have been isolated in various eukaryotic organisms from Saccharomyces cerevisiae to human. Recently, several deubiquitinating enzymes, classified into either the Ub C-terminal hydrolase (UCH) or the Ub-specific processing protease (UBP), have been reported. It has been shown that they contain conserved domains including Cys, His, and Asp residues throughout the enzyme. These proteins have been demonstrated that Cys and His domains are critical for deubiquitinating enzymatic activity. Recently, we have shown that the Asp domain localized between Cys and His domains is also essential for cleaving the ubiquitin from protein substrates. Mouse deubiquitinating enzymes including DUB-1, DUB-2, and DUB-2A have been isolated and they showed the expression specificity. Of these, DUB- 1 and DUB-2 are expressed in lymphocytes depending on the presence of cytokines (interleukin-3 in B-lymphocytes and interleukin-2 in T- lymphocytes, respectively), indicating that they are involved in cytokine signaling pathways. Isolation of all putative DUBs will help to identify their substrates and to regulate the homeostasis of cellular proteins, especially in proliferative cells.