BRAK and APRIL as novel biomarkers for ovarian tumors.

Aims: To evaluate BRAK and APRIL in serum samples from healthy patients and an ovarian tumor group and analyze their effective value as biomarkers. Materials & methods: BRAK and APRIL were measured in 197 serum samples including 34 healthy controls, 48 patients with benign ovarian cysts and 115 patients with ovarian cancer, and the best statistical cut-off values were calculated. Then, the sensitivity, specificity, accuracy, positive predictive value and negative predictive value for selected cut-off points were assessed. Results: The healthy control group had statistically significant higher BRAK and lower APRIL than the ovarian tumor group. BRAK was excellent for differentiating healthy patients from patients with ovarian tumors, showing area under the receiver operating characteristic curve 0.983, 98.16% sensitivity and 100% specificity. When BRAK was combined with APRIL and CA-125, it also played a role in distinguishing benign cysts from malignancies with area under the curve 0.864, 81.74% sensitivity and 79.17% specificity. Conclusions: BRAK and APRIL are good candidates for ovarian tumor biomarkers.

Administration of red ginseng regulates microRNA expression in a mouse model of endometriosis.

OBJECTIVE: Red ginseng (RG) exerts anti-inflammatory, anti-proliferative, and immunomodulatory effects on endometriosis through the regulation of microRNA (miRNA) expression. It may also ameliorate endometriosis by affecting the expression of multiple miRNAs simultaneously, rather than acting on a single miRNA at a given time. Since studies on the overall effects of RG on endometriosis via the regulation of miRNA expression are lacking, the current study aimed to explore the global effect of RG on miRNA expression in a mouse model of endometriosis. METHODS: To establish the mouse model, the uterine horn of donor mice was implanted into the lateral side of the recipients' peritoneum, followed by vehicle or RG treatment for 8 weeks. RESULTS: To confirm the effects of RG on the established mouse model, the size of the implanted uterus was measured; it was found to be lower in mice from the RG group than in mice from the control group. miRNA expression profiles in the implanted uterus of the mouse model of endometriosis after vehicle or RG administration were analyzed using microarray technology. Thereafter, seven candidate miRNAs and 125 candidate genes (miRNA targets) were identified through a bioinformatics analysis. CONCLUSION: The present findings suggest that RG regulates the expression of multiple miRNAs and mRNAs, thereby alleviating endometriosis in a mouse model of the disease.

Therapeutic potential of ginsenoside Rg3 and Rf for Huntington's disease.

Ginseng is a popular herbal medicine and known to have protective and therapeutic effects in various diseases. Ginsenosides are active gradients representing the diverse pharmacological efficacy of ginseng. Huntington's disease (HD) is incurable genetic disorder associated with mutant huntingtin (mHtt) aggregation in the central nervous system. This study was conducted to investigate the effects of ginsenoside Rg3 and Rf on mHtt aggregation, cell viability, mitochondrial function, and apoptotic molecules on HD model. To investigate the effect of ginsenosides on HD, neural stem cells were isolated from the R6/2 mouse brain and used as a cellular model of HD. Nuclear aggregation of mHtt was measured by immunocytochemistry, and expressions of mitochondrial biogenesis and apoptotic molecules were investigated by western blot. As a result, the number of mHtt aggregates positive cells has decreased by ginsenoside Rg3 and Rf treatment in cellular model of HD. Mitochondrial biogenesis-related molecules such as PGC-1α and phosphorylated CREB were increased or showed increased tendency by ginsenoside Rg3 and Rf. Apoptotic molecules, p53, Bax, and cleaved caspase-3, were down-regulated by treatment of ginsenoside Rg3 and Rf. In addition, Lysotracker staining result showed that cellular lysosomal content was reduced by ginsenoside Rg3 and Rf. Given that ginsenoside Rg3 and Rf have the potential to reduce mHtt aggregation and cellular apoptosis, these ginsenosides can be possible therapeutic candidates for treating HD phenotypes.

Aberrant Expression of Sodium-Potassium-Chloride Cotransporter in Endometriosis.

Cell membrane ion channels have important roles in cell migration during cancer development and metastasis. Although endometriosis is a benign gynecological disease, some migration and invasion characteristics of endometriosis are similar to those of cancer. However, only a few studies have examined cell membrane ion channels and their associations with endometriosis. This study aimed to investigate the effects of these ion channels on development of endometriosis. A total of 39 women who underwent laparoscopic ovarian cyst enucleation were included in the study population. Eutopic endometrium or ectopic endometrium tissues were obtained from each patient based on allocation to an endometriosis group (n=21) or a control group (n=18). Quantitative real-time PCR (qRT-PCR) and western blot analyses were performed to quantify NKCC1, NKCC2, and CLCN3 mRNA expression and protein concentrations. SiRNA transfection and migration assays of the endometrial stromal cells were performed to test the effects of the ion channels on the migration ability. The qRT-PCR and western blot analyses revealed significantly elevated mRNA expression and protein expression of NKCC1, NKCC2, and CLCN3 in the ectopic endometrial tissue from the patients with endometriosis (p < 0.05). Migration assay of siRNA transfected cells suggested a decreased migratory potential of the endometrial stromal cells (p < 0.001). The magnitudes of expression of NKCC1, NKCC2, and CLCN3 were positively correlated with endometrioma size. The increased expression of NKCC1, NKCC2, and CLCN3 in endometriosis offers opportunities to understand mechanisms of endometriosis and develop novel therapeutic approaches.

Identification of Serum Biomarkers for Diagnosis of Endometriosis Using Multiplex Immunoassays.

Endometriosis is a common gynecologic disorder characterized by chronic pelvic pain, dysmenorrhea, and infertility. Although this condition places significant financial burden on the healthcare system and negatively affects patient's quality of life, the pathophysiology of the disease remains unclear, and noninvasive diagnostic methods are insufficient. The object of this study was to identify potential biomarkers for endometriosis from peripheral blood. We hypothesized that serum biomarkers modified in endometriosis patients would be detected by multiplex cytokine panel, and identification of a combination of these biomarkers would improve diagnostic power. A total of 141 women, aged 15-52 years with regular menstruation, participated in this study. Twenty-one serum cytokines were detected using the commercially available MILLIPLEX MAP Human Cytokine/Chemokine Kit Panel IV. Among these cytokines, breast- and kidney-expressed chemokine (BRAK)/chemokine (C-X-C motif) ligand 14 (CXCL14) was significantly decreased, and proliferation-inducing ligand (APRIL)/tumor necrosis factor ligand superfamily member 13 (TNFSF13) was significantly increased in endometriosis group. APRIL/TNFSF13 and BRAK/CXCL14 alone or in combination, however, failed to show adequate sensitivity or specificity for the diagnosis of endometriosis. Combination of APRIL/TNFSF13 and BRAK/CXCL14 with serum CA-125 levels yielded significantly higher sensitivity (71.2%) for detecting endometriosis without compromising specificity (80.8%) than CA-125 alone in a logistic regression model (P = 0.050). In conclusion, we identified a biomarker combination that detects endometriosis better than CA125 alone. Therefore, we conclude that multiplex cytokine panel is an efficient method for detecting endometriosis, and analysis of additional cytokine panels may lead to identification of a novel biomarker combination with superior diagnostic power.