Background: This study evaluated the difference in brain metabolite profiles between normothermia and hypothermia reaching 25°C in humans in vivo. Methods: Thirteen patients who underwent thoracic aorta surgery under moderate hypothermia were prospectively enrolled. Plasma samples were collected simultaneously from the arteries and veins to estimate metabolite uptake or release. Targeted metabolomics based on liquid chromatographic mass spectrometry and direct flow injection were performed, and changes in the profiles of respective metabolites from normothermia to hypothermia were compared. The ratios of metabolite concentrations in venous blood samples to those in arterial blood samples (V/A ratios) were calculated, and log 2 transformation of the ratios [log2 (V/A)] was performed for comparison between the temperature groups. Results: Targeted metabolomics were performed for 140 metabolites, including 20 amino acids, 13 biogenic amines, 10 acylcarnitines, 82 glycerophospholipids, 14 sphingomyelins, and 1 hexose. Of the 140 metabolites analyzed, 137 metabolites were released from the brain in normothermia, and the release of 132 of these 137 metabolites was decreased in hypothermia. Two metabolites (dopamine and hexose) showed constant release from the brain in hypothermia, and 3 metabolites (2 glycophospholipids and 1 sphingomyelin) showed conversion from release to uptake in hypothermia. Glutamic acid demonstrated a distinct brain metabolism in that it was taken up by the brain in normothermia, and the uptake was increased in hypothermia. Conclusion Targeted metabolomics demonstrated various degrees of changes in the release of metabolites by the hypothermic brain. The release of most metabolites was decreased in hypothermia, whereas glutamic acid showed a distinct brain metabolism.

Objective: Adenomyosis impacts pregnancy outcomes, although there is a lack of consensus regarding the actual effects. It is likely, however, that the severity of adenomyosis or ultrasound findings or timing of diagnosis can have different effects on adverse pregnancy outcomes (APOs). Methods: In this study, we aimed to investigate the impact of the timing of adenomyosis diagnosis on pregnancy outcomes. Singleton pregnant women who delivered between 2017 and 2022 were analyzed based on the timing of adenomyosis diagnosis, using a national database. The final cohort was classified into three groups: 1) group 1, without adenomyosis; 2) group 2, those diagnosed with adenomyosis before pregnancy; and 3) group 3, those diagnosed with adenomyosis during pregnancy. Results: A total of 1,226,475 cases were ultimately included in this study. Women with a diagnosis of adenomyosis had a significantly higher risk of APOs including hypertensive disorder during pregnancy (HDP), gestational diabetes mellitus (GDM), postpartum hemorrhage, placental abruption, preterm birth, and delivery of a small-for-gestational-age infant even after adjusting for covariates. In particular, concerning HDP, the risk was highest in group 3 (group 2: adjusted odds ratio [aOR], 1.15 vs. group 3: aOR, 1.36). However, the highest GDM risk was in group 2 (GDM; group 2: aOR, 1.24 vs. group 3: aOR, 1.04). Conclusion The increased risk of APO differed depending on the timing of adenomyosis diagnosis. Therefore, efforts for more careful monitoring and prevention of APOs may be necessary when such women become pregnant.

BACKGROUND: A protocol for using human endometrium derived induced pluripotent stem cells (iPSCs) to derive hematopoietic and erythroid lineages will be elaborated, through a two-phase culture system. METHODS: Discarded endometrial tissues were obtained from women receiving hysterectomy in their 4th to 5th decade due to benign uterine conditions. pCE-Sox2, Oct4, Klf4, L-Myc and Lin28 episomal vectors were used to electrotransfect the endometrial stromal cells. The first 8 days involves commitment to hematopoietic stem cells through embryoid body with robust expansion on murine bone marrow stromal cells. The second phase involves feeder free conditions with hydrocortisone, stem cell factor, interleukin-3, and recombinant EPO. After 22 days of feeder free culture, the expression profiles of CD235a+ , CD34+ , CD43+ and CD 71+ were analyzed by flow cytometry and Wright-Giemsa staining for differential counting. The oxygen carrying capacity of cultured RBCs was measured using a hemoxanalyser. RESULTS: As a result of inducing these cells via co-culture with murine stromal fibroblasts, all endometrium derived iPSCs were differentiated into erythroblasts with a stable yield of approximately 80% for polychromatic and orthochromatic normoblasts. The protocol for complete induction of erythroid lineage cells starting from human endometrial tissue via iPS cells has been optimized. CONCLUSION Successful directed erythroid differentiation has occurred from human endometrium-derived iPS cells. A comprehensive process of actually deriving iPS cells using discarded surgical hysterectomy specimens to the erythroid fate has significance in that the scope of using human iPSC cell lines for tissue regeneration could be expanded in the future.

Objective: This study aimed to evaluate the endometrial transcriptomic patterns in the early secretory phase (ESP) and mid-secretory phase (MSP) of the natural menstrual cycle before in vitro fertilization and embryo transfer (IVF-ET). Methods: Thirty patients whose endometrial tissues were obtained from the ESP or MSP of a natural menstrual cycle immediately before IVF-ET were included. Endometrial dating was histologically confirmed as ESP (cycle days 16-18) or MSP (cycle days 19-21), according to the noyes criteria. The patients were divided into two groups depending on the IVF-ET outcome: pregnant (n=14; 7 in ESP and 7 in MSP) or non-pregnant (n=16; 8 in ESP and 8 in MSP). Differentially expressed genes (DEGs) in the MSP, compared to the ESP, were identified using NanoString nCounter (NanoString Technologies, Seattle, WA, USA) data for both the pregnant and non-pregnant groups. Results: Thirteen DEGs in the pregnant group and 11 DEGs in the non-pregnant group were identified in the MSP compared to those in the ESP. In both groups, adrenoceptor alpha 2A, interleukin 1 receptor-associated kinase 2, a disintegrin and metalloproteinase with thrombospondin repeats 15 (ADAMTS15), serpin family E member 1, integrin subunit beta 3, transmembrane protein 252 (TMEM252), huntingtin associated protein 1, C2 calcium-dependent domain containing 4A, and integrin subunit alpha 2 were upregulated in the MSP, compared to the ESP. TMEM37, galactosidase beta 1 like 2, Rho family GTPase 3, and cytochrome P450 family 24 subfamily A member 1 were upregulated in the MSP only in the pregnant group. ADAMTS8 was downregulated and monoamine oxidase A was upregulated in the MSP only in the non-pregnant group. Conclusion Transcriptomic patterns in the endometrium immediately before IVF-ET appear to differ according to the IVF-ET outcome. These novel DEGs, which have not been previously studied, may have functional significance during the window of implantation and serve as potential biomarkers of endometrial receptivity.

Background: Single nucleotide polymorphisms (SNPs) are reportedly associated with repeated abortion. Thus, genetic analysis based on race is the key to developing accurate diagnostic tests. This study analyzed the genetic polymorphisms of recurrent pregnancy loss (RPL) patients among Korean women compared to the controls. Methods: In 53 women of RPL group and 50 controls, the genetic analysis was performed.The genotype distribution and allele frequency were analyzed statistically for the difference between the two groups. The association between each SNP marker and RPL risk was analyzed. Results: The genotypes of LEPR, endothelial nitric oxide synthase (eNOS), KDR, miR-27a, miR-449b, and tumor necrosis factor-alpha (TNF-α) were analyzed using odds ratio (OR) with 95% confidence intervals (CIs). Only the AG genotype of miR-449b (A>G) polymorphism showed significant association with the risk of RPL when compared to the AA genotype (OR, 2.39). The combination of GG/AG+GG/CA+AA genotypes for eNOS/ miR-449b/TNF-α was associated with 7.36-fold higher risk of RPL (OR, 7.36). The GG/ AG+GG combination for eNOS/miR-449b showed 2.43-fold higher risk for RPL (OR, 2.43). The combination of AG+GG/CA+AA genotypes for miR-449b/TNF-α showed a significant association with the risk of RPL (OR, 7.60). From the haplotype-based analysis, the G-G-A haplotype of eNOS/miR-449b/TNF-α and the G-A haplotype of miR-449b/TNF-α were associated with increased risk of RPL (OR, 19.31; OR, 22.08, respectively). Conclusion There is a significant association between the risk of RPL and miR-449b/TNF-αcombination, and therefore, genetic analysis for specific combined genotypes can be an important screening method for RPL in Korean women.

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.

Theca lutein cysts are rare, benign lesions responsible for gross cystic enlargement of both ovaries during pregnancy. This condition is also termed hyperreactio luteinalis. Elevated human chorionic gonadotropin (hCG) levels or states of hCG hypersensitivity seem to promote these changes, which in up to 30% of patients produce clinical signs of hyperandrogenism. Given the self-limiting course of theca lutein cysts, which are subject to spontaneous postpartum resolution, conservative treatment is the mainstay of patient management. Described herein is a rare case of theca lutein cysts with maternal virilization that failed to regress by 9 months after childbirth. Surgical intervention was eventually undertaken, necessitated by adnexal torsion.

Purpose: This study aimed to elucidate whether microRNA-139-5p is involved in the pathogenesis of uterine leiomyoma. Materials and Methods: Human leiomyoma and matched human smooth muscle samples were obtained from 10 women who underwent hysterectomy for uterine leiomyoma. MicroRNA (miRNA) expression was analyzed by quantitative real-time polymerase chain reaction. To assess the effects of miR-139-5p on cultured leiomyoma cells, cell migration, collagen gel contraction, wound healing, and the expression levels of hallmark proteins were evaluated in cells transfected with a miR-139-5p mimic. Results: The expression of miR-139-5p was significantly lower in leiomyoma tissues than in matched smooth muscle tissues. Restored miR-139-5p expression in miR-139-5p mimic-transfected human leiomyoma cells resulted in decreased contractility of the ECM and cell migration. In addition, upregulation of miR-139-5p decreased the protein expression of collagen type 1 and phosphorylated p38 MAPK. Conclusion Expression of miR-139-5p is downregulated in leiomyoma cells and modulation of miR-139-5p may be involved in the pathogenesis of leiomyomas through the regulation of collagen type 1 and phosphorylated p38 MAPK. Therefore, miR-139-5p is a potential therapeutic target for leiomyoma.

Purpose: This study aimed to elucidate whether microRNA-139-5p is involved in the pathogenesis of uterine leiomyoma. Materials and Methods: Human leiomyoma and matched human smooth muscle samples were obtained from 10 women who underwent hysterectomy for uterine leiomyoma. MicroRNA (miRNA) expression was analyzed by quantitative real-time polymerase chain reaction. To assess the effects of miR-139-5p on cultured leiomyoma cells, cell migration, collagen gel contraction, wound healing, and the expression levels of hallmark proteins were evaluated in cells transfected with a miR-139-5p mimic. Results: The expression of miR-139-5p was significantly lower in leiomyoma tissues than in matched smooth muscle tissues. Restored miR-139-5p expression in miR-139-5p mimic-transfected human leiomyoma cells resulted in decreased contractility of the ECM and cell migration. In addition, upregulation of miR-139-5p decreased the protein expression of collagen type 1 and phosphorylated p38 MAPK. Conclusion Expression of miR-139-5p is downregulated in leiomyoma cells and modulation of miR-139-5p may be involved in the pathogenesis of leiomyomas through the regulation of collagen type 1 and phosphorylated p38 MAPK. Therefore, miR-139-5p is a potential therapeutic target for leiomyoma.

Purpose: To investigate the efficacy and safety of a newly developed thermo-responsive sol-gel, ABT13107, for reducing the formation of intrauterine adhesions (IUAs) after hysteroscopic surgery. Materials and Methods: In this multicenter, prospective, randomized trial (Canadian Task Force classification I), 192 women scheduled to undergo a hysteroscopic surgery at one of the eight university hospitals in South Korea were randomized into the ABT13107 group or the comparator (Hyalobarrier ® ) group in a 1:1 ratio. During hysteroscopic surgery, ABT13107 or Hyalobarrier® was injected to sufficiently cover the entire intrauterine cavity. Results: The patients returned to their respective sites for safety assessments at postoperative weeks 1 and 4 and for efficacy assessments at postoperative week 4. The post-surgery incidence of IUAs was 23.4% in the ABT13107 group and 25.8% in the comparator group; this difference met the criteria for ABT13107 to be considered as not inferior to the comparator. No differences were found in the extent of adhesions, types of adhesions, or the cumulative American Fertility Society score between the two treatment groups. Most adverse events were mild in severity, and no serious adverse events occurred. Conclusion ABT13107, a new anti-adhesive barrier containing hyaluronic acid, was not inferior to the highly viscous hyaluronic acid anti-adhesive barrier, Hyalurobarrier® in IUA formation after hysteroscopic surgery (Clinical trial registration No. NCT 04007211).