Exploring Memory Function Beyond Immune Cells: ANGPTL4-Mediated Memory Functions in Tissue Resident Stem Cells.

Adapted immune cells are known to develop memory functions that increase resistance to subsequent infections after initial pathogen exposure, however, it is unclear whether non-immune cells, like tissue-resident stem cells, have similar memory functions. Here, it is found that tissue-resident stem cells crucial for tissue regeneration show diminished adverse effects on diverse stem cell functions against successive exposure to foreign antigen (ß-glucan) to maintain tissue homeostasis and stability both in vitro and in vivo. These data suggest that endometrial stem cells may possess a robust memory function, in contrast, fully differentiated cells like fibroblasts and vesicular cells do not show these memory mechanisms upon consecutive antigen exposure. Moreover, the pivotal role of Angiopoietin-like 4 (ANGPTL4) in regulating the memory functions of endometrial stem cells is identified through specific shRNA knockdown in vitro and knockout mice in vivo experiments. ANGPTL4 is associated with the alteration of diverse stem cell functions and epigenetic modifications, notably through histone H3 methylation changes and two pathways (i.e., PI3K/Akt and FAK/ERK1/2 signaling) upon consecutive antigen exposure. These findings imply the existence of inherent self-defense mechanisms through which local stem cells can adapt and protect themselves from recurrent antigenic challenges, ultimately mitigating adverse consequences.

Identification of memory mechanism in tissue-resident stem cells via ANGPTL4 beyond immune cells upon viral antigen exposure.

Although memory functions of immune cells characterized by increased resistance to subsequent infections after initial pathogen exposure are well-established, it remains unclear whether non-immune cells, especially tissue-resident stem cells, exhibit similar memory mechanisms. The present study revealed that detrimental effects of initial viral antigen exposure (human papillomavirus [HPV]) on diverse stem cell functions were significantly exacerbated upon subsequent secondary exposure both in vitro and in vivo. Importantly, endometrial stem cells exhibited robust memory functions following consecutive HPV antigen exposures, whereas fully differentiated cells such as fibroblasts and vesicular cells did not show corresponding changes in response to the same antigen exposures. Deficiency of angiopoietin-like 4 (ANGPTL4) achieved through small hairpin RNA knockdown in vitro and knockout (KO) mice in vivo highlighted the critical role of ANGPTL4 in governing memory functions associated with various stem cell processes. This regulation occurred through histone H3 methylation alterations and PI3K/Akt signaling pathways in response to successive HPV antigen exposures. Furthermore, memory functions associated with various stem cell functions that were evident in wild-type mice following consecutive exposures to HPV antigen were not observed in ANGPTL4 KO mice. In summary, our findings strongly support the presence of memory mechanism in non-immune cells, particularly tissue-resident stem cells.

A microscale 3D organ on a chip for recapitulating reciprocal neuroendocrine crosstalk between the hypothalamus and the pituitary gland.

Conventional 2D or even recently developed 3Din vitroculture models for hypothalamus and pituitary gland cannot successfully recapitulate reciprocal neuroendocrine communications between these two pivotal neuroendocrine tissues known to play an essential role in controlling the body's endocrine system, survival, and reproduction. In addition, most currentvitroculture models for neuroendocrine tissues fail to properly reflect their complex multicellular structure. In this context, we developed a novel microscale chip platform, termed the 'hypothalamic-pituitary (HP) axis-on-a-chip,' which integrates various cellular components of the hypothalamus and pituitary gland with biomaterials such as collagen and hyaluronic acid. We used non-toxic blood coagulation factors (fibrinogen and thrombin) as natural cross-linking agents to increase the mechanical strength of biomaterials without showing residual toxicity to overcome drawbacks of conventional chemical cross-linking agents. Furthermore, we identified and verified SERPINB2 as a reliable neuroendocrine toxic marker, with its expression significantly increased in both hypothalamus and pituitary gland cells following exposure to various types of toxins. Next, we introduced SERPINB2-fluorescence reporter system into loaded hypothalamic cells and pituitary gland cells within each chamber of the HP axis on a chip, respectively. By incorporating this SERPINB2 detection system into the loaded hypothalamic and pituitary gland cells within our chip platform, Our HP axis-on-chip platform can better mimic reciprocal neuroendocrine crosstalk between the hypothalamus and the pituitary gland in the brain microenvironments with improved efficiency in evaluating neuroendocrine toxicities of certain drug candidates.

Unveiling the potential effects of acetylsalicylic acid: insights into regeneration in endometrial stem cells.

BACKGROUND: Although acetylsalicylic acid has been widely used for decades to treat and prevent various diseases, its potential effects on endometrial receptivity and subsequent pregnancy rates are still controversial due to conflicting data: many reports have shown positive effects of acetylsalicylic acid, whereas others have found that it has no effect. Furthermore, the direct effects of acetylsalicylic acid on various functions of normal endometrial cells, especially endometrial stem cells, and their underlying molecular mechanisms have not yet been proven. Recently, studies have revealed that a reduced number of active stem/progenitor cells within endometrial tissue limits cyclic endometrial regeneration and subsequently decreases pregnancy success rates, suggesting that endometrial stem cells play a critical role in endometrial regeneration and subsequent endometrial receptivity. METHODS: We assessed whether aspirin treatment can inhibit various endometrial stem cell functions related to regenerative capacity, such as self-renewal, migration, pluripotency/stemness, and differentiation capacity, in vitro. Next, we evaluated whether SERPINB2 regulates the effects of aspirin on endometrial stem cell functions by depleting SERPINB2 expression with specific shRNA targeting SERPINB2. To further investigate whether aspirin also inhibits various endometrial stem cell functions in vivo, aspirin was administered daily to mice through intraperitoneal (i.p.) injection for 7 days. RESULTS: In addition to its previously identified roles, to the best of our knowledge, we found for the first time that acetylsalicylic acid directly inhibits various human endometrial stem cell functions related to regenerative capacity (i.e., self-renewal, migration, differentiation, and capacity) through its novel target gene SERPINB2 in vitro. Acetylsalicylic acid exerts its function by suppressing well-known prosurvival pathways, such as Akt and/or ERK1/2 signaling, through a SERPINB2 signaling cascade. Moreover, we also found that acetylsalicylic acid markedly inhibits regenerative capacity-related functions in endometrial stem cells within tissue. CONCLUSIONS: We have found that acetylsalicylic acid has diverse effects on various endometrial stem cell functions related to regenerative capacity. Our findings are a critical step toward the development of more effective therapeutic strategies to increase the chances of successful pregnancy. Video Abstract.

Development of cell-laden multimodular Lego-like customizable endometrial tissue assembly for successful tissue regeneration.

BACKGROUND: The endometrium, the inner lining of the uterine cavity, plays essential roles in embryo implantation and its subsequent development. Although some positive results were preliminarily archived, the regeneration of damaged endometrial tissues by administrating stem cells only is very challenging due to the lack of specific microenvironments and their low attachment rates at the sites of injury. In this context, various biomaterial-based scaffolds have been used to overcome these limitations by providing simple structural support for cell attachment. However, these scaffold-based strategies also cannot properly reflect patient tissue-specific structural complexity and thus show only limited therapeutic effects. METHOD: Therefore, in the present study, we developed a customizable Lego-like multimodular endometrial tissue architecture by assembling individually fabricated tissue blocks. RESULTS: Each tissue block was fabricated by incorporating biodegradable biomaterials and certain endometrial constituent cells. Each small tissue block was effectively fabricated by integrating conventional mold casting and 3D printing techniques. The fabricated individual tissue blocks were properly assembled into a larger customized tissue architecture. This structure not only properly mimics the patient-specific multicellular microenvironment of the endometrial tissue but also properly responds to key reproductive hormones in a manner similar to the physiological functions. CONCLUSION: This customizable modular tissue assembly allows easy and scalable configuration of a complex patient-specific tissue microenvironment, thus accelerating various tissue regeneration procedures.

A novel role of follicle-stimulating hormone (FSH) in various regeneration-related functions of endometrial stem cells.

Follicle-stimulating hormone (FSH) promotes the production and secretion of estrogen, which in turn stimulates the growth and maturation of ovarian follicles. Therefore, consecutive FSH treatment to induce ovarian hyperstimulation (superovulation) is still considered the most cost-effective option for the majority of assisted reproductive technologies (ARTs). However, a relatively high cancellation rate and subsequent low pregnancy outcomes (approximately 15%) are the most challenging aspects of this FSH-based ART. Currently, the main cause for this low implantation rate of FSH-based ART has not yet been revealed. Therefore, we hypothesized that these high cancellation rates with FSH-based superovulation protocols might be associated with the harmful effects of consecutive FSH treatment. Importantly, several recent studies have revealed that tissue-resident stem cell deficiency can significantly reduce cyclic endometrial regeneration and subsequently decrease the pregnancy outcome. In this context, we investigated whether FSH treatment could directly inhibit endometrial stem cell functions and consequently suppress endometrial regeneration. Consistent with our hypothesis, our results revealed for the first time that FSH could inhibit various regeneration-associated functions of endometrial stem cells, such as self-renewal, migration, and multilineage differentiation capacities, via the PI3K/Akt and ERK1/2 signaling pathways both in vitro and in vivo.

Effects of smoking on the tissue regeneration-associated functions of human endometrial stem cells via a novel target gene SERPINB2.

BACKGROUND: Smokers directly inhale mainstream cigarette smoke, which contains numerous known and potential toxic substances, and thus, smoking is expected to have broad harmful effects that cause tissue injury and dysfunction. Interestingly, many studies have suggested that the recent decline in female fertility and increased rate of spontaneous abortion could be associated with increased smoking rates. Indeed, women that smoked for 10 years or more were reported to have a ~ 20% higher infertility rate than women that had never smoked. However, the reasons for the underlying harmful aspects of smoking on female fertility remain a matter of debate. Importantly, a previous study revealed that resident endometrial stem cell deficiency significantly limits the cyclic regeneration potential of endometrium, which, in turn, decreases successful pregnancy outcomes. In this context, we postulated that exposure to mainstream cigarette smoke extracts might decrease female fertility by inhibiting the functions of resident endometrial stem cells. METHODS: We investigated whether cigarette mainstream smoke exposure directly inhibits various tissue regeneration-associated functions of endometrial stem cells, such as self-renewal, migration, pluripotency, and differentiation capacity in vitro. Next, we determined whether SERPINB2 mediates cigarette smoke-induced suppressive effects on various tissue regeneration-associated functions by depleting SERPINB2 expression with specific shRNA targeting SERPINB2. Mice were injected intraperitoneally with low (0.5 mg/kg) or high (1 mg/kg) doses of cigarette smoke extract (10 times for two weeks), and endometrial stem cells were then isolated from mice uterine tissues. RESULTS: We found that exposure to cigarette smoke extracts remarkably suppressed various tissue regeneration-associated functions of endometrial stem cells, such as self-renewal, migration, multilineage differentiation ability, and pluripotency in vitro and in vivo by activating the SERPINB2 gene. Indeed, cigarette smoke-induced inhibitory effects on various endometrial stem cell functions were significantly abolished by SERPINB2 knockdown. CONCLUSIONS: These findings provide valuable information on the harmful effects of cigarette smoking on resident endometrial stem cells and hopefully will facilitate the developments of promising therapeutic strategies for subfertile or infertile women that smoke cigarettes.

Novel roles of luteinizing hormone (LH) in tissue regeneration-associated functions in endometrial stem cells.

Luteinizing hormone (LH) stimulates the synthesis and secretion of the key steroid hormone estrogen, which subsequently promotes ovarian follicular growth and development. Therefore, the administration of exogenous LH to achieve superovulation (multiple ovulations) and an LH surge is commonly used as the most effective therapeutic option in a majority of in vitro fertilization (IVF) clinics. However, a relatively low pregnancy rate (between 20% and 35%) is one of the most challenging aspects of LH-based infertility treatment. Furthermore, the major cause of this low pregnancy rate in LH-based infertility treatment remains unidentified. Recent studies have shown that endometrial stem cell loss or deficiency can significantly decrease tissue regeneration ability during the menstrual cycle and reduce endometrial receptivity. In this context, we postulated that the low pregnancy rates following LH-based ovarian hyperactivation may be the result of the adverse effects of consecutive exogenous LH administration on endometrial stem cells. To the best of our knowledge, this study revealed for the first time that in addition to its previously reported roles in stimulating ovarian functions through the pituitary-gonadal axis, LH brings about the extragonadal suppression of various tissue regeneration-associated functions in endometrial stem cells, such as self-renewal, migration ability, multilineage differentiation potential, and pluripotency/stemness, by inhibiting pro-survival Akt and ERK1/2 signaling pathways in vitro and in vivo, and as a consequence, it decreases the endometrial receptivity.

STROBE: The relationship between asthma and early menarche in Korean adolescents.

ABSTRACT: We explored the relationship between asthma and early menarche in a representative sample of Korean adolescents.Web-based self-reported data collected from 2006 to 2015 by the Korean Youth Risk Behavior Web-based Survey were used. Menarche status was divided into "early" (<12 years of age, n = 69,520) and "not early" (≥12 years of age, n = 234,065).Adolescent girls with early menarche exhibited a higher incidence of asthma (8.1% vs 7.4%, P < .001), more frequent school absences because of asthma (10.8% vs 8.7%), and more frequent ≤4-day stretches of school absence (4.6% vs 2.4%) compared with girls with "not early" menarche (all P < .001). Multivariate analysis performed after adjusting for multiple confounders revealed a 1.04-fold (95% confidence interval [CI] 1.00-1.07) greater likelihood of asthma in the early menarche than not early menarche group. In addition, the odds ratios for missing school due to asthma for 1 to 3 and ≥4 days per year in the early menarche group were 1.00 (95% CI 1.00-1.02) and 1.21 (95% CI 1.01-1.46), respectively.Adolescents with early menarche exhibited increased incidences of asthma and severe asthma.

Current techniques used to perform surgery for anterior and posterior vaginal wall prolapse in South Korea.

OBJECTIVE: This study aimed to evaluate the current surgical techniques for anterior and posterior vaginal wall prolapse repair in South Korea. METHODS: A web-based questionnaire survey was sent to 780 members of the Korean Society of Obstetrics and Gynecology. The items assessed in the questionnaire were the demographic characteristics and current surgical techniques used for the correction of anterior and posterior vaginal wall prolapse. RESULTS: The response rate was 16%. There were variations in the suture materials and methods used for anterior and posterior colporrhaphy. Most respondents used only rapid absorbable suture materials to plicate the fibromuscular layer and close the mucosal layer of the anterior and posterior vaginal wall. Simple interrupted sutures are the most popular suture method for both the fibromuscular and mucosal layers. Thirty-one and eleven percent of the respondents used mesh for surgical correction of anterior and posterior vaginal wall prolapse, respectively. Concomitant perineorrhaphy was routinely performed with posterior vaginal wall repair by 42% of the respondents, whereas 58% performed perineorrhaphy only in cases with perineal defects. CONCLUSION: There is considerable diversity in the current surgical techniques for anterior and posterior vaginal wall prolapse repair in Korea. Further research is required to standardize the surgical techniques.

The prediction of surgical intervention in patients with tubo-ovarian abscess.

The aim of this study was to compare the clinical characteristics of patients with tubo-ovarian abscess (TOA) who responded to medical treatment and those who underwent surgical intervention due to medical treatment failure. Electronic medical records were evaluated retrospectively to identify patients who were diagnosed with TOA. Demographic, clinical, and laboratory data including white blood cell (WBC) count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were compared between the medical treatment group and the surgical intervention group. Patient age, TOA diameter, WBC count, CRP, and ESR were significantly different between the groups. On multiple regression analysis, significant correlations were identified between age (p = .001), ESR (p = .045), and failure of medical treatment. TOA diameter (p = .065) showed a borderline association with surgical intervention. The risk of needing surgical intervention in TOA patients can be predicted using ESR in addition to age and TOA size as risk factors.IMPACT STATEMENTWhat is already known on this subject? For patients diagnosed with a tubo-ovarian abscess (TOA), the size of TOA and the patient's age are helpful for early identification of patients who are likely to need surgical treatment. Inflammatory markers such as C-reactive protein and white blood cell are also associated with the risk of surgical intervention.What do the results of this study add? Erythrocyte sedimentation rate (ESR) in addition to the size of TOA and the patient's age is a useful marker in determining whether to undergo surgery in patients with TOA.What are the implications of these findings for clinical practice and/or further research? ESR combined with the patient's age and the size of TOA is clinically useful in predicting the need for early surgical intervention in patients with TOA. Large prospective controlled studies are required to establish relationship between inflammatory markers and the risk of surgical intervention.

Association between early menarche and suicidal behaviors in Korean girl adolescents.

ABSTRACT: Early menarche can be the socio-psychological problems. We studied the association between early menarche and suicidal risk behaviors among South Korean girl adolescents using national-wide data.Web-based self-report data from 2006 to 2015 the Korea Youth Risk Behavior Web-based Survey data were used in this study. Menarche status was divided into an "early menarche" group (at <12 years of age) versus "not early" menarche group (at ≥12 years of age).Participants with adolescent girls with early menarche group showed a higher prevalence of substance use, higher levels of stress, poorer self-rated health status, unhappier perceiveness, more frequent depressed mood, inter-sexual kissing or petting, inter-sexual intercourse, homosexual kissing or petting, being the victim or the assailant of sexual assaults, sexual transmitted diseases experience, pregnancy, and abortion experience than the not early menarche group. Adolescent girls with early menarche who had suicidal ideation (25.4% vs 22.2%, P < .001), suicidal plans (4.1% vs 2.6%, P < .001), and suicidal attempts (6.8% vs 5.2%, P < .001) were higher than that in the adolescent girls with not early menarche. A multivariate analysis after adjusting revealed that the odds ratios for suicidal ideation, plans, and attempts were 1.07 (95% confidence interval [CI]: 1.05-1.10), 1.35 (95% CI: 1.28-1.41), and 1.13 (95% CI: 1.09-1.18), respectively.Adolescent girl with early menarche was associated with suicidal behaviors.

3D stem cell-laden artificial endometrium: successful endometrial regeneration and pregnancy.

Thin endometrium lining or severe endometrial injury which may occur during artificial abortion can cause defective endometrial receptivity and subsequent infertility. Therefore, much effort has been devoted toward regenerating thin or damaged endometrial lining by applying multiple types of stem cells. Even though there are some positive preliminary outcomes, repairing the injured endometrium with stem cells is considerably challenging, due to the lack of an adequate microenvironment for the administrated stem cells within the tissues and subsequent poor therapeutic efficiency. In this context, as an alternative, we fabricated a 3D stem cell-laden artificial endometrium by incorporating several biodegradable biomaterials (collagen and hyaluronic acid) and multiple cellular components of endometrium (endometrial stem cells, stromal cells, and vessel cells) to properly recapitulate the multicellular microenvironment and multilayered structure. Agarose was used as an inert filler substrate to enhance the mechanical integrity of the three-layered artificial endometrium. Various mechanical characteristics, such as morphology, compression properties, swelling, and viscosity, have been evaluated. Various biological features, such as steroid hormone responsiveness, specific endometrial cell-surface marker expressions, and the secretion of multiple growth factors and steroid hormones, as well as the viability of encapsulated endometrial cells are relatively well maintained within the artificial endometrium. More importantly, severe tissue injuries were significantly relieved by transplanting our 3D artificial endometrium into endometrial ablation mice. Remarkably, artificial endometrium transplantation resulted in a successful pregnancy with subsequent live birth without any morphological or chromosomal abnormalities.

Noncanonical functions of glucocorticoids: A novel role for glucocorticoids in performing multiple beneficial functions in endometrial stem cells.

Chronic stress has a negative impact on many fertility-related functions; thus, the recent decline in female fertility seems to be at least partially associated with increased stress. The secretion of glucocorticoids is a typical endocrine response to chronic stress and indirectly reduces uterine receptivity through the hypothalamus-pituitary-gonadal (HPG) axis. However, in addition to its well-known canonical role, the direct effects of chronic stress-induced glucocorticoids on various uterine functions and their underlying molecular mechanisms are complex and have not yet been revealed. Recent studies have found that resident stem cell deficiency is responsible for the limited regenerative potential of the endometrium (the innermost lining of the uterine cavity) during each menstrual cycle, which subsequently increases infertility rates. In this context, we hypothesized that stress-induced glucocorticoids directly damage endometrial stem cells and consequently negatively affect endometrial reconstruction, which is important for uterine receptivity. In addition to its well-known canonical roles, we identified for the first time that cortisol, the most abundant and potent glucocorticoid in humans, directly suppresses the multiple beneficial functions (self-renewal, transdifferentiation, and migratory potential) of human endometrial stem cells through its functional receptor, glucocorticoid receptor (GR). Glucocorticoids inhibit well-known survival signals, such as the PI3K/Akt and FAK/ERK1/2 pathways. More importantly, we also found that immobilization of stress-induced glucocorticoids suppresses the various beneficial functions of tissue resident stem cells in vivo. To the best of our knowledge, this is the first study to investigate the direct effects of glucocorticoids on the regenerative capacity of endometrial stem cells, and the findings will facilitate the development of more promising therapeutic approaches to increase female fertility.

Current use of the pelvic organ prolapse quantification system in clinical practice among Korean obstetrician-gynecologists.

BACKGROUND: To assess current use of the Pelvic Organ Prolapse Quantification (POP-Q) system in clinical practice among Korean obstetrician-gynecologists. METHODS: A web-based questionnaire was sent to 780 Korean Society of Obstetrics and Gynecology members. The items evaluated in the questionnaire were demographic characteristics and current use of the POP-Q system in the evaluation of pelvic organ prolapse (POP) and surgical decision-making. Differences between POP-Q users and nonusers were analyzed by using the two-sample t-test and chi-squared test. RESULTS: One hundred twenty-six members (16%) responded to the survey. Of the respondents, 48% reported using the POP-Q system in the evaluation of POP. Members who were female, urogynecologists, or performed a high volume of prolapse surgery were more likely to use the POP-Q system (p < 0.05). All but one of the POP-Q users reported using the specific criteria to determine whether each compartmental prolapse should be corrected during prolapse surgery. Most respondents used stage 2 or the hymen as a threshold for prolapse to be corrected for all compartments. CONCLUSIONS: Less than half of Korean obstetrician-gynecologists use the POP-Q system in the evaluation of POP. Almost all of POP-Q users make a surgical decision based on the results of the POP-Q examination.

Gasless single-port access laparoscopy using a J-shaped retractor in patients undergoing adnexal surgery.

OBJECTIVE: The aim of this study was to compare gasless single-port access (SPA) laparoscopy using a J-shaped retractor and conventional SPA laparoscopy in patients undergoing adnexal surgery. Study design The medical records of 80 patients who underwent laparoscopic adnexal surgery between May 2017 and April 2019 were reviewed. Of the 80 patients, 40 patients underwent gasless SPA laparoscopy using a J-shaped retractor and 40 underwent conventional SPA laparoscopy. All surgeries were performed by one laparoscopic surgeon. Surgical outcomes were compared between the two groups. RESULTS: There are no significant differences in age, body mass index, parity, previous abdominal surgery, tumor marker, and tumor diameter between the gasless and conventional groups. The median retraction setup time from skin incision was 7 min (range 5-12 min) in gasless SPA laparoscopic adnexal surgery. The median total operation times were 55.5 min (range 30-155 min) in the gasless group and 55 min (range 30-165 min) in the conventional group without a significant difference. Additionally, there were no differences in operation type, conversion rate of laparotomy, use of an additional trocar, and pathological outcomes between the two groups. No major complications, such as urologic, bowel, and vessel injuries, were found in both groups. CONCLUSIONS: Gasless SPA laparoscopy using a J-shaped retractor appears to offer a better alternative to conventional SPA laparoscopy that avoids the potential negative effects of carbon dioxide gas in selected cases.

Development of a novel dual reproductive organ on a chip: recapitulating bidirectional endocrine crosstalk between the uterine endometrium and the ovary.

Conventional 2D or even 3Din vitroculture models for human reproductive organs cannot properly recapitulate the bidirectional endocrine crosstalk between the uterine endometrium and the ovary. This crosstalk is essential for maintaining the various physiological features and functions of each tissue. Moreover, mostin vitromodels for the female reproductive tract also fail to mimic its multicellular structure. We therefore developed a novel 'dual reproductive organ on a chip' that reflects the bidirectional endocrine cross-talk and the complex multicellular structures by integrating various cellular components of both the human uterine endometrium and the ovary with several biodegradable natural polymers. Indeed, the bidirectional endocrine crosstalk between these two tissues is achieved through media sharing between channels, and it can markedly improve the viability of loaded cells within each chamber of the chip platform. In addition, we also identified a reliable reproductive toxicity marker, SERPINB2, which is significantly increased in response to various toxic exposures in both endometrial and ovarian follicular cells. Based on these findings, we next established a SERPINB2 luciferase reporter system that was specifically designed for detecting and quantifying the toxicity of certain substances. By introducing this SERPINB2 luciferase reporter system into the loaded cells within the chip platform, we ultimately developed an effective 'dual reproductive organ-on-chip' that was successfully used to predict the reproductive toxicity of various hazardous materials.

Non-absorbable versus absorbable sutures for anterior colporrhaphy: study protocol for a randomised controlled trial in South Korea.

INTRODUCTION: The anterior vaginal wall is the segment most commonly affected by prolapse. Traditionally, anterior vaginal wall prolapse is repaired via anterior colporrhaphy, which is known to have a high recurrence rate. Several factors might affect the outcome of anterior colporrhaphy, and the use of absorbable sutures might also be associated with the high recurrence rate because the sutures might not be able to retain adequate strength until the plicated pubocervical fascia remodels and regains maximum tensile strength. Nonetheless, no comparative data exist about the relative efficacy and safety of anterior colporrhaphy using non-absorbable versus absorbable sutures. The objective of this study is to compare the surgical outcomes of anterior colporrhaphy using non-absorbable sutures with those of anterior colporrhaphy using absorbable sutures. METHODS AND ANALYSIS: This is a randomised, multicentre, superiority trial. Anterior colporrhaphy will be performed in a traditional manner with midline plication of the fibromuscular layer using either non-absorbable or absorbable sutures. The primary outcome is composite surgical success 1 year after surgery defined as the absence of all of the following: (1) anterior vaginal descent beyond the hymen, (2) the presence of vaginal bulge symptoms and (3) retreatment for recurrent anterior vaginal wall prolapse with either surgery or pessary. The secondary outcomes include the individual components of the composite primary end point, anatomical outcomes, condition-specific quality of life and adverse events related to anterior colporrhaphy. The planned number of participants is 192. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Board of Seoul National University Hospital (H-1810-037-977). The results of the study will be published in peer-reviewed journals, and the findings will be presented at scientific meetings. TRIAL REGISTRATION NUMBER: NCT03736811.

Tryptophanyl-tRNA Synthetase, a Novel Damage-Induced Cytokine, Significantly Increases the Therapeutic Effects of Endometrial Stem Cells.

The major challenges of most adult stem cell-based therapies are their weak therapeutic effects caused by the loss of multilineage differentiation capacity and homing potential. Recently, many researchers have attempted to identify novel stimulating factors that can fundamentally increase the differentiation capacity and homing potential of various types of adult stem cells. Tryptophanyl-tRNA synthetase (WRS) is a highly conserved and ubiquitously expressed enzyme that catalyzes the first step of protein synthesis. In addition to this canonical function, we found for the first time that WRS is actively released from the site of injury in response to various damage signals both in vitro and in vivo and then acts as a potent nonenzymatic cytokine that promotes the self-renewal, migratory, and differentiation capacities of endometrial stem cells to facilitate the repair of damaged tissues. Furthermore, we also found that WRS, through its functional receptor cadherin-6 (CDH-6), activates major prosurvival signaling pathways, such as Akt and extracellular signal-regulated kinase (ERK)1/2 signaling. Our current study provides novel and unique insights into approaches that can significantly enhance the therapeutic effects of human endometrial stem cells in various clinical applications.

Gasless Total Laparoscopic Hysterectomy with New Abdominal-Wall Retraction System.

BACKGROUND AND OBJECTIVES: Gasless laparoscopy is an alternative method to reduce the number of carbon dioxide (CO2)-insufflated, pneumoperitoneum-related problems including shoulder pain, postoperative nausea/vomiting, and decreased cardiopulmonary function. In this study, we investigated the feasibility of gasless total laparoscopic hysterectomy (TLH) with a newly developed abdominal-wall retraction system. METHODS: Abdominal-wall retraction for gasless laparoscopy was performed using the newly developed J-shape retractor and the Thompson surgical retractor. Surgical outcomes between gasless TLH and conventional CO2-based TLH were compared for each of 40 patients for the period from January 2017 to October 2019. RESULTS: Between gasless TLH and conventional CO2-based TLH, no significant differences were observed for age, body mass index, parity, or surgical indications. The mean retraction setup time from skin incision was 7.4 min (range: 4-12 min) with gasless TLH. The mean total operation times were 87.9 min (range: 65-170) with gasless TLH and 90 min (range: 45-180) with conventional TLH, which showed no significant difference. Estimated blood loss and uterus weight also showed no significant intergroup difference. No major complications related to the ureter, bladder, or bowel were encountered. CONCLUSION: Our new abdominal-wall retraction system for gasless TLH allowed for easy setup and a proper operation field in the performance of laparoscopic hysterectomy.