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Aberrant activation of embryogenesis-related molecular programs in urothelial bladder cancer (BC) is associated with stemness features related to oncogenic dedifferentiation and tumor metastasis. Recently, we reported that overexpression of transcription factor CP2-like protein-1 (TFCP2L1) and its phosphorylation at Thr177 by cyclin-dependent kinase-1 (CDK1) play key roles in regulating bladder carcinogenesis. However, the clinical relevance and therapeutic potential of this novel CDK1-TFCP2L1 molecular network remain elusive. Here, we demonstrated that inhibitor of DNA binding-2 (ID2) functions as a crucial mediator by acting as a direct repressive target of TFCP2L1 to modulate the stemness features and survival of BC cells. Low ID2 and high CDK1 expression were significantly associated with unfavorable clinical characteristics. TFCP2L1 downregulated ID2 by directly binding to its promoter region. Consistent with these findings, ectopic expression of ID2 or treatment with apigenin, a chemical activator of ID2, triggered apoptosis and impaired the proliferation, suppressed the stemness features, and reduced the invasive capacity of BC cells. Combination treatment with the specific CDK1 inhibitor RO-3306 and apigenin significantly suppressed tumor growth in an orthotopic BC xenograft animal model. This study demonstrates the biological role and clinical utility of ID2 as a direct target of the CDK1-TFCP2L1 pathway for modulating the stemness features of BC cells.

Background The therapeutic effects of human embryonic stem cell-derived multipotent mesenchymal stem cells (M-MSCs) were evaluated for detrusor underactivity (DUA) in a rat model with atherosclerosis-induced chronic bladder ischemia (CBI) and associated mechanisms. Methods Sixteen-week-old male Sprague–Dawley rats were divided into five groups (n = 10). The DUA groups underwent 30 bilateral repetitions of endothelial injury to the iliac arteries to induce CBI, while the sham control group underwent a sham operation. All rats used in this study received a 1.25% cholesterol diet for 8 weeks. M-MSCs at a density of 2.5, 5.0, or 10.0 × 105 cells (250 K, 500 K, or 1000 K; K = a thousand) were injected directly into the bladder 7 weeks post-injury, while the sham and DUA group were treated only with vehicle (phosphate buffer solution). One week after M-MSC injection, awake cystometry was performed on the rats. Then, the bladders were harvested, studied in an organ bath, and prepared for histological and gene expression analyses. Results CBI by iliac artery injury reproduced voiding defects characteristic of DUA with decreased micturition pressure, increased micturition interval, and a larger residual volume. The pathological DUA properties were improved by M-MSC treatment in a dose-dependent manner, with the 1000 K group producing the best efficacy. Histological analysis revealed that M-MSC therapy reduced CBI-induced injuries including bladder fibrosis, muscular loss, and apoptosis. Transplanted M-MSCs mainly engrafted as vimentin and NG2 positive pericytes rather than myocytes, leading to increased angiogenesis in the CBI bladder. Transcriptomes of the CBI-injured bladders were characterized by the complement system, inflammatory, and ion transport-related pathways, which were restored by M-MSC therapy. Conclusions Single injection of M-MSCs directly into the bladder of a CBI-induced DUA rat model improved voiding profiles and repaired the bladder muscle atrophy in a dose-dependent manner. Graphical abstract

High blood glucose level and non-alcoholic fatty liver disease (NAFLD) in adolescents are long-term risk factors for cardiovascular diseases and poor prognosis. We investigated recent trends of high blood glucose levels and NAFLD among Korean adolescents aged 12-18 years. We conducted a cross-sectional analysis using data of 5,685 adolescents aged 12-18 years from the Korea National Health and Nutrition Examination Surveys (KNHANES), from 2007-2009 to 2016-2018. Linear trends in the prevalence of high blood glucose level, NAFLD, and associated factors were assessed using multivariable logistic regression analyses. During the study period, the odds ratios for high blood glucose level and NAFLD increased significantly in both sexes and in girls, respectively (p for trend0.05). Over-consumption of total calories in boys and fat intake in boys and girls increased significantly (p for trend0.05). In Korean adolescents, the prevalence of high blood glucose level and NAFLD has increased recently. Efforts to modify the associated factors and further research to determine the public health measures are warranted to prevent these metabolic abnormalities in adolescents.

Background Few studies have investigated the association between religion and health behaviors in Korea, where various religions coexist. The present study aimed to investigate the association between religion and health behaviors among primary care patients in Korea. Methods We analyzed data from the Family Cohort Study in Primary Care. Among the 1,040 participants in the cohort, 973 of those who had reported their religion were included in the analysis. Participants completed standardized questionnaires that included religious status and lifestyle factors, such as physical activity, smoking status, drinking status, and dietary habits. The association between religion and health behaviors was analyzed using multivariate logistic regression models. Results Among the 973 participants, 345 (35.5%) were Christian, 153 (15.7%) were Roman Catholic, 308 (31.7%) were Buddhist, and 163 (16.8%) did not have any religion. Compared with those without a religion, the odds ratio (OR) for vigorous physical activity (OR, 1.52; 95% confidence interval [CI], 1.01-2.28) increased, and that for binge drinking (OR, 0.67; 95% CI, 0.46-0.78) and problematic drinking (OR, 0.59; 95% CI, 0.35-0.99) decreased among participants with a religion. Compared with those without a religion, Catholics were more likely to engage in vigorous physical activity (OR, 2.20; 95% CI, 1.31-3.67), whereas Christians were less likely to engage in heavy (OR, 0.50; 95% CI, 0.30-0.84), binge (OR, 0.35; 95% CI, 0.22-0.54), and problematic drinking (OR, 0.46; 95% CI, 0.25-0.86). Smoking, meal regularity, and breakfast consumption were not associated with religion. Conclusion The status of drinking and physical activities were different according to religion. As religion is one of the psychosocial characteristics of patients, knowing patients' religion can be helpful for primary physicians.

We tried to establish a reliable detrusor underactivity (DUA) rat model and to investigate pathophysiology of chronic bladder ischemia (CBI) on voiding behavior and bladder function. Adult male rats were divided into five groups. The arterial injury (AI) groups (AI-10, AI-20, AI-30) underwent vascular endothelial damage (VED) of bilateral iliac arteries (with 10, 20, and 30 bilateral repetitions of injury, respectively) and received a 1.25% cholesterol diet. The sham group underwent sham operation and received the same diet. Controls received a regular diet. After 8 weeks, all rats underwent unanesthetized cystometrogram. Bladder tissues were processed for organ bath investigation, immunohistochemistry staining, and genome-wide gene expression analysis. Awake cystometry analysis showed that frequency of voiding contractions and micturition pressure were lower in the AI-30 group than in sham group (p

Glutathione (GSH) is a major antioxidant in cells, and plays vital roles in the cellular defense against oxidants and in the regulation of redox signals. In a previous report, we demonstrated that stem cell function is critically affected by heterogeneity and dynamic changes in cellular GSH concentration. Here, we present a detailed protocol for the monitoring of GSH concentration in living stem cells using FreSHtracer, a real-time GSH probe. We describe the steps involved in monitoring GSH concentration in single living stem cells using confocal microscopy and flow cytometry. These methods are simple, rapid, and quantitative, and able to demonstrate intracellular GSH concentration changes in real time. We also describe the application of FreSHtracer to the sorting of stem cells according to their GSH content using flow cytometry. Typically, microscopic or flow cytometric analyses of FreSHtracer and MitoFreSHtracer signals in living stem cells take ~2~3 h, and the fractionation of stem cells into subpopulations on the basis of cellular GSH levels takes 3~4.5 h. This method could be applied to almost every kind of mammalian cell with minor modifications to the protocol described here.

The outbreak of the novel COVID-19, declared a global pandemic by WHO, is the most serious public health threat seen in terms of respiratory viruses since the 1918 H1N1 influenza pandemic. It is surprising that the total number of COVID-19 confirmed cases and the number of deaths has varied greatly across countries. Such great variations are caused by age population, health conditions, travel, economy, and environmental factors. Here, we investigated which national factors (life expectancy, aging index, human development index, percentage of malnourished people in the population, extreme poverty, economic ability, health policy, population, age distributions, etc.) influenced the spread of COVID-19 through systematic statistical analysis. First, we employed segmented growth curve models (GCMs) to model the cumulative confirmed cases for 134 countries from January 1 to August 31, 2020 (logistic and Gompertz). Thus, each country’s COVID-19 spread pattern was summarized into three growth-curve model parameters. Secondly, we investigated the relationship of selected 31 national factors (from KOSIS and Our World in Data) to these GCM parameters. Our analysis showed that with time, the parameters were influenced by different factors, for example, the parameter related to the maximum number of predicted cumulative confirmed cases was greatly influenced by the total population size, as expected. The other parameter related to the rate of spread of COVID-19 was influenced by aging index, cardiovascular death rate, extreme poverty, median age, percentage of population aged 65 or 70 and older, and so forth. We hope that with their consideration of a country’s resources and population dynamics that our results will help in making informed decisions with the most impact against similar infectious diseases.

Mesenchymal stem cell (MSC) therapy is a promising treatment for various intractable disorders including interstitial cystitis/bladder pain syndrome (IC/BPS). However, an analysis of fundamental characteristics driving in vivo behaviors of transplanted cells has not been performed, causing debates about rational use and efficacy of MSC therapy. Here, we implemented two-photon intravital imaging and single cell transcriptome analysis to evaluate the in vivo behaviors of engrafted multipotent MSCs (M-MSCs) derived from human embryonic stem cells (hESCs) in an acute IC/BPS animal model. Two-photon imaging analysis was performed to visualize the dynamic association between engrafted M-MSCs and bladder vasculature within live animals until 28 days after transplantation, demonstrating the progressive integration of transplanted M-MSCs into a perivascular-like structure. Single cell transcriptome analysis was performed in highly purified engrafted cells after a dual MACS−FACS sorting procedure and revealed expression changes in various pathways relating to pericyte cell adhesion and cellular stress. Particularly, FOS and cyclin dependent kinase-1 (CDK1) played a key role in modulating the migration, engraftment, and anti-inflammatory functions of M-MSCs, which determined their in vivo therapeutic potency. Collectively, this approach provides an overview of engrafted M-MSC behavior in vivo, which will advance our understanding of MSC therapeutic applications, efficacy, and safety.

For the novel coronavirus disease 2019 (COVID-19), predictive modeling, in the literature, uses broadly susceptible exposed infected recoverd (SEIR)/susceptible infected recoverd (SIR), agent-based, curve-fitting models. Governments and legislative bodies rely on insights from prediction models to suggest new policies and to assess the effectiveness of enforced policies. Therefore, access to accurate outbreak prediction models is essential to obtain insights into the likely spread and consequences of infectious diseases. The objective of this study is to predict the future COVID-19 situation of Korea. Here, we employed 5 models for this analysis; SEIR, local linear regression (LLR), negative binomial (NB) regression, segment Poisson, deep-learning based long short-term memory models (LSTM) and tree based gradient boosting machine (GBM). After prediction, model performance comparison was evelauated using relative mean squared errors (RMSE) for two sets of train (January 20, 2020‒December 31, 2020 and January 20, 2020‒January 31, 2021) and testing data (January 1, 2021‒February 28, 2021 and February 1, 2021‒February 28, 2021) . Except for segmented Poisson model, the other models predicted a decline in the daily confirmed cases in the country for the coming future. RMSE values’ comparison showed that LLR, GBM, SEIR, NB, and LSTM respectively, performed well in the forecasting of the pandemic situation of the country. A good understanding of the epidemic dynamics would greatly enhance the control and prevention of COVID-19 and other infectious diseases. Therefore, with increasing daily confirmed cases since this year, these results could help in the pandemic response by informing decisions about planning, resource allocation, and decision concerning social distancing policies.

Since the outbreak of novel SARS-COV-2, each country has implemented diverse policies to mitigate and suppress the spread of the virus. However, no systematic evaluation of these policies in their alleviation of the pandemic has been done. We investigate the impact of five indices derived from 12 policies in the Oxford COVID-19 Government Response Tracker dataset and the Korean government’s index, which is the social distancing level implemented by the Korean government in response to the changing pandemic situation. We employed segmented Poisson model for this analysis. In conclusion, health and the Korean government indices are most consistently effective (with negative coefficients), while the restriction and stringency indexes are mainly effective with lagging (1~10 days), as intuitively daily confirmed cases of a given day is affected by the policies implemented days before, which shows that a period of time is required before the impact of some policies can be observed. The health index demonstrates the importance of public information campaign, testing policy and contact tracing, while the government index shows the importance of social distancing guidelines in mitigating the spread of the virus. These results imply the important roles of these polices in mitigation of the spread of COVID-19 disease.

Obesity affects health-related quality of life (QoL); however, their relationship among elderly Asians is not well known. Relationship of domain-specific QoL with body mass index (BMI) and waist circumference and the sex differences were investigated using a nationally representative sample of elderly Korean population. In the Korea National Health and Nutrition Examination Survey phase VII (2016–2018), 3659 adults aged ≥ 65 years (1551 men and 2108 women) participated. BMI and waist circumference were classified according to Asian- and Korean-specific criteria. QoL was evaluated using the European Quality of Life Scale-Five Dimensions (EQ-5D). Multivariable logistic regressions were used to examine the relationship of QoL with BMI and waist circumference. Men with BMI

Purpose Despite advances in treatment, lung cancer remains the leading cause of cancer mortality. This study aimed to characterise genome-wide tumorigenesis events and to understand the hypothesis of the multistep carcinogenesis of lung adenocarcinoma (LUAD). Materials and methods We conducted multiregion whole-exome sequencing of LUAD with synchronous atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ, or minimally invasive adenocarcinoma of 19 samples from three patients to characterize genome-wide tumorigenesis events and validate the hypothesis of the multistep carcinogenesis of LUAD. We identified potential pathogenic mutations preserved in preinvasive lesions and supplemented the finding by allelic variant level from RNA sequencing. Results Overall, independent mutational profiles were observed per patient and between patients. Some shared mutations including epidermal growth factor receptor (EGFR , p.L858R) were present across synchronous lesions. Conclusion Here, we show that there are driver gene mutations in AAH, and they may exacerbate as a sequence in a histological continuum, supporting the Darwinian evolution model of cancer genome. The intertumoral and intratumoral heterogeneity of synchronous LUAD implies that multi-biomarker strategies might be necessary for appropriate treatment.

Real-time monitoring of GSH dynamics demonstrates the functional roles of CREB1-NRF2 pathway in MSC therapeutic potency., Glutathione (GSH), the most abundant nonprotein thiol functioning as an antioxidant, plays critical roles in maintaining the core functions of mesenchymal stem cells (MSCs), which are used as a cellular immunotherapy for graft-versus-host disease (GVHD). However, the role of GSH dynamics in MSCs remains elusive. Genome-wide gene expression profiling and high-throughput live-cell imaging assays revealed that CREB1 enforced the GSH-recovering capacity (GRC) of MSCs through NRF2 by directly up-regulating NRF2 target genes responsible for GSH synthesis and redox cycling. MSCs with enhanced GSH levels and GRC mediated by CREB1-NRF2 have improved self-renewal, migratory, anti-inflammatory, and T cell suppression capacities. Administration of MSCs overexpressing CREB1-NRF2 target genes alleviated GVHD in a humanized mouse model, resulting in improved survival, decreased weight loss, and reduced histopathologic damages in GVHD target organs. Collectively, these findings demonstrate the molecular and functional importance of the CREB1-NRF2 pathway in maintaining MSC GSH dynamics, determining therapeutic outcomes for GVHD treatment.

Introduction Lung adenocarcinoma (ADC) with synchronous ground-glass/lepidic (GG/L) nodules is considered a distinct disease entity in multiple synchronous lung cancers. Few studies have performed next-generation sequencing analysis of these synchronous sequential lesions, and genetic alterations of GG/L nodules must be further investigated. Methods We performed targeted sequencing in ADC with synchronous atypical adenomatous hyperplasia (AAH), ADC in situ, or minimally invasive ADC from 16 patients. Next-generation sequencing was performed by using a customized panel including 154 cancer-associated genes. Results Multiple synchronous lesions in the same patient showed different mutation profiles, and some shared identically mutated genes. In five patients harboring EGFR-mutant ADC, their synchronous GG/L nodules had EGFR mutation; however, none was observed in EGFR wild-type ADC. The average numbers of exonic mutations were 4.2, 5.4, 4.0, and 5.4 in AAH, ADC in situ, minimally invasive ADC, and ADC, respectively. In each lesion type, various mutations, including LDL receptor related protein 1B gene (LRP1B), KRAS, EGFR, and BRAF were observed in AAH, and EGFR mutations were the most frequently observed in ADC. In all, 80% of mutations with a variant allele frequency of 20% or higher, which contained driver gene mutations, were identified in ADC. Intratumoral heterogeneity of the genetic profile was found between the lepidic and invasive areas of ADC, but the driver gene mutations were similar. Conclusions This study suggests that ADC and synchronous GG/L nodules are genetically independent tumors. Intratumoral genetic heterogeneity of ADC was present, but driver gene mutations were homogeneously distributed. Driver gene mutations with a high variant allele frequency were identified in the invasive tumor. These findings support the relevance of molecular characterization of lung ADC and synchronous GG/L nodules.

This study aimed to assess trends of underweight, obesity, and abdominal obesity and related lifestyle factors in young Korean adults.The analysis focused on adults aged 19-39 years using data from the Korea National Health and Nutrition Examination Survey (KNHANES) I-V (1998-2012). Underweight was defined as body mass index (BMI)18.5kg/mAs compared with KNHANES I, the ORs for obesity were higher in III, IV, and V and the ORs for abdominal obesity were higher in IV and V in men, which showed an increasing trend (P for trend0.001). In women, the prevalence of underweight and obesity showed a significant increasing tendency (P for trend0.001). Lifestyle analysis revealed the overconsumption of energy intake proportion was increased in men and decreased in women. The lack of physical activity and high-risk alcohol consumption proportions showed increasing trends in both men and women. The current smoking proportion was decreased in men and increased in women. The lack of adequate sleep proportion showed a continuous increasing trend in men.Prevention of obesity in young men and women, and abdominal obesity in young men is needed. Meanwhile, management of underweight in young women is simultaneously required.

Handgrip strength is strongly related to muscle power in the extremities and is an important index for diagnosing sarcopenia. We evaluated the relationship between handgrip strength and quality of life (QoL) in Korean men and women. We analyzed 4620 participants (2070 men and 2550 women) using data from the Korea National Health and Nutrition Examination Survey VI-3 (2015). Low handgrip strength was defined as the lower quartile of handgrip strength in the study population. QoL was evaluated according to the European Quality of Life Scale-Five Dimensions (EQ-5D). The relationship between handgrip strength and QoL was evaluated by multivariate logistic regression analyses. The odds ratios (ORs) for low handgrip strength significantly increased as age increased for both men and women. The ORs for low handgrip strength increased as body mass index decreased in men. In men with low handgrip strength, the OR for having problems in mobility (OR 1.93, 95% confidence interval (CI) 1.25–2.98) and having pain or discomfort (1.53, 1.04–2.24) significantly increased. In women with low handgrip strength, the OR for having problems in mobility (2.12, 1.02–2.87), problems in usual activities (2.04, 1.46–2.85), and having pain or discomfort (1.48, 1.15–1.90) significantly increased. Men with low handgrip strength had poor QoL on the mobility and pain/discomfort dimensions of EQ-5D, whereas women with low handgrip strength had poor QoL on mobility, usual activities, and pain/discomfort dimensions. Management to improve handgrip strength is necessary for achieving better QoL.

Mesenchymal stem cells (MSCs) are of particular interest for the treatment of immune-related diseases due to their immunosuppressive capacity. Here, we show that Small MSCs primed with Hypoxia and Calcium ions (SHC-MSCs) exhibit enhanced stemness and immunomodulatory functions for treating allogeneic conflicts. Compared with naïve cultured human umbilical cord blood-derived MSCs, SHC-MSCs were resistant to passage-dependent senescence mediated via the monocyte chemoattractant protein-1 and p53/p21 cascade and secreted large amounts of pro-angiogenic and immunomodulatory factors, resulting in suppression of T-cell proliferation. SHC-MSCs showed DNA demethylation in pluripotency, germline, and imprinted genes similarly to very small embryonic-like stem cells, suggesting a potential mutual relationship. Genome-wide DNA methylome and transcriptome analyses indicated that genes related to immune modulation, cell adhesion, and the cell cycle were up-regulated in SHC-MSCs. Particularly, polo-like kinase-1 (PLK1), zinc-finger protein-143, dehydrogenase/reductase-3, and friend-of-GATA2 play a key role in the beneficial effects of SHC-MSCs. Administration of SHC-MSCs or PLK1-overexpressing MSCs significantly ameliorated symptoms of graft-versus-host disease (GVHD) in a humanized mouse model, resulting in significantly improved survival, less weight loss, and reduced histopathologic injuries in GVHD target organs compared with naïve MSC-infused mice. Collectively, our findings suggest that SHC-MSCs can improve the clinical treatment of allogeneic conflicts, including GVHD.

Summary The core functions of stem cells (SCs) are critically regulated by their cellular redox status. Glutathione is the most abundant non-protein thiol functioning as an antioxidant and a redox regulator. However, an investigation into the relationship between glutathione-mediated redox capacity and SC activities is hindered by lack of probe. Here, we demonstrate that cyanoacrylamide-based coumarin derivatives are ratiometric probes suitable for the real-time monitoring of glutathione levels in living SCs. These probes revealed that glutathione levels are heterogeneous among subcellular organelles and among individual cells and show dynamic changes and heterogeneity in repopulating SCs depending on oxidative stress or culture conditions. Importantly, a subpopulation of SCs with high glutathione levels exhibited increased stemness and migration activities in vitro and showed improved therapeutic efficiency in treating asthma. Our results indicate that high glutathione levels are required for maintaining SC functions, and monitoring glutathione dynamics and heterogeneity can advance our understanding of the cellular responses to oxidative stress., Graphical Abstract, Highlights • FreSHtracer is a reversible probe for a fast and ratiometric reaction with GSH • FreSHtracer and its derivatives enable real-time monitoring of intracellular GSH • FreSHtracer reports dynamic changes and heterogeneity of GSH level in stem cells • High GSH levels are required for maintaining functional potency of stem cells, By developing and characterizing new fluorescent probes enabling fast, reversible, and ratiometric reaction with glutathione, Jeong et al. reveal considerable dynamics and heterogeneity in glutathione levels in living stem cells in response to environmental stress and also show that high glutathione levels are required for maintaining stemness of murine embryonic stem cells or therapeutic potency of mesenchymal stem cells.

Purpose To evaluate the therapeutic effect of human embryonic stem cell (hESC)-derived multipotent mesenchymal stem cells (M-MSCs) on ketamine-induced cystitis (KC) in rats. Methods To induce KC, 10-week-old female rats were injected with 25-mg/kg ketamine hydrochloride twice weekly for 12 weeks. In the sham group, phosphate buffered saline (PBS) was injected instead of ketamine. One week after the final injection of ketamine, the indicated doses (0.25, 0.5, and 1×106 cells) of M-MSCs (KC+M-MSC group) or PBS vehicle (KC group) were directly injected into the bladder wall. One week after M-MSC injection, the therapeutic outcomes were evaluated via cystometry, histological analyses, and measurement of gene expression. Next, we compared the efficacy of M-MSCs at a low dose (1×105 cells) to that of an identical dose of adult bone marrow (BM)-derived MSCs. Results Rats in the KC group exhibited increased voiding frequency and reduced bladder capacity compared to rats of the sham group. However, these parameters recovered after transplantation of M-MSCs at all doses tested. KC bladders exhibited markedly increased mast cell infiltration, apoptosis, and tissue fibrosis. Administration of M-MSCs significantly reversed these characteristic histological alterations. Gene expression analyses indicated that several genes associated with tissue fibrosis were markedly upregulated in KC bladders. However the expression of these genes was significantly suppressed by the administration of M-MSCs. Importantly, M-MSCs ameliorated bladder deterioration in KC rats after injection of a low dose (1×105) of cells, at which point BM-derived MSCs did not substantially improve bladder function. Conclusions This study demonstrates for the first time the therapeutic efficacy of hESC-derived M-MSCs on KC in rats. M-MSCs restored bladder function more effectively than did BM-derived MSCs, protecting against abnormal changes including mast cell infiltration, apoptosis and fibrotic damage.

Rationale: Mesenchymal stem cell (MSC) therapy may be a novel approach to improve interstitial cystitis/bladder pain syndrome (IC/BPS), an intractable disease characterized by severe pelvic pain and urinary frequency. Unfortunately, the properties of transplanted stem cells have not been directly analyzed in vivo, which hampers elucidation of the therapeutic mechanisms of these cells and optimization of transplantation protocols. Here, we monitored the behaviors of multipotent stem cells (M-MSCs) derived from human embryonic stem cells (hESCs) in real time using a novel combination of in vivo confocal endoscopic and microscopic imaging and demonstrated their improved therapeutic potency in a chronic IC/BPS animal model. Methods: Ten-week-old female Sprague-Dawley rats were instilled with 10 mg of protamine sulfate followed by 750 μg of lipopolysaccharide weekly for 5 weeks. The sham group was instilled with phosphate-buffered saline (PBS). Thereafter, the indicated dose (0.1, 0.25, 0.5, and 1×106 cells) of M-MSCs or PBS was injected once into the outer layer of the bladder. The distribution, perivascular integration, and therapeutic effects of M-MSCs were monitored by in vivo endoscopic and confocal microscopic imaging, awake cystometry, and histological and gene expression analyses. Results: A novel combination of longitudinal intravital confocal fluorescence imaging and microcystoscopy in living animals, together with immunofluorescence analysis of bladder tissues, demonstrated that transplanted M-MSCs engrafted following differentiation into multiple cell types and gradually integrated into a perivascular-like structure until 30 days after transplantation. The beneficial effects of transplanted M-MSCs on bladder voiding function and the pathological characteristics of the bladder were efficient and long-lasting due to the stable engraftment of these cells. Conclusion: This longitudinal bioimaging study of transplanted hESC-derived M-MSCs in living animals reveals their long-term functional integration, which underlies the improved therapeutic effects of these cells on IC/BPS.

To reduce the prevalence of obesity and provide information on evidence-based obesity treatments, the Education Committee of the Korean Society for the Study of Obesity (KSSO) has developed and launched the first Obesity Educator Training Program (OETP). After the course, we analyzed the results of a survey from 110 participants, comprising medical doctors (n=58), nutrition specialists (n=19), exercise specialists (n=14), and students (n=6). Approximately half of the participants were recruited through the Internet (48%), followed by academic leaflets, such as conference posters (21%); the reasons for participation were to learn about evidence-based treatments for obesity (47%), to receive up-to-date knowledge on obesity treatments (39%), to obtain basic information on obesity (10%), and others (4%). More than half of the participants found the date, lecture time, process, and theme of the OETP favorable. The participants indicated that there should be an in-depth course, sharing of the presented files with attendees, a longer lecture time, and a broader OETP that includes other specialties such as nursing. To improve the OETP, the educational committee of the KSSO must develop an in-depth OETP that will reflect these participant’s feedback.