Search

Salt, one of the most commonly consumed food additives worldwide, is produced in many countries. The chemical composition of edible salts is essential information for quality assessment and origin distinction. In this work, a simple laser-induced breakdown spectroscopy instrument was assembled with a diode-pumped solid-state laser and a miniature spectrometer. Its performances in analyzing Mg and Ca in six popular edible sea salts consumed in South Korea and classification of the products were investigated. Each salt was dissolved in water and a tiny amount of the solution was dropped and dried on the hydrophilicity-enhanced silicon wafer substrate, providing homogeneous distribution of salt crystals. Strong Mg II and Ca II emissions were chosen for both quantification and classification. Calibration curves could be constructed with limits-of-detection of 87 mg/kg for Mg and 45 mg/kg for Ca. Also, the Mg II and Ca II emission peak intensities were used in a k-nearest neighbors model providing 98.6% classification accuracy. In both quantification and classification, intensity normalization using a Na I emission line as a reference signal was effective. A concept of interclass distance was introduced, and the increase in the classification accuracy due to the intensity normalization was rationalized based on it. Our methodology will be useful for analyzing major mineral nutrients in various food materials in liquid phase or soluble in water, including salts.

Abstract Background Organogenesis from tonsil-derived mesenchymal cells (TMSCs) has been reported, wherein tenogenic markers are expressed depending on the chemical stimulation during tenogenesis. However, there are insufficient studies on the mechanical strain stimulation for tenogenic cell differentiation of TMSCs, although these cells possess advantages as a cell source for generating tendinous tissue. The purpose of this study was to investigate the effects of mechanical strain and transforming growth factor-beta 3 (TGF-β3) on the tenogenic differentiation of TMSCs and evaluate the expression of tendon-related genes and extracellular matrix (ECM) components, such as collagen. Results mRNA expression of tenogenic genes was significantly higher when the mechanical strain was applied than under static conditions. Moreover, mRNA expression of tenogenic genes was significantly higher with TGF-β3 treatment than without. mRNA expression of osteogenic and chondrogenic genes was not significantly different among different mechanical strain intensities. In cells without TGF-β3 treatment, double-stranded DNA concentration decreased, while the amount of normalized collagen increased as the intensity of mechanical strain increased. Conclusions Mechanical strain and TGF-β3 have significant effects on TMSC differentiation into tenocytes. Mechanical strain stimulates the differentiation of TMSCs, particularly into tenocytes, and cell differentiation, rather than proliferation. However, a combination of these two did not have a synergistic effect on differentiation. In other words, mechanical loading did not stimulate the differentiation of TMSCs with TGF-β3 supplementation. The effect of mechanical loading with TGF-β3 treatment on TMSC differentiation can be manipulated according to the differentiation stage of TMSCs. Moreover, TMSCs have the potential to be used for cell banking, and compared to other mesenchymal stem cells, they can be procured from patients via less invasive procedures.

Abstract Background Stationary cycling is commonly used for postoperative rehabilitation of physical disabilities; however, few studies have focused on the three-dimensional (3D) kinematics of rehabilitation. This study aimed to elucidate the three-dimensional lower limb kinematics of people with healthy musculoskeletal function and the effect of sex and age on kinematics using a controlled bicycle configuration. Methods Thirty-one healthy adults participated in the study. The position of the stationary cycle was standardized using the LeMond method by setting the saddle height to 85.5% of the participant’s inseam. The participants maintained a pedaling rate of 10–12 km/h, and the average value of three successive cycles of the right leg was used for analysis. The pelvis, hip, knee, and ankle joint motions during cycling were evaluated in the sagittal, coronal, and transverse planes. Kinematic data were normalized to 0–100% of the cycling cycle. The Kolmogorov-Smirnov test, Mann-Whitney U test, Kruskal-Wallis test, and k-fold cross-validation were used to analyze the data. Results In the sagittal plane, the cycling ranges of motion (ROMs) were 1.6° (pelvis), 43.9° (hip), 75.2° (knee), and 26.9° (ankle). The coronal plane movement was observed in all joints, and the specific ROMs were 6.6° (knee) and 5.8° (ankle). There was significant internal and external rotation of the hip (ROM: 11.6°), knee (ROM: 6.6°), and ankle (ROM: 10.3°) during cycling. There was no difference in kinematic data of the pelvis, hip, knee, and ankle between the sexes (p = 0.12 to 0.95) and between different age groups (p = 0.11 to 0.96) in all anatomical planes. Conclusions The kinematic results support the view that cycling is highly beneficial for comprehensive musculoskeletal rehabilitation. These results might help clinicians set a target of recovery ROM based on healthy and non-elite individuals and issue suitable guidelines to patients.

Abstract Hyperadiponectemia is paradoxically associated with renal disease progression and mortality in chronic kidney disease (CKD). Its association with health-related quality of life (HR-QOL) is unknown. This study aimed to verify the association between adiponectin and HR-QOL in Korean pre-dialysis CKD cohort. This cross-sectional study analyzed 1551 pre-dialysis CKD patients from KNOW-CKD (KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease). Participants were categorized into three tertiles (T1–T3) according to adiponectin levels. HR-QOL was assessed using SF-36. High physical component summary (PCS) and mental component summary (MCS) were defined as highest quartile of each score. Multivariate logistic regression was used to analyze odds ratio (OR) and 95% confidence interval (CI) for high PCS and MCS. Prevalence of high PCS were 33.3%, 27.5%, and 17.0% and that of high MCS were 31.7%, 24.8%, and 21.3% for T1, T2, and T3 (both p for trend

Abstract Background In order to optimize the tenogenic differentiation of mesenchymal stem cells (MSCs), researchers should consider various factors. However, this requires testing numerous experimental settings, which is costly and time-consuming. We aimed to assess the differential effects of transforming growth factor beta-3 (TGF-β3) on the tenogenesis of tonsil-derived MSCs (T-MSCs) and bone marrow-derived MSCs (BM-MSCs) using response surface methodology (RSM). Methods Bone marrow and tonsillar tissue were collected from four patients; mononuclear cells were separated and treated with 5 or 10 ng/mL of TGF-β3. A full factorial experimental design with a categorical factor of 0 was employed to study the effect of tension based on T-MSCs. Eighty-four trials were fitted with RSM and then used to obtain mathematical prediction models. Results Exposure of T-MSCs and BM-MSCs to TGF-β3 increased the expression of scleraxis (SCX), tenomodulin (TNMD), decorin, collagen I, and tenascin C. Expression of most of these factors reached a maximum after 2–3 days of treatment. The model predicted that the values of the tenocyte lineage-related factors assessed would be significantly increased at 2.5 days of culture with 2.7 ng/mL of TGF-β3 for T-MSCs and at 2.3 days of culture regardless of TGF-β3 concentration for BM-MSCs. Conclusions This study demonstrated that the RSM prediction of the culture time necessary for the tenogenic differentiation of T-MSCs and BM-MSCs under TGF-β3 stimulation was similar to the experimentally determined time of peak expression of tenocyte-related mRNAs, suggesting the potential of using the RSM approach for optimization of the culture protocol for tenogenesis of MSCs.

Background/Aims: Both arterial stiffness and coronary artery calcification (CAC) are important predictors of cardiovascular disease in the general population and in chronic kidney disease (CKD) patients. Recent studies on arterial stiffness and CAC in subjects with preserved renal function have verified the association between the two. However, the relationship is not well evaluated in CKD patients. Methods: This cross-sectional study analyzed 1,385 predialysis CKD patients from the KNOW-CKD cohort. Participants were divided into four groups according to brachial-ankle pulse wave velocity (baPWV) quartile. Coronary artery calcium scores (CACS) were assessed using cardiac computed tomography and CAC was defined as a CACS >100. Results: CAC prevalence was higher in the higher baPWV groups (6.4, 9.8, 23.7, and 43.8% for the 1st to 4th quartiles of baPWV, respectively, p < 0.001). In Tobit regression analyses that were fully adjusted for traditional and renal cardiovascular risk factors, the CACS ratio comparing the highest and lowest baPWV quartiles was 3.03 (95% CI, 1.59–6.87). Similarly, the OR for CAC in the highest baPWV quartile compared to the lowest quartile was 1.98 (95% CI, 1.09–3.60) in a fully adjusted multivariate logistic model. Results were consistent across analyses with different cutoffs for CAC or with different clinically relevant subgroups. Conclusion: Increased arterial stiffness measured by high baPWV was associated with CAC in a predialysis CKD cohort. Longitudinal studies are needed to determine the effect of arterial stiffness on the development or progression of CAC in CKD.

Background/Aims: The importance of a trace albumin on the urine dipstick test is not well known and is frequently disregarded in clinical practice. The aim of this study is to investigate the role of trace albuminuria in predicting all-cause mortality in Korean adults. Methods: In this retrospective cohort study, we analyzed 347,938 Korean adults who underwent urine dipstick test from 2002 to 2012 in a health examination program. The participants were divided into three groups according to dipstick negative, trace (±), and overt (≥1+) albuminuria. The trace group was further stratified by urine specific gravity (SG) and classified as either high (≥1.020) or low (≤1.015) SG. Mortality data was obtained from STATICS KOREA, a Korean federal statistical organization. Results: During a median follow-up period of 5.9 years, 1,855 deaths occurred. Mortality was compared to negative group and adjusted for potential risk factors. Mortality did not increase in the trace group (HR, 1.19; 95% CI, 0.97-1.47; P=0.097), but increased in the overt (HR, 1.69; 95% CI, 1.38-2.07; P< 0.001) albuminuria group. When the trace group was subdivided according to urine SG, mortality did not increase in the high SG (HR, 1.09; 95% CI, 0.86-1.37; P=0.488) group, but increased in the low SG (HR, 1.84; 95% CI, 1.19-2.83; P=0.006) and overt (HR, 1.70; 95% CI, 1.39-2.08; P< 0.001) groups. Conclusion: Trace albumin with low SG in urine dipstick test was associated with higher all-cause mortality in Korean adults. We should not neglect the significance of trace albumin and SG when interpreting urinalysis results.

Background: Red cell distribution width (RDW) is an emerging marker of inflammation and a predictor of high cardiovascular morbidity and mortality as well as all-cause mortality. A previous cross-sectional study showed that RDW was associated with microalbuminuria, an indicator of target organ damage. However, the longitudinal association of RDW and development of albuminuria is not known. Methods: We analyzed 83,040 participants without chronic kidney disease (CKD) at baseline who underwent two health check-ups at a 4-year interval during 2005 to 2014. Urine albumin was determined by single urine dipstick semi-quantitative analysis, and incident albuminuria was defined as ≥ 1+ dipstick albumin at the second check-up. We used logistic regression analysis to determine the relationship between RDW and incident albuminuria. Results: Participants were divided into quartiles according to baseline RDW. After 4 years, 982 cases of incident albuminuria were observed. The cumulative incidences of albuminuria were 0.94, 1.05, 1.18, and 1.62% for the 1st through 4th quartiles of RDW, respectively. Multivariate logistic analysis showed that the odds ratios (95% confidence interval) for incident albuminuria compared to those in the 1st quartile were 1.11 (0.92–1.34), 1.26 (1.04–1.52), and 1.88 (1.58–2.24) for the 2nd, 3rd and 4th quartiles, respectively. Conclusion: RDW was associated with development of albuminuria in relatively healthy Korean adults without CKD. Further research is needed to verify the role of RDW in the development of albuminuria and renal injury.

Abstract Endoplasmic reticulum (ER) homeostasis in the hypothalamus has been implicated in the pathogenesis of diet-induced obesity (DIO) and type 2 diabetes; however, the underlying molecular mechanism remain vague and debatable. Here we report that SEL1L-HRD1 protein complex of the highly conserved ER-associated protein degradation (ERAD) machinery in POMC-expressing neurons ameliorates diet-induced obesity and its associated complications, partly by regulating the turnover of the long isoform of Leptin receptors (LepRb). Loss of SEL1L in POMC-expressing neurons attenuates leptin signaling and predisposes mice to HFD-associated pathologies including fatty liver, glucose intolerance, insulin and leptin resistance. Mechanistically, nascent LepRb, both wildtype and disease-associated Cys604Ser variant, are misfolding prone and bona fide substrates of SEL1L-HRD1 ERAD. In the absence of SEL1L-HRD1 ERAD, LepRb are largely retained in the ER, in an ER stress-independent manner. This study uncovers an important role of SEL1L-HRD1 ERAD in the pathogenesis of central leptin resistance and leptin signaling.

Abstract Background This study aimed to evaluate the effectiveness of Egami, Kobayashi and Sano scores in predicting intravenous immunoglobulin (IVIG) resistance in infant Kawasaki disease (KD), considering its unique clinical presentation. Methods We retrospectively analysed 143 infants aged

BackgroundThe purpose of this study was to investigate the relationship between statin eligibility and the degree of renal dysfunction using the Adult Treatment Panel (ATP) III and the American College of Cardiology (ACC)/American Heart Association (AHA) guidelines in Korean adults.MethodsRenal function was assessed in 18,746 participants of the Kangbuk Samsung Health Study from January 2011 to December 2012. Subjects were divided into three groups according to estimated glomerular filtration rate (eGFR): stage 1, eGFR ≥90 mL/min/1.73 m2; stage 2, eGFR 60 to 89 mL/min/1.73 m2; and stages 3 to 5, eGFR

Background/Aims: Previous studies have shown that low muscle mass is associated with arterial stiffness, as measured by pulse wave velocity (PWV), in a population without chronic kidney disease (CKD). This link between low muscle mass and arterial stiffness may explain why patients with CKD have poor cardiovascular outcomes. However, the association between muscle mass and arterial stiffness in CKD patients is not well known. Methods: Between 2011 and 2013, 1,529 CKD patients were enrolled in the prospective Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD). We analyzed 888 participants from this cohort who underwent measurements of 24-hr urinary creatinine excretion (UCr) and brachial-ankle PWV (baPWV) at baseline examination. The mean of the right and left baPWV (mPWV) was used as a marker of arterial stiffness. Results: The baPWV values varied according to the UCr quartile (1,630±412, 1,544±387, 1,527±282 and 1,406±246 for the 1st to 4th quartiles of UCr, respectively, PConclusion: Low muscle mass estimated by low UCr was associated high baPWV in pre-dialysis CKD patients in Korea. Further studies are needed to confirm the causal relationship between UCR and baPWV, and the role of muscle mass in the development of cardiovascular disease in CKD.

Category: Basic Sciences/Biologics Introduction/Purpose: Tendon repair has been a challenging issue for surgeons in treating. Although tissue engineering with mesenchymal stem cells (MSC) have been used for tendon repair in both in vivo and in vitro, the stem cells are obtained through invasive procedures, and there is usually a lack of adequate numbers for clinical use. The purpose of this study was to compare the potential of tri-lineage differentiation and to investigate the potential of tenogenic differentiation of human tonsil derived MSCs (T-MSCs), bone marrow derived MSCs (BM-MSCs), and adipose tissue derived MSCs (AD-MSCs). Methods: Each tissue was obtained from 8 patients. After isolation of MSCs, flow cytometry analysis was used to characterize the phenotypes of the MSCs. Differentiation capacity to adipo-, osteo-, and chondrocytes were induced by culturing each MSCs for 3 weeks in commercially available media. Each MSCs was treated with 5ng/ml and 10ng/ml of TGF-ß3 with vehicle control. Results: Immunophenotypic surface marker analysis of BM-MSC, AD-MSC, and TMSCs revealed that these MSCs expressed a typical MSCs. mRNA expression levels of the markers for tri-lineage differentiation were significantly lower in TMSC than other MSCs. The tenogenic transcription factor, scleraxis, showed a statistically significant increase in all MSCs differentiation groups except for the 7th day TMSC differentiation group (Figure). Gene expression of tenascin-C, an ECM glycoprotein, was specifically expressed in the T-MSC differentiation group at 14 days (Figure). Comparing the ratio of collagen 1 to collagen 3 genes, the BM-MSC showed a decrease in the ratio on days 3 and 7 unlike AD-MSCs and TMSCs. Only TMSC showed a significant increase in the ratio compared with other MSCs on the 14th day. Conclusion: The tonsil-MSC has low fat, bone and cartilage differentiation potential and has excellent tendon-specific differentiation potential, thus being highly useful as a tendon-tailored cell therapy agent.

Category: Basic Sciences/Biologics Introduction/Purpose: Researchers should consider various potential factors that affect tenogenic differentiation of MSCs. Numerous experimental settings are associated with high cost and time. Response surface methodology (RSM), a component in the design of experiments (DOE), is gaining recognition as a powerful tool in optimizing conditions for the production of industrially important products such as chemicals and enzymes. The purpose of this study was to access the differential effects of transforming growth factor beta 3 (TGF-β3) on the tenogenesis of tonsil-derived mesenchymal stem cells (T-MSCs) and bone marrow-derived mesenchymal stem cells (BM-MSCs) using RSM. Methods: Bone marrow was collected from four patients (mean age: 79.0±2.2) and mononuclear cells were separated. The tonsillar tissues were collected from four patients (mean age: 7.6±0.6). After isolation of MSCs, they were treated with 5ng/ml and 10ng/ml of TGF-β3 with vehicle control. The full-factorial experimental design was employed to study the effect of tension based on T-MSCs. The design was composed of three levels being coded as -1, 0 and +1 and a total of 18 runs were carried out in duplicates to optimize the level of chosen variables, such as days and amount. A total of 84 trials were utilized and fitted with RSM; they were then used to obtain mathematical prediction models. Results: Exposure of TGF-β3 to T-MSCs and BM-MSCs resulted in an increase in the expression of SCX, TNMD, decorin, collagen I, and tenacin C. Most tenocyte lineage-related factors from T-MSCs and BM-MSCs presented a maximum increase in 2- 3 day treatment. Considering all of tenocyte lineage-related factors that we assessed, the predicted value of the factors was significantly induced at 2.7 ng/mL of TGF-β3 (p < 0.001) on 2.5-day culture (p = 0.001). (Fig A) Considering all of tenocyte lineage-related factors that we assessed, the predicted value of the factors was significantly induced on 2.3-day culture (p = 0.004) regardless of the concentration of TGF-β3. (Fig B) Conclusion: We demonstrated that tenocyte-like cells can be successfully differentiated from T-MSCs and BM-MSCs under TGF- β3 stimulation. This study demonstrated that T-MSCs and BM-MSCs in tenogenic stimulation with TGF-β3 have a similar tenogenic differentiation potential using RSM.

BACKGROUND:It is unclear whether sleep duration and quality are associated with chronic kidney disease (CKD) and glomerular hyperfiltration. The aim of this study was to examine the association of sleep duration and quality with CKD and glomerular hyperfiltration in young and middle-aged adults. METHODS:We conducted a cross-sectional study of men and women who underwent a health checkup examination, including assessment of sleep duration and quality (n = 241,607). Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73 m2, and glomerular hyperfiltration was defined as eGFR above the age-/sex-specific 95th percentile. RESULTS:In a multinomial logistic regression analysis adjusting for relevant confounders, the adjusted prevalence ratios for CKD (95% confidence interval) comparing sleep durations of ≤ 5, 6, 8, and 9 hours with 7 hours were 1.22 (0.95-1.55), 0.93 (0.75-1.14), 0.97 (0.75-1.26), and 1.56 (1.06-2.30) in men and 0.98 (0.68-1.43), 1.03 (0.72-1.46), 1.39 (0.97-2.00), and 1.31 (0.78-2.22) in women, respectively. The corresponding prevalence ratios (95% confidence interval) for glomerular hyperfiltration were 1.00 (0.93-1.08), 0.97 (0.91-1.03), 1.03 (0.94-1.13), and 1.39 (1.13-1.72) in men and 1.04 (0.95-1.14), 0.96 (0.90-1.04), 1.11 (1.02-1.20), and 1.28 (1.14-1.45) in women, respectively. Poor subjective sleep quality was associated with glomerular hyperfiltration in men and women. CONCLUSION:In this large study of young and middle-aged adults, we found that long sleep duration was associated with CKD and glomerular hyperfiltration. Additionally, poor subjective sleep quality was associated with increased prevalence of glomerular hyperfiltration, suggesting the importance of adequate quantity and quality of sleep for kidney function.

The chiton (Polyplacophora) occupies a significant position in molluscan evolutionary history as one of the most primitive groups within the phylum Mollusca. Acanthochitona defilippii (Tapparone-Canefri 1874) (Chitonida: Acanthochitonidae) is a commonly found intertidal chiton species in South Korea. In this study, we characterized the complete mitochondrial genome of A. defilippii (14,999 bp long), comprising 13 protein-coding genes (PCGs), 22 transfer RNA genes, two ribosomal RNA genes, and an A + T rich region (166 bp). The base composition is as follows: 31.82% for A, 11.63% for C, 16.69% for G, and 39.86% for T. We reconstructed a maximum likelihood (ML) tree to elucidate phylogenetic relationships among the eight chitonid families using the nucleotide sequences of all PCGs. The ML tree revealed that A. defilippii clustered with Acanthochitona avicula (BP 100) within the family Acanthochitonidae. Acanthochitonidae formed a sister group with Mopaliidae. The results could provide a valuable understanding the phylogenetic relationships of chitonid species.

ObjectiveA beneficial effect on endometrial thickness (EMT) and improvement of pregnancy outcome after intrauterine infusion of platelet-rich plasma (PRP) has been suggested. This study assessed the effect of intrauterine PRP infusion on live birth rate and obstetrical outcomes and analyzed cytokines that can potentially improve pregnancy outcomes through PRP.MethodThis study was a prospective cohort study conducted in a university hospital fertility center. The study included ninety-one patients who had a history of two or more failed in vitro fertilization (IVF) attempts and refractory thin endometrium that remained unresponsive after at least two conventional treatments for thin endometrium. Patients were treated with an intrauterine infusion of autologous PRP between days 7 and 14 of their hormone replacement therapy-frozen embryo transfer (HRT-FET) cycle. PRP was administered at 3-day intervals until their EMT reached 7mm. After a maximum of three PRP administrations, embryo transfer (ET) was performed. The primary outcome was the live birth rate. Secondary outcomes included the implantation rate and increase in EMT compared to the previous cycle. We compared the cytokines related to angiogenesis in a patient’s whole blood (WB) and PRP by utilizing a commercial screening kit.ResultsThe live birth rate in the PRP treatment cycle was 20.9% (19 of 91 patients), significantly superior to the previous cycle without PRP infusion (p < 0.001). The implantation rate was also significantly higher during the PRP treatment cycle (16.4%) compared to the previous cycle (3.1%) (p < 0.001). The mean EMT post-PRP treatment was 6.1 mm, showing a significant increase of 0.8 mm (p < 0.001). Nonetheless, an increase in EMT was also observed in the non-pregnancy group. No adverse effects were reported by patients treated with autologous PRP. Cytokine array analysis confirmed marked increases in well-known pro-angiogenic factors such as Ang-1, EGF, LAP (TGF-b1), MMP-8, PDGF-AA, and PDGF-AB/PDGF-BB.ConclusionIntrauterine PRP infusion offers a safe and effective treatment for patients with refractory thin endometrium and implantation failures. The angiogenic cytokines present in PRP are the primary drivers of this improvement.

Background Microalbuminuria is associated with cardiovascular disease (CVD) mortality, but whether lower levels of urine albumin excretion similarly predict CVD is uncertain. We investigated associations between urine albumin:creatinine ratio (UACR)

The percentage of energy consumed by buildings is very large in industry. Recently, the cases of applying smart technology to efficiently improve the energy waste of these buildings are increasing, and this study targets Electrochromic (EC) smart windows. Smart window means a window that can freely change Visible Light Transmittance (VLT) and Solar Heat Gain Coefficient (SHGC). Since windows are the largest medium that can cause energy loss in buildings, the application of smart windows enables efficient energy management. However, this technology currently has a high-cost problem, so a partial application to windows is proposed. This study aims to analyze the relationship between partially applied smart windows and energy loads. Smart windows require an environment control strategy because windows are primarily to provide a comfortable indoor environment. An environmental control strategy was established according to the application area of the smart window, and Useful Daylight Illuminance (UDI) was used. In addition, the energy load of the smart window in which the environmental control strategy was established was derived, and the relationship with the partially applied area was analyzed. This study provides information on how much the partial application of smart windows can save energy wastage in buildings.

Several reports promoted the potential of shellfish due to their ability to act as antioxidant, anti-inflammatory, and antimicrobial agents. Pacific abalone, Haliotis discus hannai viscera is, reported to possess bioactivities such as antioxidative stress and anti-inflammatory. In this study, anti-inflammatory potential of mucus-secreting glands from shell-shucking waste of H. discus hannai was evaluated using RAW 264.7 mouse macrophage cell model. Results indicated that presence of H. discus hannai mucosubstance by-products (AM) significantly lowered the nitric oxide (NO) production along the expressional suppression of inflammatory mediators such as cytokines TNF-α, IL-1β, and IL-6 and enzymes iNOS and COX-2. Also, AM was shown to increase expression of anti-inflammatory response mediator HO-1. Presence of AM also scavenged the free radicals in vitro. In conclusion, by-products of H. discus hannai are suggested to possess notable anti-inflammatory potential which promotes the possibility of utilization as functional food ingredient.

The homeobox transcription factor Prox1 is critical to the development of many embryonic organs and tissues, although current understanding of its expression in the developing renal medulla is limited. We examined the functional role of Prox1 during mouse kidney development with particular emphasis on the developing loop of Henle. Our data show that Prox1 is expressed in the transdifferentiating region from the NKCC2-positive thick ascending limb, into the CLC-K1-positive ascending thin limb of Henle's loop beginning at embryonic day 18. From 1 to 14 days of age, Prox1-positive cells gradually disappeared from the papillary tip, and remained in the initial part of inner medulla after 21 days. In this transforming area, no Prox1 was observed in cells undergoing apoptosis but was expressed strongly in the remaining cells, which differentiated into ascending thin limb epithelial cells. In vitro and in vivo approaches showed that Prox1 expression increases where the osmolality is near optimal range, but decreases at below- or above-optimal ranges. Renal hypoosmolality induced by furosemide (NKCC2 inhibitor) inhibited Prox1 expression and delayed maturation of the ascending limb of Henle's loop. Together, these studies suggest that Prox1 appears to be a critical stage specific regulator of specifying ascending thin limb cell fate and that its expression is regulated by osmolality.

Introduction: In this study, we aimed to comparatively analyse the indicators of availability to orphan drugs in South Korea, the United States of America, Europe Union, and Japan.Methods: For 169 drugs designated as orphan drugs in South Korea between 2012 and 2021, information on the drugs designated as orphan drugs from each jurisdiction was extracted by country. Then, the availability indicators (approval time, drug lag time, and designation gap) were analysed for the drugs approved in each jurisdiction.Results: The approval rate of drugs designated as orphan drugs were 11.22% and 6.31% in the USA and EU, respectively, which was lower than that of orphan drugs in South Korea and Japan. The highest number of approved drugs was in the USA (87 drugs), EU 27 drugs, Japan 22 drugs and Korea 21 drugs. Furthermore, the approval time significantly differed between South Korea and the other countries. South Korea had a significantly different drug lag time and designation gap compared with the USA and EU.Conclusion: Our findings show that to fundamentally improve the access to treatments for rare disease, a policy of regulatory science that can comprehensively support the early stages of research and development and commercialisation is needed.

Abstract Background Immune checkpoint inhibitor (ICI) or irinotecan-based chemotherapy is frequently used after failure of second-line paclitaxel plus ramucirumab treatment for patients with locally advanced unresectable or metastatic advanced gastric cancer (AGC). This study aimed to compare the efficacy between ICI and irinotecan-based chemotherapy as third-line treatment in patients with AGC. Methods We retrospectively reviewed patients with AGC, whose third-line treatment started between July 2019 and June 2021 at 17 institutions in Korea. The ICI group included patients who received nivolumab or pembrolizumab, and the irinotecan-based chemotherapy group included patients who received irinotecan or FOLFIRI (5-fluorouracil, leucovorin and irinotecan). Results A total of 363 patients [n = 129 (ICI) and n = 234 (irinotecan-based chemotherapy)] were analyzed. The median progression-free survival was 2.3 and 2.9 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.802). The median overall survival (OS) was 5.5 and 6.0 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.786). For all patients included in this study, multivariable analysis showed that weight loss, peritoneal metastasis, low serum sodium or albumin, and short duration of second-line treatment were associated with inferior OS (p

Oxidative stress caused by reactive oxygen species (ROS) is one of the major causes of senescence. Strategies to reduce ROS are known to be important factors in reversing senescence, but effective strategies have not been found. In this study, we screened substances commonly used as cosmetic additives to find substances with antioxidant effects. Polygonum cuspidatum (P. cuspidatum) extract significantly reduced ROS levels in senescent cells. A novel mechanism was discovered in which P. cuspidatum extract reduced ROS, a byproduct of inefficient oxidative phosphorylation (OXPHOS), by increasing OXPHOS efficiency. The reduction in ROS by P. cuspidatum extract restored senescence-associated phenotypes and enhanced skin protection. Then, we identified polydatin as the active ingredient of P. cuspidatum extract that exhibited antioxidant effects. Polydatin, which contains stilbenoid polyphenols that act as singlet oxygen scavengers through redox reactions, increased OXPHOS efficiency and subsequently restored senescence-associated phenotypes. In summary, our data confirmed the effects of P. cuspidatum extract on senescence rejuvenation and skin protection through ROS reduction. This novel finding may be used as a treatment in senescence rejuvenation in clinical and cosmetic fields.

IntroductionThe long-term effects of fenestration in patients with Fontan circulation remain unclear. We aim to evaluate the fenestration impact on early and late outcomes in patients with extracardiac Fontan (ECF) using a propensity score matching analysis.MethodsWe performed an extensive retrospective multicenter clinical data review of the Korean Fontan registry and included 1,233 patients with surgical ECF (779 fenestrated, 454 non-fenestrated). Demographics, baseline, and follow-up data were collected and comprehensively analyzed. Patients were divided into two groups according to the baseline presence or absence of surgical fenestration. Subsequently, patients were sub-divided according to the fenestration status at the last follow-up. Propensity-score matching was performed to account for collected data between the 2 groups using a multistep approach. The primary outcomes were survival and freedom from Fontan failure (FFF). We also looked at postoperative hemodynamics, cardiopulmonary exercise test results, oxygen saturations, and functional status.ResultsAfter propensity-score matching (454 matched pairs), there was no difference in survival or FFF between the 2 groups. However, ECF patients with baseline fenestration had significantly lower oxygen saturation (p = 0.001) and lower functional status (p

Primary ovarian insufficiency (POI) can lead to menstrual disturbance, resulting in ovarian dysfunction before age 40. Prevalence of POI is usually less than 1%; however, ethnicity or population characteristics may affect prevalence. POI is a heterogeneous disease that results from abnormalities in immunological and hormonal factors. Genetic factors can also contribute to POI. Here, we examine FSHR, ESR1, and BMP15 polymorphisms in patients with POI, and controls. We examined a hormonal gene that is important for pregnancy, follicle-stimulating hormone receptor (FSHR), as well as estrogen receptor 1 (ESR1), and associated it with FSHR expression, ovulation rate, and bone morphogenetic protein 15 (BMP15). We examined 139 Korean patients under age 40 with POI, and 350 Korean control participants without POI. Genotyping was performed by a polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) and TaqMan assays. Each identified genotype was subjected to statistical analysis to determine the odds ratios (ORs) and 95% confidence intervals (CIs). In combination genotype analyses, FSHR rs6165 A > G combined with ESR1 rs9340799 A > G, AG/GG (OR: 5.693; 95% CI: 1.088–29.792), as well as FSHR rs6166 A > G combined with ESR1 rs9340799 C > T, AG/GG (OR: 5.940; 95% CI: 1.134–31.131), were significantly associated with POI prevalence. Furthermore, an FSHR rs6165 A > G and BMP rs17003221 C > T, AG/CC combination was associated with POI prevalence (OR: 1.874; 95% CI: (1.059–3.316; p-value: 0.031)). In meta-analysis, FSHR rs6165 AA vs. AG + GG is associated with POI (p = 0.0013), and ESR1 rs2234693 AA vs. AG + GG is also associated with POI (p = 0.0101). Here, we compared the genotypes of FSHR, ESR1, and BMP15 in patients with POI, and controls. We found significant differences in genotype combinations between polymorphisms in FSHR and other genes. Through meta-analysis, we found that ESR1 rs9340799 and rs2234693 are associated with POI prevalence, and that BMP15 rs17003221 increases POI risk. These findings help to improve POI diagnosis in Korean women.

Idiopathic recurrent pregnancy loss (RPL) is defined as at least two pregnancy losses before 20 weeks of gestation. Approximately 5% of pregnant couples experience idiopathic RPL, which is a heterogeneous disease with various causes including hormonal, chromosomal, and intrauterine abnormalities. Although how pregnancy loss occurs is still unknown, numerous biological factors are associated with the incidence of pregnancy loss, including genetic variants. Whole-exome sequencing (WES) was conducted on blood samples from 56 Korean patients with RPL and 40 healthy controls. The WES data were aligned by means of bioinformatic analysis, and the detected variants were annotated using machine learning tools to predict the pathogenicity of protein alterations. Each indicated variant was confirmed using Sanger sequencing. A replication study was also conducted in 112 patients and 114 controls. The Variant Effect Scoring Tool, Combined Annotation Dependent Depletion tool, Sorting Intolerant from Tolerant annotation tool, and various databases detected 10 potential variants previously associated with spontaneous abortion genes in patients by means of a bioinformatic analysis of WES data. Several variants were detected in more than one patient. Interestingly, several of the detected genes were functionally clustered, including some with a secretory function (mucin 4; MUC4; rs200737893 G>A and hyaluronan-binding protein 2; HABP2; rs542838125 G>T), in which growth arrest-specific 2 Like 2 (GAS2L2; rs140842796 C>T) and dynamin 2 (DNM2; rs763894364 G>A) are functionally associated with cell protrusion and the cytoskeleton. ATP Binding Cassette Subfamily C Member 6 (ABCC6) was the only gene with two variants. HABP2 (rs542838125 G>T), MUC4 (rs200737893 G>A), and GAS2L2 (rs140842796 C>T) were detected in only the patient group in the replication study. The combination of WES and machine learning tools is a useful method to detect potential variants associated with RPL. Using bioinformatic tools, we found 10 potential variants in 9 genes. WES data from patients are needed to better understand the causes of RPL.

(1) Background: Oxidative stress adversely affects fertility by impairing oocyte fertilization potential, primarily due to meiotic segregation errors and cohesion loss. Superoxide dismutase (SOD) and Coenzyme Q10 (CoQ10) are prominent antioxidants known to mitigate oxidative damage. (2) Methods: This study recruited 86 patients undergoing in vitro fertilization (IVF) at a single center for a 12-week, randomized, double-blind, active-comparator-controlled trial. Participants were allocated into two groups: one receiving CoQ10 as an antioxidant (the CoQ10 group) and the other receiving GF Bacillus antioxidative enzyme SOD (the GF101 group). The primary endpoints were changes in serum oxidative markers (SOD and catalase) and IVF outcomes, including clinical pregnancy, miscarriage, and live birth rates. Follicular fluid (FF) SOD and catalase concentrations on the day of retrieval, the metaphase II (MII) oocyte rate, the fertilization rate, and lipid profiles were measured. (3) Results: Initially, 86 patients were enrolled, with 65 completing the protocol (30 in the GF101 group and 34 in the CoQ10 group). There were no significant differences between the GF101 and CoQ10 groups in serum SOD (p = 0.626) and catalase levels (p = 0.061) over 12 weeks. However, within the GF101 group, a significant increase in serum catalase from baseline to 12 weeks was observed (p = 0.004). The non-inferiority analysis for IVF outcomes indicated risk differences in the clinical pregnancy rate, live birth rate, and miscarriage rate of −6.27% (95% CI: −30.77% to 18.22%), −1.18% (95% CI: −25.28% to 22.93%), and −13.49% (95% CI: −41.14% to 14.15%), respectively, demonstrating non-inferiority for the GF101 group. Furthermore, the GF101 group experienced significant reductions in total cholesterol (p = 0.006) and low-density lipoprotein (LDL) levels (p = 0.009) in intra-group comparisons, with both groups exhibiting comparable safe profiles. (4) Conclusions: GF101 may be non-inferior to CoQ10 in treating infertility in women and potentially offers additional benefits for women with dyslipidemia.

Background and Aims: Time-lapse technology is an emerging assisted reproductive technology (ART) that enables simultaneous culture and monitoring of embryos in vitro during their development. It provides extra information on key events during embryo development, which can assist embryologists in selecting embryos alongside traditional morphology evaluations. Various imaging technologies have been utilised to visualise and evaluate embryos such as brightfield microscopy, darkfield microscopy, and Hoffman modulation contrast microscopy. Although these imaging technologies allow for non-invasive imaging of human embryos in a clinical setting, 3D imaging of a whole embryo with subcellular resolution remains a challenge. Method: We demonstrate 3D time-lapse label-free imaging of live mouse embryos using the 3D refractive index (RI) imaging technique. The proposed method is a quantitative phase imaging technique that measures multiple-intensity images of transmitted light through the embryos via axial scanning to reconstruct the 3D RI map of the embryos. Results: Using the proposed method, live mouse embryos were monitored at different developmental stages, ranging from 2-cell embryos to expanded blastocysts. The measured 3D RI maps of the developing embryos reveal 3D landscape of subcellular features inside the embryos (Fig. 1). In the quantitative assessment of embryonic development, various morphokinematic parameters were extracted from the measured 3D RI maps of the embryos. Conclusion: Based on the results, we envision that our method has broad applications where non-invasive and quantitative assessment of embryonic development is required.

Addressing fertility challenges, particularly those stemming from advancing maternal age, requires innovative and effective solutions. This presentation navigates the frontier of ovarian rejuvenation for diminished ovarian reserve, examining whether it remains a myth or emerges as a promising reality. The lecture offers a comprehensive review of various ovarian rejuvenation technologies available today. It will investigate the clinical studies, accumulated evidence, and overall clinical utility, creating a foundation for understanding the effectiveness and limitations of each approach. A significant portion will be dedicated to the role and potential of Platelet-Rich Plasma (PRP) treatments in ovarian rejuvenation. This segment will include clinical study data and firsthand experiences, providing a practical perspective on PRP application. Further, an exploration into the basic research that supports PRP usage will be presented. This knowledge illuminates how PRP might influence the ovarian environment and potentially restore ovarian function. In conclusion, the lecture aims to initiate dialogue on ovarian rejuvenation and rehabilitation as alternative treatment strategies for patients contending with diminished ovarian reserve. Through this exploration, the presentation hopes to offer insights into the current landscape of fertility treatments in women with diminished ovarian reserve.

The growing prevalence of in vitro fertilization-embryo transfer procedures has resulted in an increased incidence of recurrent implantation failure (RIF), necessitating focused research in this area. STAT3, a key factor in maternal endometrial remodeling and stromal proliferation, is crucial for successful embryo implantation. While the relationship between STAT3 and RIF has been studied, the impact of single nucleotide polymorphisms (SNPs) in miRNAs, well-characterized gene expression modulators, on STAT3 in RIF cases remains uncharacterized. Here, we investigated 161 RIF patients and 268 healthy control subjects in the Korean population, analyzing the statistical association between miRNA genetic variants and RIF risk. We aimed to determine whether SNPs in specific miRNAs, namely miR-218-2 rs11134527 G>A, miR-34a rs2666433 G>A, miR-34a rs6577555 C>A, and miR-130a rs731384 G>A, were significantly associated with RIF risk. We identified a significant association between miR-34a rs6577555 C>A and RIF prevalence (implantation failure [IF] ≥ 2: adjusted odds ratio [AOR] = 2.264, 95% CI = 1.007–5.092, p = 0.048). These findings suggest that miR-34a rs6577555 C>A may contribute to an increased susceptibility to RIF. However, further investigations are necessary to elucidate the precise mechanisms underlying the role of miR-34a rs6577555 C>A in RIF. This study sheds light on the genetic and molecular factors underlying RIF, offering new avenues for research and potential advancements in the diagnosis and treatment of this complex condition.

Purpose Peritoneal carcinomatosis (PC) has been considered a terminal condition and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIEPC) is regarded as an alternative therapeutic option. This study aimed to evaluate the 30-day clinical outcomes of CRS/HIPEC and the feasibility of the surgery by investigating the morbidity and mortality in Inje University Hospital. Methods Data were retrospectively collected from 19 patients with PC who underwent CRS/HIPEC at Inje University Hospital in 2018. We evaluated pre-, intra-operative parameters and postoperative clinical outcomes and early complications. Results The mean operating time was 506.95 minutes and the mean blood loss was 837.11 mL. Six cases (31.58%) had morbidity of grade III or above. A longer operating time (≥560 minutes, P=0.038) and large blood loss (≥700 mL, P=0.060) were positively correlated with grade III or worse postoperative complications. Conclusion Our early experience with CRS/HIPEC resulted in a 31.58% morbidity rate of grade III and above, with risk factors being longer operating time and greater intraoperative blood loss. As the surgical team’s skills improve, a shorter operating time with less intraoperative blood loss could result in better short-term outcomes of CRS/HIPEC.