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Abstract Background Ankylosing spondylitis (AS) has been known to have auto-inflammatory nature; hence, the efficacy of autoantibodies is low. However, studies on autoantibodies are ongoing, with some studies showing associations. Previous studies showed that anti-protein phosphatase magnesium-dependent 1A (PPM1A) IgG was increased in patients with AS and associated with radiographic progression. However, the diagnostic usefulness was limited due to relatively low sensitivity and specificity. This pilot study evaluated the diagnostic utility of anti-PPM1A-IgM and anti-PPM1A-IgG in patients with active AS. Methods Serum samples were obtained from the registry cohort of a single tertiary center in Korea. Serum levels of anti-PPM1A-IgG/IgM were measured by direct ELISA. Receiver operating characteristic (ROC) analysis was used to predict the diagnostic sensitivity and specificity of serum anti-PPM1A-IgG/IgM. Results Samples were collected from 28 patients with active AS, 16 healthy controls (HCs), and 28 patients with rheumatoid arthritis (RA). Although total serum IgM was lower in the RA and AS groups than in the HC group, anti-PPM1A-IgM was significantly lower in the AS group than in the other groups. In evaluating the diagnostic utility of anti-PPM1A-IgG/IgM for AS patients compared with HCs, the area under the curve (AUC) of anti-PPM1A-IgM was 0.998 (sensitivity 96.4%, specificity 100.0%). When ROC analysis of anti-PPM1A-IgM for AS patients compared with RA patients was conducted, sensitivity was 78.6% and specificity was 71.4%, with an AUC of 0.839. Conclusion Decreased anti-PPM1A-IgM levels in AS patients suggests a potential role for anti-PPM1A-IgM in the diagnosis of active AS.

AbstractDissolved organic carbon (DOC) in soils is released into streams, working as a main component of the carbon cycle. DOC in terrestrial and aquatic ecosystems participates in many biogeochemical reactions and processes such as heterotrophic respiration, sorption of metals, and transport of pollutants. In order to understand the connectivity of organic carbon among soil, soil water, and forest streams, we investigated the concentrations and dual carbon isotope ratios (δ13C and Δ14C) of soil organic carbon (SOC) and water-extractable organic carbon (WEOC) obtained from soils beneath two tree species stands, and compared these with stream Δ14C-DOC of the forest watershed. Soil samples were collected at different depths (0–10, 10–30, and 30–50 cm) beneath Japanese cedar (Cryptomeria japonica) and sawtooth oak (Quercus acutissima). Although the SOC concentration was not significantly different between the two tree species, the WEOC concentration ([WEOC]) of soil at 0–10 cm depth under Cryptomeria japonica was higher than that of Quercus acutissima, in general. The δ13C-SOC and δ13C-WEOC increased, while the Δ14C-SOC and Δ14C-WEOC decreased with increasing soil depth. The Δ14C-WEOC was higher than the Δ14C-SOC, indicating that WEOC could be primarily derived from the young, hydrophilic, and exchangeable fraction of SOC, rather than from SOC strongly bonded to mineral soils. However, the stream Δ14C-DOC was lower than Δ14C-WEOC in general, except during summer storms. The 14C-depleted DOC released from deep soils or groundwater might lower Δ14C-DOC of a stream, suggesting that relatively old DOC could be released into streams during baseflow. This is contrary to the results of previous studies that have reported positive stream Δ14C-DOC from temperate forests. The discrepancy warrants future research on forest stream Δ14C-DOC across entire seasons, particularly under Asian monsoon climates.

Abstract Over the past few decades, research on life in space has increased. Owing to the expensive nature of and the challenges associated with conducting experiments in real space, clinostats, which continuously randomize the gravity vector by using motors, have been used to generate simulated microgravity (SMG) on Earth. Herein, by using a 3D printing method, we develop a customized small-sized clinostat (CS clinostat) that is easy to manufacture, inexpensive, and robust. Moreover, we develop and fabricate a gas-permeable polydimethylsiloxane culture dish that fits inside the CS clinostat. To validate SMG generation, ovarian cancer cells (OV- 90, TOV-21G, and Caov-3) were applied to demonstrate a significant reduction in caveolin-1 expression, a biomarker of SMG, indicating SMG generation. The proposed CS clinostat system has good accessibility for SMG research, which makes it useful as a tool for biologists, who are unfamiliar with conventional clinostat equipment, to conduct preliminary studies in the space environment.

Abstract Atmospheric particulate matter (PM2.5) can damage human health. Biogenic organic compounds emitted from trees may increase the concentration of PM2.5 via formation of secondary aerosols. Therefore, the role of biogenic emissions in PM2.5 formation and the sources of PM2.5 need to be investigated. Dual carbon isotope and levoglucosan analyses are powerful tools to track the sources of total carbon (TC) in PM2.5. We collected a total of 47 PM2.5 samples from 2019 to 2020 inside a pine forest and in urban areas in South Korea. The average δ13C and Δ14C of TC in PM2.5 at the Taehwa Research Forest (TRF) were − 25.7 and − 380.7‰, respectively, which were not significantly different from those collected at Seoul National University (SNU) in urban areas. Contribution of fossil fuel, C3-, and C4- plants to carbonaceous component of PM2.5 were 52, 27, and 21% at SNU, whereas those were 46, 35, and 19% at TRF, respectively. The biomass burning tracer, levoglucosan, was most abundant in winter and correlated with the contribution of C4 plants derived carbon. Results indicate that biogenic aerosols emitted from trees is less likely to be an important source of PM2.5 and that trees can act as a bio-filter to reduce PM2.5.

Eco-friendly consumption is important for solving climate crisis and moving humanity toward a better future. However, few consumers are willing to pay premiums for eco-friendly products. We investigated the psychological and neural factors that can increase eco-friendly consumption. We propose an experience of awe, in which the individual self is temporarily attenuated as the importance of beings other than oneself increases. Behavioral (Study 1) and functional magnetic resonance imaging (fMRI; Study 2) experiments were conducted to explore the awe mechanisms through which climate crisis messages lead to eco-friendly consumption. In Study 1, we found participants felt awe when exposed to climate crisis messages, and their choice of eco-friendly consumption increased. In Study 2, we found that when individuals were exposed to messages depicting the climate crisis (as opposed to a control stimulus), their brains exhibited a lower level of activation in the self-awareness processing and a higher level of activation in external attention processing areas. These results suggest that the awe experience plays an important role in promoting eco-friendly consumption. Marketing must evolve from satisfying basic individual needs to a high level for the well-being of humanity, the planet, and the biosphere. This study sheds light on our understanding of human perceptions of the climate crisis and suggests an effective communication strategy to increase individuals’ eco-friendly actions.

Abstract Background The intra-abdominal cavity, surrounded by adipocytes, is the main metastatic site of epithelial ovarian, fallopian tube, and peritoneal cancer. Epidemiological and molecular studies have demonstrated a link between adipose tissue and ovarian cancer. However, the clinical significance of fatty tissue has not been elucidated. Thus, we investigated the clinical significance of body composition in patients with epithelial ovarian, fallopian tube, and peritoneal cancer. Methods Fat and skeletal muscle areas were measured using software based on pretreatment computed tomography scans at the third lumbar vertebra. Fat-to-muscle ratios were calculated using the total (visceral and subcutaneous) fat area or visceral fat area. High fat-to-muscle ratios were defined by values greater than the mean. Sarcopenia was defined as a skeletal muscle index < 38.7 cm2/m2. The clinicopathological parameters and survival of 153 patients were analyzed. Results High visceral fat-to-muscle ratios and sarcopenia at the time of diagnosis were observed in 43.8% and 33.3% of the patients, respectively. Multivariate analysis showed that high visceral fat-to-muscle ratio (p = 0.014), advanced Federation of Gynecology and Obstetrics stage (p = 0.008), and chemoresistance (p = 0.027) were independent factors for worse overall survival. Patients with high visceral fat-to-muscle ratios were older, had higher body mass indexes, and were more likely to have diabetes/hypertension, serous cancer subtypes, and implementation of neoadjuvant chemotherapy than those with low visceral fat-to-muscle ratios. The platelet count was significantly higher in the high visceral fat-to-muscle ratio group than in the low visceral fat-to-muscle ratio group (p = 0.011). Conclusions Pretreatment visceral fat area could be an independent predictive factor of overall survival in patients with epithelial ovarian, fallopian tube, and peritoneal cancer and may be significantly associated with thrombocytosis.

Abstract Background A gut–muscle axis through which the microbiome influences skeletal muscle has been hypothesized. However, sex‐specific association between the characteristics of gut microbiota and skeletal muscle mass has not yet been reported. Herein, we performed sex‐specific analyses of faecal microbiota composition for the skeletal muscle mass in a population‐based cohort. Methods We collected faecal samples of 1052 middle‐aged participants (621 men and 431 women) who attended health screenings, and we analysed the intestinal microbiota using 16S rRNA gene sequencing. Relative muscle mass was calculated using a bioelectrical impedance analysis and presented as the skeletal muscle mass index [SMI (%) = total appendicular muscle mass (kg)/weight (kg) × 100]. We categorized the subjects into four groups by the quartile of the SMI. Association tests between gut microbiota and SMI were conducted according to the microbial diversity, taxonomic profiling and functional inference in a sex‐stratified manner. Results The mean age and SMI of the total participants were 44.8 years (standard deviation [SD], 8.2) and 41.4% (SD, 3.9), respectively. After adjustments for possible covariates such as age, body mass index and regular physical activity, the highest quartile (Q4) group of SMI had higher alpha diversity than the lowest quartile (Q1) group in male participants (coefficient = 10.79, P 0.05). Conclusions In this large sample of middle‐aged individuals, this study highlights fundamental sex‐specific differences in the microbial diversity, composition and metabolic pathways inferred from gut microbiota according to SMI. The gut microbiota may provide novel insights into the potential mechanisms underlying the sex dependence of skeletal muscle mass.

Abstract Dissolved organic carbon (DOC) in throughfall plays a vital role in providing carbon and energy to organisms in forests. We utilized carbon isotope analysis to allocate the sources of throughfall DOC, including leaching from plant tissues, PM2.5 deposition on plant foliage, and precipitation. Rainwater, PM2.5, and throughfall samples were collected from pine and oak forests between March and November 2021. The mean concentration of throughfall DOC was 7.9 mg L−1, approximately six times higher than that of rainfall. The mean Δ14C of throughfall DOC was −38.2‰, ∼200‰ higher than that of rainwater or PM2.5. Mass balance estimates revealed that canopy leaching contributed to ∼83% of throughfall DOC, while desorption of PM2.5 and rainwater accounted for only ∼3% and ∼14% of throughfall DOC, respectively. These results clearly highlight canopy leaching as the primary source of carbon input to the forest floor, with a relatively minor contribution from PM2.5 desorption on leaves.

BackgroundTo evaluate the usefulness of urine SERPINC1 and ORM1 as biomarkers for early detection of lupus nephritis (LN).MethodsUsing proteomics, we screened for potential urine biomarkers that differentiate LN from systemic lupus erythematosus (SLE) patients without nephritis. In addition, urine levels of target biomarkers were measured by ELISA in 13- and 23-week-old MRL-lpr (murine model for LN) and MRL/MpJ mice. Histological analysis was also performed on the kidneys of 23-week-old mice.ResultsUrine SERPINC1 and ORM1 were elevated in SLE patients with newly diagnosed LN compared with SLE patients without LN (SERPINC1, AUC=.892, P

Loneliness is a major risk factor for morbidity and mortality. However, the effect of loneliness on subsequent prosocial behavior is not well known. Understanding the neurobiological mechanisms underlying loneliness is necessary to address this research gap. We investigate the mechanism using a modified public goods game (PGG) wherein participants can choose to act for a collective or selfish interest after being exposed to loneliness cues. Both behavioral (Study 1) and event-related potential (ERP) (Study 2) measures were used to explore this relationship. In Study 1 (N = 131), we found that participants exhibited decreased prosocial actions under the loneliness priming condition as opposed to the control condition. In Study 2 (N = 17), frontal N400 and posterior P300 components were identified under the loneliness priming condition as opposed to the control condition. Increased (decreased) frontal N400 and posterior P300 lead to selfish (prosocial) choices. These results indicate that humans instinctively perceive loneliness as inconsistency with their desired social-relational life, which in turn stimulates coping strategies for self-preservation. This study contributes to our understanding of the neurobiological basis of loneliness associated with prosocial behavior.

Nicotine, an abundant molecule in tobacco, has immunomodulatory effects on inflammatory diseases, primarily due to the activation of alpha7 nicotinic acetylcholine receptor (α7 nAChR). We aim to evaluate the expression of the α7 nAChR+ cells in joint tissue and the effect of smoking on immune cells and peripheral arthritis in curdlan-administered SKG mice, a murine model of spondyloarthropathy (SpA). The SKG mice were injected with curdlan two times at 2-week intervals and were divided into two groups; one exposed to cigarette smoke and the other not exposed. We found that the α7 nAChR+ cells increased in the joint tissue of curdlan-administered SKG mice compared to in the wild type. Furthermore, the peripheral arthritis scores and histological scores for synovial inflammation were lower in smoke-exposed curdlan-administered SKG mice than in mice not exposed to smoke. Immunofluorescence staining of the α7 nAChR+ and IL-17A+ cells was lower in the synovia of smoke-exposed mice than the control mice. The proportions of α7 nAChR+IL-17A+ and α7 nAChR+IL-17A+FOXP3+ cells also decreased in the synovia of smoke-exposed mice compared with the controls. We observed an increase in the α7 nAChR+ cells within the joint tissue of curdlan-administered SKG mice and that cigarette smoke had an influence on both peripheral arthritis and immune cell population, especially α7 nAChR+ cells. Thus, exposure to cigarette smoke after arthritogenic stimuli may have an anti-arthritogenic effect in curdlan-administered SKG mice.

Abstract Preterm birth affects approximately 5% to 7% of live births worldwide and is the leading cause of neonatal morbidity and mortality. Amniotic fluid supernatant (AFS) contains abundant cell-free nucleic acids (cfNAs) that can provide genetic information associated with pregnancy complications. In the current study, cfNAs of AFS in the early second-trimester before the onset of symptoms of preterm birth were analyzed, and we compared gene expression levels between spontaneous preterm birth (n = 5) and term birth (n = 5) groups using sequencing analysis. Differential expression analyses detected 24 genes with increased and 6 genes with decreased expression in the preterm birth group compared to term birth. Upregulated expressions of RDH14, ZNF572, VOPP1, SERPINA12, and TCF15 were validated in an extended AFS sample by quantitative PCR (preterm birth group, n = 21; term birth group, n = 40). Five candidate genes displayed a significant increase in mRNA expression in immortalized trophoblast HTR-8/SVneo cell with H2O2 treatment. Moreover, the expression of five candidate genes was increased to more than twofold by pretreatment with lipopolysaccharide in HTR-8/SVneo cells. Changes in gene expression between preterm birth and term birth is strongly correlated with oxidative stress and infection during pregnancy. Specific expression patterns of genes could be used as potential markers for the early identification of women at risk of having a spontaneous preterm birth.

Abstract Background Endometrial cancer is often the sentinel cancer in women with Lynch syndrome, among which endometrioid endometrial cancer is the most common. We found a Korean case of uterine carcinosarcoma associated with Lynch syndrome. And we reviewed 27 Korean women with endometrial cancer associated with Lynch syndrome already released in case report so far. Case presentation The proband, a 45-year-old Korean woman received treatment for endometrioid adenocarcinoma. Her older sister and niece were treated for endometrioid adenocarcinoma and carcinosarcoma, respectively. Family history met the Amsterdam II criteria and immunohistochemical analysis revealed a loss of MLH1 and PMS2. They all harbored a previously unreported germline likely pathogenic variant in c.1367delC in MLH1. They underwent staging operations including total hysterectomy, bilateral salpingo-oophorectomy, pelvic/paraaortic lymph node dissection, and washing cytology. All three women were healthy without evidence of relapse for over 4 years. Conclusion This report indicates a novel germline c.1367delC variant in MLH1, and presents a Korean case of uterine carcinosarcoma associated with Lynch syndrome. Furthermore, the c.1757_1758insC variant in MLH1 was suggested as a founder mutation in Lynch syndrome in Korean women.

Ovarian clear cell carcinoma (OCCC) reportedly develops from endometriosis. However, the molecular mechanism underlying its malignant progression to OCCC remains elusive. This study aimed to identify an essential gene in the malignant transformation of endometriosis to OCCC. We performed RNA sequencing in formalin‐fixed, paraffin‐embedded (FFPE) tissues of endometriosis (n = 9), atypical endometriosis (AtyEm) (n = 18), adjacent endometriosis to OCCC (AdjEm) (n = 7), and OCCC (n = 17). We found that tetraspanin 1 (TSPAN1) mRNA level was significantly increased by 2.4‐ (DESeq2) and 3.4‐fold (edgeR) in AtyEm and by 80.7‐ (DESeq2) and 101‐fold (edgeR) in OCCC relative to endometriosis. We confirmed that TSPAN1 protein level was similarly overexpressed in OCCC tissues and cell lines. In immortalized endometriosis cell lines, TSPAN1 overexpression enhanced cell growth and invasion. Mechanistically, TSPAN1 triggered AMP‐activated protein kinase (AMPK) activity, promoting endometriosis and cell growth. Upregulated levels of TSPAN1 are considered an early event in the development of high‐risk endometriosis that could progress to ovarian cancer. Our study suggests the potential of TSPAN1 as a screening candidate for high‐risk endometriosis.

Abstract Background Ankylosing spondylitis (AS) is characteristically male-predominant, and progressive spinal ankylosis affects male patients more severely; however, the hormonal effects in males with AS are poorly understood. Methods In the present study, the regulatory effects of dutasteride, a 5-α reductase inhibitor that blocks the conversion of testosterone to dihydrotestosterone (DHT), were examined in curdlan-administered male SKG mice to determine spinal bone formation, bone metabolism-related markers, and interleukin (IL)-17A cytokine and T cell populations. In addition, the effects of DHT on primary osteoprogenitors from the facet joints of AS patients were assessed based on osteoblast-related parameters. DHT level was measured, and the correlation with modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) was analyzed in AS patients. Results In curdlan-administered SKG mice, dutasteride treatment resulted in an increased accumulation of hydroxyapatite in the spine which was positively correlated with serum IL-17A levels. In the analysis of bone metabolism-related molecules, a decrease in sclerostin levels was observed in the sera in the dutasteride group. Continuous exposure to DHT resulted in fewer calcium deposits in AS osteoprogenitors during osteoblast differentiation. DHT-treated AS osteoprogenitors showed decreased osteocalcin and increased DKK1 and SOST1 mRNA expression, supporting the results of the in vivo experiments. Treatment with dutasteride upregulated bone formation in the spine of curdlan-administered SKG mice and DHT treatment downregulated osteoblast differentiation in vitro. Conclusions Treatment with dutasteride affected the bone formation in the spine of curdlan-treated SKG mice, and DHT treatment attenuated osteoblast differentiation in vitro. Therefore, contrary to what could be expected if osteoblasts contributed to spinal ankylosis, DHT inhibition might increase rather than decrease the progression of spinal ankylosis despite the higher levels of DHT observed in many AS patients.

Purpose Single-port laparoscopic techniques can be optimized with confined incisions. This approach has an intraoperative advantage of excellent visualization of the correct intestinal segment for exteriorization, along with direct visual control of the extraction to avoid twisting. However, only a few studies have verified the efficacy of the technique. Thus, this study assessed the results of single-port laparoscopic stoma creation for fecal diversion, specifically focusing on feasibility, safety, and efficacy. Methods Patients who underwent single-incision enterostomy performed by a single surgeon were included. Data on demographics, indications for and chosen procedure, and operation results were retrospectively collected and analyzed. Results Between April 2015 and January 2018, a total of 13 patients (8 males, 5 females) with a mean age of 57.7 years (range, 41–83 years) underwent single-port ileostomy creation. The most common reason for diversion was palliative ileostomy for colon obstruction or fistula from peritoneal malignancy (n = 12), followed by colonic fistula with necrotizing pancreatitis (n = 1). There were no cases of conversion to open or multiport laparoscopic surgery. The mean operative time was 54 minutes (range, 37–118 minutes), and the median length of hospital stay was 8 days (range, 2–211 days). A postoperative complication, aspiration pneumonia, was documented in 1 patient and treated conservatively. The mean duration of bowel movement was 0.7 days (range, 0–4 days). All stomas had good function, and there was no 30-day mortality. Conclusion Single-port laparoscopic ileostomy in patients with a palliative setting could be a safe and feasible option for fecal diversion.

Aim To evaluate the safety and efficacy of a radiofrequency ablation system with a novel endometrial tip (RFA-EMT) for the management of heavy menstrual bleeding (HMB) or abnormal uterine bleeding (AUB). Methods This is a prospective study including a total of 38 premenopausal women with heavy menstrual bleeding (HMB) or abnormal uterine bleeding (AUB) that failed to respond to medical therapy. Hysteroscopic evaluation and curettage biopsy were performed just before the procedure. The procedure was timed to occur during the early proliferative phase (cycle days 4–10). RFA-EMT procedures were performed by a single surgeon with the patient under general anesthesia with a laryngeal mask airway. Primary outcome was reduction in bleeding, reported as amenorrhea, hypomenorrhea, and eumenorrhea, which were measured via hemoglobin level and pictorial blood assessment chart (PBAC) score. Secondary outcomes were adverse events, dysmenorrhea with numeric rating scale (NRS) score, and endometrial thickening in the early proliferative phase, as assessed by transvaginal ultrasonography. Results There were no peri- or post-procedural complications. Combined amenorrhea, hypomenorrhea, and eumenorrhea rates at 3 and 6 months were 97.4% and 100%, respectively. The hemoglobin level was significantly increased, and the PBAC score, NRS score, and endometrial thickening were significantly decreased after 3 months. These trends were maintained for 6 months after the procedure. Conclusion RFA-EMT, a new technique, is safe and effective for women with HMB or AUB for which medical therapy has failed.

Abstract Background The prevalence of overactive bladder syndrome (OAB) increases with age. Sleep disturbances in elderly individuals with OAB is a common problem. The purpose of this study was to examine the effects of a biofeedback-based sleep improvement (BBSI) program on urinary symptoms and sleep patterns in elderly Korean women with OAB. Methods A non-equivalent control group pre−/post-test design was used. Elderly women with OAB were assigned to an intervention group (n = 20) or a control group (n = 18). The BBSI program was implemented in the intervention group for 12 weeks, while two educational sessions of general sleep hygiene and lifestyle modification were provided to the control group. Using SPSS 23.0, the data were analyzed by descriptive analysis using the chi-square test, Fisher’s exact test, Mann-Whitney test, and Wilcoxon test. Results After the 12-week BBSI program, significant improvements were found in the intervention group’s the square root of the mean squared differences of successive R-R intervals (p = 0.025), low frequency/high frequency ratio (p = 0.006), and epinephrine (p = 0.039). We also observed a significant difference in urinary symptoms, sleep efficiency, wake after sleep onset, number of awakenings, and number of awakenings within 3 h after sleep onset (p

Cancer: Gene mutation spurs drug resistance Mutations in a gene linked to cancer growth also underpin resistance to a common chemotherapy drug. Hyun Goo Woo and colleagues from Ajou University in Suwon, South Korea, analyzed a large database of genetic information on more than 1,000 human cancer cell lines looking for mutated genes associated with resistance to certain drugs. The top association was between mutated forms of EPHB6, a gene previously linked to tumor invasiveness, and resistance to paclitaxel, a chemotherapy drug used to treat a range of different cancers. They experimentally validated the finding in lung, skin and liver cancer cell lines. The researchers also identified two proteins activated by mutant EPHB6 that promote the cell adhesion responsible for paclitaxel resistance. Inhibiting these two proteins reversed the drug resistance in cells, suggesting the therapeutic value of targeting this pathway.

Purpose: Modulated electro-hyperthermia (mEHT), known as oncothermia, is an anticancer therapy that induces radiofrequency thermal damage to the cancer tissues. This study aimed to evaluate the potential effectiveness of mEHT as a therapeutic tool in ovarian and cervical cancer. Materials and methods: We used both tumor-bearing mice and ovarian and cervical OVCAR-3, SK-OV-3, HeLa and SNU-17 cancer cell lines to investigate the effects of mEHT in vivo and in vitro, respectively, and determine whether it was enhanced by cotreatment with an autophagy inhibitor. Results: We discovered that phosphorylation of p38, a stress-dependent kinase, was induced at the Thr180/Tyr182 residue in cancer cells exposed to mEHT. Apoptotic markers such as cleaved caspase-3 and poly-ADP ribose polymerase (PARP) were increased in OVCAR-3 and SNU-17 cells. Fluorescence-activated cell sorting (FACS) analysis showed a significant increase in the population of sub-G1 mEHT-exposed cells, which are dying and apoptotic cells. mEHT also reduced both weight and volume of xenograft tumors in mice transplanted with ovarian and cervical cancer cells and patient-derived cancer tissues. We determined that mEHT-induced cellular damage recovery was mediated by autophagy and, therefore, expectedly, cotreatment with mEHT and 3-methyladenine (3-MA), an autophagy inhibitor, more effectively inhibited cancer cell growth than individual treatment did. Conclusions: mEHT treatment alone was sufficient to inhibit cancer growth, while a combined treatment with mEHT and an autophagy inhibitor amplified this inhibition effect.

Endometriosis is one of the most common diseases in reproductive ages, and it affects patients' quality of life and fertility. However, few Korean guidelines are available for the evaluation and management of endometriosis. Korean Society of Endometriosis reviewed various literatures and trials, and to provide seventy-one evidence-based recommendations. This review presents guidelines for the diagnosis and management of endometriosis with emphasis on: it's role in infertility, treatment of recurrence, asymptomatic women, endometriosis in adolescents and menopausal women, and possible association of endometriosis with cancer.

Technological advances are bringing autonomous vehicles to the ever-evolving transportation system. Anticipating adoption of these technologies by users is essential to vehicle manufacturers for making more precise production and marketing strategies. The research investigates regulatory focus and consumer innovativeness with consumers" adoption of autonomous vehicles (AVs) and to consumers" subsequent willingness to pay for AVs. An online questionnaire was fielded to confirm predictions, and regression analysis was conducted to verify the model"s validity. The results show that a promotion focus does not have a significantly positive effect on the automation level at which consumers will adopt AVs, but a prevention focus has a significantly positive effect on conditional AV adoption. Consumer innovativeness, consumers’ novelty-seeking have a significantly positive relationship with high and full AV adoption, and consumers’ independent decision-making has a significantly positive effect on full AV adoption. The higher the level of automation at which a consumer adopts AVs, the higher the willingness to pay for them. Finally, using a neural network and decision tree analyses, we show methods with which to describe three categories for potential adopters of AVs.

Cultured meat production is an evolving method of producing animal meat using tissue engineering techniques. Cells, chemical factors, and suitable biomaterials that serve as scaffolds are all essential for the cultivation of muscle tissue. Scaffolding is essential for the development of organized meat products resembling steaks because it provides the mechanical stability needed by cells to attach, differentiate, and mature. In in vivo settings, extracellular matrix (ECM) ensures substrates and scaffolds are provided for cells. The ECM of skeletal muscle (SM) maintains tissue elasticity, creates adhesion points for cells, provides a three-dimensional (3D) environment, and regulates biological processes. Consequently, creating mimics of native ECM is a difficult task. Animal-derived polymers like collagen are often regarded as the gold standard for producing scaffolds with ECM-like properties. Animal-free scaffolds are being investigated as a potential source of stable, chemically defined, low-cost materials for cultured meat production. In this review, we explore the influence of ECM on myogenesis and its role as a scaffold and vital component to improve the efficacy of the culture media used to produce cultured meat.

Acetylated diacylglycerol 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) is a lipid molecule from the antlers of sika deer that might reduce inflammation by effectively controlling neutrophil infiltration, endothelial permeability and inflammatory chemokine production. Therefore, we evaluated the modulatory effect of PLAG on arthritis and interstitial lung disease (ILD) in an autoimmune arthritis model. We injected curdlan into SKG mice and PLAG was orally administered every day from 3 weeks to 20 weeks after the curdlan injection. The arthritis score was measured every week after the curdlan injection. At 20 weeks post-injection, the lung specimens were evaluated with H&E, Masson’s trichrome and multiplexed immunofluorescent staining. Serum cytokines were also analyzed using a Luminex multiple cytokine assay. PLAG administration decreased the arthritis score until 8 weeks after the curdlan injection. However, the effect was not sustained thereafter. A lung histology revealed severe inflammation and fibrosis in the curdlan-induced SKG mice, which was attenuated in the PLAG-treated mice. Furthermore, immunofluorescent staining of the lung tissue showed a GM-CSF+ neutrophil accumulation and a decreased citrullinated histone 3 expression after PLAG treatment. PLAG also downregulated the levels of IL-6 and TNF-α and upregulated the level of sIL-7Rα, an anti-fibrotic molecule. Our results indicate that PLAG might have a preventative effect on ILD development through the resolution of NETosis in the lung.

Abstract: Genetics play a significant role in venous thromboembolism (VTE), yet current clinical laboratory-based testing identifies a known heritable thrombophilia (factor V Leiden, prothrombin gene mutation G20210A, or a deficiency of protein C, protein S, or antithrombin) in only a minority of VTE patients. We hypothesized that a substantial number of VTE patients could have lesser-known thrombophilia mutations. To test this hypothesis, we performed whole-exome sequencing (WES) in 64 patients with VTE, focusing our analysis on a novel 55-gene extended thrombophilia panel that we compiled. Our extended thrombophilia panel identified a probable disease-causing genetic variant or variant of unknown significance in 39 of 64 study patients (60.9%), compared with 6 of 237 control patients without VTE (2.5%) (P < .0001). Clinical laboratory-based thrombophilia testing identified a heritable thrombophilia in only 14 of 54 study patients (25.9%). The majority of WES variants were either associated with thrombosis based on prior reports in the literature or predicted to affect protein structure based on protein modeling performed as part of this study. Variants were found in major thrombophilia genes, various SERPIN genes, and highly conserved areas of other genes with established or potential roles in coagulation or fibrinolysis. Ten patients (15.6%) had >1 variant. Sanger sequencing performed in family members of 4 study patients with and without VTE showed generally concordant results with thrombotic history. WES and extended thrombophilia testing are promising tools for improving our understanding of VTE pathogenesis and identifying inherited thrombophilias.

Human decision-making that involves moral dilemmas is a complex process, as individuals try to adhere to their moral values while their actual decisions can be influenced by several situational constraints. When facing a moral conflict that can bring a gain or loss for a decision-maker but a corresponding loss or gain for others, the decision-maker’s choice of resolution strategy lies in its relating to gain-loss asymmetry by placing greater utility weight on his or her immediate gains and delayed losses. Although many neuroimaging studies have unveiled the neural mechanisms that underlie moral decision-making, little attention has been paid to the temporal dynamics of how a decision-maker assesses utility weights differently for a moral (or adaptive) choice that will bring loss (or gain) to himself (and others) when the outcome will be realized in the near versus distant future. This study identifies the electrophysiological mechanisms of time-dependent assessment in individuals’ moral conflict resolution strategies. Twenty-two participants were given a set of moral dilemmas with time intervals that varied from the near future to the distant future. Participants chose between two conflicting options: a self-interest-seeking immoral choice (adaptive) and a principled moral choice (moral). Event-related potentials (ERPs) were recorded, and movement-related potentials (MRPs) were analyzed by being response-locked to individual moral choices. Behavioral results showed that participants took more time to respond and were more likely to make adaptive choices under the near-future condition. When the participants faced moral dilemmas, their brain waves manifested medial frontal negativity (MFN) at early stage ERP of 200–400 ms, possibly reflecting an internal moral conflict. Participants then exhibited larger late positive potentials (LPP) under the near-future condition. In addition, greater effort in implementing motor preparation was found under the near-future condition than under the distant future condition, as supported by the larger Bereitschaftspotential (BP) in the anterior areas. Our results illustrate the temporal dynamics of the electrophysiological mechanisms that underlie time-dependent assessments in moral decision-making, as human brains discount the decision utility of the moral outcomes that will occur in the distant future.

Objective: Uveitis is the most common extra-articular manifestation of ankylosing spondylitis (AS), for which no diagnostic biomarkers have been identified. This study was conducted to identify biomarker for uveitis in AS.Methods: To identify autoantibodies associated with uveitis in AS, we performed human protein microarray analysis using sera derived from various autoimmune diseases and ELISA analysis of sera derived from AS and rheumatoid arthritis patients. In the curdlan-induced SKG mice model, ophthalmic examination was performed at week 8 post-immunization and histologic examination of the ocular lesions performed at week 16 post-immunization. Serum levels of target antibodies were assessed at various time-points. To evaluate the functional role of specific autoantibodies, an in vitro apoptosis assay using ARPE-19 cells was performed.Results: Reactivity against prefoldin subunit 5 (PFDN5) was identified in AS with uveitis. Levels of anti-PFDN5 antibodies and PFDN5 in sera from AS with uveitis patients were significantly higher than those in AS without uveitis. At week 8, half of curdlan-treated SKG mice developed anterior uveitis, while all of them developed histologically confirmed uveitis at week 16. The levels of anti-PFDN5 antibodies increased over time in the sera of curdlan-treated SKG mice along with increased expression of PFDN5 and apoptosis in the ocular lesions. Knockdown of PFDN5 in ARPE19 cells resulted in increased apoptosis, suggesting a protective role of PFDN5 against cell death in uveitis.Conclusion: AS patients with uveitis have increased levels of anti-PFDN5 antibodies, and our findings suggest that anti-PFDN5 antibodies could provide a biomarker for uveitis in AS.

Pathophysiological background in different phenotypes of nonalcoholic fatty liver disease (NAFLD) remains to be elucidated. The aim was to investigate the association between fecal and blood microbiota profiles and the presence of NAFLD in obese versus lean subjects. Demographic and clinical data were reviewed in 268 health checkup examinees, whose fecal and blood samples were available for microbiota analysis. NAFLD was diagnosed with ultrasonography, and subjects with NAFLD were further categorized as obese (body mass index (BMI) ≥25) or lean (BMI

Type 2 diabetes mellitus (T2DM) is an increasing global public health problem, and its prevalence is expected to rise in coming decades. Dipeptidyl peptidase-4 (DPP-4) is a therapeutic target for the management of T2DM, and its inhibitors prevent the degradation of glucose-dependent insulinotropic peptide and glucagon-like peptide 1, and thus, maintain their endogenous levels and lower blood glucose levels. Various medicinal plant extracts and isolated bioactive compounds exhibit DPP-4 inhibitory activity. In this review, we discussed different natural sources that have been shown to have anti-diabetic efficacy with a particular emphasis on DPP-4 inhibition. Furthermore, the effect of DPP-4 inhibition on pancreatic beta cell function, skeletal muscle function, and the glucose-lowering mechanisms were also discussed. We believe that scientists looking for novel compounds with therapeutic promise against T2DM will be able to develop antidiabetic drugs using these natural sources.

Alzheimer’s disease (AD) is the most common form of dementia and is characterized by irreversible and progressive neurodegeneration. Cholinergic dysfunction has been reported in AD, and several cholinesterase inhibitors, including natural compounds and synthetic analogs, have been developed to treat the disease. However, there is currently no treatment for AD, as most drug-like compounds have failed in clinical trials. Acetylcholinesterase (AChE) is the target of most drugs used commercially to treat AD. This work focused on screening natural compounds obtained from the ZINC database (224, 205 compounds) against AChE to identify those possibly capable of enabling the management of AD. Indirubin and dehydroevodiamine were the best potential AChE inhibitors with free binding energies of −10.03 and −9.00 kcal/mol, respectively. The key residue (His447) of the active site of AChE was found to participate in complex interactions with these two molecules. Six H-bonds were involved in the ‘indirubin–AChE’ interaction and three H-bonds in the ‘dehydroevodiamine–AChE’ interaction. These compounds were predicted to cross the blood–brain barrier (BBB) and to exhibit high levels of intestinal absorption. Furthermore, ‘indirubin–AChE’ and ‘dehydroevodiamine–AChE’ complexes were found to be stable, as determined by root mean square deviation (RMSD) during a 50 ns molecular dynamics simulation study. Based on the free binding energies and stabilities obtained by simulation studies, we recommend that experimental studies be undertaken on indirubin and dehydroevodiamine with a view towards their potential use as treatments for AD.

Highly pure docosahexaenoic acid (DHA) was produced successfully in a packed bed reactor via the two-step lipase-catalysed esterification using the fatty acid from microalgae (from Crypthecodinium cohnii) and ethanol as substrates. Lipozyme RM IM from Rhizomucor miehei was employed as a biocatalyst. In the first step, a temperature of 40 °C, a molar ratio of 1:4 (fatty acid to ethanol), and a water content of 0.6 wt% (based on the total substrate weight) were selected as optimum conditions. A maximum DHA concentration of ca. 90 wt% was achieved in the fatty acid fraction with an 89 wt% yield after 15 min. In the second step, the fatty acids from the first step were used as the substrate and a recursive reaction was conducted using identical optimized conditions. Following this second step, a DHA concentration of 100 wt% was achieved in conjunction with an 83.2 wt% yield after 25 min.

Urinary cell-free DNA (cfDNA) is an attractive body fluid for liquid biopsy. In this study, we compared the efficiencies of four commercial kits for urinary cell-free DNA (cfDNA) isolation and of various sample storage conditions. Urinary cfDNA was isolated from 10 healthy individuals using four commercial kits: QIAamp Circulating Nucleic Acid Kit (QC; Qiagen), MagMAX™ Cell-Free DNA Isolation Kit (MM; Applied Biosystems), Urine Cell-Free Circulating DNA Purification Midi Kit (NU; Norgen Biotek), and Quick-DNA™ Urine Kit (ZQ; Zymo Research). To assess the isolation efficiency, an Agilent 2100 Bioanalyzer with High Sensitivity DNA chips was used, and cfDNA yield was defined as the amount of cfDNA obtained from 1 mL of urine. MM and QC provided the highest cfDNA yield in the 50–300 bp range, and MM and NU gave the highest cfDNA yield in the 50–100 bp range. In particular, the NU kit was efficient for isolation of more fragmented cfDNA in the range of 50–100 bp with the lowest cellular genomic DNA contamination. ZQ had the best cost-efficiency for isolating the same amount of urinary cfDNA. Samples stored at −70 °C with the addition of 10 mM EDTA resulted in the highest cfDNA yield 3 months after sample collection.

A young, healthy traveler returning to the United States presented with fever, night sweats, splenomegaly, and pancytopenia. Bone marrow biopsy revealed leishmaniasis (Leishmania infantum), likely acquired in southern France. Although many cases of endemic visceral leishmaniasis (VL) have been reported in Europe, this is a rare case of imported VL in a healthy traveler returning from Europe to the US. Despite successful initial treatment with liposomal amphotericin B (LamB), relapse occurred. Treatments for VL in immunocompetent individuals are highly effective, but relapse can occur. There is more extensive experience in endemic areas with treating relapse that may be lacking in North America. This case alerts physicians in the US that immunocompetent adults can acquire VL during brief visits to endemic areas in Europe. It is important that travelers be counseled on preventive measures. Patients should be monitored after treatment for relapse.

ObjectiveTo gain a better understanding of the pathogenesis of autoimmune arthritis-associated interstitial lung disease (ILD), we sought to identify the characteristics of lung-infiltrating cells in SKG mice with ILD.MethodsWe injected curdlan in SKG mice at 8 weeks of age, and identified the presence of ILD by PET-MRI at 20 weeks post-injection and histological analysis at 22 weeks post-injection. Lung-infiltrating cells were examined by flow cytometry. Analysis of serum cytokines by the Luminex multiplex cytokine assay was performed at 14 and 22 weeks post-injection, and cytokine profiles before and after the development of ILD were compared. Opal multiplexed immunofluorescent staining of lung tissue was also performed.ResultsAt 20 weeks post-injection, curdlan-treated SKG mice developed not only arthritis but also lung inflammation combined with fibrosis, which was identified by PET-MRI and histological analysis. The majority of inflammatory cells that accumulated in the lungs of curdlan-treated SKG mice were CD11b+Gr1+ neutrophils, which co-express IL-17A and GM-CSF, rather than TNF-α. Compared with 14 weeks post-injection, serum levels of GM-CSF, MCP1, IL-17A, IL-23, TSLP, and soluble IL-7Rα had increased at 22 weeks post-injection, whereas those of IFN-γ, IL-22, IL-6, and TNF-α remained unchanged. Furthermore, IL-23, CXCL5, IL-17A, and GM-CSF, but not TNF-α, were observed in immunofluorescent-stained lung tissue.ConclusionWe found that IL-17A+GM-CSF+ neutrophils represented the major inflammatory cells in the lungs of curdlan-treated SKG mice. In addition, GM-CSF and IL-17A appear to play a more important role than TNF-α in ILD development.

The expression of hTERT in tumor cells contributes to oncogenic transformation by promoting immortalization. For this reason, hTERT is one of the major targets for cancer therapy, and an efficient method to downregulate hTERT expression is required for treatment of hTERT-positive cancer. In this report, we demonstrated that inhibition of AMP-activated protein kinase (AMPK) downregulates the expression of hTERT. We screened cell signaling pathways in AMPK α1 knockout cells and found that AMPKα1 is required for activity of the hTERT promoter. AMPKα1 knockout cells showed decreased expression of hTERT mRNA and protein. We also demonstrated that compound C, a reversible AMPK inhibitor, suppressed the expression of hTERT. However, AMPK activators, including AICAR and metformin, did not increase the level of hTERT protein. Finally, we showed that tumor cells stably expressing hTERT are resistant to compound C treatment. These results indicate that AMPK activity is required for tumor progression.

BACKGROUND/AIMS:The seroclearance of hepatitis B virus (HBV) surface antigen (HBsAg) is regarded as a functional cure of chronic hepatitis B (CHB) although it occurs rarely. Recently, several genome-wide association studies (GWASs) revealed various genetic alterations related to the clinical course of HBV infection. However, all of these studies focused on the progression of HBV infection to chronicity and had limited application because of the heterogeneity of HBV genotypes. In the present study, we aimed to determine susceptibility genetic markers for seroclearance of HBsAg in CHB patients with a homogenous viral genotype. METHODS:One hundred patients with CHB who had experienced HBsAg seroclearance before 60 years of age and another 100 with CHB showing high serum levels of HBsAg even after 60 years of age were enrolled. Extreme-phenotype GWAS was conducted using blood samples of participants. RESULTS:We identified three single nucleotide polymorphisms, rs7944135 (P = 4.17 × 10-6, odds ratio [OR] = 4.16, 95% confidence interval [CI] = 2.27-7.63) at 11q12.1, rs171941 (P = 3.52×10-6, OR = 3.69, 95% CI = 2.13-6.42) at 5q14.1, and rs6462008 (P = 3.40×10-6, OR = 0.34, 95% CI = 0.22-0.54) at 7p15.2 as novel susceptibility loci associated with HBsAg seroclearance in patients with CHB. The flanking genes at these loci including MPEG1, DTX4, MTX3, and HOXA13 were suggested to have functional significance. In addition, through functional analysis, CXCL13 was also presumed to be related. CONCLUSIONS:To the best of our knowledge, this study is the first GWAS regarding the seroclearance of HBsAg in CHB patients. We identify new susceptibility loci for cure of CHB, providing new insights into its pathophysiology.

BACKGROUND:Human ovarian surface epithelial (HOSE) cells are a critical cell source for ovarian cancer research; however, they are difficult to obtain and maintain under standard laboratory conditions in large quantities. The aim of this study was to generate immortalized HOSE (IHOSE) cells with maintained properties to the original cell source, thereby guaranteeing a sufficiently large cell quantity for ovarian cancer research. METHODS:HOSE cells isolated from four non-cancer patients and five IHOSE cell lines were established by induction of HPV-E6/E7 expression or SV40 large T antigen using a lenti-viral system. Each of IHOSE cells was confirmed to be distinct by STR profiling. RNA-sequencing was used to compare gene expression profiles in HOSE, IHOSE and ovarian cancer cells. RESULTS:RNA-sequencing results revealed a stronger linear correlation in gene expression between IHOSE and HOSE cells (R2 = 0.9288) than between IHOSE or HOSE cells and ovarian cancer cells (R2 = 0.8562 and R2 = 0.7982, respectively). The gene expression pattern of 319 differentially expressed genes revealed minimal differences between HOSE and IHOSE cells, while a strong difference between ovarian cancer cells and HOSE or IHOSE cells was observed. Furthermore, the five IHOSE cell lines displayed morphological characteristics typical of epithelial cells but showed a lower level of EpCAM, CD133 and E-cadherin, as cancer stem marker, than ovarian cancer cells. Moreover, unlike cancer cells, IHOSE cells could not form colonies in the anchorage-independent soft agar growth assay. CONCLUSION:These findings demonstrate that five newly established IHOSE cell lines have characteristics of progenitor HOSE cells while exhibiting continuous growth, and thus, should be highly useful as control cells for ovarian cancer research.

Endoscopic thyroidectomy is gaining popularity, but it can increase the risk of certain complications. Carbon dioxide insufflation in the neck may cause adverse effects on hemodynamic and ventilatory aspects. We report the anesthetic course and complications that were encountered during endoscopic thyroidectomy. Although the surgery was successful, the patient developed signs of hypercarbia, subcutaneous emphysema and pneumothorax.

The percutaneous placement of a totally implantable vascular access port via the subclavian vein is commonly used in patients with a need for multiple intravenous infusions such as administration of chemotherapy. Unfortunately, the use of central venous ports have been associated with adverse events that are hazardous to patients. Here we report the case of a 5-year-old child who died of catastrophic hemothorax after several attempts at insertion of an implantable subclavian venous access device and removal of an infected port. Massive hemothorax occurred on the side contralateral to unsuccessful attempts at insertion of a new port and ipsilateral to the removal of an infected port. We could not confirm the cause of death and hemothorax without autopsy, but we discuss several possible causes of massive hemothorax.

Active migration in both healthy and malignant cells requires the integration of information derived from soluble signaling molecules with positional information gained from interactions with the extracellular matrix and with other cells. How a cell responds and moves involves complex signaling cascades that guide the directional functions of the cytoskeleton as well as the synthesis and release of proteases that facilitate movement through tissues. The biochemical events of the signaling cascades occur in a spatially and temporally coordinated manner then dynamically shape the cytoskeleton in specific subcellular regions. Therefore, cell migration and invasion involve a precise but constantly changing subcellular nano-architecture. A multidisciplinary effort that combines new surface chemistry and cell biological tools is required to understand the reorganization of cytoskeleton triggered by complex signaling during migration. Here we generate a class of model substrates that modulate the dynamic environment for a variety of cell adhesion and migration experiments. In particular, we use these dynamic substrates to probe in real-time how the interplay between the population of cells, the initial pattern geometry, ligand density, ligand affinity and integrin composition affects cell migration and growth. Whole genome microarray analysis indicates that several classes of genes ranging from signal transduction to cytoskeletal reorganization are differentially regulated depending on the nature of the surface conditions.

Through the past 60 years, forests, now of various age classes, have been established in the southern part of the Korean Peninsula through nationwide efforts to reestablish forests since the Korean War (1950-53), during which more than 65% of the nation's forest was destroyed. Careful evaluation of long-term changes in vegetation growth after reforestation is one of the essential steps to ensuring sustainable forest management. This study investigated nationwide variations in vegetation phenology using satellite-based growing season estimates for 1982-2008. The start of the growing season calculated from the normalized difference vegetation index (NDVI) agrees reasonably with the ground-observed first flowering date both temporally (correlation coefficient, r = 0.54) and spatially (r = 0.64) at the 95% confidence level. Over the entire 27-year period, South Korea, on average, experienced a lengthening of the growing season of 4.5 days decade(-1), perhaps due to recent global warming. The lengthening of the growing season is attributed mostly to delays in the end of the growing season. The retrieved nationwide growing season data were used to compare the spatial variations in forest biomass carbon density with the time-averaged growing season length for 61 forests. Relatively higher forest biomass carbon density was observed over the regions having a longer growing season, especially for the regions dominated by young (

The inhalation of silica particles induces silicosis, an inflammatory and fibrotic lung disease characterized by the early accumulation of macrophages and neutrophils in the airspace and subsequent appearance of silicotic nodules as a result of progressive fibrosis. This study evaluated whether apolipoprotein A1 (ApoA1) protects against ongoing fibrosis and promotes the resolution of established experimental lung silicosis. Crystallized silica was intratracheally administered to 6- to 8-week-old transgenic mice expressing human ApoA1 in their alveolar epithelial cells (day 0). ApoA1 was overexpressed beginning on day 7 (ApoA1_D7 group) or day 15 (ApoA1_D15 group). The mice were sacrificed on day 30 for an evaluation of lung histology; the measurement of collagen, transforming growth factor-b1 and lipoxin A4; and a TUNEL assay for apoptotic cells. The ApoA1_D7 and D15 groups showed significant reductions in the silica-induced increase in inflammatory cells, silicotic nodule area, and collagen deposition compared with the silica-treated ApoA1 non-overexpressing mice. The level of transforming growth factor-b1 decreased in the bronchoalveolar lavage fluid, whereas lipoxin A4 was increased in the ApoA1_D7 and D15 groups compared with the silica-treated ApoA1 non-overexpressing mice. The silica-induced increase in the number of apoptotic cells was significantly reduced in the lungs of mice overexpressing ApoA1. Overexpression of ApoA1 decreased silica-induced lung inflammation and fibrotic nodule formation. The restoration of lipoxin A4 may contribute to the protective effect of ApoA1 overexpression against silica-induced lung fibrosis.

Background/Objectives: Ultraviolet radiation (UVR) induces oxidative stress in the skin by generating reactive oxygen species (ROS), which can lead to inflammatory conditions including erythema (a sign of sunburn). This clinical study aims to develop an instrumental evaluation method to determine the minimal erythema dose (MED) for UVR. Methods: Fourteen human subjects aged 27 to 57 years (48.93 ± 8.54) participated in this study. Six subsites were designated on the test skin site of each subject and irradiated with UVR at different doses. The examiner visually assessed erythema, determining the ‘visual MED’. Additionally, the a* value (a chrominance parameter presenting greenness to redness) was measured using a spectrophotometer as an indicator of erythema. The a* values of the UVR-irradiated subsites were compared to the non-irradiated control value, and the differences were referred to as Δa*. The Δa* value of the subsites irradiated with UVR at the ‘visual MED’ was referred to as the Δa*VMED for each subject. The mean of the Δa*VMED values of all subjects was chosen as a criterion value for the ‘instrumental MED’. The ‘instrumental MED’ was defined as the lowest dose of UVR that causes an Δa* value equivalent to the criterion value. The ‘visual MED’ and ‘instrumental MED’ values of all subjects were subjected to correlation analysis. Results: The mean of the Δa*VMED values of all subjects was 1.88 ± 0.8. The means of the ‘visual MED’ and ‘instrumental MED’ values (in J m−2 unit) of all subjects were 300.14 ± 84.16 and 303.29 ± 77.99, respectively. In Pearson correlation analysis, the ‘instrumental MED’ and ‘visual MED’ values had a very strong positive correlation with each other (r = 0.864, p = 0.000). Conclusions: This study suggests that the instrumental evaluation method of MED based on the spectrophotometric measurement of the a* values can complement or replace the visual evaluation method and that this method will be useful in monitoring skin tolerance to oxidative stress affected by prooxidant factors and defensive factors.

To determine whether newer combination cytokine treatment with granulocyte colony-stimulating factor (G-CSF) and darbepoetin can improve efficacy of stem cell therapy, we evaluated safety and peripheral blood stem/progenitor cell (PBSC) mobilizing effects of combination cytokine in comparison with G-CSF alone in patients with acute myocardial infarction (AMI). We randomized 60 patients with AMI into two groups under 2:1 ratio; combination treatment with darbepoetin and G-CSF ( n = 41: Combicytokine group) and the G-CSF alone ( n = 19: G-CSF group). After coronary angioplasty, G-CSF was treated for 3 days with dose of 10 μg/kg/day in both groups. Only in the combicytokine group, additional single intravenous injection of 4.5 μg/kg of darbepoetin was administrated immediate after coronary angioplasty. Combination cytokine treatment was well tolerated as was G-CSF alone. PBSCs were obtained by apheresis for intracoronary infusion after completion of cytokine treatment and were analyzed by flow cytometry. The purity of proangiogenic cells was higher in combination cytokine group than the G-CSF group. Specifically, proportion of CD34 + /KDR + endothelial progenitor cells, CD3 + /CD31+ angiogenic T cells and Tie2 + /CXCR4 + cells in apheresis products were higher in the combicytokine group. These meant that the combicytokine treatment recruited PBSCs in higher purity and fewer unwanted inflammatory cells than G-CSF alone in apheresis products. Combination treatment with darbepoetin and G-CSF is safe and more efficient to mobilize and recruit proangiogenic cells than G-CSF alone in patients with AMI. (Trial registration: www.ClinicalTrials.gov identifier: NCT00501917)

We examined the effect of laparoscopic adjustable gastric banding (LAGB) on weight loss, inflammatory markers, and components of the Metabolic Syndrome (MeS) in morbidly obese adolescents and determined if those with MeS lose less weight post-LAGB than those without. Data from 14–18 yr adolescents were obtained at baseline, 6 and 12 months following LAGB. Significant weight loss and improvements in MeS components were observed 6 months and one year following LAGB. The incidence of MeS declined 56.8% after 6 months and 69.6% after 12 months. There was no significant difference in amount of weight lost post-LAGB between those with and without MeS at either timepoint. Correlations between change in weight parameters and components of MeS in those with and without MeS at baseline were examined and found to vary by diagnostic category. LAGB is effective for short-term improvement in weight, inflammatory markers, and components of MeS in morbidly obese adolescents.