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Purpose The poor response of breast cancer to immune checkpoint blockade might result from low immunogenicity and the immune-suppressive tumor microenvironment. We hypothesized that in situ tumor vaccination via radiation therapy (RT) and suppression of immune tolerance via phosphoinositide 3-kinase δ (PI3Kδ) inhibition would enhance the efficacy of immune checkpoint blockade. Methods and Materials 4T1 murine breast cancer cells were grown in both immune-competent and -deficient BALB/c mice, and tumors were irradiated with 24 Gy in 3 fractions. A PD-1 blockade and a PI3Kαδ inhibitor were then administered every other day for 2 weeks. Fluorescence-activated cell sorting and immunohistochemistry served to monitor subsequent changes in immune cell repertoire. Results The triple combination of RT, PD-1 blockade, and PI3Kαδ inhibitor significantly delayed tumor growth. The immune-deficient syngeneic 4T1 murine tumor model failed to show this tumor growth delay. Use of RT and PI3Kαδ inhibitor increased the proportions of CD8+ T cells; PI3Kαδ inhibitor led to a decrease in regulatory T cells and polymorphonuclear myeloid-derived suppressor cells. The triple combination resulted in a remarkable increase in cytotoxic CD8+ T cells, suggesting a prominent immune-modulatory effect. The abscopal effect was most prominent in the triple-combination therapy group, and it correlated with splenic CD8+ T cell accumulation. Conclusions These findings collectively indicate that combining RT, PI3Kαδ inhibitor, and PD-1 blockade could be a viable approach, helping to overcome the therapeutic resistance of immunologically cold tumors, such as breast cancer, with an immunosuppressive tumor microenvironment.

Purpose: This study investigated the antioxidant and enzymatic activities of 20 species of the most widely consumed edible flowers in South Korea to provide basic data on their bioactivity. Methods: After the selected edible flowers were processed based on the tea manufacturing method, the antioxidant activities (total polyphenol, flavonoid content, DPPH, and ABTS radical scavenging activities) were evaluated. Two species of edible flowers exhibiting exceptional antioxidant activities were selected and their enzymatic activities (tyrosinase, elastase, α-glucosidase, and ACE inhibitory activities) were assessed. Results: Among the 20 species of edible flowers used for tea manufacturing, Viola tricolor L. (V. tricolor L.) and Chamomilla recutita (C. recutita ) were found to have the highest overall antioxidant activity. Based on these results, V. tricolor L. and C. recutita were selected to determine their enzymatic activities; V. tricolor L. showed higher levels of tyrosinase, elastase, and ACE inhibitory activities, whereas C. recutita showed a higher level of α-glucosidase inhibitory activity. Conclusion: Based on their exceptional antioxidant and enzymatic activities among the 20 species of edible flowers, V. tricolor L. and C. recutita are predicted to be of greater use in the development of inner beauty products.

Pancreatic cancer is one of the most lethal diseases which lack an early diagnostic marker. We investigated whether serum ferritin (SF) reflects risk for pancreatic cancer and potential genes that may contribute ferritin and pancreatic cancer risks. We performed a meta-analysis of relevant studies on SF and pancreatic cancer risk by searching articles in PUBMED and EMBASE published up to 1 March 2020. We also collected serum samples from Taipei Medical University Joint Biobank and compared SF levels in 34 healthy controls and 34 pancreatic cancer patients. An Oncomine database was applied as a platform to explore a series of genes that exhibited strong associations between ferritin and pancreatic cancer. Herein, we show that high levels of SF can indicate risk of pancreatic cancer, suggesting SF as the new tumor marker that may be used to help pancreatic cancer diagnosis. We also found that expressions of iron homeostasis genes (MYC, FXN) and ferroptosis genes (ALOX15, CBS, FDFT1, LPCAT3, RPL8, TP53, TTC35) are significantly altered with pancreatic tumor grades, which may contribute to differential expression of ferritin related to pancreatic cancer prognosis.

Pulpitis (toothache) is a painful inflammation of the dental pulp and is a prevalent problem throughout the world. This pulpal inflammation occurs in the cells inside the dental pulp, which have host defense mechanisms to combat oral microorganisms invading the pulp space of exposed teeth. This innate immunity has been well studied, with a focus on Toll-like receptors (TLRs). The function of TLR4, activated by Gram-negative bacteria, has been demonstrated in trigeminal ganglion (TG) neurons for dental pain. Although Gram-positive bacteria predominate in the teeth of patients with caries and pulpitis, the role of TLR2, which is activated by Gram-positive bacteria, is poorly understood in dental primary afferent (DPA) neurons that densely innervate the dental pulp. Using Fura-2 based Ca2+ imaging, we observed reproducible intracellular Ca2+ responses induced by Pam3CSK4 and Pam2CSK4 (TLR2-specific agonists) in TG neurons of adult wild-type (WT) mice. The response was completely abolished in TLR2 knock-out (KO) mice. Single-cell RT-PCR detected Tlr2 mRNA in DPA neurons labeled with fluorescent retrograde tracers from the upper molars. Using the mouse pulpitis model, real-time RT-PCR revealed that Tlr2 and inflammatory-related molecules were upregulated in injured TG, compared to non-injured TG, from WT mice, but not from TLR2 KO mice. TLR2 protein expression was also upregulated in injured DPA neurons, and the change was corresponded with a significant increase in calcitonin gene-related peptide (CGRP) expression. Our results provide a better molecular understanding of pulpitis by revealing the potential contribution of TLR2 to pulpal inflammatory pain.

Background: A causative role between cervical ureaplasma colonization and adverse outcomes during pregnancy has remained controversial. We investigated whether cervical ureaplasma colonization affects the biochemically or histologically intraamniotic inflammation in preterm birth.Methods: Amniotic fluid was retrieved during delivery. Various chorioamnionitis-related cytokines (interleukin (IL)-1β, -6, -8, -10, and tumor necrosis factor-α) and regulators (matrix metalloproteins (MMP)-8 and MMP-9) were measured with Human Magnetic Luminex screening assay. We tested cervical swab specimens using real-time polymerase chain reaction assays for the detection of ureaplasma spp. colonization. Considering the clinical situation that causes intraamniotic infection, we arbitrarily divided into three categories of preterm labor with intact membrane, preterm premature rupture of membrane (PPROM), and control group with no exposure to preterm labor or preterm premature rupture of membrane.Results: The incidence of cervical ureaplasma colonization was 49.3% (136/276). The incidence of histologic chorioamnionitis was 27.5% (76/200). All differences in cytokines and regulators according to histologic chorioamnionitis were significant. Of the 153 cases that experienced preterm labor with intact membrane, IL-10, MMP-8, and MMP-9 levels in the ureaplasma positive group were significantly higher than those of the ureaplasma negative group. According to logistic regression analysis adjusted to preterm labor with intact membrane, PPROM, and gestational age at delivery, cervical ureaplasma colonization was an independent risk factor of histologic chorioamnionitis (odd ratio: 2.622, 95% confidence interval: 1.443-4.766).Conclusions: Cervical ureaplasma colonization augments biochemically intraamniotic inflammation in preterm labor with intact membrane, and was an independent risk factor of histologic chorioamnionitis.

Objective The objective of this study was to evaluate the pharmacokinetics and bioequivalence of two formulations (the original capsule ("reference") and the new tablet ("test") formulations) of 135-mg choline fenofibrate under fed and fasted conditions. Materials and methods This was an open-label, randomized, single-dose, crossover bioequivalence study in healthy Korean males. A total of 40 individuals were separately enrolled in the high-fat fed and the fasting study, respectively, and were randomized in a 1:1 ratio into two sequences. Serial blood samples were collected over 72 hours after drug administration. Plasma concentrations of fenofibric acid were determined by a validated LC-MS/MS method. Pharmacokinetic (PK) parameters were estimated using noncompartmental methods. Results Overall, 37 and 35 individuals completed the fed and the fasting study, respectively, as planned. The estimated Cmax, AUC0-∞, and AUC0-last were comparable between the test and the reference formulations in both fed and fasting studies (p > 0.05). The 90% confidence intervals for the geometric mean ratios of Cmax, AUC0-∞, and AUC0-last were 0.92 - 1.06, 0.95 - 1.01, and 0.95 - 1.01 in the fed study; and 0.94 - 1.12, 0.94 - 1.00, and 0.94 - 1.00 in the fasting study, respectively. For both formulations, tmax was significantly prolonged under fed condition compared to fasting condition (p 0.05). Conclusion The reference and the test formulations of 135 mg choline fenofibrate show comparable pharmacokinetic profiles of fenofibric acid under both fed and fasted conditions and are considered bioequivalent. .

Background: Treating aged animals with plasma of an early developmental stage (e.g, umbilical cord plasma) showed an impressive potential to slow age-associated degradation of neuronal and cognitive functions. Translating such findings to clinical realities, however, requires effective ways for assessing treatment efficacy; ideal methods should be minimally invasive, amenable for serial assays, cost-effective, and quantitative. Methods: We developed a new biosensor approach to monitor anti-aging therapy. We advanced two key sensor components: i) a blood-borne metabolite was identified as a surrogate aging-marker; and ii) a compact and cost-effective assay system was developed for on-site applications. We treated aged mice either with human umbilical cord plasma or saline; unbiased metabolite profiling on mouse plasma revealed arachidonic acid (AA) as a potent indicator associated with anti-aging effect. We next implemented a competitive magneto-electrochemical sensor (cMES) optimized for AA detection directly from plasma. The developed platform could detect AA directly from small volumes of plasma (0.5 µL) within 1.5 hour. Results: cMES assays confirmed a strong correlation between AA levels and anti-aging effect: AA levels, while decreasing with aging, increased in the plasma-treated aged mice which also showed improved learning and memory performance. Conclusions: The cMES platform will empower both pre- and clinical anti-aging research by enabling minimally invasive, longitudinal treatment surveillance; these capacities will accelerate the development of anti-aging therapies, improving the quality of individual lives.

This study aimed to determine the association between consumption of ultra-processed foods and obesity among Korean adults. We used the data of 7364 participants (men 3219, women 4145) aged 19–64 years from the Korea National Health and Nutrition Examination Survey (KNHANES), 2016–2018. Food items were classified using the NOVA food classification system, depending on the extent and purpose of food processing: (1) unprocessed or minimally processed foods, (2) processed culinary ingredients, (3) processed foods, and (4) ultra-processed foods. Consumption of ultra-processed foods accounted for 26.8% of the total energy intake. After adjusting for potential confounders including sociodemographic and lifestyle characteristics, subjects with the highest consumption of ultra-processed foods (fourth quartile of % energy intake from ultra-processed foods) had 0.61 kg/m2 higher body mass index (BMI, 95% confidence interval [CI] 0.23–0.99, p-trend 0.0047), 1.34 cm higher waist circumference (WC, 95% CI 0.35–2.34, p-trend 0.0146), 51% higher odds of being obese (BMI &gt, 25 kg/m2, odds ratio [OR] 1.51, 95% CI 1.14–1.99, p-trend 0.0037), and 64% higher odds of abdominal obesity (men: WC ≥90 cm, women: WC ≥85 cm, OR 1.64, 95% CI 1.24–2.16, p-trend 0.0004) than those with the lowest consumption (first quartile) among women. However, no association was found in men. These findings provide evidence that high consumption of ultra-processed foods is positively associated with obesity in Korean women. Further studies with a large-scale cohort or intervention trial are needed to identify the mechanism of associations between consumption of ultra-processed foods and health-related outcomes including obesity in Korea.

Cancer cells can secrete exosomes under various stressful conditions, whose functions are involved in the delivery of various biologically active materials into host cells and/or modulation of host immune responses. Therefore, an improved understanding of the immunological interventions that stress-induced tumor exosomes have may provide novel therapeutic approaches and more effective vaccine designs. Here, we confirmed the phenotypical and functional alterations of dendritic cells (DCs), which act as a bridge between the innate and adaptive arms of immunity, following non-irradiated (N-exo) and gamma-irradiated melanoma cancer cell-derived exosome (G-exo) stimulation, and evaluated the N-exo- and G-exo-stimulated DCs as therapeutic cancer vaccine candidates. We demonstrated that G-exo-stimulated DCs result in DC maturation by the upregulation of surface molecule expression, pro-inflammatory cytokine release, and antigen-presenting ability, and the downregulation of endocytic capacity. In addition, these cells promoted T cell proliferation and the generation of T helper type 1 (Th1) and interferon (IFN)-&gamma, producing CD8+ T cells. However, N-exo-stimulated DCs induced semi-mature phenotypes and functions, eventually inhibiting T cell proliferation, decreasing IFN-&gamma, and increasing IL-10-producing CD4+ T cells. In addition, although N-exo and G-exo stimulations showed similar levels of antigen-specific IFN-&gamma, production, which served as tumor antigen sources in melanoma-specific T cells, G-exo-stimulated DC vaccination conferred a stronger tumor growth inhibition than N-exo-stimulated DC vaccination, further, this was accompanied by a high frequency of tumor-specific, multifunctional effector T cells. These results suggest that gamma irradiation could provide important clues for designing and developing effective exosome vaccines that can induce strong immunogenicity, especially tumor-specific multifunctional T cell responses.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus 2019 (COVID-19). No treatment is available. Micro-RNAs (miRNAs) in mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are potential novel therapeutic agents because of their ability to regulate gene expression by inhibiting mRNA. Thus, they may degrade the RNA genome of SARS-CoV-2. EVs can transfer miRNAs to recipient cells and regulate conditions within them. MSC-EVs harbor major therapeutic miRNAs that play important roles in the biological functions of virus-infected host cells. Here, we examined their potential impact on viral and immune responses. MSC-EVs contained 18 miRNAs predicted to interact directly with the 3’ UTR of SARS-CoV-2. These EVs suppressed SARS-CoV-2 replication in Vero E6 cells. In addition, five major miRNAs suppressed virus activity in a luciferase reporter assay by binding the 3’ UTR. MSC-EVs showed strong regenerative effects and potent anti-inflammatory activity which may prevent lethal cytokine storms. We confirmed that EVs regulated inflammatory responses by several cell types, including human brain cells that express the viral receptor ACE2, suggesting that the brain may be targeted by SARS-CoV-2. miRNAs in MSC-EVs have several advantages as therapeutic agents against SARS-CoV-2: 1) they bind specifically to the viral 3’ UTR, and are thus unlikely to have side effects; 2) because the 3’ UTR is highly conserved and rarely mutates, MSC-EV miRNAs could be used against novel variants arising during viral replication; and 3) unique cargoes carried by MSC-EVs can have diverse effects, such as regenerating damaged tissue and regulating immunity.

OBJECTIVES: This study aimed to investigate changes in serum antioxidant vitamin levels after consumption of balanced Korean diet (BKD), recommended American diet (RAD), and typical American diet (TAD) among Korean adults from a randomized controlled trial. METHODS: Among 54 adults aged 25–65 years with body mass index ≥23 kg/m(2) and blood LDL-cholesterol ≥120 mg/dL who finished a crossover feeding study conducted between 2015–2017, 16 subjects were selected for analyses of serum β-carotene, retinol, and α-tocopherol levels at baseline and after consumption of each diet for 4 weeks. Serum antioxidant vitamin levels were measured by high-performance liquid chromatography. RESULTS: Mean levels of serum β-carotene, retinol, and α-tocopherol at baseline were 0.37, 0.34, and 7.19 mg/L, respectively. After consumption of BKD, increase in serum β-carotene and retinol levels was observed compared to the baseline, whereas α-tocopherol level was decreased. After consumption of RAD, serum β-carotene, retinol, and α-tocopherol levels were increased. However, retinol level was reduced after consumption of TAD. CONCLUSIONS: This study may provide evidences about effects of diets on antioxidant vitamin levels in human body. FUNDING SOURCES: This work was carried out with the support of ‘Research Program for Agricultural Science and Technology Development’, National Institute of Agricultural Science, Rural Development Administration, Republic of Korea (Project No. PJ013475022018).

There are reports that pregnant women infected with SARS-CoV-2 not only have increased morbidity but also increased complications and evidence of maternal and fetal vascular malperfusion on placental pathology. This was a retrospective study of pregnant women diagnosed with SARS-CoV-2 infection after March 2020. The results of reverse transcription polymerase chain reaction testing and IgM and IgG antibody testing of the amniotic fluid, cord blood, placenta, and maternal blood were confirmed at delivery. Placentas were evaluated histopathologically. The study included seven pregnant women diagnosed with SARS-CoV-2 infection during pregnancy at a mean gestational age of 14.5 weeks. Out of the seven women, five were infected during the first trimester. The mean gestational age at delivery was 38.4 weeks. The reverse transcription polymerase chain reaction results for maternal plasma, cord blood, placenta, and amniotic fluid were negative and IgG antibodies were detected in maternal plasma and cord blood. On placental pathology, maternal vascular malperfusion was found in only one case, fetal vascular malperfusion in four cases, and inflammatory changes were found in two cases. Pregnancy outcomes for women diagnosed with SARS-CoV-2 infection during early pregnancy are positive and it is likely that maternal antibodies are passed to the fetus, which results in a period of immunity.

Objective To investigate the anti-inflammatory effects of decursin and decursinol angelate-rich Angelica gigas Nakai (AGNE) on dextran sulfate sodium (DSS)-induced murine ulcerative colitis (UC). Methods The therapeutic effect of an AGNE was analyzed in a mouse model of UC induced by DSS. Disease activity index values were measured by clinical signs such as a weight loss, stool consistency, rectal bleeding and colon length. A histological analysis was performed using hematoxylin and eosin staining. Key inflammatory cytokines and mediators including IL-6, TNF-α, PGE2, COX-2 and HIF-1α were assayed by enzyme-linked immunosorbent assay or western blotting. Results Treatment with the AGNE at 10, 20, and 40 mg/kg alleviated weight loss, decreased disease activity index scores, and reduced colon shortening in mice with DSS-induced UC. AGNE inhibited the production of IL-6 and TNF-α in serum and colon tissue. Moreover, AGNE suppressed the increased expression of COX-2 and HIF-1α and the increased production of PGE2 in colon tissue were observed in mice with DSS-induced UC. Additionally, histological damage was also alleviated by AGNE treatment. Conclusions The findings of this study verified that AGNE significantly improves clinical symptoms and reduces the activity of various inflammatory mediators. These results indicate the AGNE has the therapeutic potential in mice with DSS-induced UC.

// Taeryool Koo 1, * , Bong Jun Cho 2, * , Dan Hyo Kim 2 , Ji Min Park 1, 2 , Eun Jung Choi 2 , Hans H. Kim 2 , David J Lee 2 and In Ah Kim 1, 2, 3, 4 1 Department of Radiation Oncology, Graduate School of Medicine, Seoul National University, Seoul, Republic of Korea 2 Medical Science Research Institute, Seoul National University Bundang Hospital, Seongnam, Republic of Korea 3 Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Republic of Korea 4 Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea * These authors contributed equally to this work Correspondence to: In Ah Kim, email: inah228@snu.ac.kr Keywords: microRNA-200c, EGFR-associated signaling network, radiosensitization, human cancer cells Received: February 13, 2016 Accepted: February 06, 2017 Published: July 03, 2017 ABSTRACT MicroRNA-200c (miR-200c) recently was found to have tumor-suppressive properties by inhibiting the epithelial-mesenchymal transition (EMT) in several cancers. miR-200c also interacts with various cellular signaling molecules and regulates many important signaling pathways. In this study, we investigated the radiosensitizing effect of miR-200c and its mechanism in a panel of human cancer cell lines. Malignant glioma (U251, T98G), breast cancer (MDA-MB-468), and lung carcinoma (A549) cells were transfected with control pre-microRNA, pre-miR-200c, or anti-miR-200c. Then, RT-PCR, clonogenic assays, immunoblotting, and immunocytochemisty were performed. To predict the potential targets of miR-200c, microRNA databases were used for bioinformatics analysis. Ectopic overexpression of miR-200c downregulated p-EGFR and p-AKT and increased the radiosensitivity of U251, T98G, A549, and MDA-MB-468 cells. In contrast, miR-200c inhibition upregulated p-EGFR and p-AKT, and decreased radiation-induced cell killing. miR-200c led to persistent γH2AX focus formation and downregulated pDNA-PKc expression. Autophagy and apoptosis were major modes of cell death. Bioinformatics analysis predicted that miR-200c may be associated with EGFR, AKT2, MAPK1, VEGFA, and HIF1AN . We also confirmed that miR-200c downregulated the expression of VEGF, HIF-1α, and MMP2 in U251 and A549 cells. In these cells, overexpressing miR-200c inhibited invasion, migration, and vascular tube formation. These phenotypic changes were associated with E-cadherin and EphA2 downregulation and N-cadherin upregulation. miR-200c showed no observable cytotoxic effect on normal human fibroblasts and astrocytes. Taken together, our data suggest that miR-200c is an attractive target for improving the efficacy of radiotherapy via a unique modulation of the complex regulatory network controlling cancer pro-survival signaling and EMT.

To explore optic disc and peripapillary retinal nerve fiber layer (RNFL) features associated with glaucomatous optic disc (GOD) in young myopia. Presence of GOD, optic disc tilt, and disc torsion were determined using fundus photographs. If the measured disc tilt ratio was >1.3, the optic disc was classified as tilted. Optic disc torsion was defined as a >15° deviation in the long axis of the optic disc from the vertical meridian. The average and four quadrants RNFL thicknesses were assessed using spectral domain optical coherence tomography (SD-OCT). Logistic regression analyses were performed to identify factors associated with the presence of GOD. Nine hundred and sixty myopic subjects were recruited from four refractive surgery clinic databases. The mean age was 26.6 ± 5.7 years and spherical equivalent (SE) was −5.5 ± 2.5 diopters. Among 960 eyes, 26 (2.7%) received GOD group classification. Among 934 normal eyes, 290 (31.0%) had titled optic discs. Eighteen eyes (69.2%) in the GOD group had tilted optic discs. When compared to normal eyes, the GOD group had significantly higher tilt ratios (1.4 ± 0.2 vs. 1.2 ± 0.1, p

Background Pancreatic polypeptide (PP) hormone is a 36-amino-acid peptide released from the pancreas, the serum levels of which have been shown to rise upon food intake. The underlying mechanism for metabolic surgery in the treatment of patients with type 2 diabetes mellitus (T2DM) remains intriguing. We compared post-oral glucose challenge PP levels between patients undergoing laparoscopic gastric bypass (GB) and sleeve gastrectomy (SG) at 1 year after surgery. Methods This hospital-based, prospective study followed up a total of 12 laparoscopic GB and 12 laparoscopic SG patients and evaluated their glucose homeostasis. One year after metabolic surgery, 75-g oral glucose tolerance tests (OGTTs) were performed in the patients in the GB and SG groups and the blood levels of PP were evaluated. Results The laparoscopic GB group had stable serum PP levels within 120 min after OGTT; however, the levels were significantly higher in the laparoscopic SG group at 30 min after OGTT. The patients with complete T2DM remission did not exhibit significantly different PP levels at fasting and post-OGTT than those in patients without remission after GB. Similarly, after SG, patients with T2DM remission did not show significantly different PP levels at fasting and post-OGTT than those in patients without T2DM remission. Conclusions No significant difference was found in plasma PP levels after OGTT in T2DM patients that received either GB or SG, or in T2DM remitters or non-remitters 1 year after metabolic surgery.

A lipolytic, Gram-stain-negative, aerobic, non-motile and coccoid, ovoid or rod-shaped bacterial strain, designated BPTF-M16T, was isolated from tidal flat sediment on the Yellow Sea in the Republic of Korea. Strain BPTF-M16T grew optimally at 30 °C and in the presence of 2.0–3.0 % (w/v) NaCl. A phylogenetic tree of 16S rRNA gene sequences showed that strain BPTF-M16T fell within the clade comprising the type strains of Altererythrobacter species. Strain BPTF-M16T exhibited 16S rRNA gene sequence similarity values of 98.0 and 97.1 % to the type strains of Altererythrobacter ishigakiensis and A ltererythrobacter marinus , respectively, and of less than 97.0 % to the type strains of the other recognized species. Strain BPTF-M16T contained Q-10 as the predominant ubiquinone and C18 : 1 ω7c as the major fatty acid. The major polar lipids detected in strain BPTF-M16T were phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, sphingoglycolipid and one unidentified glycolipid. Mean DNA–DNA relatedness values of strain BPTF-M16T with the type strains of A. ishigakiensis and A. marinus were 22 and 13 %, respectively. The average nucleotide identity value between strain BPTF-M16T and the type strain of A. ishigakiensis was 76.80 %. Differential phenotypic properties, together with the phylogenetic and genetic data, revealed that strain BPTF-M16T is separated from recognized Altererythrobacter species. On the basis of the data presented here, strain BPTF-M16T is considered to represent a novel species of the genus Altererythrobacter , for which the name Altererythrobacter insulae sp. nov. is proposed. The type strain is BPTF-M16T (=KCTC 62421T=KACC 19609T=NBRC 113190T).

Background: The oncogenic Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation was reported to be the signature genetic event in most cases of pancreatic ductal adenocarcinoma (PDAC). Hepassocin (HPS/FGL1) is involved in regulating lipid metabolism and the progression of several cancer types, however, the underlying mechanism of HPS/FGL1 in the KRAS mutant PDAC cells undergoing eicosapentaenoic acid (EPA) treatment remains unclear. Methods: We measured HPS/FGL1 protein expressions in a human pancreatic ductal epithelial (HPNE) normal pancreas cell line, a KRAS-wild-type PDAC cell line (BxPC-3), and KRAS-mutant PDAC cell lines (PANC-1, MIA PaCa-2, and SUIT-2) by Western blot methods. HEK293T cells were transiently transfected with corresponding KRAS-expressing plasmids to examine the level of HPS expression with KRAS activation. We knocked-down HPS/FGL1 using lentiviral vectors in SUIT-2 cells and measured the cell viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clonogenicity assays. Furthermore, a lipidomic analysis was performed to profile changes in lipid metabolism after HPS/FGL1 knockdown. Results: We found that the HPS/FGL1 level was significantly upregulated in KRAS-mutated PDAC cells and was involved in KRAS/phosphorylated (p)-signal transduction and activator of transcription 3 (STAT3) signaling, and the knockdown of HPS/FGL1 in SUIT-2 cells decreased cell proliferation through increasing G2/M cell cycle arrest and cyclin B1 expression. In addition, the knockdown of HPS/FGL1 in SUIT-2 cells significantly increased omega-3 polyunsaturated fatty acids (PUFAs) and EPA production but not docosahexaenoic acid (DHA). Moreover, EPA treatment in SUIT-2 cells reduced the expression of de novo lipogenic protein, acetyl coenzyme A carboxylase (ACC)-1, and decreased p-STAT3 and HPS/FGL1 expressions, resulting in the suppression of cell viability. Conclusions: Results of this study indicate that HPS is highly expressed by KRAS-mutated PDAC cells, and HPS/FGL1 plays a crucial role in altering lipid metabolism and increasing cell growth in pancreatic cancer. EPA supplements could potentially inhibit or reduce ACC-1-involved lipogenesis and HPS/FGL1-mediated cell survival in KRAS-mutated pancreatic cancer cells.

A Gram-stain-negative, aerobic, non-flagellated, motile by gliding and ovoid or rod-shaped bacterial strain, designated YKTF-7T, was isolated from a tidal flat sediment on the Yellow Sea, South Korea. Strain YKTF-7T grew optimally at pH 7.0-8.0, at 30-37 °C and in the presence of 0.5-2.0 % (w/v) NaCl. A neighbour-joining phylogenetic tree based on 16S rRNA gene sequences showed that strain YKTF-7T fell within the clade comprising the type strains of species of the genus Pontibacter, clustering with the type strains of Pontibacterodishensis and Pontibacterkorlensis with which it exhibited 98.0-98.7 % sequence similarity. Strain YKTF-7T exhibited 16S rRNA gene sequence similarities of 94.7-96.8 % to the type strains of the other species of the genus Pontibacter and of less than 91.7 % to those of other recognized species. Strain YKTF-7T contained MK-7 as the predominant menaquinone and summed feature 4 (iso-C17 : 1 I and/or anteiso-C17 : 1 B) and iso-C15 : 0 as the major fatty acids. The major polar lipids were phosphatidylethanolamine and two unidentified lipids. The DNA G+C content of strain YKTF-7T was 54.0 mol%, and its mean DNA-DNA relatedness values with the type strains of P. odishensis and P. korlensis were 25 and 14 %, respectively. Differential phenotypic properties, together with the phylogenetic and genetic distinctiveness, revealed that strain YKTF-7T is separated from recognized species of the genus Pontibacter. On the basis of the data presented, strain YKTF-7T is considered to represent a novel species of the genus Pontibacter, for which the name Pontibacterlitorisediminis sp. nov. is proposed. The type strain is YKTF-7T(=KCTC 52252T=NBRC 112298T).

The α1D-adrenergic receptor (ADRA1D) is a key regulator of cardiovascular, prostate, and central nervous system functions. This clinically relevant G protein-coupled receptor has proven difficult to study, as it must form an obligate modular homodimer containing the PDZ proteins scribble and syntrophin or become retained in the endoplasmic reticulum as non-functional protein. We previously determined that targeted removal of the N-terminal (NT) 79 amino acids facilitates ADRA1D plasma membrane expression and agonist-stimulated functional responses. However, whether such an event occurs in physiological contexts was unknown. Herein, we report the ADRA1D is subjected to innate NT processing in cultured human cells. SNAP near-infrared imaging and tandem-affinity purification revealed the ADRA1D is expressed as both full-length and NT truncated forms in multiple human cell lines. Serial truncation mapping identified the cleavage site as Leu(90)/Val(91) in the 95-amino acid ADRA1D NT domain, suggesting human cells express a Δ1-91 ADRA1D species. Tandem-affinity purification MS/MS and co-immunoprecipitation analysis indicate NT processing of ADRA1D is not required to form scribble-syntrophin macromolecular complexes. Yet, label-free dynamic mass redistribution signaling assays demonstrate that Δ1-91 ADRA1D agonist responses were greater than WT ADRA1D. Mutagenesis of the cleavage site nullified the processing event, resulting in ADRA1D agonist responses less than the WT receptor. Thus, we propose that processing of the ADRA1D NT domain is a physiological mechanism employed by cells to generate a functional ADRA1D isoform with optimal pharmacodynamic properties.

To compare progression of primary open angle glaucoma (POAG) in asymmetrically myopic eyes within the same subject and evaluate whether the degree of myopia is related to glaucoma progression. POAG patients with asymmetric myopia (axial length [AXL] ≥24 mm in both eyes, and the AXL difference between the right and left eyes to be ≥0.5 mm) were included. Glaucoma progression was determined either by optic disc/retinal nerve fiber layer (RNFL) photographs or by serial visual field (VF) data. The progression rates of VF mean deviation (dB/year) and spectral domain optical coherence tomography measured RNFL thickness (μm/year) were compared between the more myopic eye (MME) and the less myopic eye (LME) within the same subject. A total of 55 patients (mean follow up period; 4.5 ± 1.0 years) were included. The mean AXL demonstrated a significant difference between MME and LME (26.3 ± 1.7 vs. 25.6 ± 1.7 mm; p = 0.036). The mean baseline VF MD (−3.8 ± 5.4 vs. −2.6 ± 4.7 dB; p = 0.21) and average RNFL thickness (77.5 ± 10.6 vs. 79.9 ± 12.3 μm; p = 0.36) did not differ between the MME and LME. Among the 55 patients, optic disc/RNFL photographic progression was noted in the MME in 15 patients, in the LME in 19 patients, and in both eyes in seven patients. VF progression was noted in the MME in seven patients, in the LME in seven patients, and in both eyes in four patients. The VF MD progression rates were −0.25 ± 0.34 dB/year in MME and −0.26 ± 0.34 dB/year in LME cases (p = 0.91). The mean progression rate of the average RNFL thickness also did not differ between the MME and LME (−0.59 ± 0.67 vs. -0.66 ± 0.72 μm/year, p = 0.68). The degree of myopia was not associated with glaucoma progression when assessing the same patient using either the VF or optic disc/RNFL criteria in asymmetrically myopic patients.

We investigated the effect of chikusetsusaponin IVa (CS) and chikusetsusaponin IVa methyl ester (CS-ME) from the roots of Achyranthes japonica NAKAI on lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production in RAW264.7 macrophages. CS-ME more potently inhibited LPS-induced NO and PGE2 production than CS. CS-ME concentration-dependently inhibited LPS-induced tumor necrosis factor (TNF)-α and interleukin (IL)-6 and IL-1β production in RAW264.7 macrophages and mouse peritoneal macrophages. Consistent with these findings, CS-ME suppressed LPS-induced expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 at protein level as well as iNOS, COX-2, TNF-α, IL-6, and IL-1β at mRNA level. In addition, CS-ME suppressed LPS-induced transcriptional activity of nuclear factor (NF)-κB and activator protein (AP)-1. The anti-inflammatory properties of CS-ME might result from suppression of iNOS, COX-2, TNF-α, IL-6, and IL-1β expression through downregulation of NF-κB and AP-1 in macrophages.

The severe acute respiratory syndrome coronavirus (SARS-CoV)-2 disease (COVID)-19 is having profound effects on the global economy and food trade. Limited data are available on how this pandemic is affecting our dietary and lifestyle-related behaviors at the global level. Google Trends was used to obtain worldwide relative search volumes (RSVs) covering a timeframe from before the COVID-19 pandemic 1 June 2019 to 27 April 2020. Spearman&rsquo, s rank-order correlation coefficients were used to measure relationships between daily confirmed cases and aforementioned RSVs between 31 December 2019 and 15 April 2020. RSV curves showed increased interest in multiple keywords related to dietary and lifestyle behaviors during the COVID-19 lockdown period in March and April 2020. Spearman&rsquo, s correlation analysis showed that the strongest variables in each keyword category were (1) food security (food shortage: r = 0.749, food bank: r = 0.660, and free food: r = 0.555, all p &lt, 0.001), (2) dietary behaviors (delivery: r = 0.780, restaurant: r = &minus, 0.731, take-away: r = 0.731, and food-delivery: r = 0.693, 0.001), (3) outdoor-related behaviors (resort: r = &minus, 0.922, hotel: r = &minus, 0.913, cinema: r = &minus, 0.844, park: r = &minus, 0.827, fitness: r = &minus, 0.817, gym: r = &minus, 0.811, plant: r = 0.749, sunbathing: r = 0.668, and online: r = 0.670, 0.001), and (4) immune-related nutrients/herbs/foods (vitamin C: r = 0.802, vitamin A: r = 0.780, zinc: r = 0.781, immune: r = 0.739, vitamin E: r = 0.707, garlic: r = 0.667, omega-3 fatty acid: r = &minus, 0.633, vitamin D: r = 0.549, and turmeric: r = 0.545, 0.001). Restricted movement has affected peoples&rsquo, dietary and lifestyle behaviors as people tend to search for immune-boosting nutrients/herbs and have replaced outdoor activities with sedentary indoor behaviors.

Objective Breast cancer is the second leading cause of cancer deaths in women worldwide and represents a highly aggressive nature with limited therapeutic options; thus, investigating novel therapeutic agents for breast cancer is much needed. In this study, we investigated the anticancer effects of a novel camptothecin derivative, CPT211, against human breast cancer. Methods We used hormone receptor-positive MCF-7, triple-negative (TNBC) MDA-MB-231, and HER2-positive BT-474 human breast cancer cells to examine cytotoxicity of CPT211. We measured cell viability with dose dependence of CPT211 treatments by an MTT assay and investigated the potential underlying mechanism through flow cytometric and Western blot methods. Furthermore, we evaluated the efficacy of the treatment combination of CPT211 and doxorubicin in a mouse model bearing MDA-MB-231 xenografts. Results CPT211 treatment led to dose-dependent decreases in cell viability of both MCF-7 and MDA-MB-231 cells, but not BT-474 cells. Analysis of the underlying molecular mechanism revealed that CPT211 activated p53-mediated apoptosis, by triggering intrinsic and extrinsic apoptotic pathways in MCF-7 cells. Additionally, CPT211 induced apoptosis and cell cycle arrest of MDA-MB-231 cells by activating Fas/FADD/caspase-8 signaling, suggesting that CPT211-mediated MDA-MB-231 cell apoptosis may occur through an extrinsic apoptosis pathway. CPT211 treatment with doxorubicin in mice bearing MDA-MB-231 xenografts was shown to enhance caspase-8 and caspase-7 activation, resulting in significant inhibition of tumor growth. Conclusions These results indicate that Fas/FADD/caspase-8 activation plays an important role in CPT211-mediated tumor growth suppression in TNBC, and the novel camptothecin derivative, CPT211, can be exploited for specific targeted therapies and potentially improve approaches to combination treatments for human breast cancer.

Early blindness causes fundamental alterations of neural function across more than 25% of cortex—changes that span the gamut from metabolism to behavior and collectively represent one of the most dramatic examples of plasticity in the human brain. The goal of this review is to describe how the remarkable behavioral and neuroanatomical compensations demonstrated by blind individuals provide insights into the extent, mechanisms, and limits of human brain plasticity.

Objectives : The aim of this study is to investigate the state of cervical disc herniation according to the degree of cervical lordosis and age. Methods : 67 records of inpatients who were diagnosed with herniated intervertebral disc(HIVD) of the cervical spine were analyzed. Cobb’s method, Jochumsen method and the Ishihara index were used to measure the degree of cervical lordosis. The state of the cervical disc was identified using magnetic resonance imaging(MRI) of the cervical spine. Then correlations among cervical lordosis, age and cervical disc herniation were analyzed. Results : Disc bulging was associated with hypolordosis and disc protrusion was associated with hyperlordosis and age. Disc extrusion was not associated with either cervical lordosis or age. The number of disc herniations in the cervical spine was correlated with age significantly, but not with cervical lordosis. Conclusions : Cervical disc herniation had a tendency to correlate with age and cervical lordosis, although this is not definite. Future studies that analyze more radiographic images of patients with HIVD of the cervical spine might be necessary to identify the influence of cervical lordosis on cervical disc herniation.

Two-component systems (TCSs) are an important signaling transduction pathway that adapt to changing environments. Commonly, a TCS comprises a sensor kinase that is usually an integral membrane histidine sensor kinase and a response regulator that mediates the cellular responses. Presently, however, we cloned a novel sensor kinase gene (tcsK) that is not adjacent to its cognate response regulator from Streptomyces acidiscabies that produces two secondary metabolites, thaxtomin A and WS5995B, and identified its functional involvement in the production of secondary metabolites and morphological differentiation. The elevated expression and disruption of the tcsK gene enhanced 7.1-fold and almost abolished WS5995B production in S. acidiscabies, respectively, but did not affect the production of thaxtomin A. In addition, spore formation of S. acidiscabies was decreased 120-fold by the disruption of tcsK, and the actinorhodin production of Streptomyces lividans TK24 was increased 5.7-fold by the high expression of tcsK. These results indicate that the novel unpaired tcsK gene may be related to the control of secondary metabolite production and spore formation in actinomycetes.

Recombinant expression in Escherichia coli allows the simple, economical, and effective production of bioactive peptides. On the other hand, the production of native peptides, particularly those rich in disulfide bonds, is a major problem. Previous studies have reported that the use of carrier proteins for fusion expression can result in good peptide yields, but few are folded correctly. In this study, two transmembrane small proteins in E. coli, YoaJ and YkgR, which both orientate with their N-termini in cytoplasm and their C-termini in periplasm, were used for fusion expression. The recombinant production of two peptides, asteropsin A (ASPA) and β-defensin (BD), was induced in the periplasm of E. coli using a selected carrier protein. Both peptides were expressed at high levels, at yields of approximately 5-10 mg/L of culture. Mass spectrometry showed that the resulting peptide had the same molecular weight as their natural forms. After purification, single peaks were observed by reversed phase high-performance liquid chromatography (RP-HPLC), demonstrating the absence of isoforms. Furthermore, cytoplasmically expressed fusion proteins with a carrier at their C-termini did not contain disulfide bonds. This study provides new carrier proteins for fusion expression of disulfide bond-rich peptides in E. coli.

AimTo evaluate the progressive change in peripapillary atrophy (PPA) according to its shape and to explore the relationship between PPA progression and glaucoma worsening in myopic eyes.MethodsA total of 159 eyes of 159 patients with myopic (axial length (AXL) >24 mm) glaucoma (mean follow-up 4.4 years, 35 eyes with minimal PPA, 40 concentric-type PPA eyes (>270° around the optic disc) and 84 eccentric-type PPA eyes (ResultsPatients with concentric PPA were older than patients with eccentric PPA (54.1±11.7 vs 44.1±11.7 years; PConclusionsRelationship between glaucoma worsening and PPA progression was strongest in myopic glaucomatous eyes with eccentric type PPA.

Results : After 21 days of treatment, the patient showed improvement in VAS, JOA, grip and release test and finger escape sign. The patient also expressed satisfaction with the treatment. Conclusions : The results suggest that warm needling therapy may be an effective additional treatment for cervical myelopathy and other symptoms related to ossification of posterior longitudinal ligament(OPLL). Further studies should be carried out regarding possible long-lasting effects. Cervical myelopathy; Ossification of posterior longitudinal ligament(OPLL); VAS; JOA; Warm needling therapy

The aim of this study was to compare the efficacy of combination therapy with desmopressin and an anticholinergic to desmopressin monotherapy for the first-line treatment of children with primary monosymptomatic nocturnal enuresis (PMNE).A total of 98 children with PMNE (male:female 71:27) aged 5-16 (mean age 7.18 ± 1.8) years were retrospectively analyzed. The patients were divided into two groups: the monotherapy group (n = 49) was given oral desmopressin alone, and the combination therapy group (n = 49) was given desmopressin plus an anticholinergic (propiverine 10 mg) as a first-line treatment. The two groups were matched according to the following criteria: age, gender, and baseline frequency of nocturnal enuresis. The efficacy was evaluated by International Children's Continence Society criteria at 1 and 3 months after treatment initiation.The combination therapy group showed a higher rate of complete response than the monotherapy group (20.4 vs. 6.1% at 1 month of treatment; 46.9 vs. 22.4% at 3 months of treatment). In terms of success (response and complete response), there was a significant difference between the two groups after 3 months of treatment (P = 0.002).Our results indicate that combination therapy with desmopressin plus an anticholinergic is quicker and more effective than desmopressin monotherapy in reducing PMNE.

To compare the clinical courses of patients with myopic primary open angle glaucoma (POAG) with and without optic disc shape alterations.In this longitudinal retrospective study, 146 eyes from 146 patients with myopic (axial length(AXL),24 mm) POAG were classified according to optic disc shape alterations defined by optic disc tilt and/or rotation. Glaucomatous progression was determined by either serial optic disc/retinal nerve fibre layer photographs or visual field (VF) exams. Rate of progression was calculated from serial VF mean deviation (MD) and visual field index values.Mean age, AXL and follow-up duration were 50.1±12.7 years, 26.1±1.6 mm and 4.6±1.3 years, respectively. The progression rate was faster in eyes with a non-tilted optic disc than with a tilted optic disc (-0.30(95% CI; -0.42 to -0.16) vs 0.05(-0.07 to 0.17) dB/year, -0.85(-1.20 to -0.49) vs -0.35(-0.68 to -0.03) %/year, all p0.05). Twenty eyes (21.3%) in the non-tilted group but only one eye (1.9%) in the tilted group showed VF progression in both superior and inferior hemifields. By logistic regression analysis, worse initial VF MD and less optic disc tilt were significantly associated with both superior and inferior VF progression (OR=0.909 and 0.561 (for 0.1 tilt ratio); p=0.020 and 0.018, respectively).Significant differences in glaucomatous progression were found between eyes with and without optic disc shape alterations, particularly disc tilt. More localised and stable courses of glaucoma progression were observed in eyes with tilted optic discs.

Background:Breast cancer has been showing relatively poor response to immune checkpoint blockades potentially due to low immunogenicity of tumor and immunosuppressive tumor microenvironment. Radiation (RT) has been showing immune stimulatory effect and PI3Kδhas immune suppressive effect via modulation of regulatory T cell (Treg). Therefore, we hypothesize that in situ tumor vaccination via RT and suppression of immune tolerance via PI3Kαδ inhibition could enhance the clinical efficacy of immune checkpoint blockade. As PI3Kα controls a key oncogenic signaling pathway, we evaluated whether RT or novel PI3Kαδ inhibitor or both could enhance the efficacy of antitumor effect of a PD-1 blockade in immune competent syngenic triple negative breast cancer (TNBC) model. Materials & Methods:4T1 murine breast cancer cells were grown subcutaneously in the hind limb of BALB/c mice. The mice were grouped as following seven groups: control, RT, PI3Kαδ inhibitor, PI3Kαδ inhibitor + RT, PD-1 blockade, PD-1 blockade + RT, and triple combination group. Tumors were irradiated using 24 Gy/3 fractions. PD-1 blockade (10 mg/kg) and PI3Kαδ inhibitor (4 mg/kg) were administered every other day for two weeks, respectively. Tumor size was measured periodically using a Vernier caliper and bioluminescence imaging to evaluate efficacy of each modality and combination therapy. Immune-modulatory function was evaluated using FACS and immunohistochemical (IHC) study. Results:Triple combination of RT, PD-1 blockade, and PI3Kαδ inhibitor significantly delayed tumor regrowth whereas PD-1 inhibitor alone showed only modest effect in 4T1 syngenic TNBC model. FACS and IHC study for immune repertoire using tumor samples showed that RT and PD-1 blockade modestly increased the proportion of cytotoxic CD8+ T cells and PI3Kαδ inhibitor led to decrease the proportion of Treg. Triple combination showed remarkable increase of cytotoxic CD8+ T cells suggesting synergistic immune modulatory effect of RT, PD-1 blockade and PI3Kαδ inhibitor. Triple combination led to significant upregulation of c-GAS/STING pathway in the tumor and increased IFN-γ level in blood as well compared to each modality alone. Conclusions:Taken together, combination of RT and PI3Kαδ inhibitors maximized immune stimulatory effect in immune competent syngenic TNBC model and enhanced the response of PD-1 blockade via non-redundant synergistic immune modulatory effect. This study provides a preclinical rationale for the combination of PI3Kαδ inhibitor and RT with PD-1 blockade to overcome the immune tolerance of breast cancer. (Work supported by the grants from NRF #2017R1A2B4002710 & #2017M2A2A7A01018438 to In Ah Kim) Citation Format: Ji Min Park, Joo Ho Lee, Danhyo Kim, Eric Eunsik Kim, Jun Hyung Bae, In Ah Kim. A PI3Kαδ inhibitor combined with irradiation enhance the effect of PD-1 blockade in syngenic triple negative breast cancer model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 529.

Senescence in stem cells, which occurs as a consequence of chronic responses to the environment, defines the capacity of stem cells for proliferation and differentiation as well as their potential for tissue regeneration and homeostasis maintenance. Although stem cells reside under low oxygen pressure and the availability of oxygen is known to be a crucial determinant in their fate, the key modulators in stem cell aging and the underlying mechanism have yet to be unraveled. Human placenta‐derived mesenchymal stem cells (hpMSCs) were cultured under hypoxia (3% O2) or normoxia (21% O2) to investigate the key factors that regulate stem cell senescence under hypoxic conditions. RNA sequencing results suggested that the expression of aminoacyl‐tRNA synthetase‐interacting multifunctional protein 3 (AIMP3, EEF1E1), an aging inducer, in the hpMSCs was dramatically repressed under hypoxia with concurrent suppression of the aging marker p16INK4a. The hpMSCs that overexpressed AIMP3 under hypoxic conditions displayed significantly decreased proliferation and fewer stem cell characteristics, whereas the downregulation of AIMP3 ameliorated the age‐related senescence of MSCs. Consistent with the results of the hpMSCs, MSCs isolated from the adipose tissue of AIMP3‐overexpressing mice exhibited decreased stem cell functions. Interestingly, AIMP3‐induced senescence is negatively regulated by hypoxia‐inducible factor 1α (HIF1α) and positively regulated by Notch3. Furthermore, we showed that AIMP3 enhanced mitochondrial respiration and suppressed autophagic activity, indicating that the AIMP3‐associated modulation of metabolism and autophagy is a key mechanism in the senescence of stem cells and further suggesting a novel target for interventions against aging.

Objectives : To assess the test-retest reliability and the intratest repeatability in measuring the cervical range of motion of healthy subjects with wireless microelectromechanical system inertial measurement unit(MEMS-IMU) system and to discuss the feasibility of this system in the clinical setting to evaluate the cervical spine musculoskeletal . Methods : 12 healthy people who were evaluated as noor mild-disability with neck disability index were participated. Their cervical motion were measured with IMU twice in consecutive two days for the test-retest reliability study. Intratest repeatability was calculated in the two tests separately. The calculated intraclass correlation coefficients(ICC) were discussed and compared with the those of the previous studies. Results : Cervical range of motion data were acquired and statistically processed: left rotation(61.64°), right rotation(65.12°), extension(61.98°), flexion(52.81°), left bending(39.31°), right bending(41.08°). ICCs were 0.77∼0.98(intratest repeatability) and 0.74∼0.93 (test-retest reliability) in the primary motion. In the coupling motion, intratest repeatability ICCs were 0.93∼ 0.99(transverse primary plane), 0.88∼0.97(saggital primay plane), and 0.77∼0.93(coronal primary plane). Test-retest reliability of coupling motion were 0.90∼0.97(transverse primary plane), 0.00∼0.72(saggital primary plane), and 0.04∼0.76(coronal primary plane). Conclusions : Several types of range-of-motion devices are now on use in many fields including medicine, but the practicality of the devices in clinical use is questionable for the convenient and economical aspects. In this study, we presented the reliability of cervical range of motion test with the developed wireless MEMS-IMU system and discussed its potential utility in clinical use.

LRRK2 (leucine-rich repeat kinase 2) has been identified as a gene corresponding to PARK8, an autosomal-dominant gene for familial Parkinson’s disease (PD). LRRK2 pathogenicspecific mutants induce neurotoxicity and shorten neurites. To elucidate the mechanism underlying LRRK2 expression, we constructed the LRRK2-promoter-luciferase reporter and used it for promoter analysis. We found that the glucocorticoid receptor (GR) transactivated LRRK2 in a ligand-dependent manner. Using quantitative RT-PCR and Western analysis, we further showed that treatment with dexamethasone, a synthetic GR ligand, induced LRRK2 expression at both the transcriptional and translational levels, in dopaminergic MN9D cells. Dexamethasone treatment also increased expression of α-synuclein, another PD causative gene, and enhanced transactivation of the α-synuclein promoter-luciferase reporter. In addition, dexamethasone treatment to MN9D cells weakly induced cytotoxicity based on an LDH assay. Because glucocorticoid hormones are secreted in response to stress, our data suggest that stress might be a related factor in the pathogenesis of PD. [BMB Reports 2013; 46(9): 454-459]

The performance of sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NCT) was investigated in patients with locally advanced breast cancer (LABC).After NCT of 178 patients with cytology-proven axillary/supraclavicular nodes metastasis at the time of diagnosis, SLNB using radioisotope was performed including completion node dissection between 2008 and 2011. The detection rate, sensitivity, false negative rate (FNR), negative predictive value (NPV) and accuracy of SLNB were analyzed.SLNB was successfully performed in 169 (94.9%) patients. Tumor nonresponse and extensive residual nodal disease were found to be significantly associated with detection failure of sentinel nodes. Sensitivity, FNR, NPV, and accuracy of SLNB were 78.0, 22.0, 75.8, and 87.0%, respectively, and a greater number of retrieved SLNs increased all four of these performance measures. Conversion to node-negative disease was achieved in 69 (40.8%) patients: 24% of patients with the luminal A subtype, 51.6% of patients with the luminal B, 51.7% of patients with the HER2-enriched, and 58.5% of patients with the triple-negative breast cancer (TNBC) subtype. Luminal B, HER2-enriched, and TNBC subtypes showed comparable responses to NCT; however, the TNBC subtype had a significantly better FNR and accuracy.SLNB was found to be technically feasible, but its routine use was not recommended for LABCs after NCT. However, acceptable performance was noted for locally advanced TNBCs, and thus SLNB might be safely considered in these selected patients.

A Gram-stain-negative, aerobic, non-motile and ovoid or rod-shaped bacterial strain, designated KEM-4T, was isolated from water of an estuary environment on the Yellow Sea, South Korea, and subjected to a polyphasic taxonomic study. Strain KEM-4T grew optimally at pH 7.0–8.0, at 30 °C and in the presence of 1.0–2.0 % (w/v) NaCl. The phylogenetic trees based on 16S rRNA gene sequences showed that strain KEM-4T fell within the clade comprising the type strains of species of the genus Altererythrobacter , clustering with the type strains of Altererythrobacter aestiaquae, Altererythrobacter gangjinensis and Altererythrobacter luteolus, showing 95.0–96.5 % sequence similarity. Sequences similarities to the type strains of the other species of the genus Altererythrobacter were 93.1–95.1 %. Strain KEM-4T contained Q-10 as the predominant ubiquinone and C18 : 1ω7c, summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c) and C17 : 1ω6c as the major fatty acids. The major polar lipids were phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol and sphingoglycolipid. The DNA G+C content of strain KEM-4T was 59.5 mol%. Differential phenotypic properties, together with the phylogenetic distinctiveness, revealed that strain KEM-4T is separated from species of the genus Altererythrobacter with validly published names. On the basis of the data presented, strain KEM-4T is considered to represent a novel species of the genus Altererythrobacter , for which the name Altererythrobacter confluentissp. nov. is proposed. The type strain is KEM-4T (=KCTC 52259T=NBRC 112305T).