Publications by authors named "Min-Young Kim"

365 Publications

Therapies for Chronic Allograft Rejection.

Front Pharmacol 2021 15;12:651222. Epub 2021 Apr 15.

Department of Internal Medicine, Johns Hopkins School of Medicine, Baltimore, MD, United States.

Remarkable advances have been made in the pathophysiology, diagnosis, and treatment of antibody-mediated rejection (ABMR) over the past decades, leading to improved graft outcomes. However, long-term failure is still high and effective treatment for chronic ABMR, an important cause of graft failure, has not yet been identified. Chronic ABMR has a relatively different phenotype from active ABMR and is a slowly progressive disease in which graft injury is mainly caused by donor specific antibodies (DSA). Since most trials of current immunosuppressive therapies for rejection have focused on active ABMR, treatment strategies based on those data might be less effective in chronic ABMR. A better understanding of chronic ABMR may serve as a bridge in establishing treatment strategies to improve graft outcomes. In this in-depth review, we focus on the pathophysiology and characteristics of chronic ABMR along with the newly revised Banff criteria in 2017. In addition, in terms of chronic ABMR, we identify the reasons for the resistance of current immunosuppressive therapies and look at ongoing research that could play a role in setting better treatment strategies in the future. Finally, we review non-invasive biomarkers as tools to monitor for rejection.
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http://dx.doi.org/10.3389/fphar.2021.651222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082459PMC
April 2021

Natural Course of Residual Hearing with Reference to GJB2 and SLC26A4 Genotypes: Clinical Implications for Hearing Rehabilitation.

Ear Hear 2021 Jan 6;42(3):644-653. Epub 2021 Jan 6.

Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Bundang Hospital, Seongnam, South Korea.

Background: Understanding the characteristics of residual hearing at low frequencies and its natural course in relation to molecular genetic etiology may be important in developing rehabilitation strategies. Thus, we aimed to explore the characteristics and natural course of residual hearing at low frequencies associated with the two most frequent deafness genes: GJB2 and SLC26A4.

Methods: Initially, 53 GJB2 and 65 SLC26A4 subjects were enrolled, respectively. Only those whose audiograms exhibited hearing thresholds ≤70 dB at 250 and 500 Hz, and who had at least 1-year follow-up period between the first and last audiograms, were included. Collectively, the clinical characteristics of 14 ears from eight subjects with GJB2 variants, and 31 ears from 22 subjects with SLC26A4 variants fulfilled the strict criteria. In this study, a dropout rate refers to an incidence of dropping out of the cohort by cochlear implant surgery due to severe hearing deterioration.

Results: Among the ears with complete serial audiogram data set, significant residual hearing at low frequencies at the time of inclusion was observed in 18.8% of those with GJB2 variants (15 out of 80 ears) and 42.6% of those with SLC26A4 variants (46 out of 108 ears), revealing a difference between two deafness genes. Subsequently, ears with SLC26A4 variants (11 of 46 ears, 23.9%) turned out to have a higher dropout rate for cochlear implantation due to hearing deterioration within the first year than those with GJB2 variants (1 of 15, 6.7%), albeit with no statistical significance. Throughout the follow-up period (mean: 37.2 ± 6.8, range: 12 to 80 months), deterioration of residual hearing at low frequencies at 250 Hz (dB HL/y) and 500 Hz (dB HL/y) of those with GJB2 variants exhibited 3.1 ± 1.3 (range: 0 to 15) and 5.2 ± 1.6 (range: 0 to 20), respectively, suggesting the deterioration of residual hearing in GJB2 variants was rather slow and gradual. Specifically, GJB2 p.Leu79Cysfs*3 show less remarkable residual hearing at low frequencies, but then a relatively stable nature. In contrast, SLC26A4 variants demonstrated a significantly higher dropout rate due to severe hearing deterioration requiring cochlear implantation compared with the GJB2 variants. This trend was observed not only in the first-year follow-up period but also in the follow-up periods thereafter. The p.His723Arg;c.919-2A>G genotype of SLC26A4, in particular, was associated with a high propensity for sudden hearing deterioration, as indicated by the dropout rate, which was as high as 46.2% for cochlear implantation due to hearing deterioration during the first year follow-up period. Furthermore, the dropout rate for cochlear implantation was observed in 7.1% of those with GJB2 variants (one out of 14 ears) and 30.3% of those with SLC26A4 variants (10 out of 33 ears) throughout the entire follow-up period.

Conclusions: Our results suggest that there is a difference with respect to the progressive nature of residual hearing at low frequencies between the two most common genes responsible for hearing loss, which may provide clinical implications of having individualized rehabilitation and timely intervention.
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http://dx.doi.org/10.1097/AUD.0000000000000965DOI Listing
January 2021

Rising of as a signature causative gene of down-sloping hearing loss in people in their teens and 20s.

J Med Genet 2021 Mar 22. Epub 2021 Mar 22.

Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea

Background: Down-sloping sensorineural hearing loss (SNHL) in people in their teens and 20s hampers efficient learning and communication and in-depth social interactions. Nonetheless, its aetiology remains largely unclear, with the exception of some potential causative genes, none of which stands out especially in people in their teens and 20s. Here, we examined the role and genotype-phenotype correlation of lipoxygenase homology domain 1 () in down-sloping SNHL through a cohort study.

Methods: Based on the Seoul National University Bundang Hospital (SNUBH) genetic deafness cohort, in which the patients show varying degrees of deafness and different onset ages (n=1055), we have established the 'SNUBH Teenager-Young Adult Down-sloping SNHL' cohort (10-35 years old) (n=47), all of whom underwent exome sequencing. Three-dimensional molecular modelling, minigene splicing assay and short tandem repeat marker genotyping were performed, and medical records were reviewed.

Results: accounted for 33.3% of all genetically diagnosed cases of down-sloping SNHL (n=18) and 12.8% of cases in the whole down-sloping SNHL cohort (n=47) of young adults. We identified a potential common founder allele, as well as an interesting genotype-phenotype correlation. We also showed that transcript 6 is necessary and probably sufficient for normal hearing.

Conclusions: exceeds other genes in its contribution to down-sloping SNHL in young adults, rising as a signature causative gene, and shows a potential but interesting genotype-phenotype correlation.
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http://dx.doi.org/10.1136/jmedgenet-2020-107594DOI Listing
March 2021

Biotransformation of whey by Weissella cibaria suppresses 3T3-L1 adipocyte differentiation.

J Dairy Sci 2021 Apr 19;104(4):3876-3887. Epub 2021 Feb 19.

Department of Food Science and Biotechnology, College of Life Science and Biotechnology, Dongguk University-Seoul, Goyang 10326, Republic of Korea. Electronic address:

Biotransformation, the structural modification of chemical compounds, has proved to be an indispensable tool in providing beneficial health effects. Although the health benefits of biotransformation using plant sources has been widely studied, the anti-adipogenic effect of biotransformed dairy products, such as whey, have not yet been demonstrated. Here, we investigated the anti-adipogenic effect of whey biotransformed by Weissella cibaria in 3T3-L1 adipocytes. Weissella cibaria-biotransformed whey considerably reduced the accumulation of lipid droplets and intracellular triglycerides in 3T3-L1 cells. In the presence of W. cibaria-biotransformed whey, the mRNA and protein expression of a key transcription factor, peroxisome proliferator-activated receptor γ (PPARγ), for adipogenesis was markedly suppressed in 3T3-L1 cells. Additionally, W. cibaria-biotransformed whey also decreased the mRNA and protein expressions of lipoprotein lipase and adipocyte fatty acid-binding protein, which are regulated by PPARγ. Moreover, W. cibaria-biotransformed whey inhibited the expression of adipokines, resistin, and leptin. Collectively, these results suggest that whey biotransformed by W. cibaria has the potential to exert anti-adipogenic effects by inhibiting intracellular signaling events of adipogenic-related transcription factors and target genes.
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http://dx.doi.org/10.3168/jds.2020-19677DOI Listing
April 2021

Antioxidant and anti-inflammatory effects of Peanut (.) skin extracts of various cultivars in oxidative-damaged HepG2 cells and LPS-induced raw 264.7 macrophages.

Food Sci Nutr 2021 Feb 20;9(2):973-984. Epub 2020 Dec 20.

Department of Central Area Crop Science National Institute of Crop Science Rural Development Administration Suwon Korea.

This study was performed to investigate the distribution of phenolic compounds in the peanut skins of various cultivars, as well as their antioxidant and anti-inflammatory effect L. cv. K-Ol, cv. Sinpalkwang, cv. Daan, cv. Heuksaeng) and extraction solvent. The major components of red peanut cultivars (K-Ol, Sinpalkwang, and Daan) were identified as proanthocyanidin, catechin, gallic acid, coumaric acid, and hesperidine, whereas the major components of black peanut cultivar (Heuksaeng) were identified as anthocyanin, ferulic acid, and quercetin. The DPPH and ABTS radical scavenging activities, and FRAP values were the highest in Daan followed by Sinpalkwng, K-Ol, and Heuksang. Furthermore, the skin extracts of red peanuts effectively improved cell viability, reactive oxygen species generation, MDA concentration, and antioxidant enzyme activity (GR, GPx, CAT, and superoxide dismutase) in oxidative stress-induced HepG2 cells, and reduced the expression of pro-inflammatory factors (NO, TNF-α, IL-6, and IL-1β) in LPS-stimulated RAW 264.7 macrophages. These results suggest that red peanut skin extracts could effectively mediate physiological activity and provide valuable information for the use of peanut byproducts as functional food materials.
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http://dx.doi.org/10.1002/fsn3.2064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866586PMC
February 2021

Genotoxicity of Water Extract from Bark-Removed Stokes.

Molecules 2021 Feb 8;26(4). Epub 2021 Feb 8.

Institute of Bioscience & Integrative Medicine, Daejeon University, 176 split 75 Daedeokdae-ro Seo-gu, Daejeon 35235, Korea.

(RVS) has been traditionally used as an herbal remedy to support the digestive functions in traditional Korean medicine. Additionally, the pharmacological effects of RVS, including antioxidative, antimicrobial and anticancer activities, have been well-reported. The genotoxicity of RVS, however, is elusive; thus, we evaluated the genotoxicity of RVS without bark (RVX) for safe application as a resource of functional food or a medical drug. To evaluate the genotoxicity of RVX, we used a bacterial reverse mutation test, chromosomal aberration test and comet assay, according to the "Organization for Economic Co-operation and Development" (OECD) guidelines. Briefly, for the reverse mutation test, samples (5000, 1667, 556, 185, 62 and 0 μg/plate of RVX or the positive control) were treated with a precultured strain (TA98, TA100, TA1535, TA1537 or WP2µvrA) with or without the S9 mix, in which RVX partially induced a reverse mutation in four bacterial strains. From the chromosomal aberration test and comet assay, the RVX samples (556, 185, 62, 20 and 0 μg/mL of RVX or the positive control) were treated in a Chinese hamster ovary cell line (CHO-K1 cells) in the conditions of the S9 mix absent or S9 mix present and in Chang liver cells and C2C12 myoblasts, respectively. No chromosomal aberrations in CHO-K1 or DNA damage in Chang liver cells and C2C12 myoblasts was observed. In conclusion, our results suggest the non-genotoxicity of RVX, which would be helpful as a reference for the safe application of bark-removed as functional raw materials in the food, cosmetics or pharmaceutical fields.
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http://dx.doi.org/10.3390/molecules26040896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914431PMC
February 2021

The Association Between Continuous Glucose Monitoring-Derived Metrics and Cardiovascular Autonomic Neuropathy in Outpatients with Type 2 Diabetes.

Diabetes Technol Ther 2021 Apr 5. Epub 2021 Apr 5.

Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Continuous glucose monitoring (CGM)-derived metrics, including time in range (TIR), are attracting attention as new indicators, beyond hemoglobin A1c, of glycemic control and diabetes complications. This study investigated the associations between CGM-derived TIR, hyperglycemia, and hypoglycemia metrics and cardiovascular autonomic neuropathy (CAN) in patients with type 2 diabetes. A total of 284 patients with type 2 diabetes who underwent CGM using GOLD™ (Medtronic MiniMed) for 3 days or iPro™2 (Medtronic MiniMed) for 6 days and autonomic function tests within 3 months based on outpatient data were recruited. The definition of CGM-derived metrics was subject to the most recent international consensus. CAN was defined as an abnormal result in two or more parasympathetic test, and the severity of CAN was estimated as the sum of the scores of the five cardiovascular autonomic function tests. A total of 84 patients (29.6%) were diagnosed with CAN, and the mean TIR was 57.0% ± 7.0%. A multiple logistic regression analysis revealed that the odds ratio (OR) of presence of CAN was 0.876 [95% confidence interval (CI): 0.79-0.98] per 10% increase in the TIR 70-180 mg/dL, after adjusting for age, sex, diabetes duration, any medications, and glycemic variability. A 10% increase in the TIR was significantly inversely associated with the severity of CAN (OR: 0.89, 95% CI: 0.81-0.98). Among the metrics of hyperglycemia, each 10% increase in a time above range (TAR) >180 mg/dL was also independently correlated with the presence of CAN (OR: 1.141, 97.5% CI: 1.01-1.29) and the severity of CAN (OR: 1.13, 97.5% CI: 1.01-1.26). A TIR 70-180 mg/dL and a TAR >180 mg/dL were significantly associated with CAN in outpatients with type 2 diabetes.
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http://dx.doi.org/10.1089/dia.2020.0599DOI Listing
April 2021

Targeting the ectopy-triggering ganglionated plexuses without pulmonary vein isolation prevents atrial fibrillation.

J Cardiovasc Electrophysiol 2021 Feb 19;32(2):235-244. Epub 2021 Jan 19.

Myocardial Function Section, National Heart and Lung Institute, Imperial College London, London, UK.

Background: Ganglionated plexuses (GPs) are implicated in atrial fibrillation (AF). Endocardial high-frequency stimulation (HFS) delivered within the local atrial refractory period can trigger ectopy and AF from specific GP sites (ET-GP). The aim of this study was to understand the role of ET-GP ablation in the treatment of AF.

Methods: Patients with paroxysmal AF indicated for ablation were recruited. HFS mapping was performed globally around the left atrium to identify ET-GP. ET-GP was defined as atrial ectopy or atrial arrhythmia triggered by HFS. All ET-GP were ablated, and PVs were left electrically connected. Outcomes were compared with a control group receiving pulmonary vein isolation (PVI). Patients were followed-up for 12 months with multiple 48-h Holter ECGs. Primary endpoint was ≥30 s AF/atrial tachycardia in ECGs.

Results: In total, 67 patients were recruited and randomized to ET-GP ablation (n = 39) or PVI (n = 28). In the ET-GP ablation group, 103 ± 28 HFS sites were tested per patient, identifying 21 ± 10 (20%) GPs. ET-GP ablation used 23.3 ± 4.1 kWs total radiofrequency (RF) energy per patient, compared with 55.7 ± 22.7 kWs in PVI (p = <.0001). Duration of procedure was 3.7 ± 1.0 and 3.3 ± 0.7 h in ET-GP ablation group and PVI, respectively (p = .07). Follow-up at 12 months showed that 61% and 49% were free from ≥30 s of AF/AT with PVI and ET-GP ablation respectively (log-rank p = .27).

Conclusions: It is feasible to perform detailed global functional mapping with HFS and ablate ET-GP to prevent AF. This provides direct evidence that ET-GPs are part of the AF mechanism. The lower RF requirement implies that ET-GP targets the AF pathway more specifically.
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http://dx.doi.org/10.1111/jce.14870DOI Listing
February 2021

Vibration Alert to the Brain: Evoked and Induced MEG Responses to High-Frequency Vibrotactile Stimuli on the Index Finger of Dominant and Non-dominant Hand.

Front Hum Neurosci 2020 5;14:576082. Epub 2020 Nov 5.

Quantum Technology Institute, Korea Research Institute of Standards and Science, Daejeon, South Korea.

In recent years, vibrotactile haptic feedback technology has been widely used for user interfaces in the mobile devices. Although functional neuroimaging studies have investigated human brain responses to different types of tactile inputs, the neural mechanisms underlying high-frequency vibrotactile perception are still relatively unknown. Our aim was to investigate neuromagnetic brain responses to high-frequency vibrotactile stimulation, using magnetoencephalography (MEG). We measured 152-channel whole-head MEG in 30 healthy, right-handed volunteers (aged 20-28 years, 15 females). A total of 300 vibrotactile stimuli were presented at the tip of either the left index finger or the right index finger in two separate sessions. Sinusoidal vibrations at 150 Hz for 200 ms were generated with random inter-stimulus intervals between 1.6 and 2.4 s. Both time-locked analysis and time-frequency analysis were performed to identify peak responses and oscillatory modulations elicited by high-frequency vibrations. The significance of the evoked and induced responses for dominant and non-dominant hand stimulation conditions was statistically tested, respectively. The difference in responses between stimulation conditions was also statistically evaluated. Prominent peak responses were observed at 56 ms (M50) and at 100 ms (M100) for both stimulation conditions. The M50 response revealed clear dipolar field patterns in the contralateral side with significant cortical activations in the contralateral primary sensorimotor area, whereas the M100 response was not as prominent as the M50. Vibrotactile stimulation induced significant suppression of both alpha (8-12 Hz) and beta (20-30 Hz) band activity during the mid-latency period (0.2-0.4 s), primarily in sensorimotor areas contralateral to the stimulation side. In addition, a significant alpha enhancement effect in posterior regions was accompanied with alpha suppressions in sensorimotor regions. The alpha suppression was observed in a broader distribution of cortical areas for the non-dominant hand stimulation. Our data demonstrate that high-frequency tactile vibrations, which is known to primarily activate Pacinian corpuscles, elicit somatosensory M50 and M100 responses in the evoked fields and induce modulations of alpha and beta band oscillations during mid-latency periods. Our study is also consistent with that the primary sensorimotor area is significantly involved in the processing of high-frequency vibrotactile information with contralateral dominance.
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http://dx.doi.org/10.3389/fnhum.2020.576082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674801PMC
November 2020

Regulating the Regulators: The Role of Histone Deacetylase 1 (HDAC1) in Erythropoiesis.

Int J Mol Sci 2020 Nov 11;21(22). Epub 2020 Nov 11.

Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.

Histone deacetylases (HDACs) play important roles in transcriptional regulation in eukaryotic cells. Class I deacetylase HDAC1/2 often associates with repressor complexes, such as Sin3 (Switch Independent 3), NuRD (Nucleosome remodeling and deacetylase) and CoREST (Corepressor of RE1 silencing transcription factor) complexes. It has been shown that HDAC1 interacts with and modulates all essential transcription factors for erythropoiesis. During erythropoiesis, histone deacetylase activity is dramatically reduced. Consistently, inhibition of HDAC activity promotes erythroid differentiation. The reduction of HDAC activity not only results in the activation of transcription activators such as GATA-1 (GATA-binding factor 1), TAL1 (TAL BHLH Transcription Factor 1) and KLF1 (Krüpple-like factor 1), but also represses transcription repressors such as PU.1 (Putative oncogene Spi-1). The reduction of histone deacetylase activity is mainly through HDAC1 acetylation that attenuates HDAC1 activity and trans-repress HDAC2 activity through dimerization with HDAC1. Therefore, the acetylation of HDAC1 can convert the corepressor complex to an activator complex for gene activation. HDAC1 also can deacetylate non-histone proteins that play a role on erythropoiesis, therefore adds another layer of gene regulation through HDAC1. Clinically, it has been shown HDACi can reactivate fetal globin in adult erythroid cells. This review will cover the up to date research on the role of HDAC1 in modulating key transcription factors for erythropoiesis and its clinical relevance.
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http://dx.doi.org/10.3390/ijms21228460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696854PMC
November 2020

General Approach to the Clinical Care of Solid Organ Transplant Recipients with COVID-19 Infection: Management for Transplant Recipients.

Curr Transplant Rep 2020 Oct 29:1-13. Epub 2020 Oct 29.

Department of Internal Medicine, Johns Hopkins School of Medicine, Baltimore, MD USA.

Purpose Of Review: Insufficient knowledge about COVID-19 and the potential risks of COVID-19 are limiting organ transplantation in wait-listed candidates and deferring essential health care in solid organ transplant recipients. In this review, we expand the understanding and present an overview of the optimized management of COVID-19 in solid organ transplant recipients.

Recent Findings: Transplant recipients are at an increased risk of severe COVID-19. The unique characteristics of transplant recipients can make it more difficult to identify COVID-19 Based on the COVID-19 data to date and our experience, we present testing, management, and prevention methods for COVID-19. Comprehensive diagnostic tests should be performed to determine disease severity, phase of illness, and identify other comorbidities in transplant recipients diagnosed with COVID-19. Outpatients should receive education for preventative measures and optimal health care delivery minimizing potential infectious exposures. Multidisciplinary interventions should be provided to hospitalized transplant recipients for COVID-19 because of the complexity of caring for transplant recipients.

Summary: Transplant recipients should strictly adhere to infection prevention measures. Understanding of the transplant specific pathophysiology and development of effective treatment strategies for COVID-19 should be prioritized.
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http://dx.doi.org/10.1007/s40472-020-00305-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594940PMC
October 2020

Anti-tumor efficacy of CKD-516 in combination with radiation in xenograft mouse model of lung squamous cell carcinoma.

BMC Cancer 2020 Nov 3;20(1):1057. Epub 2020 Nov 3.

Laboratory of Medical Oncology, Cancer Research Institute, The Catholic University of Korea, Seoul, Republic of Korea.

Background: Hypoxic tumors are known to be highly resistant to radiotherapy and cause poor prognosis in non-small cell lung cancer (NSCLC) patients. CKD-516, a novel vascular disrupting agent (VDA), mainly affects blood vessels in the central area of the tumor and blocks tubulin polymerization, thereby destroying the aberrant tumor vasculature with a rapid decrease in blood, resulting in rapid tumor cell death. Therefore, we evaluated the anti-tumor efficacy of CKD-516 in combination with irradiation (IR) and examined tumor necrosis, delayed tumor growth, and expression of proteins involved in hypoxia and angiogenesis in this study.

Methods: A xenograft mouse model of lung squamous cell carcinoma was established, and the tumor was exposed to IR 5 days per week. CKD-516 was administered with two treatment schedules (day 1 or days 1 and 5) 1 h after IR. After treatment, tumor tissues were stained with hematoxylin and eosin, and pimonidazole. HIF-1α, Glut-1, VEGF, CD31, and Ki-67 expression levels were evaluated using immunohistochemical staining.

Results: Short-term treatment with IR alone and CKD-516 + IR (d1) significantly reduced tumor volume (p = 0.006 and p = 0.048, respectively). Treatment with CKD-516 + IR (d1 and d1, 5) resulted in a marked reduction in the number of blood vessels (p < 0.005). More specifically, CKD-516 + IR (d1) caused the most extensive tumor necrosis, which resulted in a significantly large hypoxic area (p = 0.02) and decreased HIF-1α, Glut-1, VEGF, and Ki-67 expression. Long-term administration of CKD-516 + IR reduced tumor volume and delayed tumor growth. This combination also greatly reduced the number of blood vessels (p = 0.0006) and significantly enhanced tumor necrosis (p = 0.004). CKD-516 + IR significantly increased HIF-1α expression (p = 0.0047), but significantly reduced VEGF expression (p = 0.0046).

Conclusions: Taken together, our data show that when used in combination, CKD-516 and IR can significantly enhance anti-tumor efficacy compared to monotherapy in lung cancer xenograft mice.
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http://dx.doi.org/10.1186/s12885-020-07566-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607852PMC
November 2020

Inhibitory effect of ginsenoside Rg3 on cancer stemness and mesenchymal transition in breast cancer via regulation of myeloid-derived suppressor cells.

PLoS One 2020 22;15(10):e0240533. Epub 2020 Oct 22.

Department of Research Center, Dongnam Institute of Radiological & Medical Sciences, Busan, Republic of Korea.

Ginsenoside Rg3 (Rg3) has been studied in several cancer models and is suggested to act through various pharmacological effects. We investigated the anticancer properties of Rg3 through myeloid-derived suppressor cell (MDSC) modulation in FM3A mouse mammary carcinoma cells. The effects of Rg3 on MDSCs and consequent changes in cancer stem-like cells (CSCs) and epithelial-mesenchymal transition (EMT) were evaluated by diverse methods. MDSCs promoted cancer by enhancing breast cancer stemness and promoting EMT. Rg3 at a dose without obvious cytotoxicity downregulated MDSCs and repressed MDSC-induced cancer stemness and EMT. Mechanistic investigations suggested that these inhibitory effects of Rg3 on MDSCs and corresponding cancer progression depend upon suppression of the STAT3-dependent pathway, tumor-derived cytokines, and the NOTCH signaling pathway. In a mouse model, MDSCs accelerated tumor progression, and Rg3 delayed tumor growth, which is consistent with the results of in vitro experiments. These results indicated that Rg3 could effectively inhibit the progression of breast cancer. The anticancer effect of Rg3 might be partially due to its downregulation of MDSCs and consequent repression of cancer stemness and EMT in breast cancer. Hence, we suggest the regulation of MDSCs through Rg3 treatment as an effective therapeutic strategy for breast cancer patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240533PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7580975PMC
December 2020

Influence of Thermal Processing on Free and Bound Forms of Phenolics and Antioxidant Capacity of Rice Hull ( L.).

Prev Nutr Food Sci 2020 Sep;25(3):310-318

Department of Food Science and Biotechnology, Chungbuk National University, Chungbuk 28644, Korea.

The objective of this study was to evaluate the effects of heat treatment on the phenolics and antioxidant activity of rice hull. Heat treatment was performed at temperatures 80∼140°C for 1∼5 h, and the heated rice hull was extracted with 80% (v/v) methanol in an ultrasonic bath. The highest total polyphenol and flavonoid content (10.68 mg gallic acid equivalents/g and 1.83 mg catechin equivalents/g, respectively) occurred in rice hull heated at 130°C for 5 h. During heat treatment, the content of free phenolic acids increased compared with that of the bound phenolic acids. The highest 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activity and reducing power was observed in rice hull heated at 140°C for 3 h. The highest OH radical scavenging activity was 75.30% in rice hull heated at 140°C for 5 h. These results suggested that heat treatment was an efficient method to enhance the antioxidant characteristics of rice hull.
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http://dx.doi.org/10.3746/pnf.2020.25.3.310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541924PMC
September 2020

A nationwide, multicenter retrospective study on the effectiveness and safety of eribulin in Korean breast cancer patients (REMARK).

Breast 2020 Dec 16;54:121-126. Epub 2020 Sep 16.

Department of Surgery, Gangnam Severance Hospital Yonsei University, Seoul, South Korea. Electronic address:

Purpose: Approval of eribulin for metastatic breast cancer was based on data primarily from Western patients, and there is a paucity of data on the effectiveness and safety of eribulin for Asian patients. To determine the effectiveness and safety of eribulin in Korean women with breast cancer in a real-world setting, we conducted a nationwide, multicenter, retrospective study.

Methods: Patients with locally advanced or metastatic breast cancer who were treated with eribulin in 14 centers throughout Korea were included in this study. Eribulin was generally administered at a dose of 1.23 mg/m (equivalent to 1.4 mg/m eribulin mesylate) by intravenous infusion for 2-5 min, or as a diluted solution, on Days 1 and 8 of every 21-day cycle. The primary endpoint was progression-free survival (PFS) rate at 6 months. Secondary endpoints included median PFS, overall survival (OS), time-to-treatment failure (TTF), tumor response rate, and incidence of hematologic treatment-emergent adverse events (TEAEs).

Results: The safety and full analysis populations included 398 and 360 (38 had no efficacy data) patients, respectively. The PFS rate at 6 months was 37.8%. Median PFS, OS, and TTF were 134, 631, and 120 days, respectively. Objective response rate, clinical benefit rate, and disease control rate were 18.1%, 50.6%, and 49.4%, respectively. Hematologic TEAEs were reported in 65.1% of patients; neutropenia (56.8%) and anemia (11.3%) were most common.

Conclusion: Real-world effectiveness and safety of eribulin in Korean breast cancer patients were consistent with previous reports; no new safety concerns were identified.
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http://dx.doi.org/10.1016/j.breast.2020.09.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519365PMC
December 2020

Relationship of breastfeeding duration with joint pain and knee osteoarthritis in middle-aged Korean women: a cross-sectional study using the Korea National Health and Nutrition Examination Survey.

BMC Womens Health 2020 09 24;20(1):213. Epub 2020 Sep 24.

Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, 3F JS tower, 538 Gangnam-daero, Gangnam-gu, Seoul, 06110, Republic of Korea.

Background: The effect of joint health on the quality of life of middle-aged and older women is becoming more widely recognized with the aging of the world's population. However, the association of long-term breastfeeding with joint pain and knee osteoarthritis has not been fully examined. The aim of this study was to determine the association of prior breastfeeding duration with current joint pain and knee osteoarthritis in middle-aged Korean women.

Methods: This cross-sectional study was conducted among 3454 women aged ≥50 years who underwent knee radiography and answered a questionnaire on breastfeeding and joint pain for the 5th Korea National Health and Nutrition Examination Survey (2010-2011). After adjusting for confounding sociodemographic, medical history, and obstetric and gynecologic variables, logistic regression analysis was conducted to analyze the prevalence of joint pain and knee osteoarthritis according to breastfeeding and its duration.

Results: Among the 3454 participants, 298 had not breastfed and 1042, 815, and 1299 had breastfed for 1-24, 25-48, and ≥ 49 months, respectively. Of all participants, 1731 had joint pain and 739 were diagnosed with knee osteoarthritis after radiography. Using the non-breastfeeding group as a reference, the odds ratio (OR) for joint pain among women who breastfed ≥1 month was 1.49 (95% confidence interval [CI] 1.01-2.21). As the breastfeeding duration increased, the OR of joint pain prevalence also increased (p for trend; p = 0.002). For knee osteoarthritis, the OR was 2.30 in the 25-48 months group (95% CI 1.09-4.86). The OR of knee osteoarthritis in the ≥49 months group was 2.17 (95% CI 1.01-4.64). Sensitivity analysis after selecting only participants aged ≥60 years showed that the prevalence of joint pain and knee osteoarthritis was more positively correlated with extended breastfeeding duration (joint pain, p for trend; p = 0.005) (knee osteoarthritis, p for trend; p = 0.012).

Conclusions: Long-term feeding for more than 25 months was associated with an increased prevalence of joint pain and degenerative arthritis in Korean women aged ≥50 years.
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http://dx.doi.org/10.1186/s12905-020-01078-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517693PMC
September 2020

NO-Reduction Performance Test for TiO Paint.

Molecules 2020 Sep 7;25(18). Epub 2020 Sep 7.

School of Architecture and Building Science, Chung-Ang University, Seoul 06974, Korea.

In South Korea, the gradual increase in particulate matter generation has received significant attention from central and local governments. Exhaust gas, which contains nitrogen oxides (NO), is one of the main sources of particulate matter. In this study, the reduction of NO using a coating material mixed with a titanium dioxide (TiO) photocatalyst was demonstrated. The NO reduction performance of the TiO photocatalyst-infused coating was evaluated by applying the ISO 22197-1: 2007 standard. Subsequently, the performance was evaluated by changing the NO gas concentration and ultraviolet (UV)-A irradiance under standard experimental conditions. It was determined that NO reduction can be achieved even if the NO gas concentration and UV-A irradiance are lower than those under the standard conditions when the TiO photocatalyst-infused coating was used. This study revealed that NO reduction can be realized through TiO photocatalyst-infused coating in winter or cloudy days with a low solar altitude. It was also confirmed that compared with the UV-A irradiance, the NO gas concentration has a greater effect on the NO reduction performance of the TiO photocatalyst-infused coating. These findings can be used to evaluate a variety of construction materials with TiO photocatalysts in the future.
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http://dx.doi.org/10.3390/molecules25184087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571102PMC
September 2020

Nurses' Perspectives on Health Education and Health Literacy of Older Patients.

Int J Environ Res Public Health 2020 09 4;17(18). Epub 2020 Sep 4.

College of Nursing, Dankook University, Cheonan 31116, Korea.

In the context of population aging, enhancing the health of older patients has become an urgent issue for public health. Health education and health literacy need to be further understood from the healthcare providers' standpoint to increase older patients' effective application of such information into their daily lives. We aimed to further understand nurses' perspectives on the education of older patients and their health literacy, as nurses are one of the frontline providers interacting with older patients. In total, 16 nurses and nurse practitioners who had 5 or more years of clinical experience participated. Data were collected via face-to-face interviews and emails. Data analysis followed the thematic analysis suggested by Braun and Clarke. Five themes emerged from the analysis, as follows: attitudes that are hard to change; physical and cognitive functional barriers to understanding teaching materials; family caregivers-surrogate vs. gatekeeper; major contexts that moderate the elderly's health literacy; and strategies to enhance teaching effectiveness and health literacy. These findings illustrate the conditions pertinent to communication with older adults from the patients', providers' and healthcare delivery viewpoints. Systemic assistance and interventions specialized for older patients and their healthcare providers need to be developed and tested to improve clinical practice and patient health literacy.
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http://dx.doi.org/10.3390/ijerph17186455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7558471PMC
September 2020

Flexible Real-Time Polymerase Chain Reaction-Based Platforms for Detecting Deafness Mutations in Koreans: A Proposed Guideline for the Etiologic Diagnosis of Auditory Neuropathy Spectrum Disorder.

Diagnostics (Basel) 2020 Sep 4;10(9). Epub 2020 Sep 4.

Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea.

Routine application of next-generation sequencing in clinical settings is often limited by time- and cost-prohibitive complex filtering steps. Despite the previously introduced genotyping kit that allows screening of the 11 major recurring variants of sensorineural hearing loss (SNHL) genes in the Korean population, the demand for phenotype- and variant-specific screening kits still remains. Herein, we developed a new real-time PCR-based kit (U-TOP™ HL Genotyping Kit Ver2), comprising six variants from two auditory neuropathy spectrum disorder (ANSD) genes ( and ) and five variants from three SNHL genes (, , and ), with a distinct auditory phenotype, making this the first genotyping kit dedicated to ANSD. The concordance rate with Sanger sequencing, sensitivity, and specificity of this genotyping kit were all 100%, suggesting reliability. The kit not only allows timely and cost-effective identification of recurring variants, but it also allows timely detection of cochlear nerve deficiency for those without variants. Herein, we provide a clinical guideline for an efficient, rapid, and cost-effective etiologic diagnosis of prelingual ANSD. Our study provides a good example of continuing to update new key genetic variants, which will continuously be revealed through NGS, as targets for the newly developed genotyping kit.
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http://dx.doi.org/10.3390/diagnostics10090672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554951PMC
September 2020

Development of a pro-arrhythmic ex vivo intact human and porcine model: cardiac electrophysiological changes associated with cellular uncoupling.

Pflugers Arch 2020 10 1;472(10):1435-1446. Epub 2020 Sep 1.

Faculty of Medicine, National Heart and Lung Institute, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK.

We describe a human and large animal Langendorff experimental apparatus for live electrophysiological studies and measure the electrophysiological changes due to gap junction uncoupling in human and porcine hearts. The resultant ex vivo intact human and porcine model can bridge the translational gap between smaller simple laboratory models and clinical research. In particular, electrophysiological models would benefit from the greater myocardial mass of a large heart due to its effects on far-field signal, electrode contact issues and motion artefacts, consequently more closely mimicking the clinical setting. Porcine (n = 9) and human (n = 4) donor hearts were perfused on a custom-designed Langendorff apparatus. Epicardial electrograms were collected at 16 sites across the left atrium and left ventricle. A total of 1 mM of carbenoxolone was administered at 5 ml/min to induce cellular uncoupling, and then recordings were repeated at the same sites. Changes in electrogram characteristics were analysed. We demonstrate the viability of a controlled ex vivo model of intact porcine and human hearts for electrophysiology with pharmacological modulation. Carbenoxolone reduces cellular coupling and changes contact electrogram features. The time from stimulus artefact to (-dV/dt) increased between baseline and carbenoxolone (47.9 ± 4.1-67.2 ± 2.7 ms) indicating conduction slowing. The features with the largest percentage change between baseline and carbenoxolone were fractionation + 185.3%, endpoint amplitude - 106.9%, S-endpoint gradient + 54.9%, S point - 39.4%, RS ratio + 38.6% and (-dV/dt) - 20.9%. The physiological relevance of this methodological tool is that it provides a model to further investigate pharmacologically induced pro-arrhythmic substrates.
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http://dx.doi.org/10.1007/s00424-020-02446-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476990PMC
October 2020

Novel genotype-phenotype correlation of functionally characterized LMX1A variants linked to sensorineural hearing loss.

Hum Mutat 2020 Nov 9;41(11):1877-1883. Epub 2020 Sep 9.

Department of Otorhinolaryngology-Head and Neck Surgery, Bundang Hospital, College of Medicine, Seoul National University, Seongnam, Korea.

LMX1A, encoding the LIM homeobox transcription factor, is essential for inner ear development. Despite previous reports of three human LMX1A variants with nonsyndromic hearing loss (NSHL) in the literature, functional characterization of these variants has never been performed. Encouraged by identification of a de novo, heterozygous, missense variant (c.595A > G; p.Arg199Gly) located in the homeodomain of LMX1A in a subject with congenital severe-to-profound deafness through Exome sequencing, we performed luciferase assay to evaluate transcriptional activity of all LMX1A variants reported in the literature including p.Arg199Gly. Resultantly, p.Arg199Gly manifesting the most severe NSHL showed the biggest reduction of transcriptional activity in contrast with moderately reduced activity of p.Cys97Ser and p.Val241Leu associated with less severe progressive NSHL, proposing a genotype-phenotype correlation. Further, our dominant LMX1A variant exerted pathogenic effects via haploinsufficiency rather than dominant-negative effect. Collectively, we provide a potential genotype-phenotype correlation of LMX1A variants as well as the pathogenic mechanism of LMX1A-related NSHL.
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http://dx.doi.org/10.1002/humu.24095DOI Listing
November 2020

The ectopy-triggering ganglionated plexuses in atrial fibrillation.

Auton Neurosci 2020 11 21;228:102699. Epub 2020 Jul 21.

Myocardial Function Section, NHLI, Imperial College London, UK; Department of Cardiology, Imperial College Healthcare NHS Trust, London, UK; Imperial Centre for Cardiac Engineering, Imperial College London, London, UK. Electronic address:

Background: Epicardial ganglionated plexuses (GP) have an important role in the pathogenesis of atrial fibrillation (AF). The relationship between anatomical, histological and functional effects of GP is not well known. We previously described atrioventricular (AV) dissociating GP (AVD-GP) locations. In this study, we hypothesised that ectopy triggering GP (ET-GP) are upstream triggers of atrial ectopy/AF and have different anatomical distribution to AVD-GP.

Objectives: We mapped and characterised ET-GP to understand their neural mechanism in AF and anatomical distribution in the left atrium (LA).

Methods: 26 patients with paroxysmal AF were recruited. All were paced in the LA with an ablation catheter. High frequency stimulation (HFS) was synchronised to each paced stimulus for delivery within the local atrial refractory period. HFS responses were tagged onto CARTO™ 3D LA geometry. All geometries were transformed onto one reference LA shell. A probability distribution atlas of ET-GP was created. This identified high/low ET-GP probability regions.

Results: 2302 sites were tested with HFS, identifying 579 (25%) ET-GP. 464 ET-GP were characterised, where 74 (16%) triggered ≥30s AF/AT. Median 97 (IQR 55) sites were tested, identifying 19 (20%) ET-GP per patient. >30% of ET-GP were in the roof, mid-anterior wall, around all PV ostia except in the right inferior PV (RIPV) in the posterior wall.

Conclusion: ET-GP can be identified by endocardial stimulation and their anatomical distribution, in contrast to AVD-GP, would be more likely to be affected by wide antral circumferential ablation. This may contribute to AF ablation outcomes.
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http://dx.doi.org/10.1016/j.autneu.2020.102699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511599PMC
November 2020

Anatomical Distribution of Ectopy-Triggering Plexuses in Patients With Atrial Fibrillation.

Circ Arrhythm Electrophysiol 2020 09 27;13(9):e008715. Epub 2020 Jul 27.

Myocardial Function Section, Imperial Centre for Translational and Experimental Medicine (M.-Y.K., B.C.S., M.B.S., C.D.C., F.S.N., N.S.P., P.B.L., N.W.F.L., P.K.), Imperial College London, United Kingdom.

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http://dx.doi.org/10.1161/CIRCEP.120.008715DOI Listing
September 2020

Physicochemical Characteristics of Starch in Sweet Potato Cultivars Grown in Korea.

Prev Nutr Food Sci 2020 Jun;25(2):212-218

Department of Central Area Crop Science, National Institute of Crop Science, Rural Development Administration, Gyeonggi 16613, Korea.

The objective of this study was to investigate the structural and physicochemical properties of starch from seven sweet potato cultivars (Shinyulmi, Sinjami, Hogammi, Jeonmi, Jinyulmi, Juhwangmi, and Pungwonmi). Jeonmi and Jinyulmi had amylose contents of 40.04% and 37.39%, respectively, whereas Juhwangmi and Pungwonmihad amylose contents of 30.95% and 32.37%, respectively. As a result of amylopectin polymerization, the seven cultivars were found to have high (>48%) contents of the degree of polymerization (DP) 13∼24 fraction, whereas the DP≥37 fraction content was <3.45%. The level of resistant starch was highest in Jeonmi (>30%) and lowest in Pungwonmi (<5%). The digestibility of Pungwonmi was greater than that of the other cultivars. Starch X-ray patterns did not differ among the cultivars. The results of this study provide useful information for the food industry regarding the application of sweet potato starches.
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http://dx.doi.org/10.3746/pnf.2020.25.2.212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333007PMC
June 2020

3D Contact Position Estimation of Image-Based Areal Soft Tactile Sensor with Printed Array Markers and Image Sensors.

Sensors (Basel) 2020 Jul 7;20(13). Epub 2020 Jul 7.

School of Electronics Engineering, Kyungpook National University, Daegu 41566, Korea.

Tactile sensors have been widely used and researched in various fields of medical and industrial applications. Gradually, they will be used as new input devices and contact sensors for interactive robots. If a tactile sensor is to be applied to various forms of human-machine interactions, it needs to be soft to ensure comfort and safety, and it should be easily customizable and inexpensive. The purpose of this study is to estimate 3D contact position of a novel image-based areal soft tactile sensor (IASTS) using printed array markers and multiple cameras. First, we introduce the hardware structure of the prototype IASTS, which consists of a soft material with printed array markers and multiple cameras with LEDs. Second, an estimation algorithm for the contact position is proposed based on the image processing of the array markers and their Gaussian fittings. A series of basic experiments was conducted and their results were analyzed to verify the effectiveness of the proposed IASTS hardware and its estimation software. To ensure the stability of the estimated contact positions a Kalman filter was developed. Finally, it was shown that the contact positions on the IASTS were estimated with a reasonable error value for soft haptic applications.
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http://dx.doi.org/10.3390/s20133796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7374373PMC
July 2020

Observational study on effectiveness and safety of integrative Korean medicine treatment for inpatients with sciatica due to lumbar intervertebral disc herniation.

Medicine (Baltimore) 2020 May;99(21):e20083

Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation.

We developed a protocol for a prospective registry to prove the effectiveness and safety of integrative Korean medicine treatment for inpatients with sciatica due to lumbar intervertebral disc herniation. We plan on recruiting 1000 inpatients receiving integrative Korean medicine treatment for lumbar intervertebral disc herniation at four spine specialized Korean medical hospitals. Patients enrolled in the registry will be evaluated at the time of hospitalization, 2 weeks after hospitalization, at discharge, and 6 months after hospitalization on predefined outcome variables such as intensity of back and leg pain, Oswestry Disability Index, quality of life, Patient Global Impression of Change, and adverse effects. The protocol of this study was registered in CRIS (KCT0003709) and Clinical trial gov (NCT03750591). This study is significant in that it cannot only be a basis for safety-related evidence of complementary alternative medicine, which has been lacking, but it also gives clear evidence on the effectiveness and validity of treatment effects such as accompaniment of stenosis, sex, age, and type of disc herniation.
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http://dx.doi.org/10.1097/MD.0000000000020083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7249894PMC
May 2020

MMTR/Dmap1 Sets the Stage for Early Lineage Commitment of Embryonic Stem Cells by Crosstalk with PcG Proteins.

Cells 2020 05 11;9(5). Epub 2020 May 11.

Department of Life Science and Research Institute for Natural Sciences, College of Natural Sciences, Hanyang University, Seoul 04763, Korea.

Chromatin remodeling, including histone modification, chromatin (un)folding, and nucleosome remodeling, is a significant transcriptional regulation mechanism. By these epigenetic modifications, transcription factors and their regulators are recruited to the promoters of target genes, and thus gene expression is controlled through either transcriptional activation or repression. The -mediated transcriptional repressor (MMTR)/DNA methyltransferase 1 (DNMT1)-associated protein (Dmap1) is a transcription corepressor involved in chromatin remodeling, cell cycle regulation, DNA double-strand break repair, and tumor suppression. The Tip60-p400 complex proteins, including MMTR/Dmap1, interact with the oncogene Myc in embryonic stem cells (ESCs). These proteins interplay with the stem cell-related proteome networks and regulate gene expressions. However, the detailed mechanisms of their functions are unknown. Here, we show that MMTR/Dmap1, along with other Tip60-p400 complex proteins, bind the promoters of differentiation commitment genes in mouse ESCs. Hence, MMTR/Dmap1 controls gene expression alterations during differentiation. Furthermore, we propose a novel mechanism of MMTR/Dmap1 function in early stage lineage commitment of mouse ESCs by crosstalk with the polycomb group (PcG) proteins. The complex controls histone mark bivalency and transcriptional poising of commitment genes. Taken together, our comprehensive findings will help better understand the MMTR/Dmap1-mediated transcriptional regulation in ESCs and other cell types.
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http://dx.doi.org/10.3390/cells9051190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290897PMC
May 2020

LI-RADS M (LR-M) criteria and reporting algorithm of v2018: diagnostic values in the assessment of primary liver cancers on gadoxetic acid-enhanced MRI.

Abdom Radiol (NY) 2020 08;45(8):2440-2448

Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea.

Purpose: To evaluate diagnostic values of the liver imaging reporting and data system (LI-RADS) M (LR-M) category based on novel explicit criteria that accept both targetoid and nontargetoid LR-M features and the suggested reporting algorithm of LI-RADS v2018 to assess primary liver cancers (PLCs) on gadoxetic acid-enhanced MRI (Gd-EOB-MRI).

Methods: This retrospective study included 165 patients at high risk for hepatocellular carcinoma (HCC) with pathologically confirmed PLCs (HCC, n = 113; intrahepatic cholangiocarcinoma [iCCA], n = 23; and combined hepatocellular cholangiocarcinoma [cHCC-CCA], n = 29). Two radiologists independently analyzed Gd-EOB-MRI features and determined LI-RADS category for each tumor and categorized the likely etiology either as HCC or non-HCC malignancy if LR-M was assigned. Diagnostic performances for HCC or those for malignancy were compared according to imaging criteria.

Results: LR-M was assigned in 95.7%/91.3% of iCCAs; 55.2%/58.6% of cHCC-CCAs; and 21.2%/17.7% of HCCs in reviewers 1/2. Combination of LR-5 plus LR-M resulted in sensitivity of 95.2%/97.6% to diagnose PLCs as malignant, which were significantly higher than that of LR-5 plus "LR-M with ≥ 1 targetoid appearances" (84.8%/91.5%, Ps < 0.01). In comparison to LR-5, LR-5 plus "LR-M of HCC as likely etiology" resulted in significant increase in sensitivity (73.5%/79.6% versus 87.6%/92.9%, Ps < 0.001) but significant decrease in specificity (76.9%/75.0% versus 57.7%/50.0%, P = 0.002 and < 0.001) in the diagnosis of HCC.

Conclusion: The LR-M criteria v2018 are useful to differentiate non-HCC malignancies from HCCs and to accurately diagnose PLCs as a malignancy. Reporting the likely etiology in LR-M may facilitate a more sensitive detection of HCC, but along with a considerable decrease in specificity.
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http://dx.doi.org/10.1007/s00261-020-02545-zDOI Listing
August 2020

Automatic segmentation of mitochondria and endolysosomes in volumetric electron microscopy data.

Comput Biol Med 2020 04 3;119:103693. Epub 2020 Mar 3.

Faculty of Computer and Information Science, University of Ljubljana, Večna pot 113, 1000 Ljubljana, Slovenia. Electronic address:

Automatic segmentation of intracellular compartments is a powerful technique, which provides quantitative data about presence, spatial distribution, structure and consequently the function of cells. With the recent development of high throughput volumetric data acquisition techniques in electron microscopy (EM), manual segmentation is becoming a major bottleneck of the process. To aid the cell research, we propose a technique for automatic segmentation of mitochondria and endolysosomes obtained from urinary bladder urothelial cells by the dual beam EM technique. We present a novel publicly available volumetric EM dataset - the first of urothelial cells, evaluate several state-of-the-art segmentation methods on the new dataset and present a novel segmentation pipeline, which is based on supervised deep learning and includes mechanisms that reduce the impact of dependencies in the input data, artefacts and annotation errors. We show that our approach outperforms the compared methods on the proposed dataset.
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http://dx.doi.org/10.1016/j.compbiomed.2020.103693DOI Listing
April 2020

Evaluation of Two Mutation Tests on Tumor and Plasma from Patients with Non-Small Cell Lung Cancer.

Cancers (Basel) 2020 Mar 26;12(4). Epub 2020 Mar 26.

Laboratory of Medical Oncology, Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.

Epidermal growth factor receptor () mutation testing is essential for individualized treatment using tyrosine kinase inhibitors. We evaluated two mutation tests, cobas v2 and PANAMutyper, for detection of activating mutations Ex19del, L858R, and T790M in tumor tissue and plasma from 244 non-small cell lung cancer (NSCLC) patients. The Kappa coefficient (95% CI) between the tests was 0.82 (0.74-0.92) in tumor samples (suggesting almost perfect agreement) and 0.69 (0.54-0.84) in plasma (suggesting substantial agreement). In plasma samples, both tests showed low to moderate sensitivity depending on disease stage but high diagnostic precision (86%-100%) in all disease stages (sensitivity: percentage of mutations in tumors that are also detected in plasma; precision: percentage of mutations in plasma which are also detected in tumors). Among the 244 patients, those previously diagnosed as T790M carriers who received osimertinib treatment showed dramatically better clinical outcomes than T790M carriers without osimertinib treatment. Taken together, our study supports interchangeable use of cobas v2 and PANAMutyper in tumor and plasma testing. Both tests have high diagnostic precision in plasma but are particularly valuable in late-stage disease. Our clinical data in T790M carriers strongly support the clinical benefits of osimertinib treatment guided by both mutation tests.
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http://dx.doi.org/10.3390/cancers12040785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226165PMC
March 2020