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4. Niacinamide Down-Regulates the Expression of DKK-1 and Protects Cells from Oxidative Stress in Cultured Human Dermal Papilla Cells

Author

Choi YH, Shin JY, Kim J, Kang NG, and Lee S

Subjects
anti-hair loss, hair follicle, ros, cell cycle, Dermatology, RL1-803
Abstract

Yun-Ho Choi, Jae Young Shin, Jaeyoon Kim, Nae-Gyu Kang, Sanghwa Lee LG Household & Health Care (LG H&H) R&D Center, Seoul, 07795, KoreaCorrespondence: Sanghwa LeeLG Household & Health Care (LG H&H) R&D Center, 70, Magokjoongang 10-ro, Gangseo-gu, Seoul, 07795, KoreaTel +82-2-6980-1210Fax +82-2-6980-1615Email shleek@lghnh.comPurpose: An increasing number of people are suffering from hair loss disorders. Niacinamide has long been used as an active ingredient for anti-hair loss preparations but the exact mechanism has not been clearly elucidated yet. The effects of niacinamide were investigated in cultured human dermal papilla cells (hDPCs).Methods: To investigate the anti-hair loss effect of niacinamide and its molecular mechanisms, Western blot analysis, ELISA, quantitative RT-PCR and immunocytochemistry were performed. To study the protective effects of niacinamide against H2O2-induced oxidative stress, ROS generation and cytotoxicity were evaluated by DCF-DA assay and LDH release assay, respectively. Minoxidil was used as a positive control.Results: Niacinamide decreased the protein expression level of DKK-1 which promotes regression of hair follicles by inducing catagen. The protein expression levels of cell senescence markers, p21 (CDKN1A) and p16 (CDKN2A) which are related to cell cycle arrest, were decreased. The expression of versican was increased by niacinamide treatment in cultured hDPCs. We have found that niacinamide decreased the H2O2-induced intracellular ROS production in cultured hDPCs. Moreover, niacinamide decreased the protein expression levels of H2O2-induced p21 and p16 and diminished the secretion of H2O2-induced DKK-1.Conclusion: Our data demonstrate that niacinamide could enhance hair growth by preventing oxidative stress-induced cell senescence and premature catagen entry of hair follicles.Keywords: anti-hair loss, hair follicle, ROS, cell cycle

Published
2021

6. Effects of Inflammatory Disease on Clinical Progression and Treatment of Ischiogluteal Bursitis: A Retrospective Observational Study

Author

Roh YH, Yoo SJ, Choi YH, Yang HC, and Nam KW

Subjects
ischiogluteal bursitis, clinical course, inflammatory disease, treatment responsiveness, risk factor, Orthopedic surgery, RD701-811
Abstract

INTRODUCTION: The symptoms of Ischiogluteal Bursitis (IGB) are often nonspecific and atypical, and its diagnosis is more challenging. Moreover, it is difficult to predict cases of chronic progression or poor treatment response. Therefore, the aim of this study was to investigate the clinical course of IGB patients and identify factors that are predictive of failure of conservative treatment. MATERIALS AND METHODS: Our study consisted of IGB patients diagnosed between 2010 March and 2016 December who had been followed-up for at least one year. Structured questionnaires and medical records were reviewed to analyse demographic characteristics, lifestyle patterns, blood tests, and imaging studies. We categorized the cases into two groups based on the response to conservative treatment and the need for surgical intervention. RESULTS: The most common initial chief symptoms were buttock pains in 24 patients (37.5%). Physical examinations showed the tenderness of ischial tuberosity area in 59 (92.2%) patients, but no specific findings were confirmed in 5 patients (7.8%). 51 patients (79.7%) responded well to the conservative management, 11 patients (17.2%) needed injection, and 2 patients (3.1%) had surgical treatment performed due to continuous recurrence. There was no difference in demographic and blood lab data between the two groups. However, the incidence of inflammatory diseases (response group: 10.3% vs non-response group: 66.7%, p=0.004) was significantly different between the two groups. CONCLUSION: The diagnosis of IGB can be missed due to variations in clinical symptoms, and cautions should be exercised in patients with inflammatory diseases as conservative treatment is less effective in them, leading to chronic progression of IGB.

Published
2020
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12. Early postoperative delirium after hemiarthroplasty in elderly patients aged over 70 years with displaced femoral neck fracture

Author

Choi YH, Kim DH, Kim TY, Lim T, Kim SW, and Yoo JH

Subjects
Delirium, Elderly patients, Femoral neck fracture, Hemiarthroplasty, Geriatrics, RC952-954.6
Abstract

Yi-Hwa Choi,1 Dae-Hwan Kim,2 Tae-Young Kim,2 Tae-Wan Lim,1 Seok-Woo Kim,2 Je-Hyun Yoo2 1Department of Anesthesiology and Pain Medicine, Hallym Sacred Heart Hospital, Hallym University College of Medicine, 2Department of Orthopaedic Surgery, Hallym Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Republic of Korea Purpose: Postoperative delirium is a risk factor for worse outcome after hip fracture surgery in elderly patients. Postoperative delirium is associated with anesthesia, postoperative pain, and patient factors. We investigated the incidence, predictors, and prognostic implications of postoperative delirium after hemiarthroplasty (HA) in elderly patients with femoral neck fracture.Patients and methods: A total of 356 consecutive patients aged >70 years who underwent HA for femoral neck fracture were enrolled. Diagnosis of delirium was made by a psychiatrist based on patient status and an objective scoring system. The patients were divided into 2 categories according to the HA onset time (immediate [≤24 h after surgery] vs delayed delirium [>24 h after surgery]) and its incidence, predictors and mortality were evaluated.Results: Postoperative delirium was diagnosed in 110 patients (30.9%) during hospitalization. Immediate and delayed delirium occurred in 59 (53.6%), and 51 (46.4%) patients, respectively. The independent predictors of immediate delirium included age (odds ratio [OR] 1.47, 95% CI 0.98–2.23, p=0.066), and general anesthesia (OR 2.25, 95% CI 1.17–4.43, p=0.015). The independent predictors of delayed delirium were parkinsonism (OR 5.75, 95% CI 1.66–19.96, p=0.006), intensive care unit stay (OR 1.85, 95% CI 0.97–3.56, p=0.064), and higher American Society of Anesthesiologists grade (OR 2.33, 95% CI 0.90–6.07, p=0.083). On Kaplan–Meier survival analysis, the 2-year survival rate was significantly lower in the immediate delirium group than those in the delayed and control groups (71.0% vs 83.6% vs 87.8%, respectively; p=0.031).Conclusion: Immediate and delayed delirium after HA for femoral neck fracture had different predictors and immediate delirium was associated with worse prognosis. Keywords: delirium, elderly patients, femoral neck fracture, hemiarthroplasty

Published
2017

13. Sex differences in the effect of aging on dry eye disease

Author

Ahn JH, Choi YH, Paik HJ, Kim MK, Wee WR, and Kim DH

Subjects
Dry eye disease, Risk factors, Sex differences, Aging, Previous ocular surgery, Geriatrics, RC952-954.6
Abstract

Jong Ho Ahn,1 Yoon-Hyeong Choi,2 Hae Jung Paik,1 Mee Kum Kim,3 Won Ryang Wee,3 Dong Hyun Kim1 1Department of Ophthalmology, Gachon University Gil Medical Center, 2Department of Preventive Medicine, Gachon University College of Medicine, Incheon, 3Department of Ophthalmology, Seoul National University College of Medicine, Seoul, South Korea Purpose: Aging is a major risk factor in dry eye disease (DED), and understanding sexual differences is very important in biomedical research. However, there is little information about sex differences in the effect of aging on DED. We investigated sex differences in the effect of aging and other risk factors for DED.Methods: This study included data of 16,824 adults from the Korea National Health and Nutrition Examination Survey (2010–2012), which is a population-based cross-sectional survey. DED was defined as the presence of frequent ocular dryness or a previous diagnosis by an ophthalmologist. Basic sociodemographic factors and previously known risk factors for DED were included in the analyses. Linear regression modeling and multivariate logistic regression modeling were used to compare the sex differences in the effect of risk factors for DED; we additionally performed tests for interactions between sex and other risk factors for DED in logistic regression models.Results: In our linear regression models, the prevalence of DED symptoms in men increased with age (R=0.311, P=0.012); however, there was no association between aging and DED in women (P>0.05). Multivariate logistic regression analyses showed that aging in men was not associated with DED (DED symptoms/diagnosis: odds ratio [OR] =1.01/1.04, each P>0.05), while aging in women was protectively associated with DED (DED symptoms/diagnosis: OR =0.94/0.91, P=0.011/0.003). Previous ocular surgery was significantly associated with DED in both men and women (men/women: OR =2.45/1.77 [DED symptoms] and 3.17/2.05 [DED diagnosis], each P

Published
2017

14. Structural insights into the multifunctionality of rabies virus P3 protein

Author

Sethi, A, Rawlinson, SM, Dubey, A, Ang, C-S, Choi, YH, Yan, F, Okada, K, Rozario, AM, Brice, AM, Ito, N, Williamson, NA, Hatters, DM, Bell, TDM, Arthanari, H, Moseley, GW, Gooley, PR, Sethi, A, Rawlinson, SM, Dubey, A, Ang, C-S, Choi, YH, Yan, F, Okada, K, Rozario, AM, Brice, AM, Ito, N, Williamson, NA, Hatters, DM, Bell, TDM, Arthanari, H, Moseley, GW, and Gooley, PR

Abstract

Viruses form extensive interfaces with host proteins to modulate the biology of the infected cell, frequently via multifunctional viral proteins. These proteins are conventionally considered as assemblies of independent functional modules, where the presence or absence of modules determines the overall composite phenotype. However, this model cannot account for functions observed in specific viral proteins. For example, rabies virus (RABV) P3 protein is a truncated form of the pathogenicity factor P protein, but displays a unique phenotype with functions not seen in longer isoforms, indicating that changes beyond the simple complement of functional modules define the functions of P3. Here, we report structural and cellular analyses of P3 derived from the pathogenic RABV strain Nishigahara (Nish) and an attenuated derivative strain (Ni-CE). We identify a network of intraprotomer interactions involving the globular C-terminal domain and intrinsically disordered regions (IDRs) of the N-terminal region that characterize the fully functional Nish P3 to fluctuate between open and closed states, whereas the defective Ni-CE P3 is predominantly open. This conformational difference appears to be due to the single mutation N226H in Ni-CE P3. We find that Nish P3, but not Ni-CE or N226H P3, undergoes liquid-liquid phase separation and this property correlates with the capacity of P3 to interact with different cellular membrane-less organelles, including those associated with immune evasion and pathogenesis. Our analyses propose that discrete functions of a critical multifunctional viral protein depend on the conformational arrangements of distant individual domains and IDRs, in addition to their independent functions.

Published
2023

15. Schisandrae fructus enhances myogenic differentiation and inhibits atrophy through protein synthesis in human myotubes

Author

Kim CH, Shin JH, Hwang SJ, Choi YH, Kim DS, and Kim CM

Subjects
Schisandrae fructus, mTOR signaling, Human skeletal muscle cells, Myotube, Medicine (General), R5-920
Abstract

Cy Hyun Kim,1,2,* Jin-Hong Shin,1,3,* Sung Jun Hwang,1,2 Yung Hyun Choi,4 Dae-Seong Kim,1,3 Cheol Min Kim2,51Research Institute of Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, 2Center for Anti-Aging Industry, Pusan National University, Busan, 3Department of Neurology, Pusan National University Yangsan Hospital, Yangsan, 4Department of Biochemistry, Dong-eui University College of Korean Medicine, Busan, 5Department of Biomedical Informatics, Pusan National University School of Medicine, Yangsan, Republic of Korea*These authors contributed equally to this work Abstract: Schisandrae fructus (SF) has recently been reported to increase skeletal muscle mass and inhibit atrophy in mice. We investigated the effect of SF extract on human myotube differentiation and its acting pathway. Various concentrations (0.1–10 µg/mL) of SF extract were applied on human skeletal muscle cells in vitro. Myotube area and fusion index were measured to quantify myotube differentiation. The maximum effect was observed at 0.5 µg/mL of SF extract, enhancing differentiation up to 1.4-fold in fusion index and 1.6-fold in myotube area at 8 days after induction of differentiation compared to control. Phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1 and 70 kDa ribosomal protein S6 kinase, which initiate translation as downstream of mammalian target of rapamycin pathway, was upregulated in early phases of differentiation after SF treatment. SF also attenuated dexamethasone-induced atrophy. In conclusion, we show that SF augments myogenic differentiation and attenuates atrophy by increasing protein synthesis through mammalian target of rapamycin/70 kDa ribosomal protein S6 kinase and eukaryotic translation initiation factor 4E-binding protein 1 signaling pathway in human myotubes. SF can be a useful natural dietary supplement in increasing skeletal muscle mass, especially in the aged with sarcopenia and the patients with disuse atrophy.Keywords: Schisandrae fructus, mTOR signaling, human skeletal muscle cells, myotubes

Published
2016

16. Association of systolic blood pressure drop with intravenous administration of itraconazole in children with hemato-oncologic disease

Author

Lee HJ, Lee B, Park JD, Jeong HJ, Choi YH, Ju HY, Hong CR, Lee JW, Kim H, Suh DI, Park KD, Kang HJ, Shin HY, and Ahn HS

Subjects
itraconazole, blood pressure, hemato-oncologic disease, hypotensive drug, intropics, CRRT, Therapeutics. Pharmacology, RM1-950
Abstract

Hyeong Jin Lee,1,* Bongjin Lee,2,* June Dong Park,2 Hyung Joo Jeong,2 Yu Hyeon Choi,2 Hee Young Ju,1 Che Ry Hong,1 Ji Won Lee,1 Hyery Kim,1 Dong In Suh,3 Kyung Duk Park,1 Hyoung Jin Kang,1 Hee Young Shin,1 Hyo Seop Ahn1 1Department of Pediatrics, Cancer Research Institute, 2Division of Pediatric Intensive Care, Department of Pediatrics, 3Division of Pulmonology, Department of Pediatrics, Seoul National University College of Medicine, Seoul National University, Seoul, South Korea *These authors contributed equally to this work Purpose: Although few adverse effects have been reported for itraconazole, a widely used antifungal therapy for febrile neutropenia, we found intravenous (IV) itraconazole to be associated with serious cases of blood pressure (BP) drop. We therefore evaluated the incidence and risk factors for BP drop during IV administration of the drug.Materials and methods: We reviewed the medical records of children with hemato-oncologic disease who were treated with IV itraconazole from January 2012 to December 2013. By analyzing systolic BP (SBP) measurements made from 4 hours before through to 4 hours after itraconazole administration, we evaluated the changes in SBP and the risk factors for an SBP drop, especially clinically meaningful (≥20%) drops.Results: Itraconazole was administered 2,627 times to 180 patients. The SBP during the 4 hours following itraconazole administration was lower than during the 4 hours before administration (104 [53.0–160.33 mmHg] versus 105 [59.8–148.3 mmHg]; P

Published
2015

17. Anti-inflammatory effects of cordycepin in lipopolysaccharide-stimulated RAW 264.7 macrophages through Toll-like receptor 4-mediated suppression of mitogen-activated protein kinases and NF-κB signaling pathways

Author

Choi YH, Kim GY, and Lee HH

Subjects
Therapeutics. Pharmacology, RM1-950
Abstract

Yung Hyun Choi,1,2 Gi-Young Kim,3 Hye Hyeon Lee4 1Department of Biochemistry, Dongeui University College of Korean Medicine, Busan, 2Anti-Aging Research Center and Blue-Bio Industry RIC, Dongeui University, Busan, 3Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju, 4Daegu Gyeongbuk Institute of Science and Technology, Daegu, Republic of Korea Abstract: Cordycepin is the main functional component of the Cordyceps species, which has been widely used in traditional Oriental medicine. This compound possesses many pharmacological properties, such as an ability to enhance immune function, as well as antioxidant, antiaging, and anticancer effects. In the present study, we investigated the anti-inflammatory effects of cordycepin using a murine macrophage RAW 264.7 cell model. Our data demonstrated that cordycepin suppressed production of proinflammatory mediators such as nitric oxide (NO) and prostaglandin E2 by inhibiting inducible NO synthase and cyclooxygenase-2 gene expression. Cordycepin also inhibited the release of proinflammatory cytokines, including tumor necrosis factor-alpha and interleukin-1-beta, through downregulation of respective mRNA expression. In addition, pretreatment with cordycepin significantly inhibited lipopolysaccharide (LPS)-induced phosphorylation of mitogen-activating protein kinases and attenuated nuclear translocation of NF-κB by LPS, which was associated with abrogation of inhibitor kappa B-alpha degradation. Furthermore, cordycepin potently inhibited the binding of LPS to macrophages and LPS-induced Toll-like receptor 4 and myeloid differentiation factor 88 expression. Taken together, the results suggest that the inhibitory effects of cordycepin on LPS-stimulated inflammatory responses in RAW 264.7 macrophages are associated with suppression of mitogen-activating protein kinases and activation of NF-κB by inhibition of the Toll-like receptor 4 signaling pathway. Keywords: cordycepin, anti-inflammation, mitogen-activated protein kinases, NF-κB, Toll-like receptor 4

Published
2014

18. Sequence grammar underlying the unfolding and phase separation of globular proteins

Author

Ruff, KM, Choi, YH, Cox, D, Ormsby, AR, Myung, Y, Ascher, DB, Radford, SE, V. Pappu, R, Hatters, DM, Ruff, KM, Choi, YH, Cox, D, Ormsby, AR, Myung, Y, Ascher, DB, Radford, SE, V. Pappu, R, and Hatters, DM

Abstract

Aberrant phase separation of globular proteins is associated with many diseases. Here, we use a model protein system to understand how the unfolded states of globular proteins drive phase separation and the formation of unfolded protein deposits (UPODs). We find that for UPODs to form, the concentrations of unfolded molecules must be above a threshold value. Additionally, unfolded molecules must possess appropriate sequence grammars to drive phase separation. While UPODs recruit molecular chaperones, their compositional profiles are also influenced by synergistic physicochemical interactions governed by the sequence grammars of unfolded proteins and cellular proteins. Overall, the driving forces for phase separation and the compositional profiles of UPODs are governed by the sequence grammars of unfolded proteins. Our studies highlight the need for uncovering the sequence grammars of unfolded proteins that drive UPOD formation and cause gain-of-function interactions whereby proteins are aberrantly recruited into UPODs.

Published
2022

19. Infant hospitalisations and fatalities averted by the maternal pertussis vaccination programme in England, 2012-2017: Post-implementation economic evaluation

Author

Sandmann, F, Jit, M, Andrews, N, Buckley, HL, Campbell, H, Ribeiro, S, Sile, B, Stowe, J, Tessier, E, Ramsay, M, Choi, YH, and Amirthalingam, G

Abstract

In October 2012, a maternal pertussis vaccination programme was implemented in England following an increased incidence and mortality in infants. We evaluated the cost-effectiveness of the programme by comparing pertussis-related infant hospitalisations and deaths in 2012-2017 with non-vaccination scenarios. Despite considerable uncertainties, findings support the cost-effectiveness of the programme.

Published
2020

20. Can we trust the prediction model? Demonstrating the importance of external validation by investigating the COVID-19 Vulnerability (C-19) Index across an international network of observational healthcare datasets

Author

Reps, J, Kim, C, Williams, R, Markus, A, Yang, C, Salles, TD, Falconer, T, Jonnagaddala, J, Williams, A, Fernández-Bertolín, S, DuVall, S, Kostka, K, Rao, G, Shoaibi, A, Ostropolets, A, Spotnitz, M, Zhang, L, Casajust, P, Steyerberg, E, Nyberg, F, Kaas-Hansen, BS, Choi, YH, Morales, D, Liaw, S-T, Fernandes Abrahão, MT, Areia, C, Matheny, M, Aragón, M, Park, RW, Hripcsak, G, Reich, C, Suchard, M, You, SC, Ryan, P, Prieto-Alhambra, D, Rijnbeek, P, Reps, J, Kim, C, Williams, R, Markus, A, Yang, C, Salles, TD, Falconer, T, Jonnagaddala, J, Williams, A, Fernández-Bertolín, S, DuVall, S, Kostka, K, Rao, G, Shoaibi, A, Ostropolets, A, Spotnitz, M, Zhang, L, Casajust, P, Steyerberg, E, Nyberg, F, Kaas-Hansen, BS, Choi, YH, Morales, D, Liaw, S-T, Fernandes Abrahão, MT, Areia, C, Matheny, M, Aragón, M, Park, RW, Hripcsak, G, Reich, C, Suchard, M, You, SC, Ryan, P, Prieto-Alhambra, D, and Rijnbeek, P

Abstract

Background

SARS-CoV-2 is straining healthcare systems globally. The burden on hospitals during the pandemic could be reduced by implementing prediction models that can discriminate between patients requiring hospitalization and those who do not. The COVID-19 vulnerability (C-19) index, a model that predicts which patients will be admitted to hospital for treatment of pneumonia or pneumonia proxies, has been developed and proposed as a valuable tool for decision making during the pandemic. However, the model is at high risk of bias according to the Prediction model Risk Of Bias ASsessment Tool and has not been externally validated.

Methods

We followed the OHDSI framework for external validation to assess the reliability of the C-19 model. We evaluated the model on two different target populations: i) 41,381 patients that have SARS-CoV-2 at an outpatient or emergency room visit and ii) 9,429,285 patients that have influenza or related symptoms during an outpatient or emergency room visit, to predict their risk of hospitalization with pneumonia during the following 0 to 30 days. In total we validated the model across a network of 14 databases spanning the US, Europe, Australia and Asia.

Findings

The internal validation performance of the C-19 index was a c-statistic of 0.73 and calibration was not reported by the authors. When we externally validated it by transporting it to SARS-CoV-2 data the model obtained c-statistics of 0.36, 0.53 (0.473-0.584) and 0.56 (0.488-0.636) on Spanish, US and South Korean datasets respectively. The calibration was poor with the model under-estimating risk. When validated on 12 datasets containing influenza patients across the OHDSI network the c-statistics ranged between 0.40-0.68.

Interpretation

The results show that the discriminative performance of the C-19 model is low for influenza cohorts, and even worse amongst COVID-19 patients in the US, Spain and South Korea. These results suggest that C-19 s

Published
2020

21. Seek COVER: Development and validation of a personalized risk calculator for COVID-19 outcomes in an international network

Author

Williams, R, Markus, A, Yang, C, Salles, TD, DuVall, S, Falconer, T, Jonnagaddala, J, Kim, C, Rho, Y, Williams, A, Alberga, A, An, MH, Aragón, M, Areia, C, Burn, E, Choi, YH, Drakos, I, Fernandes Abrahão, MT, Fernández-Bertolín, S, Hripcsak, G, Kaas-Hansen, BS, Kandukuri, P, Kors, J, Kostka, K, Liaw, S-T, Lynch, K, Machnicki, G, Matheny, M, Morales, D, Nyberg, F, Park, RW, Prats-Uribe, A, Pratt, N, Rao, G, Reich, C, Rivera, M, Seinen, T, Shoaibi, A, Spotnitz, M, Steyerberg, E, Suchard, M, You, SC, Zhang, L, Zhou, L, Ryan, P, Prieto-Alhambra, D, Reps, J, Rijnbeek, P, Williams, R, Markus, A, Yang, C, Salles, TD, DuVall, S, Falconer, T, Jonnagaddala, J, Kim, C, Rho, Y, Williams, A, Alberga, A, An, MH, Aragón, M, Areia, C, Burn, E, Choi, YH, Drakos, I, Fernandes Abrahão, MT, Fernández-Bertolín, S, Hripcsak, G, Kaas-Hansen, BS, Kandukuri, P, Kors, J, Kostka, K, Liaw, S-T, Lynch, K, Machnicki, G, Matheny, M, Morales, D, Nyberg, F, Park, RW, Prats-Uribe, A, Pratt, N, Rao, G, Reich, C, Rivera, M, Seinen, T, Shoaibi, A, Spotnitz, M, Steyerberg, E, Suchard, M, You, SC, Zhang, L, Zhou, L, Ryan, P, Prieto-Alhambra, D, Reps, J, and Rijnbeek, P

Abstract

Objective

To develop and externally validate COVID-19 Estimated Risk (COVER) scores that quantify a patient’s risk of hospital admission (COVER-H), requiring intensive services (COVER-I), or fatality (COVER-F) in the 30-days following COVID-19 diagnosis.

Methods

We analyzed a federated network of electronic medical records and administrative claims data from 14 data sources and 6 countries. We developed and validated 3 scores using 6,869,127 patients with a general practice, emergency room, or outpatient visit with diagnosed influenza or flu-like symptoms any time prior to 2020. The scores were validated on patients with confirmed or suspected COVID-19 diagnosis across five databases from South Korea, Spain and the United States. Outcomes included i) hospitalization with pneumonia, ii) hospitalization with pneumonia requiring intensive services or death iii) death in the 30 days after index date.

Results

Overall, 44,507 COVID-19 patients were included for model validation. We identified 7 predictors (history of cancer, chronic obstructive pulmonary disease, diabetes, heart disease, hypertension, hyperlipidemia, kidney disease) which combined with age and sex discriminated which patients would experience any of our three outcomes. The models achieved high performance in influenza. When transported to COVID-19 cohorts, the AUC ranges were, COVER-H: 0.69-0.81, COVER-I: 0.73-0.91, and COVER-F: 0.72-0.90. Calibration was overall acceptable.

Conclusions

A 9-predictor model performs well for COVID-19 patients for predicting hospitalization, intensive services and fatality. The models could aid in providing reassurance for low risk patients and shield high risk patients from COVID-19 during de-confinement to reduce the virus’ impact on morbidity and mortality.

Published
2020

24. The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research

Author

McAlpine, JB, Chen, SN, Kutateladze, A, Macmillan, JB, Appendino, G, Barison, A, Beniddir, MA, Biavatti, MW, Bluml, S, Boufridi, A, Butler, MS, Capon, RJ, Choi, YH, Coppage, D, Crews, P, Crimmins, MT, Csete, M, Dewapriya, P, Egan, JM, Garson, MJ, Genta-Jouve, G, Gerwick, WH, Gross, H, Harper, MK, Hermanto, P, Hook, JM, Hunter, L, Jeannerat, D, Ji, NY, Johnson, TA, Kingston, DGI, Koshino, H, Lee, HW, Lewin, G, Li, J, Linington, RG, Liu, M, McPhail, KL, Molinski, TF, Moore, BS, Nam, JW, Neupane, RP, Niemitz, M, Nuzillard, JM, Oberlies, NH, Ocampos, FMM, Pan, G, Quinn, RJ, Reddy, DS, Renault, JH, Rivera-Chávez, J, Robien, W, Saunders, CM, Schmidt, TJ, Seger, C, Shen, B, Steinbeck, C, Stuppner, H, Sturm, S, Taglialatela-Scafati, O, Tantillo, DJ, Verpoorte, R, Wang, BG, Williams, CM, Williams, PG, Wist, J, Yue, JM, Zhang, C, Xu, Z, Simmler, C, Lankin, DC, Bisson, J, Pauli, GF, McAlpine, JB, Chen, SN, Kutateladze, A, Macmillan, JB, Appendino, G, Barison, A, Beniddir, MA, Biavatti, MW, Bluml, S, Boufridi, A, Butler, MS, Capon, RJ, Choi, YH, Coppage, D, Crews, P, Crimmins, MT, Csete, M, Dewapriya, P, Egan, JM, Garson, MJ, Genta-Jouve, G, Gerwick, WH, Gross, H, Harper, MK, Hermanto, P, Hook, JM, Hunter, L, Jeannerat, D, Ji, NY, Johnson, TA, Kingston, DGI, Koshino, H, Lee, HW, Lewin, G, Li, J, Linington, RG, Liu, M, McPhail, KL, Molinski, TF, Moore, BS, Nam, JW, Neupane, RP, Niemitz, M, Nuzillard, JM, Oberlies, NH, Ocampos, FMM, Pan, G, Quinn, RJ, Reddy, DS, Renault, JH, Rivera-Chávez, J, Robien, W, Saunders, CM, Schmidt, TJ, Seger, C, Shen, B, Steinbeck, C, Stuppner, H, Sturm, S, Taglialatela-Scafati, O, Tantillo, DJ, Verpoorte, R, Wang, BG, Williams, CM, Williams, PG, Wist, J, Yue, JM, Zhang, C, Xu, Z, Simmler, C, Lankin, DC, Bisson, J, and Pauli, GF

Abstract

Covering: up to 2018 With contributions from the global natural product (NP) research community, and continuing the Raw Data Initiative, this review collects a comprehensive demonstration of the immense scientific value of disseminating raw nuclear magnetic resonance (NMR) data, independently of, and in parallel with, classical publishing outlets. A comprehensive compilation of historic to present-day cases as well as contemporary and future applications show that addressing the urgent need for a repository of publicly accessible raw NMR data has the potential to transform natural products (NPs) and associated fields of chemical and biomedical research. The call for advancing open sharing mechanisms for raw data is intended to enhance the transparency of experimental protocols, augment the reproducibility of reported outcomes, including biological studies, become a regular component of responsible research, and thereby enrich the integrity of NP research and related fields.

Published
2019

25. World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions

Author

Kaptoge, S, Pennells, L, De Bacquer, D, Cooney, MT, Kavousi, M, Stevens, G, Riley, LM, Savin, S, Khan, T, Altay, S, Amouyel, P, Assmann, G, Bell, S, Ben-Shlomo, Y, Berkman, L, Beulens, JW, Björkelund, C, Blaha, M, Blazer, DG, Bolton, T, Bonita Beaglehole, R, Brenner, H, Brunner, EJ, Casiglia, E, Chamnan, P, Choi, YH, Chowdry, R, Coady, S, Crespo, CJ, Cushman, M, Dagenais, GR, D'Agostino, RB, Daimon, M, Davidson, KW, Engström, G, Ford, I, Gallacher, J, Gansevoort, RT, Gaziano, TA, Giampaoli, S, Grandits, G, Grimsgaard, S, Grobbee, DE, Gudnason, V, Guo, Q, Tolonen, H, Humphries, S, Iso, H, Jukema, JW, Kauhanen, J, Kengne, AP, Khalili, D, Koenig, W, Kromhout, D, Krumholz, H, Lam, TH, Laughlin, G, Marín Ibañez, A, Meade, TW, Moons, KGM, Nietert, PJ, Ninomiya, T, Nordestgaard, BG, O'Donnell, C, Palmieri, L, Patel, A, Perel, P, Price, JF, Providencia, R, Ridker, PM, Rodriguez, B, Rosengren, A, Roussel, R, Sakurai, M, Salomaa, V, Sato, S, Schöttker, B, Shara, N, Shaw, JE, Shin, HC, Simons, LA, Sofianopoulou, E, Sundström, J, Völzke, H, Wallace, RB, Wareham, NJ, Willeit, P, Wood, D, Wood, A, Zhao, D, Woodward, M, Danaei, G, Roth, G, Mendis, S, Onuma, O, Varghese, C, Ezzati, M, Graham, I, Jackson, R, Danesh, J, Kaptoge, S, Pennells, L, De Bacquer, D, Cooney, MT, Kavousi, M, Stevens, G, Riley, LM, Savin, S, Khan, T, Altay, S, Amouyel, P, Assmann, G, Bell, S, Ben-Shlomo, Y, Berkman, L, Beulens, JW, Björkelund, C, Blaha, M, Blazer, DG, Bolton, T, Bonita Beaglehole, R, Brenner, H, Brunner, EJ, Casiglia, E, Chamnan, P, Choi, YH, Chowdry, R, Coady, S, Crespo, CJ, Cushman, M, Dagenais, GR, D'Agostino, RB, Daimon, M, Davidson, KW, Engström, G, Ford, I, Gallacher, J, Gansevoort, RT, Gaziano, TA, Giampaoli, S, Grandits, G, Grimsgaard, S, Grobbee, DE, Gudnason, V, Guo, Q, Tolonen, H, Humphries, S, Iso, H, Jukema, JW, Kauhanen, J, Kengne, AP, Khalili, D, Koenig, W, Kromhout, D, Krumholz, H, Lam, TH, Laughlin, G, Marín Ibañez, A, Meade, TW, Moons, KGM, Nietert, PJ, Ninomiya, T, Nordestgaard, BG, O'Donnell, C, Palmieri, L, Patel, A, Perel, P, Price, JF, Providencia, R, Ridker, PM, Rodriguez, B, Rosengren, A, Roussel, R, Sakurai, M, Salomaa, V, Sato, S, Schöttker, B, Shara, N, Shaw, JE, Shin, HC, Simons, LA, Sofianopoulou, E, Sundström, J, Völzke, H, Wallace, RB, Wareham, NJ, Willeit, P, Wood, D, Wood, A, Zhao, D, Woodward, M, Danaei, G, Roth, G, Mendis, S, Onuma, O, Varghese, C, Ezzati, M, Graham, I, Jackson, R, and Danesh, J

Abstract

Background: To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions. Methods: In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40–80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance. Findings: Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0·685 (95% CI 0·629–0·741) to 0·833 (0·783–0·882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a

Published
2019

26. A Genome-Wide Knockout Screen in Human Macrophages Identified Host Factors Modulating Salmonella Infection.

Author

Buchrieser, C, Yeung, ATY, Choi, YH, Lee, AHY, Hale, C, Ponstingl, H, Pickard, D, Goulding, D, Thomas, M, Gill, E, Kim, JK, Bradley, A, Hancock, REW, Dougan, G, Buchrieser, C, Yeung, ATY, Choi, YH, Lee, AHY, Hale, C, Ponstingl, H, Pickard, D, Goulding, D, Thomas, M, Gill, E, Kim, JK, Bradley, A, Hancock, REW, and Dougan, G

Abstract

A genome-scale CRISPR knockout library screen of THP-1 human macrophages was performed to identify loss-of-function mutations conferring resistance to Salmonella uptake. The screen identified 183 candidate genes, from which 14 representative genes involved in actin dynamics (ACTR3, ARPC4, CAPZB, TOR3A, CYFIP2, CTTN, and NHLRC2), glycosaminoglycan metabolism (B3GNT1), receptor signaling (PDGFB and CD27), lipid raft formation (CLTCL1), calcium transport (ATP2A2 and ITPR3), and cholesterol metabolism (HMGCR) were analyzed further. For some of these pathways, known chemical inhibitors could replicate the Salmonella resistance phenotype, indicating their potential as targets for host-directed therapy. The screen indicated a role for the relatively uncharacterized gene NHLRC2 in both Salmonella invasion and macrophage differentiation. Upon differentiation, NHLRC2 mutant macrophages were hyperinflammatory and did not exhibit characteristics typical of macrophages, including atypical morphology and inability to interact and phagocytose bacteria/particles. Immunoprecipitation confirmed an interaction of NHLRC2 with FRYL, EIF2AK2, and KLHL13.IMPORTANCESalmonella exploits macrophages to gain access to the lymphatic system and bloodstream to lead to local and potentially systemic infections. With an increasing number of antibiotic-resistant isolates identified in humans, Salmonella infections have become major threats to public health. Therefore, there is an urgent need to identify alternative approaches to anti-infective therapy, including host-directed therapies. In this study, we used a simple genome-wide screen to identify 183 candidate host factors in macrophages that can confer resistance to Salmonella infection. These factors may be potential therapeutic targets against Salmonella infections.

Published
2019

27. Predicting the impact of pneumococcal conjugate vaccine programme options in Vietnam.

Author

Le Polain De Waroux, O, Edmunds, WJ, Takahashi, K, Ariyoshi, K, Mulholland, EK, Goldblatt, D, Choi, YH, Anh, DD, Yoshida, LM, Flasche, S, Le Polain De Waroux, O, Edmunds, WJ, Takahashi, K, Ariyoshi, K, Mulholland, EK, Goldblatt, D, Choi, YH, Anh, DD, Yoshida, LM, and Flasche, S

Abstract

Although catch-up campaigns (CCs) at the introduction of pneumococcal conjugate vaccines (PCVs) may accelerate their impact, supply constraints may limit their benefit if the need for additional PCV doses results in introduction delay. We studied the impact of PCV13 introduction with and without CC in Nha Trang, Vietnam - a country that has not yet introduced PCV - through a dynamic transmission model. We modelled the impact on carriage and invasive pneumococcal disease (IPD) of routine vaccination (RV) only and that of RV with CCs targeting <1y olds (CC1), <2y olds (CC2) and <5y olds (CC5). The model was fitted to nasopharyngeal carriage data, and post-PCV predictions were based on best estimates of parameters governing post-PCV dynamics. With RV only, elimination in carriage of vaccine-type (VT) serotypes is predicted to occur across all age groups within 10 years after introduction, with near-complete replacement by non-VT. Most of the benefit of CCs is predicted to occur within the first 3 years with the highest impact at one year, when IPD incidence is predicted to be 11% (95%CrI 9 - 14%) lower than RV with CC1, 25% (21 - 30 %) lower with CC2 and 38% (32 - 46%) lower with CC5. However, CCs would only prevent more cases of IPD insofar as such campaigns do not delay introduction by more than about 6, 12 and 18 months for CC1, CC2 and CC5. Those findings are important to help guide vaccine introduction in countries that have not yet introduced PCV, particularly in Asia.

Published
2018

28. Changes in cerebral blood flow after cognitive behavior therapy in patients with panic disorder: a SPECT study

Author

Seo HJ, Choi YH, Chung YA, Rho W, and Chae JH

Subjects
mental disorders, behavioral disciplines and activities, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, lcsh:Neurology. Diseases of the nervous system, lcsh:RC346-429, lcsh:RC321-571
Abstract

Ho-Jun Seo,1 Young Hee Choi,2 Yong-An Chung,3 Wangku Rho,1 Jeong-Ho Chae11Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, South Korea; 2Metta Institute of Cognitive Behavior Therapy, Seoul, South Korea; 3Department of Radiology, Nuclear Medicine, College of Medicine, The Catholic University of Korea, Seoul, South KoreaAim: Inconsistent results continue to be reported in studies that examine the neural correlates of cognitive behavioral therapy (CBT) in patients with panic disorder. We examined the changes in regional cerebral blood flow (rCBF) associated with the alleviation of anxiety by CBT in panic patients.Methods: The change in rCBF and clinical symptoms before and after CBT were assessed using single photon emission computed tomography and various clinical measures were analyzed.Results: Fourteen subjects who completed CBT showed significant improvements in symptoms on clinical measures, including the Panic and Agoraphobic Scale and the Anxiety Sensitivity Index-Revised. After CBT, increased rCBF was detected in the left postcentral gyrus (BA 43), left precentral gyrus (BA 4), and left inferior frontal gyrus (BA 9 and BA 47), whereas decreased rCBF was detected in the left pons. Correlation analysis of the association between the changes in rCBF and changes in each clinical measure did not show significant results.Conclusion: We found changes in the rCBF associated with the successful completion of CBT. The present findings may help clarify the effects of CBT on changes in brain activity in panic disorder.Keyword: single photon emission computed tomography (SPECT), anxiety, neural correlate, brain activity

Published
2014

30. Population-level impact, herd immunity and elimination after HPV vaccination: a systematic review and meta-analysis of predictions of 16 transmission-dynamic models

Author

Brisson M, Bénard E, Drolet M, Bogaards JA, Baussano I, Vanska S, Jit M, Boily MC, Smith MA, Berkhof J, Canfell K, Chesson HW, Burger EA, Choi YH, De Blasio BF, De Vlas SJ, Guzzetta G, Hontelez JAC, Jepsen MR, Kim JJ, Lazzarato F, Mattijsse SM, Mikolajczyk R, Pavelyev A, Pillsbury M, Shafer LA, Tully SP, Turner HC, Usher C, and Walsh C

Subjects
Cancer Control, Survivorship, and Outcomes Research - Resources and Infrastructure, Cancer Type - Cervical Cancer
Abstract

Background Modelling studies have been widely used to inform human papillomavirus (HPV) vaccination policy decisions; however, many models exist and it is not known whether they produce consistent predictions of population-level effectiveness and herd effects. We did a systematic review and meta-analysis of model predictions of the long-term population-level effectiveness of vaccination against HPV 16, 18, 6, and 11 infection in women and men, to examine the variability in predicted herd effects, incremental benefit of vaccinating boys, and potential for HPV-vaccine-type elimination. Methods We searched MEDLINE and Embase for transmission-dynamic modelling studies published between Jan 1, 2009, and April 28, 2015, that predicted the population-level impact of vaccination on HPV 6, 11, 16, and 18 infections in high-income countries. We contacted authors to determine whether they were willing to produce new predictions for standardised scenarios. Strategies investigated were girls-only vaccination and girls and boys vaccination at age 12 years. Base-case vaccine characteristics were 100% efficacy and lifetime protection. We did sensitivity analyses by varying vaccination coverage, vaccine efficacy, and duration of protection. For all scenarios we pooled model predictions of relative reductions in HPV prevalence (RRprev) over time after vaccination and summarised results using the median and 10th and 90th percentiles (80% uncertainty intervals [UI]). Findings 16 of 19 eligible models from ten high-income countries provided predictions. Under base-case assumptions, 40% vaccination coverage and girls-only vaccination, the RRprev of HPV 16 among women and men was 0·53 (80% UI 0·46–0·68) and 0·36 (0·28–0·61), respectively, after 70 years. With 80% girls-only vaccination coverage, the RRprev of HPV 16 among women and men was 0·93 (0·90–1·00) and 0·83 (0·75–1·00), respectively. Vaccinating boys in addition to girls increased the RRprev of HPV 16 among women and men by 0·18 (0·13–0·32) and 0·35 (0·27–0·39) for 40% coverage, and 0·07 (0·00–0·10) and 0·16 (0·01–0·25) for 80% coverage, respectively. The RRprev were greater for HPV 6, 11, and 18 than for HPV 16 for all scenarios investigated. Finally at 80% coverage, most models predicted that girls and boys vaccination would eliminate HPV 6, 11, 16, and 18, with a median RRprev of 1·00 for women and men for all four HPV types. Variability in pooled findings was low, but increased with lower vaccination coverage and shorter vaccine protection (from lifetime to 20 years). Interpretation Although HPV models differ in structure, data used for calibration, and settings, our population-level predictions were generally concordant and suggest that strong herd effects are expected from vaccinating girls only, even with coverage as low as 20%. Elimination of HPV 16, 18, 6, and 11 is possible if 80% coverage in girls and boys is reached and if high vaccine efficacy is maintained over time.

Published
2016

31. Inhibition of Nitric Oxide and Prostaglandin E2 Expression by Methanol Extract of Polyopes affinis in Lipopolysaccharide-stimulated BV2 Microglial Cells through Suppression of Akt-dependent NF-kB Activity and MAPK Pathway

Author

Jayasooriya, RGPT, Jang, Y-J, Kang, C-H, Dilshara, MG, Moon, D-O, Nam, T-J, Choi, YH, and Kim, G-Y

Subjects
Polyopes affinis, Nitric oxide, Prostaglandin E2, Nuclear factor-kB
Abstract

Purpose: To determine whether the methanol extract of Polyopes affinis (MEPA) down-regulates the expression of pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated BV2 microglial cells.Methods: The production of nitric oxide (NO) and prostaglandin E2 (PGE2) was measured by the Griess reagents and enzyme-linked immunosorbent assay (ELISA), respectively. Expression levels of mRNA and protein in LPS-stimulated BV2 microglial cells were assessed by reverse transcription-polymerase (RT-PCR) and Western blot analysis. Activation of nuclear factor-êB (NF-êB) was detected by electrophoretic mobility shift assay (EMSA).Results: MEPA inhibited the expression of LPS-induced pro-inflammatory mediators, NO and PGE2, as well as their respective genes, iNOS and COX-2, at both protein and mRNA levels, without any accompanying cytotoxicity. Moreover, treatment with MEPA significantly suppressed the LPS-induced DNA-binding activity of NF-êB, which is known as a main transcription factor for the regulation of proinflammatory genes, as well as the nuclear translocation of its subunit p65 and p50, by degrading IêBá.MEPA increased Akt dephosphorylation which leads to suppression of the DNA-binding activity of NF-kB in LPS-stimulated BV2 microglial cells and suppressed phosphorylation of ERK and JNK, which are involved in the mitogen-activated protein kinase (MAPK) signaling pathway for regulating proinflammatory genes.Conclusion: Our results indicate that MEPA down-regulates pro-inflammatory mediators such as NO and PGE2 by suppressing Akt-dependent NF-êB activity as well as phosphorylation of ERK and JNK inLPS-stimulated BV2 microglial cells.Keywords: Polyopes affinis, Nitric oxide, Prostaglandin E2, Nuclear factor-kB

Published
2013

32. 3rd EACTS Meeting on Cardiac and Pulmonary Regeneration Berlin-Brandenburgische Akademie, Berlin, Germany, 14-15 December 2012

Author

Bader, A, Brodarac, A, Hetzer, R, Kurtz, A, Stamm, C, Baraki, H, Kensah, G, Asch, S, Rojas, S, Martens, A, Gruh, I, Haverich, A, Kutschka, I, Cortes Dericks, L, Froment, L, Kocher, G, Schmid, Ra, Delyagina, E, Schade, A, Scharfenberg, D, Skorska, A, Lux, C, Li, W, Steinhoff, G, Drey, F, Lepperhof, V, Neef, K, Fatima, A, Wittwer, T, Wahlers, T, Saric, T, Choi, Yh, Fehrenbach, D, Lehner, A, Herrmann, F, Hollweck, T, Pfeifer, S, Wintermantel, E, Kozlik Feldmann, R, Hagl, C, Akra, B, Gyöngyösi, M, Zimmermann, M, Pavo, N, Mildner, M, Lichtenauer, M, Maurer, G, Ankersmit, J, Hacker, S, Mittermayr, R, Haider, T, Nickl, S, Beer, L, Lebherz Eichinger, D, Schweiger, T, Mitterbauer, A, Keibl, C, Werba, G, Frey, M, Ankersmit, Hj, Herrmann, S, Lux, Ca, Holfeld, J, Tepeköylü, C, Wang, Fs, Kozaryn, R, Schaden, W, Grimm, M, Wang, Cj, Urbschat, A, Zacharowski, K, Paulus, P, Avaca, Mj, Kempf, H, Malan, D, Sasse, P, Fleischmann, B, Palecek, J, Dräger, G, Kirschning, A, Zweigerdt, R, Martin, U, Katsirntaki, K, Haller, R, Ulrich, S, Sgodda, M, Puppe, V, Duerr, J, Schmiedl, A, Ochs, M, Cantz, T, Mall, M, Mauritz, C, Lara, Ar, Dahlmann, J, Schwanke, K, Hegermann, J, Skvorc, D, Gawol, A, Azizian, A, Wagner, S, Krause, A, Klopsch, C, Gaebel, R, Kaminski, A, Chichkov, B, Jockenhoevel, S, Klose, K, Roy, R, Kang, Ks, Bieback, K, Nasseri, B, Polchynska, O, Kruttwig, K, Brüggemann, C, Xu, G, Baumgartner, A, Hasun, M, Podesser, Bk, Ludwig, M, Tölk, A, Noack, T, Margaryan, R, Assanta, N, Menciassi, Arianna, Burchielli, S, Matteucci, Marco, Lionetti, Vincenzo, Luchi, C, Cariati, E, Coceani, F, Murzi, B, Rojas, Sv, Rotärmel, A, Nasseri, Ba, Ebell, W, Dandel, M, Kukucka, M, Gebker, R, Mutlak, H, Ockelmann, P, Tacke, S, Scheller, B, Pereszlenyi, A, Meier, M, Schecker, N, Rathert, C, Becher, Pm, Drori Carmi, N, Bercovich, N, Zahavi Goldstein, E, Jack, M, Netzer, N, Pinzur, L, Chajut, A, Tschöpe, C, Ruch, U, Strauer, Be, Tiedemann, G, Schlegel, F, Dhein, S, Akhavuz, O, Mohr, Fw, Dohmen, Pm, Salameh, A, Oelmann, K, Kiefer, P, Merkert, S, Templin, C, Jara Avaca, M, Müller, S, von Haehling, S, Slavic, S, Curato, C, Altarche Xifro, W, Unger, T, Li, J, Zhang, Y, Li, Wz, Ou, L, Ma, N, Haase, A, Alt, R, and Martin, U.

Published
2013

33. Methanol Extract of Polyopes lancifolius Suppresses Tumor Necrosis Factor-α-Induced Matrix Metalloproteinase-9 Expression in T24 Bladder Carcinoma Cells

Author

Jayasooriya, RGPT, Nam, TJ, Kim, GY, and Choi, YH

Subjects
Polyopes lancifolius, Matrix metalloproteinase-9, Invasion, Nuclear factor-κB
Abstract

Purpose: To investigate the effects of the methanol extract of Polyopes lancifolius (MEPL) on the expression of matrix metalloproteinase-9 (MMP-9) and invasion in T24 human bladder carcinoma cells.Methods: Reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analyses were performed to assess the expression of MMP-9 and its regulatory proteins. MMP-9 activity was evaluated using zymography while matrigel infiltration was performed to assess T24 bladder carcinoma invasion. Electrophoretic mobility assay was used to investigate the nuclear factor-κB (NF-κB) activity.Results: The expression and activity of MMP-9 were significantly increased in response to TNF-α, but MEPL suppressed TNF-α-induced MMP-9 expression and activity. MEPL also inhibited TNF-α-induced MMP-9 expression at the transcriptional level by blocking the activation of the NF-κB signaling pathway. Furthermore, the extract suppressed TNF-α-induced phosphorylation of IκBα and consequently sustained cytosolic p65 and p50 expression. Matrigel invasion assay showed that MEPL significantly reduced TNF-α-induced invasion of T24 bladder carcinoma cells.Conclusion: Collectively, these data indicate that MEPL regulates TNF-α-induced MMP-9 expression by suppressing NF-κB activity.

Published
2012

34. Inhibition of Lipopolysaccharide-Induced iNOS, COX- 2, and TNF-&#945 Expression by Aqueous Extract of Orixa Japonica in RAW 264.7 Cells via Suppression of NF- kB Activity

Author

Kang, C-H, Choi, YH, Choi, I-W, Lee, J-D, and Kim, G-Y

Subjects
Orixa japonica, Nitric oxide, Prostaglandin E2, Tumor necrosis factor-, Nuclear factor-B
Abstract

Purpose: To investigate the anti-inflammatory effects of aqueous extract of Orixa japonica (AEOJ) in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells.Methods: The expression of mRNA and protein using RT-PCR and Western blot analysis was investigated. The level of nitric oxide (NO) production was analyzed using Griess reaction. Release of prostaglandin E2 (PGE2) and tumor necrosis factor- (TNF-) was determined using sandwich ELISA.Results: AEOJ potently inhibited the production of nitric oxide (NO), prostaglandin E2 (PGE2), and tumor necrosis factor- (TNF-) in LPS-stimulated RAW 264.7 cells. Consistent with these findings, AEOJ wasalso found to significantly reduce LPS-induced expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and TNF- at the transcriptional level. Additionally, AEOJ attenuated LPSinducedNF-B activity via the inhibition of IB phosphorylation and degradation. It was also found that the NF-B inhibitor N-acetyl cysteine (NAC) attenuated LPS-induced gene expression of iNOS, COX-2,and TNF-. These results indicate that AEOJ attenuates LPS-induced inflammatory mediators such as NO, PGE2, and TNF- via suppression of NF-B activity.Conclusion: These results suggest that AEOJ has a potential activity to alleviate LPS-induced inflammation.

Published
2011

35. Pharmacokinetic interaction between itraconazole and metformin in rats: competitive inhibition of metabolism of each drug by each other via hepatic and intestinal CYP3A1/2

Author

Choi, YH, Lee, U, Lee, BK, and Lee, MG

Subjects
Male, Antifungal Agents, Membrane Proteins, Research Papers, Metformin, Rats, Intestines, Rats, Sprague-Dawley, Cytochrome P-450 Enzyme System, Liver, Area Under Curve, Microsomes, Liver, Animals, Cytochrome P-450 CYP3A, Humans, Hypoglycemic Agents, Drug Interactions, Tissue Distribution, Aryl Hydrocarbon Hydroxylases, Intestinal Mucosa, Itraconazole
Abstract

Fungal infection is prevalent in patients with diabetes mellitus. Thus, we investigated whether a pharmacokinetic interaction occurs between the anti-fungal agent itraconazole and the anti-glycaemic drug metformin, as both drugs are commonly administered together to diabetic patients and are metabolized via hepatic CYP3A subfamily in rats.Itraconazole (20 mg·kg(-1)) and metformin (100 mg·kg(-1)) were simultaneously administered i.v. and p.o. to rats. Concentrations (I) of each drug in the liver and intestine, maximum velocity (V(max)), Michaelis-Menten constant (K(m)) and intrinsic clearance (CL(int) ) for the disappearance of each drug, apparent inhibition constant (K(i) ) and [I]/K(i) ratios of each drug in the liver and intestine were determined. Also the metabolism of each drug in rat and human CYPs was measured in vitro.After simultaneous administration of both drugs, either i.v. or p.o., the total area under the plasma concentration-time curve from time zero to infinity (AUC)s of itraconazole and metformin were significantly greater than that of either drug administered alone. The metabolism of itraconazole and metformin was significantly inhibited by each other via CYP3A1 and 3A2 in rat and 3A4 in human microsomes.The significantly greater AUCs of itraconazole and metformin after i.v. administration of both drugs are probably due to competitive inhibition of the metabolism of each drug by each other via hepatic CYP3A1/2. Whereas after oral administration of both drugs, the significantly greater AUCs of each drug administered together than that of either drug alone is mainly due to competitive inhibition of intestinal metabolism of each drug by each other via intestinal CYP3A1/2.

Published
2010

37. The relationship between body fat mass and erectile dysfunction in Korean men: Hallym Aging Study

Author

Song Hj, Choi Yh, Jeong Jy, Choi Mg, Jang Sn, Cho Yg, Ian D. Caterson, Kang Jh, Kim Dh, Hong Ks, Lee Sk, and Kang Sh

Subjects
Male, medicine.medical_specialty, Aging, Urology, Health Status, Body fat percentage, Body Mass Index, Erectile Dysfunction, Internal medicine, Surveys and Questionnaires, medicine, Electric Impedance, Odds Ratio, Humans, Obesity, Risk factor, Adiposity, Aged, Korea, Anthropometry, business.industry, Hemodynamics, Odds ratio, Middle Aged, medicine.disease, Health Surveys, Lipids, Erectile dysfunction, Endocrinology, Logistic Models, business, Bioelectrical impedance analysis, Body mass index
Abstract

The aim of this study was to assess the relationship between body fat mass (BFM) and erectile dysfunction (ED) in Korean men. This study was a cross-sectional study using data on 208 men (the mean age=67.4+/-8.2). ED was diagnosed by the International Index of Erectile Function (IIEF)-5 and body fat percentage (BF%) was quantified with bioelectrical impedance. BF% was divided into quintiles (quintile 1:or =20.5%, quintile 2: 20.6-23.2%, quintile 3: 23.3-25.8%, quintile 4: 25.9-28.8%, quintile 5:or =28.9%). Using subjects with quintile 3 of BF% as reference, the adjusted odds ratios of subjects with the lowest quintile of BF% and with the highest quintile were 9.29 (95% CI: 2.29-37.72) and 4.99 (95% CI: 1.37-18.09), respectively. This study showed that BFM and ED had a U-shaped relationship in Korean men. These findings suggest that not only obesity but also a low BFM may be a risk factor of ED in Asians.

Published
2009

38. A promoter nucleotide variant of the dendritic cell-specific DCNP1 associates with serum IgE levels specific for dust mite allergens among the Korean asthmatics

Author

Kuchan Kimm, Park Sg, Hyoung Doo Shin, Park Cs, Oh B, Lee Jy, Jang As, Choi Yh, Cheong Hs, Kim Y, Lee Jk, Choi Jw, Lee Ej, Park Sw, Lee Ym, Han Bg, and Park Bl

Subjects
Adult, Male, Adolescent, Genotype, Immunology, Antigen presentation, Gene Expression, Immunoglobulin E, medicine.disease_cause, Polymorphism, Single Nucleotide, Antigen, Genetic variation, Genetics, Mite, medicine, Humans, Genetic Predisposition to Disease, Antigens, Dermatophagoides, Child, Promoter Regions, Genetic, Genetics (clinical), Asthma, Aged, Aged, 80 and over, Antigen Presentation, Korea, biology, Nuclear Proteins, Dendritic Cells, Allergens, Middle Aged, biology.organism_classification, medicine.disease, respiratory tract diseases, Case-Control Studies, Child, Preschool, Allergic response, biology.protein, Female
Abstract

Dendritic cells (DCs), the most abundant antigen-presenting cells in the lung, have been drawing attention for their roles in specific allergic responses to aeroallergens with support of Th lymphocytes, and in persistent inflammatory changes in allergic asthma. To identify genetic factors that may be involved in the asthma susceptibility and development of the disease phenotypes, we examined association of DC-specific DCNP1 polymorphisms with the disease risk. The case-control study revealed association of the nucleotide variants with serum immunoglobulin E (IgE) levels specific for Dermatophagoides farinae (Der f 1) and Dermatophagoides pteronyssinus (Der p 1), major aeroallergens of dust mites, among subjects with asthma. In particular, the T-allele-carrying genotype frequencies for one of the variants (c.-1289C>T) located in the promoter region were found increased in the asthmatic group with low levels of the mite-specific IgE (odds ratio (OR)=0.63 (0.48-0.83) for Der p 1). Results from functional analyses indicated that the promoter variant would affect the gene expression by modulating DNA-protein interaction. We propose that the genetic polymorphism of DCNP1 may influence production of specific IgE by altering DC functions in the mite allergen presenting and/or processing. The functional relevance of the genetic variation would provide an important insight into the genetic basis of allergic response to the mite antigens.

Published
2007

40. Regulation of platelet-leukocyte interaction in simulated ECC: attenuation with heparin surface modification

Author

H. Oelert, F-X Schmid, P Habermehl, Michael Hilker, X Zhou, Choi Yh, and F Zepp

Subjects
business.industry, Attenuation, Extracorporeal circulation, Heparin, Pharmacology, Critical Care and Intensive Care Medicine, Bioinformatics, Respiratory burst, Text mining, Meeting Abstract, medicine, Surface modification, Platelet, Platelet activation, business, medicine.drug
Published
1999

44. Role for phosphodiesterase 3B in regulation of lipolysis and insulin secretion

Author

Derek LeRoith, Simeon I. Taylor, Jerrold M. Olefsky, Degerman, E, Landstrom, Tr, Holst, L, Goransson, O, Harndahal, L, Ahmad, F, Choi, Yh, Masciarelli, Silvia, Liu, H, Manganiello, V., Masciarelli S, Derek LeRoith, Simeon I. Taylor, Jerrold M. Olefsky, Degerman, E, Landstrom, Tr, Holst, L, Goransson, O, Harndahal, L, Ahmad, F, Choi, Yh, Masciarelli, Silvia, Liu, H, Manganiello, V., and Masciarelli S

Abstract

Thoroughly revised and updated, this Third Edition encompasses the most recent advances in molecular and cellular research and describes the newest therapeutic modalities for type 1 and type 2 diabetes mellitus. Chapters by leading experts integrate the latest basic science and clinical research on diabetes mellitus and its complications. The text is divided into ten major sections, including extensive sections on therapeutics, diabetes during pregnancy, and complications. New chapters cover stem cell therapy for type 1 diabetes; genetics and treatment of obesity; new therapies to promote insulin action; vasculopathy; islet cell protocols; triglycerides in muscle; hypoglycemia in the adult; and the Diabetes Prevention Program.

Published
2004

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