Publications by authors named "Minji Kang"

116 Publications

Fast and reliable analysis of veterinary metomidate and etomidate in human blood samples by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in a postmortem case.

J Forensic Sci 2021 Aug 18. Epub 2021 Aug 18.

Department of Pharmaceutical Analysis, College of Pharmacy, Chung-Ang University, Seoul, South Korea.

Metomidate and etomidate belong to the non-barbiturate imidazole family of sedative-hypnotics and elicit little analgesic action when used alone. Metomidate, in particular, has little analgesic activity in humans and is, therefore, used for veterinary purposes. In 2019, a Korean woman in her twenties was found unconscious in a motel bath and eventually died. Etomidate, alprazolam, escitalopram, and metomidate were detected in the postmortem specimens. To our knowledge, this is the first case of human metomidate abuse reported in the Republic of Korea. In this research, a simple and reliable method was developed for the analysis of metomidate and etomidate in human blood samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Blood samples were deproteinized with acetonitrile, filtered, and analyzed by LC-MS/MS. Linear calibration curves were obtained with six concentrations ranging from 1 to 50 ng/ml for metomidate and 10 to 500 ng/ml for etomidate. The method was validated by assessing the selectivity, linearity, limit of detection (LOD), limit of quantitation (LOQ), intra- and inter-day precision and accuracy, matrix effect, and stability and successfully applied to the analysis of metomidate and etomidate in human blood samples. In a postmortem case, the concentrations of metomidate and etomidate were found to be 8 and 110 ng/ml in femoral blood and 6 and 210 ng/ml in cardiac blood, respectively.
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http://dx.doi.org/10.1111/1556-4029.14823DOI Listing
August 2021

Distribution of mcr genes among carbapenem-resistant Enterobacterales clinical isolates: High prevalence of mcr-positive Enterobacter cloacae complex in Seoul, Republic of Korea.

Int J Antimicrob Agents 2021 Aug 12:106418. Epub 2021 Aug 12.

Bacteria Team, Seoul Metropolitan Government Research Institute of Public Health and Environment, Gyeonggi-do, Republic of Korea.

Colistin is usually used as a drug of last resort against infections caused by multidrug-resistant gram-negative bacteria, including carbapenem-resistant Enterobacterales (CRE). Recently, the acquisition of mobile colistin resistance (mcr) genes by CRE is a cause for worry. Here, we investigated the prevalence of mcr genes in CRE isolates in Seoul, Korea. A total of 3,675 CRE strains were collected from patients between 2018 and 2019 and initially screened for mcr genes using multiplex-PCR assays. Upon the identification of mcr-harboring strains, colistin susceptibility tests, identification of carbapenemase and β-lactamase genes, and plasmid replicon typing were performed. Clonal analysis was conducted using pulsed-field gel electrophoresis. mcr genes were detected in 2.2% (80/3,675) CRE strains. There were three mcr-1, one mcr-4.3, one mcr-4.3/mcr-9, 58 mcr-9, one mcr-9/mcr-10, and 16 mcr-10 carriers from various Enterobacterales species, of which 60 were in Enterobacter cloacae complex (ECC) strains. The mcr prevalence in ECC was 20.5%. Molecular detection confirmed that 21.3% and 13.8% of the mcr-harboring strains shared bla or bla, respectively. In addition, an IncHI2 replicon was identified in 71.7% of the mcr-9 strains. Comparative analysis revealed not only a notable diversity of mcr carriers, but also clonal spreading or nosocomial outbreak of some ECC strains. Our findings revealed a silent distribution of mcr in CRE strains with high genetic heterogeneity in Seoul, underscoring the urgent need for timely intervention to control and prevent mcr dissemination.
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http://dx.doi.org/10.1016/j.ijantimicag.2021.106418DOI Listing
August 2021

The anti-diabetic drug trelagliptin induces vasodilation via activation of Kv channels and SERCA pumps.

Life Sci 2021 Oct 3;283:119868. Epub 2021 Aug 3.

Department of Physiology, Kangwon National University School of Medicine, Chuncheon 24341, South Korea. Electronic address:

Aims: In this study, we investigated the vasodilatory effects of trelagliptin (a dipeptidyl peptidase-4 inhibitor) and its related mechanisms using rabbit aortic rings.

Main Methods: Arterial tone measurement was performed in rabbit thoracic aortic rings.

Key Findings: Trelagliptin induced vasodilation in a dose-dependent manner. Pretreatment with the ATP-sensitive K channel inhibitor glibenclamide, large-conductance Ca-activated K channel inhibitor paxilline, and inwardly rectifying K channel inhibitor Ba did not affect the vasodilatory effect of trelagliptin. However, pretreatment with the voltage-dependent K (Kv) channel inhibitors 4-aminopyridine and tetraethylammonium significantly attenuated the vasodilatory effect of trelagliptin, suggesting that the vasodilatory effect of trelagliptin is associated with Kv channel activation. Although pretreatment with Kv1.5 and Kv2.1 subtype inhibitors did not affect the response to trelagliptin, pretreatment with a Kv7.X subtype inhibitor effectively reduced the vasodilatory effect of trelagliptin. Furthermore, sarco/endoplasmic reticulum Ca-ATPase (SERCA) pump inhibitors also significantly attenuated the vasodilatory effect of trelagliptin. These effects, however, were not affected by pretreatment with Ca channel inhibitors, adenylyl cyclase/PKA inhibitors, guanylyl cyclase/PKG inhibitors, or removal of the endothelium.

Significance: From these results, we concluded that the vasodilatory effect of trelagliptin was associated with the activation of Kv channels (primary the Kv7.X subtype) and SERCA pump regardless of other K channels, Ca channels, cAMP/PKA-related or cGMP/PKG-related signaling pathways, and the endothelium. Therefore, caution is required when prescribing trelagliptin to the patients with hypotension and diabetes.
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http://dx.doi.org/10.1016/j.lfs.2021.119868DOI Listing
October 2021

Improved tumor-suppressive effect of OZ-001 combined with cisplatin mediated by mTOR/p70S6K and STAT3 inactivation in A549 human lung cancer cells.

Biomed Pharmacother 2021 Jul 28;142:111961. Epub 2021 Jul 28.

Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, 26, Kyungheedae-ro, Seoul 02447, Republic of Korea; Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Seoul 02447, Republic of Korea. Electronic address:

We previously reported the anticancer activity of 4-(4-fluorobenzylcarbamoylmethyl)-3-(4-cyclohexylphenyl)-2-[3-(N,N-dimethylureido)-N'-methylpropylamino]-3,4-dihydroquinazoline (OZ-001), a T-type calcium channel (TTCC) blocker, against non-small cell lung cancer (NSCLC) in vitro and in vivo. Here, we evaluated the synergistic effect of OZ-001 and cisplatin on A549 human lung cancer cells and A549 xenograft mice. Our study demonstrated that treatment with OZ-001 and cisplatin sensitized A549 cells to cisplatin and significantly inhibited cell growth, increased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells, and induced poly (ADP-ribose) polymerase (PARP) cleavage in A549 cells and an A549 xenograft tumor mouse model. Moreover, our findings showed that mechanistic target of rapamycin (mTOR), ribosomal protein S6 kinase (p70S6K), and signal transducer and activator of transcription (STAT3) inactivation was required for apoptosis induced by the combination of OZ-001 and cisplatin in in vitro and in vivo experiments. Our results suggest that combined treatment with OZ-001 and cisplatin could potentiate antiproliferative effects via suppression of the mTOR/p70S6K and STAT3 pathways and may be considered a potential therapeutic agent for NSCLC.
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http://dx.doi.org/10.1016/j.biopha.2021.111961DOI Listing
July 2021

Is Body Mass Index Related to Skin Reactivity to Histamine but not to Specific Allergens? A 2-Year Follow-up Study on Korean Children.

Am J Rhinol Allergy 2021 Jul 21:19458924211032469. Epub 2021 Jul 21.

Department of Otorhinolaryngology, Gangnam Severance Hospital,Yonsei University College of Medicine, Seoul, Republic of Korea.

Background: Skin prick tests are widely used to diagnose allergic sensitization. The influence of obesity on the skin prick test result has not been clearly established, even though the association between allergic disease and obesity is relatively well known.

Objective: To determine whether a change in body mass index (BMI) contributes to skin reactivity to histamine and allergens in a skin prick test, we performed a 2-year follow-up study on Korean children.

Methods: Skin prick tests for common aeroallergens were performed on elementary school students from Jeju Island, Korea. BMI was calculated using weight and height after measuring both, and demographic characteristics were surveyed. The same tests were repeated after 2 years.

Results: The sensitization rate increased during the 2 years between tests and the children's mean BMI also increased, along with their age. The wheal sizes induced by , , Japanese cedar, and histamine were significantly increased during 2 years; however, only the histamine reaction associated with increased BMI had statistical significance. Furthermore, other variables-including the number of sensitized allergens-were not related to histamine skin reactivity.

Conclusion: Histamine skin reactivity increased in children over time and some allergens showed increased specific reactions; however, BMI gain is a specific predictor of histamine reactivity. Further studies are needed to elucidate the clinical significance of these changes.
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http://dx.doi.org/10.1177/19458924211032469DOI Listing
July 2021

Association Between Diet Quality and Prevalence of Obesity, Dyslipidemia, and Insulin Resistance Among Filipino Immigrant Women in Korea: The Filipino Women's Diet and Health Study.

Front Public Health 2021 1;9:647661. Epub 2021 Jul 1.

Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul, South Korea.

Diet quality may be a key modifiable factor for the prevention of non-communicable disease. We aimed to investigate the association between diet quality and prevalence of obesity, dyslipidemia, and insulin resistance among Filipino immigrant women in Korea. A total of 413 participants from the 2014-2016 baseline population of the Filipino Women's Diet and Health Study (FiLWHEL) were examined. Individual dietary intakes were evaluated through 24-h recalls and then converted into two dietary quality assessments: Minimum Dietary Diversity for Women (MDD-W) developed by the Food and Agriculture Organization (FAO) and the Data Derived Inflammation Index (DDII) originally developed by our group. Fasting blood levels of triglycerides, high-density lipoprotein cholesterols, glucose, and insulin were measured. We used logistic regression models for odds ratios (ORs) with 95% confidence intervals (CIs). We found a statistically significant association between MDD-W scores and decreased prevalence of abdominal obesity; ORs (95% CIs) of the 3rd vs. 1st tertiles were 0.58 (0.36-0.94; for trend = 0.029). Increased DDII was associated with elevated prevalence of dyslipidemia and insulin resistance; ORs (95% CIs) of the 5th vs. 1-3rd quintiles were 6.44 (2.56-16.20) for triglycerides (TG), 3.90 (1.92-7.90) for low-density lipoprotein (LDL) cholesterol, 3.36 (1.81-6.24) for total cholesterol (TC), 6.25 (2.53-15.41) for abnormal TG/HDL ratios, 3.59 (1.96-6.59) for HbA1c, 2.61 (1.11-6.17) for fasting blood glucose levels, 9.67 (4.16-22.48) for insulin levels, and 9.73 (4.46-21.25) for homeostasis model assessment of insulin resistance (HOMA-IR) ( for trend <0.001 for all, except 0.033 for fasting blood glucose). Greater dietary diversity was inversely associated with the prevalence of abdominal obesity in Filipino immigrant women. Proinflammatory scores based on diet and lifestyle factors were associated with an increased prevalence of dyslipidemia and insulin resistance. Further, epidemiological studies on the relationship between dietary acculturation and chronic disease are warranted.
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http://dx.doi.org/10.3389/fpubh.2021.647661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281297PMC
July 2021

Has Hypofractionated Whole-Breast Radiation Therapy Become the Standard of Care in the United States? An Updated Report from National Cancer Database.

Clin Breast Cancer 2021 Jun 7. Epub 2021 Jun 7.

Department of Public Health Sciences, University of Chicago, Chicago, IL. Electronic address:

Introduction/background: We aimed to update the previous evaluation of hypofractionated whole-breast irradiation (HF-WBI) use over time in the United States and factors related to its adoption for patients undergoing a lumpectomy from 2004 to 2016.

Materials And Methods: Among the patients who underwent a lumpectomy, we identified 688,079 patients with early-stage invasive breast cancer and 248,218 patients with ductal carcinoma in situ in the National Cancer Database from 2004 to 2016. We defined HF-WBI as 2.5 to 3.33 Gy/fraction to the breast and conventional fractionated whole-breast irradiation as 1.8 to 2.0 Gy/fraction. We evaluated the trend of HF-WBI use and examined factors associated with HF-WBI use using logistic regression models.

Results: Among invasive cancer patients, the use of HF-WBI increased exponentially from 0.7% in 2004 to 15.6% in 2013 and then to 38.1% in 2016. Among patients with ductal carcinoma in situ, the use of HF-WBI has increased significantly from 0.42% in 2004 to 13.4% in 2013 and then to 34.3% in 2016. Factors found to be associated with HF-WBI use included age, patient geographical location, race/ethnicity, tumor stage, grade, treating facility type, and volume.

Conclusion: HF-WBI use in the United States has more than doubled from 2013 to 2016. Although its use is close to that of conventional fractionated whole-breast irradiation, HF-WBI is still far from the preferred standard of care in the United States. We identified several patient and facility factors that can impact the uptake of HF-WBI treatment. Microabstract Using the National Cancer Database from 2004 to 2016, we evaluated the trend of hypofractionated whole-breast radiation therapy use and factors associated with use. Use in the United States has more than doubled from 2013 to 2016, but it has not become the standard of care. We identified several patient and facility factors that impact the uptake of hypofractionated whole-breast radiation therapy treatment.
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http://dx.doi.org/10.1016/j.clbc.2021.05.016DOI Listing
June 2021

The front-line during the coronavirus disease 2019 pandemic: healthcare personnel.

Curr Opin Infect Dis 2021 08;34(4):372-383

Division of Infectious Diseases and Geographic Medicine, Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Purpose Of Review: An estimated four to 11% of reported coronavirus disease 2019 (COVID-19) cases occurs in healthcare personnel (HCP). HCP are at high risk of acquiring and transmitting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) given their close contact with individuals with recognized and unrecognized COVID-19. We summarize the literature to date describing the epidemiology, identifying risk factors associated with COVID-19, and analyzing clinical characteristics and outcomes of SARS-CoV-2 infection in HCP.

Recent Findings: The prevalence of SARS-CoV-2 antibodies among HCP ranges from 0.7 to 45%. Although there is heterogeneity in the seroprevalence rate reported in the literature, HCP may be at increased risk of SARS-CoV-2 infection from exposure to patients with COVID-19. The literature supports that this can be minimized with adequate personal protective equipment (PPE) supply, proper hand hygiene, appropriate PPE use, and other infection prevention measures. In addition, infections in HCP are commonly acquired in the community as well as in nonclinical care settings including break rooms or work rooms.

Summary: While much focus has been on minimizing patient-to-HCP transmission of SARS-CoV-2, additional efforts are needed to prevent exposures in nonclinical care settings and in the community.
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http://dx.doi.org/10.1097/QCO.0000000000000734DOI Listing
August 2021

Atypical antipsychotic olanzapine inhibits voltage-dependent K channels in coronary arterial smooth muscle cells.

Pharmacol Rep 2021 Jun 19. Epub 2021 Jun 19.

Department of Physiology, Kangwon National University School of Medicine, 1 Kangwondaehak-gil, Chuncheon, 24341, South Korea.

Background: Olanzapine, an FDA-approved atypical antipsychotic, is widely used to treat schizophrenia and bipolar disorder. In this study, the inhibitory effect of olanzapine on voltage-dependent K (Kv) channels in rabbit coronary arterial smooth muscle cells was investigated.

Methods: Electrophysiological recordings were performed in freshly isolated coronary arterial smooth muscle cells.

Results: Olanzapine inhibited the Kv channels in a concentration-dependent manner with an IC value of 7.76 ± 1.80 µM and a Hill coefficient of 0.82 ± 0.09. Although olanzapine did not change the steady-state activation curve, it shifted the inactivation curve to a more negative potential, suggesting that it inhibited Kv currents by affecting the voltage sensor of the Kv channel. Application of 1 or 2 Hz train pulses did not affect the olanzapine-induced inhibition of Kv channels, suggesting that its effect on Kv channels occurs in a use (state)-independent manner. Pretreatment with DPO-1 (Kv1.5 subtype inhibitor) reduced the olanzapine-induced inhibition of Kv currents. In addition, pretreatment with guangxitoxin (Kv2.1 subtype inhibitor) and linopirdine (Kv7 subtype inhibitor) partially decreased the degree of Kv current inhibition. Olanzapine induced membrane depolarization.

Conclusion: From these results, we suggest that olanzapine inhibits the Kv channels in a concentration-dependent, but state-independent, manner by affecting the gating properties of Kv channels. The primary Kv channel target of olanzapine is the Kv1.5 subtype.
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http://dx.doi.org/10.1007/s43440-021-00299-zDOI Listing
June 2021

Identification of a carbapenem-resistant Enterobacter kobei clinical strain co-harbouring mcr-4.3 and mcr-9 in Republic of Korea.

J Glob Antimicrob Resist 2021 Sep 13;26:114-116. Epub 2021 Jun 13.

Bacteria Team, Seoul Metropolitan Government Research Institute of Public Health and Environment, Gyeonggi-do, Republic of Korea.

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http://dx.doi.org/10.1016/j.jgar.2021.05.008DOI Listing
September 2021

Influenza vaccination among healthcare personnel during the coronavirus disease 2019 (COVID-19) pandemic.

Infect Control Hosp Epidemiol 2021 Jun 9:1-2. Epub 2021 Jun 9.

Division of Infectious Diseases and Geographic Medicine, Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.

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http://dx.doi.org/10.1017/ice.2021.263DOI Listing
June 2021

Neural stem cells derived from human midbrain organoids as a stable source for treating Parkinson's disease: Midbrain organoid-NSCs (Og-NSC) as a stable source for PD treatment.

Prog Neurobiol 2021 Sep 28;204:102086. Epub 2021 May 28.

Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul, Republic of Korea; Hanyang Biomedical Research Institute, Hanyang University, Seoul, Republic of Korea; Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Republic of Korea. Electronic address:

Successful clinical translation of stem cell-based therapy largely relies on the scalable and reproducible preparation of donor cells with potent therapeutic capacities. In this study, midbrain organoids were yielded from human pluripotent stem cells (hPSCs) to prepare cells for Parkinson's disease (PD) therapy. Neural stem/precursor cells (NSCs) isolated from midbrain organoids (Og-NSCs) expanded stably and differentiated into midbrain-type dopamine(mDA) neurons, and an unprecedentedly high proportion expressed midbrain-specific factors, with relatively low cell line and batch-to-batch variations. Single cell transcriptome analysis followed by in vitro assays indicated that the majority of cells in the Og-NSC cultures are ventral midbrain (VM)-patterned with low levels of cellular senescence/aging and mitochondrial stress, compared to those derived from 2D-culture environments. Notably, in contrast to current methods yielding mDA neurons without astrocyte differentiation, mDA neurons that differentiated from Og-NSCs were interspersed with astrocytes as in the physiologic brain environment. Thus, the Og-NSC-derived mDA neurons exhibited improved synaptic maturity, functionality, resistance to toxic insults, and faithful expressions of the midbrain-specific factors, in vitro and in vivo long after transplantation. Consequently, Og-NSC transplantation yielded potent therapeutic outcomes that are reproducible in PD model animals. Collectively, our observations demonstrate that the organoid-based method may satisfy the demands needed in the clinical setting of PD cell therapy.
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http://dx.doi.org/10.1016/j.pneurobio.2021.102086DOI Listing
September 2021

Deep hierarchical embedding for simultaneous modeling of GPCR proteins in a unified metric space.

Sci Rep 2021 May 5;11(1):9543. Epub 2021 May 5.

Bioinformatics Institute, Seoul National University, Seoul, 08826, Republic of Korea.

GPCR proteins belong to diverse families of proteins that are defined at multiple hierarchical levels. Inspecting relationships between GPCR proteins on the hierarchical structure is important, since characteristics of the protein can be inferred from proteins in similar hierarchical information. However, modeling of GPCR families has been performed separately for each of the family, subfamily, and sub-subfamily level. Relationships between GPCR proteins are ignored in these approaches as they process the information in the proteins with several disconnected models. In this study, we propose DeepHier, a deep learning model to simultaneously learn representations of GPCR family hierarchy from the protein sequences with a unified single model. Novel loss term based on metric learning is introduced to incorporate hierarchical relations between proteins. We tested our approach using a public GPCR sequence dataset. Metric distances in the deep feature space corresponded to the hierarchical family relation between GPCR proteins. Furthermore, we demonstrated that further downstream tasks, like phylogenetic reconstruction and motif discovery, are feasible in the constructed embedding space. These results show that hierarchical relations between sequences were successfully captured in both of technical and biological aspects.
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http://dx.doi.org/10.1038/s41598-021-88623-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100104PMC
May 2021

The Coronavirus Health and Impact Survey (CRISIS) reveals reproducible correlates of pandemic-related mood states across the Atlantic.

Sci Rep 2021 04 14;11(1):8139. Epub 2021 Apr 14.

Genetic Epidemiology Research Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, USA.

The COVID-19 pandemic and its social and economic consequences have had adverse impacts on physical and mental health worldwide and exposed all segments of the population to protracted uncertainty and daily disruptions. The CoRonavIruS health and Impact Survey (CRISIS) was developed for use as an easy to implement and robust questionnaire covering key domains relevant to mental distress and resilience during the pandemic. Ongoing studies using CRISIS include international studies of COVID-related ill health conducted during different phases of the pandemic and follow-up studies of cohorts characterized before the COVID pandemic. In the current work, we demonstrate the feasibility, psychometric structure, and construct validity of this survey. We then show that pre-existing mood states, perceived COVID risk, and lifestyle changes are strongly associated with negative mood states during the pandemic in population samples of adults and in parents reporting on their children in the US and UK. These findings are highly reproducible and we find a high degree of consistency in the power of these factors to predict mental health during the pandemic.
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http://dx.doi.org/10.1038/s41598-021-87270-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046981PMC
April 2021

Discovery of N-amido-phenylsulfonamide derivatives as novel microsomal prostaglandin E synthase-1 (mPGES-1) inhibitors.

Bioorg Med Chem Lett 2021 06 26;41:127992. Epub 2021 Mar 26.

Research Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University, Seoul 02447, Republic of Korea; KHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul 02447, Republic of Korea. Electronic address:

Our previous research showed that N-carboxy-phenylsulfonyl hydrazide (scaffold A) could reduce LPS-stimulated PGE levels in RAW 264.7 macrophage cells by an inhibition of mPGES-1 enzyme. However, a number of scaffold A derivatives showed the drawbacks such as the formation of regioisomers and poor liver metabolic stability. In order to overcome these synthetic and metabolic problems, therefore, we decided to replace N-carboxy-phenylsulfonyl hydrazide (scaffold A) with N-carboxy-phenylsulfonamide (scaffold B) or N-amido-phenylsulfonamide frameworks (scaffold C) as a bioisosteric replacement. Among them, MPO-0186 (scaffold C) inhibited the production of PGE (IC: 0.24 μM) in A549 cells via inhibition of mPGES-1 (IC: 0.49 μM in a cell-free assay) and was found to be approximately 9- and 8-fold more potent than MK-886 as a reference inhibitor, respectively. A molecular docking study theoretically suggests that MPO-0186 could inhibit PGE production by blocking the PGH binding site of mPGES-1 enzyme. Furthermore, MPO-0186 demonstrated good liver metabolic stability and no significant inhibition observed in clinically relevant CYP isoforms except CYP2C19. This result provides a potential starting point for the development of selective and potent mPGES-1 inhibitor with a novel scaffold.
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http://dx.doi.org/10.1016/j.bmcl.2021.127992DOI Listing
June 2021

Neddylation is required for presynaptic clustering of mGlu7 and maturation of presynaptic terminals.

Exp Mol Med 2021 Mar 25;53(3):457-467. Epub 2021 Mar 25.

Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.

Neddylation is a posttranslational modification in which NEDD8 is conjugated to a target substrate by cellular processes similar to those involved in ubiquitination. Recent studies have identified PSD-95 and cofilin as substrates for neddylation in the brain and have shown that neddylation modulates the maturation and stability of dendritic spines in developing neurons. However, the precise substrates and functional consequences of neddylation at presynaptic terminals remain elusive. Here, we provide evidence that the mGlu7 receptor is a target of neddylation in heterologous cells and rat primary cultured neurons. We found that mGlu7 neddylation is reduced by agonist treatment and is required for the clustering of mGlu7 in the presynaptic active zone. In addition, we observed that neddylation is not required for the endocytosis of mGlu7, but it facilitates the ubiquitination of mGlu7 and stabilizes mGlu7 protein expression. Finally, we demonstrate that neddylation is necessary for the maturation of excitatory presynaptic terminals, providing a key role for neddylation in synaptic function.
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http://dx.doi.org/10.1038/s12276-021-00585-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080653PMC
March 2021

The anti-diabetic drug alogliptin induces vasorelaxation via activation of Kv channels and SERCA pumps.

Eur J Pharmacol 2021 May 5;898:173991. Epub 2021 Mar 5.

Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, Chuncheon, 24341, South Korea. Electronic address:

In the present study, we investigated the vasorelaxant effects of alogliptin, an oral antidiabetic drug in the dipeptidyl peptidase-4 (DPP-4) inhibitor class, using phenylephrine (Phe)-induced pre-contracted aortic rings. Alogliptin induced vasorelaxation in a dose-dependent manner. Pre-treatment with the voltage-dependent K (Kv) channel inhibitor 4-aminopyridine (4-AP) significantly decreased the vasorelaxant effect of alogliptin, whereas pre-treatment with the inwardly rectifying K (Kir) channel inhibitor Ba, ATP-sensitive K (K) channel inhibitor glibenclamide, and large-conductance Ca-activated K (BK) channel inhibitor paxilline did not alter the effects of alogliptin. Although pre-treatment with the Ca channel inhibitor nifedipine did not affect the vasorelaxant effect of alogliptin, pre-treatment with the sarco/endoplasmic reticulum Ca-ATPase (SERCA) pump inhibitors thapsigargin and cyclopiazonic acid effectively attenuated the vasorelaxant response of alogliptin. Neither cGMP/protein kinase G (PKG)-related signaling pathway inhibitors (guanylyl cyclase inhibitor ODQ and PKG inhibitor KT 5823) nor cAMP/protein kinase A (PKA)-related signaling pathway inhibitors (adenylyl cyclase inhibitor SQ 22536 and PKA inhibitor KT 5720) reduced the vasorelaxant effect of alogliptin. Similarly, the vasorelaxant effect of alogliptin was not changed by endothelium removal or pre-treatment with the nitric oxide (NO) synthase inhibitor L-NAME or the small- and intermediate-conductance Ca-activated K (SK and IK) channel inhibitors apamin and TRAM-34. Based on these results, we suggest that alogliptin induced vasorelaxation in rabbit aortic smooth muscle by activating Kv channels and the SERCA pump independent of other K channels, cGMP/PKG-related or cAMP/PKA-related signaling pathways, and the endothelium.
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http://dx.doi.org/10.1016/j.ejphar.2021.173991DOI Listing
May 2021

The effects of tegaserod, a gastrokinetic agent, on voltage-gated K channels in rabbit coronary arterial smooth muscle cells.

Clin Exp Pharmacol Physiol 2021 05 23;48(5):748-756. Epub 2021 Feb 23.

Department of Physiology, Institute of Medical Sciences, Kangwon National University School of Medicine, Chuncheon, South Korea.

Tegaserod, a gastroprokinetic agent, is used to treat irritable bowel syndrome. Despite its extensive clinical use, little is known about the effects of tegaserod on vascular ion channels, especially K channels. Therefore, we examined the effects of tegaserod on voltage-gated K (Kv) channels in rabbit coronary arterial smooth muscle cells using the whole-cell patch-clamp technique. Tegaserod inhibited Kv channels in a concentration-dependent manner with an IC value of 1.26 ± 0.31 µmol/L and Hill coefficient of 0.81 ± 0.10. Although tegaserod had no effect on the steady-state activation curves of the Kv channels, the steady-state inactivation curve was shifted toward a more negative potential. These results suggest that tegaserod inhibits Kv channels by influencing their voltage sensors. The recovery time constant of channel inactivation was extended in the presence of tegaserod. Furthermore, application of train steps (1 and 2 Hz) in the presence of tegaserod progressively increased the inhibition of Kv currents suggesting that tegaserod-induced Kv channel inhibition is use (state)-dependent. Pretreatment with a Kv1.5 subtype inhibitor suppressed the Kv current. However, additional application of tegaserod did not induce further inhibition. Pretreatment with a Kv2.1 or Kv7 inhibitor did not affect the inhibitory effect of tegaserod on Kv channels. Based on these results, we conclude that tegaserod inhibits vascular Kv channels in a concentration- and use (state)-dependent manner independent of its own functions. Furthermore, the major Kv channel target of tegaserod is the Kv1.5 subtype.
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http://dx.doi.org/10.1111/1440-1681.13477DOI Listing
May 2021

Similarity-Based Unsupervised Spelling Correction Using BioWordVec: Development and Usability Study of Bacterial Culture and Antimicrobial Susceptibility Reports.

JMIR Med Inform 2021 Feb 22;9(2):e25530. Epub 2021 Feb 22.

Division of Infectious Disease, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.

Background: Existing bacterial culture test results for infectious diseases are written in unrefined text, resulting in many problems, including typographical errors and stop words. Effective spelling correction processes are needed to ensure the accuracy and reliability of data for the study of infectious diseases, including medical terminology extraction. If a dictionary is established, spelling algorithms using edit distance are efficient. However, in the absence of a dictionary, traditional spelling correction algorithms that utilize only edit distances have limitations.

Objective: In this research, we proposed a similarity-based spelling correction algorithm using pretrained word embedding with the BioWordVec technique. This method uses a character-level N-grams-based distributed representation through unsupervised learning rather than the existing rule-based method. In other words, we propose a framework that detects and corrects typographical errors when a dictionary is not in place.

Methods: For detected typographical errors not mapped to Systematized Nomenclature of Medicine (SNOMED) clinical terms, a correction candidate group with high similarity considering the edit distance was generated using pretrained word embedding from the clinical database. From the embedding matrix in which the vocabulary is arranged in descending order according to frequency, a grid search was used to search for candidate groups of similar words. Thereafter, the correction candidate words were ranked in consideration of the frequency of the words, and the typographical errors were finally corrected according to the ranking.

Results: Bacterial identification words were extracted from 27,544 bacterial culture and antimicrobial susceptibility reports, and 16 types of spelling errors and 914 misspelled words were found. The similarity-based spelling correction algorithm using BioWordVec proposed in this research corrected 12 types of typographical errors and showed very high performance in correcting 97.48% (based on F1 score) of all spelling errors.

Conclusions: This tool corrected spelling errors effectively in the absence of a dictionary based on bacterial identification words in bacterial culture and antimicrobial susceptibility reports. This method will help build a high-quality refined database of vast text data for electronic health records.
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http://dx.doi.org/10.2196/25530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939936PMC
February 2021

Similarity-Based Unsupervised Spelling Correction Using BioWordVec: Development and Usability Study of Bacterial Culture and Antimicrobial Susceptibility Reports.

JMIR Med Inform 2021 Feb 22;9(2):e25530. Epub 2021 Feb 22.

Division of Infectious Disease, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.

Background: Existing bacterial culture test results for infectious diseases are written in unrefined text, resulting in many problems, including typographical errors and stop words. Effective spelling correction processes are needed to ensure the accuracy and reliability of data for the study of infectious diseases, including medical terminology extraction. If a dictionary is established, spelling algorithms using edit distance are efficient. However, in the absence of a dictionary, traditional spelling correction algorithms that utilize only edit distances have limitations.

Objective: In this research, we proposed a similarity-based spelling correction algorithm using pretrained word embedding with the BioWordVec technique. This method uses a character-level N-grams-based distributed representation through unsupervised learning rather than the existing rule-based method. In other words, we propose a framework that detects and corrects typographical errors when a dictionary is not in place.

Methods: For detected typographical errors not mapped to Systematized Nomenclature of Medicine (SNOMED) clinical terms, a correction candidate group with high similarity considering the edit distance was generated using pretrained word embedding from the clinical database. From the embedding matrix in which the vocabulary is arranged in descending order according to frequency, a grid search was used to search for candidate groups of similar words. Thereafter, the correction candidate words were ranked in consideration of the frequency of the words, and the typographical errors were finally corrected according to the ranking.

Results: Bacterial identification words were extracted from 27,544 bacterial culture and antimicrobial susceptibility reports, and 16 types of spelling errors and 914 misspelled words were found. The similarity-based spelling correction algorithm using BioWordVec proposed in this research corrected 12 types of typographical errors and showed very high performance in correcting 97.48% (based on F1 score) of all spelling errors.

Conclusions: This tool corrected spelling errors effectively in the absence of a dictionary based on bacterial identification words in bacterial culture and antimicrobial susceptibility reports. This method will help build a high-quality refined database of vast text data for electronic health records.
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http://dx.doi.org/10.2196/25530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939936PMC
February 2021

Déjà Vu: Coronaviruses and Transmission in Health Care Settings.

Ann Intern Med 2021 06 9;174(6):864-865. Epub 2021 Feb 9.

University of Texas Southwestern Medical Center Dallas, Texas.

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http://dx.doi.org/10.7326/M21-0526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926185PMC
June 2021

Pathogenic Mutations Associated with Neurodevelopmental Disorders Impair Axon Outgrowth and Presynaptic Terminal Development.

J Neurosci 2021 03 26;41(11):2344-2359. Epub 2021 Jan 26.

Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, South Korea

Metabotropic glutamate receptor 7 (mGlu7) is an inhibitory heterotrimeric G-protein-coupled receptor that modulates neurotransmitter release and synaptic plasticity at presynaptic terminals in the mammalian central nervous system. Recent studies have shown that rare mutations in glutamate receptors and synaptic scaffold proteins are associated with neurodevelopmental disorders (NDDs). However, the role of presynaptic mGlu7 in the pathogenesis of NDDs remains largely unknown. Recent whole-exome sequencing (WES) studies in families with NDDs have revealed that several missense mutations (c.1865G>A:p.R622Q; c.461T>C:p.I154T; c.1972C>T:p.R658W and c.2024C>A:p.T675K) or a nonsense mutation (c.1757G>A:p.W586X) in the gene may be linked to NDDs. In the present study, we investigated the mechanistic links between point mutations and NDD pathology. We find that the pathogenic GRM7 I154T and R658W/T675K mutations lead to the degradation of the mGlu7 protein. In particular, the GRM7 R658W/T675K mutation results in a lack of surface mGlu7 expression in heterologous cells and cultured neurons isolated from male and female rat embryos. We demonstrate that the expression of mGlu7 variants or exposure to mGlu7 antagonists impairs axon outgrowth through the mitogen-activated protein kinase (MAPK)-cAMP-protein kinase A (PKA) signaling pathway during early neuronal development, which subsequently leads to a decrease in the number of presynaptic terminals in mature neurons. Treatment with an mGlu7 agonist restores the pathologic phenotypes caused by mGlu7 I154T but not by mGlu7 R658W/T675K because of its lack of neuronal surface expression. These findings provide evidence that stable neuronal surface expression of mGlu7 is essential for neural development and that mGlu7 is a promising therapeutic target for NDDs. Neurodevelopmental disorders (NDDs) affect brain development and function by multiple etiologies. Metabotropic glutamate receptor 7 (mGlu7) is a receptor that controls excitatory neurotransmission and synaptic plasticity. Since accumulating evidence indicates that the gene locus is associated with NDD risk, we analyzed the functional effects of human variants identified in patients with NDDs. We demonstrate that stable neuronal surface expression of mGlu7 is essential for axon outgrowth and presynaptic terminal development in neurons. We found that mitogen-activated protein kinase (MAPK)-cAMP-protein kinase A (PKA) signaling and subsequent cytoskeletal dynamics are defective because of the degradation of mGlu7 variants. Finally, we show that the defects caused by mGlu7 I154T can be reversed by agonists, providing the rationale for proposing mGlu7 as a potential therapeutic target for NDDs.
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http://dx.doi.org/10.1523/JNEUROSCI.2108-20.2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984599PMC
March 2021

The Impact of an Inpatient Nurse-Triggered Sepsis Alert on Antimicrobial Utilization.

Jt Comm J Qual Patient Saf 2021 03 14;47(3):157-164. Epub 2020 Nov 14.

Introduction: A nurse-triggered sepsis alert called "Code Sepsis" was implemented for early recognition and management of sepsis. The researchers analyzed its impact on antimicrobial use and identified factors associated with infection as source of Code Sepsis.

Methods: The medical records of hospitalized patients with Code Sepsis between January 1 and June 30, 2018, were reviewed. Patients were classified as "Infection" when probable or definitive infection was identified or "No Infection" when a probable or definitive noninfectious source was identified. Patients were categorized as "Escalation" with addition or change to broader-spectrum antimicrobials or "No Escalation" with no change or change to narrower-spectrum antimicrobials. Escalation was classified as "Indicated" with appropriate escalation or "Not Indicated" with inappropriate escalation. Logistic regression model was used to identify factors associated with Infection as Code Sepsis trigger.

Results: Code Sepsis was activated in 529 patients, with Escalation in 246 (46.5%) and No Escalation in 283 (53.5%) patients. Escalation was Indicated in 157 (63.8%) and Not Indicated in 89 (36.2%) patients. Infection was identified in 356 (67.3%) and No Infection in 173 (32.7%) patients. History of HIV (odds ratio [OR] = 2.75, p = 0.03), temperature > 38.3°C or < 36°C (OR = 2.63, p < 0.01), and respiratory rate > 20/minute (OR = 1.56, p = 0.02) were associated with Infection, while surgery within 3 days (OR = 0.30, p < 0.01) was associated with No Infection.

Conclusion: One hospital system's Code Sepsis inadvertently identified patients without infections and led to antimicrobial overuse. By refocusing Code Sepsis on early recognition of severe sepsis and septic shock only, the organization hopes to optimize resource utilization and improve patient outcomes.
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http://dx.doi.org/10.1016/j.jcjq.2020.11.004DOI Listing
March 2021

Dietary intake and nutritional status of Korean children and adolescents: a review of national survey data.

Clin Exp Pediatr 2021 Sep 28;64(9):443-458. Epub 2020 Dec 28.

Department of Pediatrics, Kosin University Gospel Hospital, Kosin University School of Medicine, Busan, Korea.

In Korea, several national cross-sectional surveys monitor the diet, nutritional status, and health status of children. This continual dedicated national surveillance system contributes to the identification of nutritional and health issues, establishment of public health policies, and development of nutrition recommendations. This paper provides recent information about the Korea National Health and Nutrition Examination Survey and the Korean Youth Risk Behavior Web-based Survey and describes key nationwide survey findings published in the last 5 years on infant feeding practices and the dietary intake and nutritional status of Korean infants, children, and adolescents. There have been increasing trends in children, and teenagers who skip breakfast, eat fast food, consume sugary drinks, have vitamin D deficiency, and are obese. This review will inform pediatricians, nutritionists, and other health care practitioners who track children's growth and development. It may also help researchers and policymakers identify diet-related policies and strategies for chronic disease prevention in Korean infants, children, and adolescents.
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http://dx.doi.org/10.3345/cep.2020.01655DOI Listing
September 2021

Changes in diet quality and body weight over 10 years: the Multiethnic Cohort Study.

Br J Nutr 2021 Jan 14:1-9. Epub 2021 Jan 14.

Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI96813, USA.

High-quality diets have been found to be beneficial in preventing long-term weight gain. However, concurrent changes in diet quality and body weight over time have rarely been reported. We examined the association between 10-year changes in diet quality and body weight in the Multiethnic Cohort Study. Analyses included 53 977 African Americans, Native Hawaiians, Japanese Americans, Latinos and Whites, who completed both baseline (1993-1996, 45-69 years) and 10-year follow-up (2003-2008) surveys including a FFQ and had no history of heart disease or cancer. Using multivariable regression, weight changes were regressed on changes in four diet quality indexes, Healthy Eating Index-2015, Alternative Healthy Eating Index-2010, alternate Mediterranean Diet and Dietary Approaches to Stop Hypertension scores. Mean weight change over 10 years was 1·2 (sd 6·8) kg in men and 1·5 (sd 7·2) kg in women. Compared with stable diet quality (< 0·5 sd change), the greatest increase (≥ 1 sd increase) in the diet scores was associated with less weight gain (by 0·55-1·17 kg in men and 0·62-1·31 kg in women). Smaller weight gain with improvement in diet quality was found in most subgroups by race/ethnicity, baseline age and baseline BMI. The inverse association was stronger in younger age and higher BMI groups. Ten-year improvement in diet quality was associated with a smaller weight gain, which varied by race/ethnicity and baseline age and BMI. Our findings suggest that maintaining a high-quality diet and improving diet quality over time may prevent excessive weight gain.
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http://dx.doi.org/10.1017/S000711452100012XDOI Listing
January 2021

Suppression of voltage-gated K channels by darifenacin in coronary arterial smooth muscle cells.

Eur J Pharmacol 2021 Jan 31;891:173707. Epub 2020 Oct 31.

Department of Physiology, Kangwon National University School of Medicine, Chuncheon, 24341, South Korea. Electronic address:

Darifenacin, an anticholinergic agent, has been used to treat overactive bladder syndrome. Despite its extensive clinical use, there is little information about the effect of darifenacin on vascular ion channels, specifically K channels. This study aimed to investigate the effect of the anti-muscarinic drug darifenacin on voltage-gated K (Kv) channels, vascular contractility, and coronary blood flow in rabbit coronary arteries. We used the whole-cell patch-clamp technique to evaluate the effect of darifenacin on Kv channels. Darifenacin inhibited the Kv current in a concentration-dependent manner. Applying 1 μM darifenacin shifted the activation and inactivation curves toward a more positive and negative potential, respectively. Darifenacin slowed the time constants of recovery from inactivation. Furthermore, blockade of the Kv current with darifenacin was increased gradually by applying a train of pulses, indicating that darifenacin inhibited Kv currents in a use- (state)-dependent manner. The darifenacin-mediated inhibition of Kv currents was associated with the Kv1.5 subtype, not the Kv2.1 or Kv7 subtype. Applying another anti-muscarinic drug atropine or ipratropium did not affect the Kv current or change the inhibitory effect of darifenacin. Isometric organ bath experiments using isolated coronary arteries were applied to evaluate whether darifenacin-induced inhibition of the Kv channel causes vasocontraction. Darifenacin substantially induced vasocontraction. Furthermore, darifenacin caused membrane depolarization and decreased coronary blood flow. From these results, we concluded that darifenacin inhibits the Kv currents in concentration- and use- (state)-dependent manners. Inhibition of the Kv current with darifenacin occurred by shifting the steady-state activation and inactivation curves regardless of its anti-muscarinic effect.
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http://dx.doi.org/10.1016/j.ejphar.2020.173707DOI Listing
January 2021

Learning Cell-Type-Specific Gene Regulation Mechanisms by Multi-Attention Based Deep Learning With Regulatory Latent Space.

Front Genet 2020 30;11:869. Epub 2020 Sep 30.

Bioinformatics Institute, Seoul National University, Seoul, South Korea.

Epigenetic gene regulation is a major control mechanism of gene expression. Most existing methods for modeling control mechanisms of gene expression use only a single epigenetic marker and very few methods are successful in modeling complex mechanisms of gene regulations using multiple epigenetic markers on transcriptional regulation. In this paper, we propose a multi-attention based deep learning model that integrates multiple markers to characterize complex gene regulation mechanisms. In experiments with 18 cell line multi-omics data, our proposed model predicted the gene expression level more accurately than the state-of-the-art model. Moreover, the model successfully revealed cell-type-specific gene expression control mechanisms. Finally, the model was used to identify genes enriched for specific cell types in terms of their functions and epigenetic regulation.
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http://dx.doi.org/10.3389/fgene.2020.00869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561362PMC
September 2020

Association between ARID2 and RAS-MAPK pathway in intellectual disability and short stature.

J Med Genet 2020 Oct 13. Epub 2020 Oct 13.

Medical Genetics Center, Asan Medical Center, Seoul, Republic of Korea

Background: ARID2 belongs to the Switch/sucrose non-fermenting complex, in which the genetic defects have been found in patients with dysmorphism, short stature and intellectual disability (ID). As the phenotypes of patients with mutations partially overlap with those of RASopathy, this study evaluated the biochemical association between ARID2 and RAS-MAPK pathway.

Methods: The phenotypes of 22 patients with either an heterozygous mutation or haploinsufficiency were reviewed. Comprehensive molecular analyses were performed using somatic and induced pluripotent stem cells (iPSCs) of a patient with haploinsufficiency as well as using the mouse model of haploinsufficiency by CRISPR/Cas9 gene editing.

Results: The phenotypic characteristics of deficiency include RASopathy, Coffin-Lowy syndrome or Coffin-Siris syndrome or undefined syndromic ID. Transient knockout HeLa cells using an shRNA increased ERK1 and ERK2 phosphorylation. Impaired neuronal differentiation with enhanced RAS-MAPK activity was observed in patient-iPSCs. In addition, haploinsufficient mice exhibited reduced body size and learning/memory deficit. haploinsufficiency was associated with reduced IFITM1 expression, which interacts with caveolin-1 (CAV-1) and inhibits ERK activation.

Discussion: haploinsufficiency is associated with enhanced RAS-MAPK activity, leading to reduced IFITM1 and CAV-1 expression, thereby increasing ERK activity. This altered interaction might lead to abnormal neuronal development and a short stature.
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http://dx.doi.org/10.1136/jmedgenet-2020-107111DOI Listing
October 2020

Verbascoside-Rich Nakai Leaf Extracts Prevent LPS-Induced Preterm Birth Through Inhibiting the Expression of Proinflammatory Cytokines from Macrophages and the Cell Death of Trophoblasts Induced by TNF-α.

Molecules 2020 Oct 7;25(19). Epub 2020 Oct 7.

Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon 35365, Korea.

: Preterm birth is a known leading cause of neonatal mortality and morbidity. The underlying causes of pregnancy-associated complications are numerous, but infection and inflammation are the essential high-risk factors. However, there are no safe and effective preventive drugs that can be applied to pregnant women. : The objectives of the study were to investigate a natural product, leaf (ADL) extract, to examine the possibility of preventing preterm birth caused by inflammation. Methods: We used a mouse preterm birth model by intraperitoneally injecting lipopolysaccharides (LPS). ELISA, Western blot, real-time PCR and immunofluorescence staining analyses were performed to confirm the anti-inflammatory efficacy and related mechanisms of the ADL extracts. Cytotoxicity and cell death were measured using Cell Counting Kit-8 (CCK-8) analysis and flow cytometer. : A daily administration of ADL extract significantly reduced preterm birth, fetal loss, and fetal growth restriction after an intraperitoneal injection of LPS in mice. The ADL extract prevented the LPS-induced expression of TNF-α in maternal serum and amniotic fluid and attenuated the LPS-induced upregulation of placental proinflammatory genes, including IL-1β, IL-6, IL-12p40, and TNF-α and the chemokine gene CXCL-1, CCL-2, CCL3, and CCL-4. LPS-treated THP-1 cell-conditioned medium accelerated trophoblast cell death, and TNF-α played an essential role in this effect. The ADL extract reduced LPS-treated THP-1 cell-conditioned medium-induced trophoblast cell death by inhibiting MAPKs and the NF-κB pathway in macrophages. ADL extract prevented exogenous TNF-α-induced increased trophoblast cell death and decreased cell viability. : We have demonstrated that the inhibition of LPS-induced inflammation by ADL extract can prevent preterm birth, fetal loss, and fetal growth restriction.
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http://dx.doi.org/10.3390/molecules25194579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583932PMC
October 2020

Implementation of a Home-Based mHealth App Intervention Program With Human Mediation for Swallowing Tongue Pressure Strengthening Exercises in Older Adults: Longitudinal Observational Study.

JMIR Mhealth Uhealth 2020 10 16;8(10):e22080. Epub 2020 Oct 16.

Graduate Program in Speech-Language Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea.

Background: Tongue pressure is an effective index of swallowing function, and it decreases with aging and disease progression. Previous research has shown beneficial effects of swallowing exercises combined with myofunctional tongue-strengthening therapy on tongue function. Tongue exercises delivered through mobile health (mHealth) technologies have the potential to advance health care in the digital age to be more efficient for people with limited resources, especially older adults.

Objective: The purpose of this study is to explore the immediate and long-term maintenance effects of an 8-week home-based mHealth app intervention with biweekly (ie, every 2 weeks) human mediation aimed at improving the swallowing tongue pressure in older adults.

Methods: We developed an mHealth app intervention that was used for 8 weeks (3 times/day, 5 days/week, for a total of 120 sessions) by 11 community-dwelling older adults (10 women; mean age 75.7 years) who complained of swallowing difficulties. The app included a swallowing monitoring and intervention protocol with 3 therapy maneuvers: effortful prolonged swallowing, effortful pitch glide, and effortful tongue rotation. The 8-week intervention was mediated by biweekly face-to-face meetings to monitor each participant's progress and ability to implement the training sessions according to the given protocol. Preintervention and postintervention isometric and swallowing tongue pressures were measured using the Iowa Oral Performance Instrument. We also investigated the maintenance effects of the intervention on swallowing tongue pressure at 12 weeks postintervention.

Results: Of the 11 participants, 8 adhered to the home-based 8-week app therapy program with the optimal intervention dosage. At the main trial end point (ie, 8 weeks) of the intervention program, the participants demonstrated a significant increase in swallowing tongue pressure (median 17.5 kPa before the intervention and 26.5 kPa after the intervention; P=.046). However, long-term maintenance effects of the training program on swallowing tongue pressure at 12 weeks postintervention were not observed.

Conclusions: Swallowing tongue pressure is known to be closely related to dysphagia symptoms. This is the first study to demonstrate the effectiveness of the combined methods of effortful prolonged swallowing, effortful pitch glide, and effortful tongue rotation using mobile app training accompanied by biweekly human mediation in improving swallowing tongue pressure in older adults. The mHealth app is a promising platform that can be used to deliver effective and convenient therapeutic service to vulnerable older adults. To investigate the therapeutic efficacy with a larger sample size and observe the long-term effects of the intervention program, further studies are warranted.

International Registered Report Identifier (irrid): RR2-10.2196/19585.
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http://dx.doi.org/10.2196/22080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600016PMC
October 2020
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