Publications by authors named "Y Eugene Chin"

900 Publications

Identification of curcumin as a potential α-glucosidase and dipeptidyl-peptidase 4 inhibitor: Molecular docking study, in vitro and in vivo biological evaluation.

J Food Biochem 2021 Apr 4:e13686. Epub 2021 Apr 4.

Human Health Research Laboratory, College of Food Science and Engineering, Ocean University of China, Qingdao, China.

Natural compounds have tremendous potential to regulate glucose metabolism, but conventional methods for studying their bioactivities are usually labor intensive. Here, hypoglycemic properties in 22 selected food-derived compounds were examined using molecular docking. The results indicated that curcumin is an inhibitor of both α-glucosidase and dipeptidyl-peptidase 4 (DPP-4), which are important for glycemic control. These effects of curcumin were also confirmed by enzymatic determination in vitro. Furthermore, curcumin significantly improved diet-induced hyperglycemia (e.g., fasting plasma glucose levels and glycogen storage in muscle or liver) in mice. This might be attributed to its inhibitory effects on the activities of α-glucosidase and DPP-4 in vivo. Curcumin also upregulated the expression of genes (e.g., glucagon-like peptide 1) related to DPP-4 activity in the small intestine. In conclusion, curcumin is a potential ingredient of functional foods used for diet-induced hyperglycemia management. PRACTICAL APPLICATIONS: Curcumin has been widely used as a colorant in the food industry. Moreover, a growing number of studies have described its diverse biological functions, such as anti-inflammatory, anti-oxidant, and anti-angiogenic activities. Thus, curcumin is regarded as a potential ingredient in functional foods. Our results highlighted the hyperglycemic effect of curcumin, suggesting that curcumin may be included in food products for hyperglycemic patients.
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http://dx.doi.org/10.1111/jfbc.13686DOI Listing
April 2021

Combinatorial Effects of Protective Agents on Survival Rate of the Yeast Starter, 88-4, after Freeze-Drying.

Microorganisms 2021 Mar 16;9(3). Epub 2021 Mar 16.

Research Group of Traditional Food, Korea Food Research Institute, Iseo-myeon, Wanju-gun 55365, Jeollabuk-do, Korea.

A yeast starter is formulated for commercial practices, including storage and distribution. The cell viability of the yeast starter is one of the most important factors for manufacturing alcoholic beverages to ensure their properties during the fermentation and formulation processes. In this study, 64 potential protective agents were evaluated to enhance the survival rate of the brewing yeast 88-4 after freeze-drying. In addition, the optimized combination of protective agents was assessed for long-term storage. Finally, response surface methodology was applied to investigate the optimal concentration of each protectant. Twenty of the 64 additives led to an increase in the survival rate of freeze-dried 88-4. Among the various combinations of protectants, four had a survival rate >95%. The combination of skim milk, maltose, and maltitol exhibited the best survival rate of 61% after 42 weeks in refrigerated storage, and the composition of protectants optimized by response surface methodology was 6.5-10% skim milk, 1.8-4.5% maltose, and 16.5-18.2% maltitol. These results demonstrated that the combination of multiple protectants could alleviate damage to yeasts during freeze-drying and could be applied to the manufacturing starters for fermented foods.
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http://dx.doi.org/10.3390/microorganisms9030613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002499PMC
March 2021

Dilignans with a Chromanol Motif Discovered by Molecular Networking from the Stem Barks of and Their Proprotein Convertase Subtilisin/Kexin Type 9 Expression Inhibitory Activity.

Biomolecules 2021 Mar 19;11(3). Epub 2021 Mar 19.

College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Korea.

Natural products have been fundamental materials in drug discovery. Traditional strategies for observing natural products with novel structure and/or biological activity are challenging due to large cost and time consumption. Implementation of the MS/MS-based molecular networking strategy with the in silico annotation tool is expected to expedite the dereplication of secondary metabolites. In this study, using this tool, two new dilignans with a 2-phenyl-3-chromanol motif, obovatolins A () and B (), were discovered from the stem barks of Thunb. along with six known compounds (-), expanding chemical diversity of lignan skeletons in this natural source. Their structures and configurations were elucidated using spectroscopic data. All isolates were evaluated for their PCSK9 mRNA expression inhibitory activity. Obovatolins A () and B (), and magnolol () showed potent lipid controlling activities. To identify transcriptionally controlled genes by along with downregulation of PCSK9, using small set of genes (42 genes) related to lipid metabolism selected from the database, focused bioinformatic analysis was carried out. As a result, it showed the correlations between gene expression under presence of , which led to detailed insight of the lipid metabolism caused by .
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http://dx.doi.org/10.3390/biom11030463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003705PMC
March 2021

Erratum: Choi, Y.H., et al. Multifaceted Factors Causing Conflicting Outcomes in Herb-Drug Interactions. 2021, , 43.

Pharmaceutics 2021 Mar 5;13(3). Epub 2021 Mar 5.

College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Korea.

The authors wish to make the following correction to the funding information [...].
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http://dx.doi.org/10.3390/pharmaceutics13030337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000952PMC
March 2021

A Time-Based Meta-Analysis on the Incidence of New Onset Diabetes after Liver Transplantation.

J Clin Med 2021 Mar 3;10(5). Epub 2021 Mar 3.

Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.

NODAT (new-onset diabetes after transplantation) is an important complication after liver transplant, however, there is variation in the reported incidence of NODAT. Therefore, a meta-analysis was performed to estimate the incidence of NODAT in liver transplant. Electronic databases were searched for articles regarding NODAT incidence after liver transplantation. Incidence of NODAT were analyzed at six different timepoints. Summary statistics were calculated using a generalized linear mixed model in random effects. 28 articles were included and out of a pooled population of 71,257 patients, overall incidence of NODAT was found to be 15.51%, 16.09%, 18.30%, 20.86%, 18.08%, 25.05% for three-months, six-months, one-year, three-year, five-year, and ten-year timepoints respectively. After a sensitivity analysis which only included articles with clear definitions of NODAT, the incidence of NODAT was found to be higher at three-year (21.79%), five-year (25.82%), and ten-year (44.95%) timepoints. Subgroup analysis according to ethnicity found no significant differences for all timepoints. However, studies with predominantly Asian participants generally had a higher incidence of NODAT. In conclusion, this meta-analysis provides a pooled estimate of the incidence of NODAT following liver transplantation. Further studies are required to provide a more comprehensive understanding on how ethnicity can affect the incidence of NODAT.
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http://dx.doi.org/10.3390/jcm10051045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959476PMC
March 2021

Identification of miR‑25‑3p as a tumor biomarker: Regulation of cellular functions via TOB1 in breast cancer.

Mol Med Rep 2021 Jun 31;23(6). Epub 2021 Mar 31.

Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P.R. China.

Breast cancer is the most common cancer in women and is one of the three most common malignancies worldwide. Serum microRNAs (miRNAs/miRs) are ideal biomarkers for tumor diagnosis and prognosis due to their specific biological characteristics. In several different types of cancer, miRNAs are associated with cell migration and invasion. In the present study, miR‑25‑3p expression levels were detected in tissue and serum samples derived from patients with breast cancer, and the diagnostic and prognostic value of miR‑25‑3p in breast cancer was evaluated. Cellular function assays were performed to evaluate the role of miR‑25‑3p in breast cancer. Moreover, dual‑luciferase reporter assays and western blotting were performed to investigate the target of miR‑25‑3p. miR‑25‑3p expression was upregulated in breast cancer tissue and serum samples compared with normal breast tissue and serum samples. Patients with breast cancer with high serum miR‑25‑3p levels were more likely to have lymph node metastasis compared with those with low serum miR‑25‑3p levels. The area under the curve for miR‑25‑3p in the diagnosis of breast cancer was 0.748, with 57.1% sensitivity and 95.0% specificity. Moreover, the Kaplan‑Meier survival curves demonstrated that patients with breast cancer with a low expression of serum miR‑25‑3p had a higher overall survival rate compared with patients with a high serum miR‑25‑3p expression. miR‑25‑3p knockdown suppressed breast cancer cell proliferation and invasion, and transducer of ERBB2, 1 () was identified as a potential target gene regulated by miR‑25‑3p. Therefore, the present study suggested that miR‑25‑3p regulated cellular functions via in breast cancer; therefore, miR‑25‑3p may serve as a breast cancer biomarker.
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http://dx.doi.org/10.3892/mmr.2021.12045DOI Listing
June 2021

Inhibitory effects of -Mangostin on T cell cytokine secretion ORAI1 calcium channel and K channels inhibition.

PeerJ 2021 3;9:e10973. Epub 2021 Mar 3.

Channelopathy Research Center (CRC), College of Medicine, Dongguk University, Goyang, Gyeonggi-do, Republic of Korea.

Background: As one of the main components of mangosteen (), a tropical fruit, -mangostin has been reported to have numerous pharmacological benefits such as anti-cancer, anti-inflammatory, and anti-allergic effects through various mechanisms of action. The effects of -mangostin on intracellular signaling proteins is well studied, but the effects of -mangostin on ion channels and its physiological effects in immune cells are unknown. Generation of intracellular calcium signaling is a fundamental step for T cell receptor stimulation. This signaling is mediated not only by the ORAI1 calcium channel, but also by potassium ion channels, which provide the electrical driving forces for generating sufficient calcium ion influx. This study investigated whether -mangosteen suppress T cell stimulation by inhibiting ORAI1 and two kinds of potassium channels (K1.3 and K3.1), which are normally expressed in human T cells.

Methods: This study analyzed the inhibitory effect of -mangostin on immune cell activity via inhibition of calcium and potassium ion channels expressed in immune cells.

Results: -mangostin inhibited ORAI1 in a concentration-dependent manner, and the IC value was 1.27 ± 1.144 µM. K1.3 was suppressed by 41.38 ± 6.191% at 3 µM, and K3.1 was suppressed by 51.16 ± 5.385% at 3 µM. To measure the inhibition of cytokine secretion by immune cells, Jurkat T cells were stimulated to induce IL-2 secretion, and -mangostin was found to inhibit it. This study demonstrated the anti-inflammatory effect of -mangostin, the main component of mangosteen, through the regulation of calcium signals.
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http://dx.doi.org/10.7717/peerj.10973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936567PMC
March 2021

Selaginellin Derivatives from and Their Upregulating Effects on Low-Density Lipoprotein Receptor Expression.

J Nat Prod 2021 Mar 11;84(3):857-864. Epub 2021 Mar 11.

College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 1, Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.

Two new dimeric selaginellins, diselaginellins C and D ( and ), a new unusual derivative, selapiginellin A (), a new selaginpulvilin U (), and a known derivative, diselaginellin A (), were isolated from (P. Beauv.) Spring. Among these compounds, selapiginellin A () is the first naturally occurring compound comprising an ether-linked dimer of a selaginellin and a selaginpulvilin. The absolute configurations of , , and were elucidated by spectroscopic data analyses. Compound was found to regulate mRNA expression of the low-density lipoprotein receptor (LDLR) gene and LDLR-related genes.
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http://dx.doi.org/10.1021/acs.jnatprod.0c01123DOI Listing
March 2021

Long-term Monitoring of Changes in Blood Pressure, Blood Glucose, and Total Cholesterol Levels among Frail Older Individuals Receiving Home Health Care Nursing in South Korea.

J Community Health Nurs 2021 Jan-Mar;38(1):13-23

Department of Health Administration, Dongseo University, Busan, Korea.

This study identified changes in blood pressure, blood glucose, and cholesterol levels in frail elderly adults who received home health care nursing over 8 years in Korea. Secondary data extracted from nursing records (2010-2018) of a public health center were analyzed using a mixed model of repeated measure. Study participants were elderly people ( = 499) with a mean age of 81.9 ± 5.56 years. Systolic and diastolic blood pressure decreased by 8.97 and 15.78 mmHg, and by 2.92 and 5.01 mmHg, respectively, at 4-year and 8-year monitoring. This demonstrates that home health care nursing is effective and has both short- and long-term benefits.
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http://dx.doi.org/10.1080/07370016.2021.1869424DOI Listing
March 2021

Risk Factors of Thyroid Eye Disease.

Endocr Pract 2021 Mar 14;27(3):245-253. Epub 2020 Dec 14.

Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Medicine, National University Hospital, Singapore. Electronic address:

Objective: To examine risk factors that might be associated with thyroid eye disease (TED) in patients with Graves' disease (GD), which may guide physicians in the prevention and management of TED.

Methods: Medline and Embase were searched for articles discussing risk factors of TED. Comparisons were made between GD patients with and without TED, and between active and inactive TED GD patients. Weighted mean differences (WMDs) and odds ratios (ORs) were determined for continuous and dichotomous outcomes, respectively. Results were pooled with random effects using the DerSimonian and Laird model.

Results: Fifty-six articles were included in the analysis. Smoking, inclusive of current and previous smoking status, was a significant risk factor for TED (OR: 2.401; CI: 1.958-2.945; P < .001). Statistical significance was found upon meta-regression between male sex and the odds of smoking and TED (β = 1.195; SE = 0.436; P = .013). Other risk factors were also examined, and patients with TED were significantly older than those without TED (WMD: 1.350; CI: 0.328-2.372; P = .010). While both age (WMD: 5.546; CI: 3.075-8.017; P < .001) and male sex (OR: 1.819; CI: 1.178-2.808; P = .007) were found to be significant risk factors for active TED patients compared to inactive TED patients, no statistical significance was found for family history, thyroid status, cholesterol levels, or body mass index.

Conclusion: Factors such as smoking, sex, and age predispose GD patients to TED, and TED patients to active TED. A targeted approach in the management of GD and TED is required to reduce the modifiable risk factor of smoking.
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http://dx.doi.org/10.1016/j.eprac.2020.11.011DOI Listing
March 2021

Sodium-Glucose Co-Transporter 2 Inhibitors for Non-Alcoholic Fatty Liver Disease in Asian Patients With Type 2 Diabetes: A Meta-Analysis.

Front Endocrinol (Lausanne) 2020 11;11:609135. Epub 2021 Feb 11.

Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

Objective: Non-alcoholic fatty liver disease (NAFLD) is a very common disorder among patients with type 2 diabetes and may share causal relationship. Type 2 diabetes is a risk factor for progression and potential poor outcomes in NAFLD patients. This meta-analysis aimed to analyze the current evidence of sodium-glucose co-transporter-2 inhibitors (SGLT2i), a glucose-lowering drug to improve NAFLD in patients with Type 2 Diabetes.

Methods: Medline, Embase and Cochrane Central Register of Controlled Trials were searched for articles examining efficacy of SGLT2i on treatments of NAFLD in type 2 diabetes in July 2020, and articles were sieved. Continuous data were extracted in the form of mean and standard deviation and were pooled with standardized mean difference (SMD).

Results: 10 articles involving 555 patients from seven randomized controlled trials (RCTs) and three cohort studies, were included in this meta-analysis. Our analysis revealed significant improvements in hepatic fat content (after treatment: -0.789 (-1.404 to -0.175), p = 0.012; compared with control: -0.923 (-1.562 to -0.285), p = 0.005), AST (After Treatment: -0.539 (-0.720 to -0.357), p < 0.001; compared with control: -0.421 (-0.680 to -0.161), p = 0.001), ALT (after treatment: -0.633 (-0.892 to -0.373), p < 0.001; compared with Control: -0.468 (-0.685 to -0.251), p < 0.001), body composition (BMI: after treatment: -0.225 (-0.456 to 0.005), p = 0.055; compared with Control: -1.092 (-2.032 to -0.153), p = 0.023), glycemic control (HbA1c: After Treatment: -0.701 (-1.098 to -0.303), p = 0.001; compared with control: -0.210 (-0.603 to 0.183), p = 0.295), lipid parameters (Triglycerides: after treatment: -0.230 (-0.409 to -0.052), p = 0.011; compared with control: -0.336 (-0.597 to -0.076), p = 0.011), inflammatory markers (serum ferritin: after treatment: -0.409 (-0.694 to -0.124), p = 0.005; compared with control: -0.814 (-1.688 to 0.059), p = 0.068) after SGLT2i treatment, and when compared against controls. There was a trend in the improvement in fibrosis markers after SGLT2i treatment.

Conclusions: SGLT2i is an effective treatment to improve NAFLD among patients with type 2 diabetes. Further studies are needed to understand the direct and indirect effects of SGLT2i on NAFLD and if SGLT2i could prevent the progression of NAFLD or NASH. SGLT2i could potentially be considered for patients with type 2 diabetes and NAFLD, if there are no contraindications.
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http://dx.doi.org/10.3389/fendo.2020.609135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905212PMC
February 2021

Evolution of IgA nephropathy in Singapore over four decades and a comparison of two cohorts from the first and fourth decade.

Clin Nephrol 2021 May;95(5):256-272

Objective: In this study, we trace the changes in the clinical and histological pattern of IgA nephritis (IgAN) in Singapore as it has evolved over 4 decades and compare the clinical, demographic, histological, and renal outcome of patients with IgAN from the 1 decade and the 4 decade.

Materials And Methods: This is a retrospective study of all histologically proven IgAN diagnosed between 1976 and 2018. Clinical, laboratory, and histological characteristics between the 1 and the 4 decade, including treatment which could influence the disease progression and renal outcome of these two groups, were compared. We used the Oxford classification to compare the renal biopsy changes for these 2 decades as we were able to retrieve 125 renal biopsy tissues for the 1 cohort of IgAN studied in the 1970s for the comparative study.

Results: The commonest clinical presentation throughout the first 3 decades was asymptomatic hematuria and proteinuria (63, 52, and 49%, respectively). In the 4 decade, nephrotic syndrome (31%) was the commonest followed by asymptomatic hematuria and proteinuria (30%), hypertension (21%), and chronic renal failure (11%). The data showed that treatment can modify the Oxford MEST - Crescent scores. Renin-angiotensin system (RAS) blockers modified the S scores, immunosuppressants modified the T and C scores, and combination therapy with RAS blockers and immunosuppressants modified the E, S, and T scores.

Conclusion: The Oxford MEST classification offers a robust and expressive classification for early and late disease progression with respect to the development of end-stage renal disease (ESRD). E and S seem to be indices of continuing disease activity with progressive glomerulosclerosis, probably still amenable to therapy, but T was a predictive indicator for those destined for ESRD and no longer amenable to therapy.
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http://dx.doi.org/10.5414/CN110317DOI Listing
May 2021

The effects of weight fluctuation on the components of metabolic syndrome: a 16-year prospective cohort study in South Korea.

Arch Public Health 2021 Feb 18;79(1):21. Epub 2021 Feb 18.

College of Nursing, Jeonbuk National University, 567 Baekje-daero, Deokjin-gu, Jeonju-si, Jeollabuk-do, 54896, Republic of Korea.

Background: Weight fluctuation (WF) is highly prevalent in parallel with the high prevalence of intentional or unintentional dieting. The health risks of frequent WF for metabolic syndrome (MS) have become a public health concern, especially for health care providers who supervise dieting as an intervention to prevent obesity-related morbidity or to improve health, as well as for the general population for whom dieting is of interest. The aim of this study was to investigate the long-term effect of WF on the risk of MS in Koreans.

Methods: This study analyzed secondary data from the Korean Genome and Epidemiology Study, a 16-year prospective cohort study, on 8150 individuals using time-dependent Cox regression.

Results: WF did not increase the risk of MS in either normal-weight or obese subjects. In an analysis of the components of MS, greater WF significantly increased the risk of abdominal obesity (HR = 1.05, 95% CI = 1.02-1.07, p < 0.001) in normal-weight individuals. However, WF did not increase the risk of hyperglycemia, low high-density lipoprotein cholesterol levels, elevated blood pressure, or raised fasting glucose in normal-weight individuals, and it did not influence any of the components of MS in obese individuals.

Conclusion: Since WF was found to be a risk factor for abdominal obesity, which is the most reliable predictor of MS, it should be considered when addressing weight control. Further studies on cut-off points for the degree of weight loss in a certain period need to be conducted to help clinicians provide guidance on appropriate weight control.
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http://dx.doi.org/10.1186/s13690-021-00539-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893930PMC
February 2021

Sesquiterpenoids from the Aerial Parts of with Inhibitory Activities on Proprotein Convertase Subtilisin/Kexin Type 9 Expression.

J Nat Prod 2021 02 11;84(2):220-229. Epub 2021 Feb 11.

College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea.

Phytochemical investigation of the methanol extract of the aerial parts of aided by a proprotein convertase subtilisin/kexin type 9 (PCSK9) mRNA expression screening assay in HepG2 cells led to the identification of 19 compounds including one new norsesquiterpene (), six new eudesmane sesquiterpenoids (-, , and ), and 12 known compounds. The structures of all compounds were elucidated by interpretation of their 1D and 2D NMR spectroscopic and MS data. Furthermore, computational prediction of ECD or chemical shifts was used to propose the absolute configurations of the new structures. All isolates were assessed for their inhibitory activities against PCSK9 mRNA expression and PCSK9-low-density lipoprotein receptor (LDLR) interactions. None of the isolated compounds inhibited PCSK9 and LDLR interactions. However, compounds , , and downregulated PCSK9 mRNA expression.
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http://dx.doi.org/10.1021/acs.jnatprod.0c00829DOI Listing
February 2021

A novel method to retrieve alerts from a homegrown Computerized Physician Order Entry (CPOE) system of an academic medical center: Comprehensive alert characteristic analysis.

PLoS One 2021 9;16(2):e0246597. Epub 2021 Feb 9.

Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.

Background: The collection and analysis of alert logs are necessary for hospital administrators to understand the types and distribution of alert categories within the organization and reduce alert fatigue. However, this is not readily available in most homegrown Computerized Physician Order Entry (CPOE) systems.

Objective: To present a novel method that can collect alert information from a homegrown CPOE system (at an academic medical center in Taiwan) and conduct a comprehensive analysis of the number of alerts triggered and alert characteristics.

Methods: An alert log collector was developed using the Golang programming language and was implemented to collect all triggered interruptive alerts from a homegrown CPOE system of a 726-bed academic medical center from November 2017 to June 2018. Two physicians categorized the alerts from the log collector as either clinical or non-clinical (administrative).

Results: Overall, 1,625,341 interruptive alerts were collected and classified into 1,474 different categories based on message content. The sum of the top 20, 50, and 100 categories of most frequently triggered alerts accounted for approximately 80, 90 and 97 percent of the total triggered alerts, respectively. Among alerts from the 100 most frequently triggered categories, 1,266,818 (80.2%) were administrative and 312,593 (19.8%) were clinical alerts.

Conclusion: We have successfully developed an alert log collector that can serve as an extended function to retrieve alerts from a homegrown CPOE system. The insight generated from the present study could also potentially bring value to hospital system designers and hospital administrators when redesigning their CPOE system.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246597PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872273PMC
February 2021

Correction: Pharmacokinetic Properties of Moracin C in Mice.

Planta Med 2021 Feb 5. Epub 2021 Feb 5.

College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, Gyeonggi-do, Republic of Korea.

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http://dx.doi.org/10.1055/a-1384-8484DOI Listing
February 2021

Inadequate Gestational Weight Gain and Exposure to Second-Hand Smoke during Pregnancy Increase the Risk of Low Birth Weight: A Cross-Sectional Study among Full-Term Infants.

Int J Environ Res Public Health 2021 01 26;18(3). Epub 2021 Jan 26.

Department of Community Health, Faculty of Medicine & Health Sciences, Universiti Putra Malaysia, Selangor 43400, Malaysia.

Despite the advancement of the healthcare system, low birth weight (LBW) remains as one of the leading causes of under-five mortality. This cross-sectional study aimed to determine the prevalence of LBW and its associated factors among 483 third trimester pregnant women recruited from six selected public health clinics in the Federal Territory of Kuala Lumpur and the state of Selangor, Malaysia. Pregnant women were interviewed for information on socio-demographic characteristics, smoking behaviour, and second-hand smoke (SHS) exposure at home and in the workplace. Information on the obstetrical history and prenatal care visits history were retrieved from the maternal medical records, while infant's birth outcomes were retrieved from infant medical records. The prevalence of LBW (<2.5 kg) in infants was 10.4%, with a mean birth weight of 3.0 [standard deviation (SD) 0.4] kg. Results from the multivariable logistic regression model showed that inadequate weight gained during pregnancy [odds ratio (OR) = 2.41, 95% confidence interval (CI) = 1.18-4.90] and exposure to SHS at home (OR = 1.92, 95% CI = 1.03-3.55) were significantly associated with LBW. In conclusion, pregnant women should monitor their rate of weight gain throughout pregnancy and avoid SHS exposure at home to reduce the risk of delivering LBW infants.
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http://dx.doi.org/10.3390/ijerph18031068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907990PMC
January 2021

Oncologist-led counselling improves access to cancer genetic testing in middle-income Asian country, with no significant impact on psychosocial outcomes.

J Med Genet 2021 Feb 1. Epub 2021 Feb 1.

Cancer Prevention and Population Science, Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia.

Background: Identifying patients with mutations is clinically important to inform on the potential response to treatment and for risk management of patients and their relatives. However, traditional referral routes may not meet clinical needs, and therefore, mainstreaming cancer genetics has been shown to be effective in some high-income and high health-literacy settings. To date, no study has reported on the feasibility of mainstreaming in low-income and middle-income settings, where the service considerations and health literacy could detrimentally affect the feasibility of mainstreaming.

Methods: The Mainstreaming Genetic Counselling for Ovarian Cancer Patients (MaGiC) study is a prospective, two-arm observational study comparing oncologist-led and genetics-led counselling. This study included 790 multiethnic patients with ovarian cancer from 23 sites in Malaysia. We compared the impact of different method of delivery of genetic counselling on the uptake of genetic testing and assessed the feasibility, knowledge and satisfaction of patients with ovarian cancer.

Results: Oncologists were satisfied with the mainstreaming experience, with 95% indicating a desire to incorporate testing into their clinical practice. The uptake of genetic testing was similar in the mainstreaming and genetics arm (80% and 79%, respectively). Patient satisfaction was high, whereas decision conflict and psychological impact were low in both arms of the study. Notably, decisional conflict, although lower than threshold, was higher for the mainstreaming group compared with the genetics arm. Overall, 13.5% of patients had a pathogenic variant in or and there was no difference between psychosocial measures for carriers in both arms.

Conclusion: The MaGiC study demonstrates that mainstreaming cancer genetics is feasible in low-resource and middle-resource Asian setting and increased coverage for genetic testing.
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http://dx.doi.org/10.1136/jmedgenet-2020-107416DOI Listing
February 2021

Protective Effect of γ-mangostin Isolated from the Peel of against Glutamate-Induced Cytotoxicity in HT22 Hippocampal Neuronal Cells.

Biomolecules 2021 Jan 27;11(2). Epub 2021 Jan 27.

College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 1 Gwanak-lo, Gwanak-gu, Seoul 08826, Korea.

The aim of the present study was to examine the protective effect of γ-mangostin, a component of the mangosteen shell, against oxidative damage to nerve cells induced by excessive glutamate, a known excitatory neurotransmitter. To investigate the effect of γ-mangostin on apoptosis, 5 mM of glutamate was used to induce apoptotic cell death in mouse hippocampal HT22 cells. In this study, γ-mangostin was found to exert a stronger protection than N-acetyl cysteine against glutamate-induced cell damage. γ-Mangostin showed prevented glutamate-induced apoptosis in HT22 cells by reducing the production of reactive oxygen species and stimulating the expression of heme oxygenase-1 protein. In addition, glutamate significantly induced the accumulation of intracellular calcium ions, whereas treatment with γ-mangostin markedly reduced it. Hoechst 33342 staining showed an improvement in glutamate-induced nuclear condensation following γ-mangostin treatment. Furthermore, the number of annexin V-positive cells was significantly reduced following treatment with γ-mangostin. Western blot analysis showed the inhibition of glutamate-induced mitogen-activated protein kinase phosphorylation by γ-mangostin. γ-mangostin also inhibited the regulation of the intrinsic mitochondrial apoptotic pathway. Thus, the results of this study suggest that γ-mangostin is an active ingredient of mangosteen and exerts neuroprotective activities in HT22 cells.
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http://dx.doi.org/10.3390/biom11020170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910862PMC
January 2021

Assessing the International Transferability of a Machine Learning Model for Detecting Medication Error in the General Internal Medicine Clinic: Multicenter Preliminary Validation Study.

JMIR Med Inform 2021 Jan 27;9(1):e23454. Epub 2021 Jan 27.

Division of General Internal Medicine and Primary Care, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.

Background: Although most current medication error prevention systems are rule-based, these systems may result in alert fatigue because of poor accuracy. Previously, we had developed a machine learning (ML) model based on Taiwan's local databases (TLD) to address this issue. However, the international transferability of this model is unclear.

Objective: This study examines the international transferability of a machine learning model for detecting medication errors and whether the federated learning approach could further improve the accuracy of the model.

Methods: The study cohort included 667,572 outpatient prescriptions from 2 large US academic medical centers. Our ML model was applied to build the original model (O model), the local model (L model), and the hybrid model (H model). The O model was built using the data of 1.34 billion outpatient prescriptions from TLD. A validation set with 8.98% (60,000/667,572) of the prescriptions was first randomly sampled, and the remaining 91.02% (607,572/667,572) of the prescriptions served as the local training set for the L model. With a federated learning approach, the H model used the association values with a higher frequency of co-occurrence among the O and L models. A testing set with 600 prescriptions was classified as substantiated and unsubstantiated by 2 independent physician reviewers and was then used to assess model performance.

Results: The interrater agreement was significant in terms of classifying prescriptions as substantiated and unsubstantiated (κ=0.91; 95% CI 0.88 to 0.95). With thresholds ranging from 0.5 to 1.5, the alert accuracy ranged from 75%-78% for the O model, 76%-78% for the L model, and 79%-85% for the H model.

Conclusions: Our ML model has good international transferability among US hospital data. Using the federated learning approach with local hospital data could further improve the accuracy of the model.
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http://dx.doi.org/10.2196/23454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875695PMC
January 2021

Pharmacokinetic Properties of Moracin C in Mice.

Planta Med 2021 Jan 26. Epub 2021 Jan 26.

College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, Gyeonggi-do, Republic of Korea.

Moracin C from fruits, also known as the mulberry, has been proven to exhibit inhibitory activities against lipoxygenase enzymes, TNF- and interleukin-1 secretion, and proprotein convertase subtilisin/kexin type 9 expression. Despite the various pharmacological activities of moracin C, its pharmacokinetic characteristics have yet to be reported. Here, the pharmacokinetic parameters and tissue distribution of moracin C have been investigated in mice, and the plasma concentration of moracin C with multiple dosage regimens was simulated via pharmacokinetic modeling. Our results showed that moracin C was rapidly and well absorbed in the intestinal tract, and was highly distributed in the gastrointestinal tract, liver, kidneys, and lungs. Moracin C was distributed in the ileum, cecum, colon, and liver at a relatively high concentration compared with its plasma concentration. It was extensively metabolized in the liver and intestine, and its glucuronidated metabolites were proposed. In addition, the simulated plasma concentrations of moracin C upon multiple treatments (i.e., every 12 and 24 h) were suggested. We suggest that the pharmacokinetic characteristics of moracin C would be helpful to select a disease model for evaluation. The simulated moracin C concentrations under various dosage regimens also provide helpful knowledge to support its pharmacological effect.
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http://dx.doi.org/10.1055/a-1321-1519DOI Listing
January 2021

No Interaction Effect between Interleukin-6 Polymorphisms and Acid Ash Diet with Bone Resorption Marker in Postmenopausal Women.

Int J Environ Res Public Health 2021 01 19;18(2). Epub 2021 Jan 19.

Department of Orthopedics, Faculty of Medicine and Health Sciences, University Putra Malaysia (UPM), UPM Serdang, Seri Kembangan 43400, Selangor, Malaysia.

Background: Evidence is growing that a high-acid diet might accelerate the rate of bone loss, and gene polymorphisms such as Interleukin 6 () -174G/C and -572G/C are related to bone deterioration. However, no study of the interaction between diet and polymorphisms has been conducted among Asians. Thus, the objective of this study was to determine whether IL6 gene polymorphisms modified the association between dietary acidity and the rate of bone resorption.

Methods: This cross-sectional study recruited 203 postmenopausal women (age ranged from 51 to 85 years old) in community settings. The dietary intakes of the participants were assessed using a validated interviewer-administered semi-quantitative food frequency questionnaire (FFQ), while dietary acid load (DAL) was estimated using net endogenous acid production (NEAP). Agena MassARRAY genotyping analysis and serum collagen type 1 cross-linked C-telopeptide (CTX1) were used to identify the genotype and as a bone resorption marker, respectively. The interactions between diet and single-nucleotide polymorphisms (SNPs) were assessed using linear regressions.

Results: A total of 203 healthy postmenopausal women aged between 51 and 85 years participated in this study. The mean BMI of the participants was 24.3 kg/m. In -174 G/C, all the participants carried the GG genotype, while the C allele was absent. Approximately 40% of the participants had a high dietary acid load. Dietary acid load (B = 0.15, = 0.031) and the -572 CC genotype group (B = 0.14, = 0.044) were positively associated with a higher bone resorption. However, there was no moderating effect of the genetic polymorphism on the relationship between and acid ash diet and bone resorption markers among the postmenopausal women ( = 0.79).

Conclusion: High consumption of an acid ash diet and the -572 C allele seem to attribute to high bone resorption among postmenopausal women. However, our finding does not support the interaction effect of dietary acidity and (-174G/C and -572G/C) polymorphisms on the rate of bone resorption. Taken together, these results have given scientific research other candidate genes to focus on which may interact with DAL on bone resorption, to enhance planning for preventing or delaying the onset of osteoporosis among postmenopausal women.
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http://dx.doi.org/10.3390/ijerph18020827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835771PMC
January 2021

Contribution of insulin resistance to the relationship between sugar-sweetened beverage intake and a constellation of cardiometabolic abnormalities in adolescents.

Int J Obes (Lond) 2021 Apr 20;45(4):828-839. Epub 2021 Jan 20.

Department of Public Health, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan.

Background: Insulin resistance (IR) is a pathophysiological construct that derives a series of metabolic disturbances that promote cardiometabolic dysfunction. This study evaluated mediating and modifying effects of homeostatic model assessment-based IR (HOMA-IR) on the association between sugar-sweetened beverage (SSB) consumption and a constellation of adolescent cardiometabolic abnormalities.

Methods: Comprehensive data on sociodemographics, diet, physical activity, and anthropometric and biochemical parameters for 1454 adolescents were obtained from a large-scale representative study for adolescent metabolic syndrome (MetS) conducted in Taiwan. The original (HOMA1-IR) and updated nonlinear (HOMA2-IR) HOMA-IR indicators were used as IR biomarkers. Principal component (PC) analysis was employed to create reduced groups of variables and risk scores for retained PCs.

Results: Higher SSB intake was associated with higher levels of HOMA1-IR and HOMA2-IR, and the two IR biomarkers were positively correlated with metabolic dysfunction clustering. Compared with SSB nondrinkers, adolescents who consumed >500 mL/day of hand-shaken high-fructose corn syrup beverages (HHB) had a 0.22 increase in the number of abnormal MetS components, and HOMA-IR mediation explained 33.9-37.9% of the effect. IR biomarkers accounted for 26.5-31.0% of the relationship between >500 mL/day of SSB consumption and bodyweight-enhanced PC scores. The effects of HOMA-IR indicators on all bodyweight-related factors were consistently intensified among >350 mL/day HHB drinkers (all P < 0.05).

Conclusions: Fructose-rich SSB intake correlates with a constellation of cardiometabolic abnormalities in adolescents, and this association may be partly mediated by HOMA-IR levels. The adverse effects of HOMA-IR on bodyweight-associated cardiometabolic risk factors depend on the type of SSB consumption, with enhanced risks observed in the intake of high amounts of HFCS-containing SSBs.
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http://dx.doi.org/10.1038/s41366-021-00745-1DOI Listing
April 2021

Moving beyond the initial colonoscopy: a call for action.

Eur J Cancer Prev 2021 Jan 18. Epub 2021 Jan 18.

Department of Medicine, Devi Yong Loo Lin School of Medicine, National University Singapore Department of Surgery, Division of Colorectal Surgery, National University Hospital Department of Nursing, Alice Lee Centre for Nursing Studies, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Introduction: The evolution of colorectal screening has made headway with continual efforts globally to increase screening rates for colonoscopy-naïve patients. However, little has been done to encourage repeat colonoscopies after the initial scope despite recommendations to repeat colonoscopy every 10 years, with the uptake rates of repeat colonoscopy remaining abysmal at 22%.

Methods: Previously, a qualitative systematic review evaluated the barriers and facilitators patients faced in their decisions to undergo colonoscopy, analyzing articles from Medline, Embase, CINAHL, PsycINFO and Web of Science. Key findings from articles which highlighted factors influencing patients' decisions to return for repeat colonoscopies were summarized.

Results: Three articles were identified in the search. Facilitators for repeat colonoscopy included patients' assurance garnered from fostered trust in the patient-provider relationship, their intrinsic motivations from fear of cancer and an innate appreciation for the significance of obtaining repeated colonoscopies. Procedural factors such as the option for procedural visualization, its comprehensiveness and the utilization of anesthesia were also crucial motivators. Barriers that patients highlighted comprised of cumbersome bowel preparation and potential complications.

Discussion: Recently, minimal research has been conducted on the sentiments of healthcare providers and patients regarding repeat colonoscopy. The lack of emphasis from healthcare institutions on encouraging patients to repeat colonoscopy after 10 years prevents effective colorectal cancer screening. To proficiently alleviate the burden of colorectal cancer, patient counseling has to shift beyond explaining colonoscopy risks and complications to promoting regular follow-up scopes. This article thus calls for more studies to focus on evaluating the uptake of repeat colonoscopies.
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http://dx.doi.org/10.1097/CEJ.0000000000000647DOI Listing
January 2021

Antioxidants protect against gingival overgrowth induced by cyclosporine A.

J Periodontal Res 2021 Apr 14;56(2):397-407. Epub 2021 Jan 14.

Department of Dentistry, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Xindian, Taiwan.

Objective: We investigated the importance of reactive oxygen species (ROS) on developing gingival overgrowth (GO) and then introduced the antioxidant strategy to prevent, or even reduce GO.

Background: Gingival overgrowth is a common side effect of the patients receiving cyclosporine A (CsA), an immune suppressant. Although it has been broadly investigated, the exact pathogenesis of the induced GO is still uncertain.

Methods: We cultured human primary gingival fibroblasts and used animal model of GO to investigate the ameliorative effects of antioxidants on CsA-induced GO. To examine the CsA-induced oxidative stress, associated genes and protein expression, and the overgrown gingiva of rats by using immunocytochemistry, confocal laser scanning microscopy, real-time PCR, ELISA, gelatin zymography, gingival morphological, and immunohistochemical analysis.

Results: We found for the first time that ROS was responsible for the CsA-induced oxidative stress and TGF-β1 expression in human primary gingival fibroblasts, as well as the GO of rats. The antioxidants (oxidative scavenger of vitamin E and an antioxidative enzyme inducer of hemin) ameliorated CsA-induced pathological and morphological alterations of GO without affected the CsA-suppressed il-2 expression in rats. CsA-induced oxidative stress, HO-1, TGF-β1, and type II EMT were also rescued by antioxidants treatment.

Conclusions: We concluded that CsA repetitively stimulating the production of ROS is the cause of CsA-GO which is ameliorated by treating antioxidants, including vitamin E and sulforaphane. Furthermore, the immunosuppressive effect of CsA is not interfered by antioxidant treatments in rats. This finding may thus help the clinician devise better prevention strategies in patients susceptible to GO.
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http://dx.doi.org/10.1111/jre.12832DOI Listing
April 2021

Acetylation-dependent glutamate receptor GluR signalosome formation for STAT3 activation in both transcriptional and metabolism regulation.

Cell Death Discov 2021 Jan 14;7(1):11. Epub 2021 Jan 14.

Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, 215123, Suzhou, Jiangsu, China.

Besides their original regulating roles in the brain, spinal cord, retina, and peripheral nervous system for mediating fast excitatory synaptic transmission, glutamate receptors consisting of metabotropic glutamate receptors (GluRs) and ionotropic glutamate receptors (iGluRs) have emerged to have a critical role in the biology of cancer initiation, progression, and metastasis. However, the precise mechanism underpinning the signal transduction mediated by ligand-bound GluRs is not clearly elucidated. Here, we show that iGluRs, GluR1 and GluR2, are acetylated by acetyltransferase CREB-binding protein upon glutamate stimulation of cells, and are targeted by lysyl oxidase-like 2 for deacetylation. Acetylated GluR1/2 recruit β-arrestin1/2 and signal transducer and activator of transcription 3 (STAT3) to form a protein complex. Both β-arrestin1/2 and STAT3 are subsequently acetylated and activated. Simultaneously, activated STAT3 acetylated at lysine 685 translocates to mitochondria to upregulate energy metabolism-related gene transcription. Our results reveal that acetylation-dependent formation of GluR1/2-β-arrestin1/2-STAT3 signalosome is critical for glutamate-induced cell proliferation.
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http://dx.doi.org/10.1038/s41420-020-00389-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809112PMC
January 2021

Hyperglycaemia converting to persistent hypoglycaemia.

Diabet Med 2021 Mar 28;38(3):e14519. Epub 2021 Jan 28.

Department of Endocrinology, Singapore General Hospital, Singapore, Singapore.

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http://dx.doi.org/10.1111/dme.14519DOI Listing
March 2021

Patient-reported outcomes for nipple reconstruction: Review of literature.

Surgeon 2021 Jan 7. Epub 2021 Jan 7.

Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Birmingham B15 2TH, UK.

Background: There is currently no validated patient-reported outcome measure (PROM) that is specific to nipple-areola complex (NAC) reconstruction. This paper evaluates all patient-reported outcomes for NAC reconstruction in the literature.

Methods: Systematic literature searches of The Cochrane Central Register of Controlled Trials, MEDLINE and World Health Organization International Clinical Trials Registry Platform were conducted to identify all primary studies with patient-reported outcomes for NAC reconstruction. The primary outcome measures were patient satisfaction rates for appearance and symmetry of NAC reconstruction.

Results: Fifty-nine papers were included in this review. Reported patient satisfaction was generally high, with the pooled average satisfaction rate for appearance being 81.9% and symmetry 80.3%. 89.5% of respondents would do it again and 94.8% would recommend it to others. There is no standardised or validated PROM specific to NAC reconstruction and this contributes to a lack of conclusive findings from studies in this area.

Conclusion: There is a need for a validated PROM that is specific to NAC reconstruction, in order to serve as a standardised outcome assessment to guide further research and improve patient care.
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http://dx.doi.org/10.1016/j.surge.2020.11.005DOI Listing
January 2021

Memory-Enhancing Effects of Mangosteen Pericarp Water Extract through Antioxidative Neuroprotection and Anti-Apoptotic Action.

Antioxidants (Basel) 2020 Dec 30;10(1). Epub 2020 Dec 30.

College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, Dongguk-ro 32, Ilsandong-gu, Goyang, Gyeonggi 10326, Korea.

Mangosteen has long been utilized as a traditional medicine in Southeast Asia. Diverse extracts of mangosteen pericarp and its bioactive xanthones exhibit various bioactivities. However, the pharmacological potential of mangosteen pericarp water extract (MPW) has not been reported yet. This study used primary cultured rat cortical cells to investigate the effect of MPW on neurotoxicity. We found that MPW inhibited neurotoxicity and production of reactive oxygen species triggered by Aβ or excitatory amino acids. MPW inhibited caspase 3 activation and DNA fragmentation in Aβ- or N-methyl-D-aspartate-treated cells, suggesting an anti-apoptotic action. Additionally, MPW reduced lipid peroxidation and scavenged 1,1-diphenyl-2-picrylhydrazyl radicals, assuring its antioxidant property. Furthermore, MPW suppressed β-secretase and acetylcholinesterase activities. These findings prompted us to evaluate its effect on memory dysfunction in scopolamine-treated mice using Morris water maze test. Oral administration of MPW at the dosage of 50, 100, or 300 mg/kg for four days significantly decreased the latency time to find the platform and markedly increased the swimming time in the target quadrant. Taken together, our results suggest that MPW exerts memory-enhancing effect through antioxidative neuroprotection and anti-apoptotic action. Accordingly, MPW may have a potential to prevent or treat memory impairment associated with Alzheimer's disease.
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http://dx.doi.org/10.3390/antiox10010034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823671PMC
December 2020