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Fulltext Chest discomfort in a patient with dengue - is it an acute myocardial infarction?

Koh KC, Hong HC

Malays Fam Physician, 2018;13(2):29-31.
PMID: 30302181

Cardiovascular symptoms presenting in a patient with dengue fever may post a diagnostic dilemma. We describe a case of dengue myocarditis mimicking an acute myocardial infarction in a 56-year-old woman.
Development and Validation of Decision Forest Model for Estrogen Receptor Binding Prediction of Chemicals Using Large Data Sets

Ng HW, Doughty SW, Luo H, Ye H, Ge W, Tong W, et al.

Chem Res Toxicol, 2015 Dec 21;28(12):2343-51.
PMID: 26524122 DOI: 10.1021/acs.chemrestox.5b00358

Some chemicals in the environment possess the potential to interact with the endocrine system in the human body. Multiple receptors are involved in the endocrine system; estrogen receptor α (ERα) plays very important roles in endocrine activity and is the most studied receptor. Understanding and predicting estrogenic activity of chemicals facilitates the evaluation of their endocrine activity. Hence, we have developed a decision forest classification model to predict chemical binding to ERα using a large training data set of 3308 chemicals obtained from the U.S. Food and Drug Administration's Estrogenic Activity Database. We tested the model using cross validations and external data sets of 1641 chemicals obtained from the U.S. Environmental Protection Agency's ToxCast project. The model showed good performance in both internal (92% accuracy) and external validations (∼ 70-89% relative balanced accuracies), where the latter involved the validations of the model across different ER pathway-related assays in ToxCast. The important features that contribute to the prediction ability of the model were identified through informative descriptor analysis and were related to current knowledge of ER binding. Prediction confidence analysis revealed that the model had both high prediction confidence and accuracy for most predicted chemicals. The results demonstrated that the model constructed based on the large training data set is more accurate and robust for predicting ER binding of chemicals than the published models that have been developed using much smaller data sets. The model could be useful for the evaluation of ERα-mediated endocrine activity potential of environmental chemicals.
Fulltext Real-world experiences of folic acid supplementation (5 versus 30 mg/week) with methotrexate in rheumatoid arthritis patients: a comparison study

Koh KT, Teh CL, Cheah CK, Ling GR, Yong MC, Hong HC, et al.

Reumatismo, 2016 Sep 09;68(2):90-6.
PMID: 27608797 DOI: 10.4081/reumatismo.2016.872

The objective of this study was to compare the tolerability of methotrexate in two different regimes of folic acid (FA) supplementation in rheumatoid arthritis (RA). We performed a multicenter, cross-sectional observational cohort study on 240 RA patients with 120 patients each in 5 mg of FA weekly and 30 mg of FA weekly supplementation. There were no significant differences for side effects (14.2 versus 22.5%, P=0.523) and discontinuation of methotrexate (3.6 versus 13.3%, P=0.085). RA patients given 5 mg of FA weekly supplementation had a lower disease activity score 28 compared to 30 mg of FA weekly supplementation [3.44 (1.10) versus 3.85 (1.40), P=0.014]. FA supplementation of 5 mg per week and 30 mg per week was associated with similar tolerability of methotrexate in RA patients.
Ultrasound mediated efficient synthesis of new 4-oxoquinazolin-3(4H)-yl)furan-2-carboxamides as potent tyrosinase inhibitors: Mechanistic approach through chemoinformatics and molecular docking studies

Dige NC, Mahajan PG, Raza H, Hassan M, Vanjare BD, Hong H, et al.

Bioorg Chem, 2019 11;92:103201.
PMID: 31445195 DOI: 10.1016/j.bioorg.2019.103201

We have carried out the synthesis of new 4-oxoquinazolin-3(4H)-yl)furan-2-carboxamide derivatives by the reaction between isatoic anhydride, 2-furoic hydrazide and substituted salicylaldehydes in ethanol: water (5:5 v/v) solvent system using p-TSA as a catalyst under ultrasound irradiation at room temperature. The structures of newly synthesized compounds were confirmed through spectral techniques such as IR, 1H NMR, 13C NMR, and LCMS. The important features of this protocol include simple and easy workup procedure, reaction carried out at ambient temperature, use of ultrasound and high yield of oxoquinazolin-3(4H)-yl)furan-2-carboxamides in short reaction time. The synthesized compounds 4a-4j were screened against tyrosinase enzyme and all these compounds found to be potent inhibitors with much lower IC50 value of 0.028 ± 0.016 to 1.775 ± 0.947 µM than the standard kojic acid (16.832 ± 1.162 µM). The kinetics mechanism for compound 4e was analyzed by Lineweaver-Burk plots which revealed that compound inhibited tyrosinase non-competitively by forming an enzyme-inhibitor complex. Along with this all the synthesized compounds (4a-4j) were scanned for their DPPH free radical scavenging ability. The outputs received through in vitro and in silico analysis are coherent to the each other with good binding energy values (kcal/mol) posed by synthesized ligands.
Synthesis and characterization of new 4H-chromene-3-carboxylates ensuring potent elastase inhibition activity along with their molecular docking and chemoinformatics properties

Dige NC, Mahajan PG, Raza H, Hassan M, Vanjare BD, Hong H, et al.

Bioorg Chem, 2020 07;100:103906.
PMID: 32422387 DOI: 10.1016/j.bioorg.2020.103906

A new series of 4H-chromene-3-carboxylate derivatives were synthesized using multicomponent reaction of salicylaldehyde, ethyl acetoacetate and dimedone in ethanol with K3PO4 as a catalyst at 80 °C. The structures of all newly synthesized compounds were confirmed by spectral techniques viz. IR, 1H NMR, 13C NMR, and LCMS analysis. The newly synthesized compounds 4a to 4j were screened against elastase enzyme. Interestingly, all these compounds found to be potent elastase inhibitors with much lower IC50 value. The compound 4b was found to be most potent elastase inhibitor (IC50 = 0.41 ± 0.01 µM) amongst the synthesized series against standard Oleanolic Acid (IC50 value = 13.45 ± 0.0 µM). The Kinetics mechanism for compound 4b was analyzed by Lineweaver-Burk plots which revealed that compound inhibited elastase competitively by forming an enzyme-inhibitor complex. Along with this, all the synthesized compounds (4a - 4j) exhibits excellent DPPH free radical scavenging ability. The inhibition constant Ki for compound 4b was found to be 0.6 µM. The computational study was comprehensible with the experimental results with good docking energy values (Kcal/mol). Therefore, these molecules can be considered as promising medicinal scaffolds for the treatment of skin-related maladies.
Modeling flood susceptibility using data-driven approaches of naïve Bayes tree, alternating decision tree, and random forest methods

Chen W, Li Y, Xue W, Shahabi H, Li S, Hong H, et al.

Sci Total Environ, 2020 Jan 20;701:134979.
PMID: 31733400 DOI: 10.1016/j.scitotenv.2019.134979

Floods are one of the most devastating types of disasters that cause loss of lives and property worldwide each year. This study aimed to evaluate and compare the prediction capability of the naïve Bayes tree (NBTree), alternating decision tree (ADTree), and random forest (RF) methods for the spatial prediction of flood occurrence in the Quannan area, China. A flood inventory map with 363 flood locations was produced and partitioned into training and validation datasets through random selection with a ratio of 70/30. The spatial flood database was constructed using thirteen flood explanatory factors. The probability certainty factor (PCF) method was used to analyze the correlation between the factors and flood occurrences. Consequently, three flood susceptibility maps were produced using the NBTree, ADTree, and RF methods. Finally, the area under the curve (AUC) and statistical measures were used to validate the flood susceptibility models. The results indicated that the RF method is an efficient and reliable model in flood susceptibility assessment, with the highest AUC values, positive predictive rate, negative predictive rate, sensitivity, specificity, and accuracy for the training (0.951, 0.892, 0.941, 0.945, 0.886, and 0.915, respectively) and validation (0.925, 0.851, 0.938, 0.945, 0.835, and 0.890, respectively) datasets.
Synthesis, molecular docking, dynamic simulations, kinetic mechanism, cytotoxicity evaluation of N-(substituted-phenyl)-4-{(4-[(E)-3-phenyl-2-propenyl]-1-piperazinyl} butanamides as tyrosinase and melanin inhibitors: In vitro, in vivo and in silico approaches

Raza H, Abbasi MA, Aziz-Ur-Rehman, Siddiqui SZ, Hassan M, Abbas Q, et al.

Bioorg Chem, 2020 01;94:103445.
PMID: 31826809 DOI: 10.1016/j.bioorg.2019.103445

In the current research work, different N-(substituted-phenyl)-4-{(4-[(E)-3-phenyl-2-propenyl]-1-piperazinyl}butanamides have been synthesized according to the protocol described in scheme 1. The synthesis was initiated by reacting various substituted anilines (1a-e) with 4-chlorobutanoyl chloride (2) in aqueous basic medium to give various electrophiles, 4-chloro-N-(substituted-phenyl)butanamides (3a-e). These electrophiles were then coupled with 1-[(E)-3-phenyl-2-propenyl]piperazine (4) in polar aprotic medium to attain the targeted N-(substituted-phenyl)-4-{(4-[(E)-3-phenyl-2-propenyl]-1-piperazinyl}butanamides (5a-e). The structures of all derivatives were identified and characterized by proton-nuclear magnetic resonance (1H NMR), carbon-nuclear magnetic resonance (13C NMR) and Infra-Red (IR) spectral data along with CHN analysis. The in vitro inhibitory potential of these butanamides was evaluated against Mushroom tyrosinase, whereby all compounds were found to be biologically active. Among them, 5b exhibited highest inhibitory potential with IC50 value of 0.013 ± 0.001 µM. The same compound 5b was also assayed through in vivo approach, and it was explored that it significantly reduced the pigments in zebrafish. The in silico studies were also in agreement with aforesaid results. Moreover, these molecules were profiled for their cytotoxicity through hemolytic activity, and it was found that except 5e, all other compounds showed minimal toxicity. The compound 5a also exhibited comparable results. Hence, some of these compounds might be worthy candidates for the formulation and development of depigmentation drugs with minimum side effects.
Survival predictors of major salivary gland cancer

Elhusseiny KM, Abd-Elhay FA, Kamel MG, Abd El Hamid Hassan HH, Muhammad El Tanany HH, Hong HT, et al.

Ann Oncol, 2018 Nov;29 Suppl 9:ix104.
PMID: 32177708 DOI: 10.1093/annonc/mdy438.035
A prognostic index for natural killer cell lymphoma after non-anthracycline-based treatment: a multicentre, retrospective analysis

Kim SJ, Yoon DH, Jaccard A, Chng WJ, Lim ST, Hong H, et al.

Lancet Oncol, 2016 Mar;17(3):389-400.
PMID: 26873565 DOI: 10.1016/S1470-2045(15)00533-1

BACKGROUND: The clinical outcome of extranodal natural killer T-cell lymphoma (ENKTL) has improved substantially as a result of new treatment strategies with non-anthracycline-based chemotherapies and upfront use of concurrent chemoradiotherapy or radiotherapy. A new prognostic model based on the outcomes obtained with these contemporary treatments was warranted.
METHODS: We did a retrospective study of patients with newly diagnosed ENKTL without any previous treatment history for the disease who were given non-anthracycline-based chemotherapies with or without upfront concurrent chemoradiotherapy or radiotherapy with curative intent. A prognostic model to predict overall survival and progression-free survival on the basis of pretreatment clinical and laboratory characteristics was developed by filling a multivariable model on the basis of the dataset with complete data for the selected risk factors for an unbiased prediction model. The final model was applied to the patients who had complete data for the selected risk factors. We did a validation analysis of the prognostic model in an independent cohort.
FINDINGS: We did multivariate analyses of 527 patients who were included from 38 hospitals in 11 countries in the training cohort. Analyses showed that age greater than 60 years, stage III or IV disease, distant lymph-node involvement, and non-nasal type disease were significantly associated with overall survival and progression-free survival. We used these data as the basis for the prognostic index of natural killer lymphoma (PINK), in which patients are stratified into low-risk (no risk factors), intermediate-risk (one risk factor), or high-risk (two or more risk factors) groups, which were associated with 3-year overall survival of 81% (95% CI 75-86), 62% (55-70), and 25% (20-34), respectively. In the 328 patients with data for Epstein-Barr virus DNA, a detectable viral DNA titre was an independent prognostic factor for overall survival. When these data were added to PINK as the basis for another prognostic index (PINK-E)-which had similar low-risk (zero or one risk factor), intermediate-risk (two risk factors), and high-risk (three or more risk factors) categories-significant associations with overall survival were noted (81% [95% CI 75-87%], 55% (44-66), and 28% (18-40%), respectively). These results were validated and confirmed in an independent cohort, although the PINK-E model was only significantly associated with the high-risk group compared with the low-risk group.
INTERPRETATION: PINK and PINK-E are new prognostic models that can be used to develop risk-adapted treatment approaches for patients with ENKTL being treated in the contemporary era of non-anthracycline-based therapy.
FUNDING: Samsung Biomedical Research Institute.