2.45GHz radiofrequency fields alter gene expression in cultured human cells

AbstractThe biological effect of radiofrequency (RF) fields remains controversial. We address this issue by examining whether RF fields can cause changes in gene expression. We used the pulsed RF fields at a frequency of 2.45GHz that is commonly used in telecommunication to expose cultured human HL-60 cells. We used the serial analysis of gene expression (SAGE) method to measure the RF effect on gene expression at the genome level. We observed that 221 genes altered their expression after a 2-h exposure. The number of affected genes increased to 759 after a 6-h exposure. Functional classification of the affected genes reveals that apoptosis-related genes were among the upregulated ones and the cell cycle genes among the downregulated ones. We observed no significant increase in the expression of heat shock genes. These results indicate that the RF fields at 2.45GHz can alter gene expression in cultured human cells through non-thermal mechanism

Inhibition of the function of class IIa HDACs by blocking their interaction with MEF2

Enzymes that modify the epigenetic status of cells provide attractive targets for therapy in various diseases. The therapeutic development of epigenetic modulators, however, has been largely limited to direct targeting of catalytic active site conserved across multiple members of an enzyme family, which complicates mechanistic studies and drug development. Class IIa histone deacetylases (HDACs) are a group of epigenetic enzymes that depends on interaction with Myocyte Enhancer Factor-2 (MEF2) for their recruitment to specific genomic loci. Targeting this interaction presents an alternative approach to inhibiting this class of HDACs. We have used structural and functional approaches to identify and characterize a group of small molecules that indirectly target class IIa HDACs by blocking their interaction with MEF2 on DNA.Weused X-ray crystallography and 19F NMRto show that these compounds directly bind to MEF2. We have also shown that the small molecules blocked the recruitment of class IIa HDACs to MEF2-targeted genes to enhance the expression of those targets. These compounds can be used as tools to study MEF2 and class IIa HDACs in vivo and as leads for drug development

Molecular docking and ADMET based study to identify potential phytochemical inhibitors for papain-like protease of SARS-CoV-2

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative pathogen for the novel COVID-19 disease. SARS-CoV-2 papain-like protease (PLpro) is responsible for viral replication and host innate immunity suppression. Thus, this study aimed to explore potential phytochemical inhibitors against this dual therapeutic target using virtual screening methods. Thirty-one phytochemicals with reported anti-SARS-CoV-1 PLpro activity were used to construct the phytochemical library along with two positive controls. Molecular docking using AutoDock 4.2 was employed to calculate binding affinity and inhibition constant of each compound within the S3/S4 binding pocket of SARS-CoV-2 PLpro. Based on the docking results, twelve compounds were subjected to non-covalent interaction analysis utilizing the Discovery Studio Visualizer software. Further, their physicochemical, pharmacokinetics and toxicity descriptors were evaluated using molinspiration and pkCSM web servers, respectively. Hirsutenone from Alnus japonica and broussoflavan A from Broussonetia papyrifera, displayed the strongest binding affinity (-8.23 kcal/mol and -8.13 kcal/mol), lowest inhibition constant (920.39 nM and 1.1 μM) and highest ligand efficiency (0.34 and 0.26) among all phytochemicals towards the binding pocket of SARS-CoV-2 PLpro, demonstrating superiority to PLpro inhibitors, 3k and GRL0617 which were used as positive controls. Additionally, hirsutenone, broussoflavan A and broussochalcone A (from Broussonetia papyrifera) possessed favorable physicochemical properties for oral drug development, satisfying Lipinski’s and Veber’s rules. Furthermore, in silico pharmacokinetics and toxicity predictions revealed that the three aforementioned phytochemicals are water soluble, non-mutagenic, non-hepatotoxic and biologically safe. Hence these lead compounds might be exploited to accelerate the drug discovery process against the ongoing COVID-19 infection

Effect of Chain Length and Saturation of the Fatty Acids in Dietary Triglycerides on Lipid Metabolism in Wistar Rats

Dietary fatty acids are associated with lipid health. We investigated the effect of the chain length and the degree of saturation of fatty acids in dietary triglycerides on serum lipid profiles and hepatic lipid metabolism in Wistar rats. Fat component of the basal diet (soybean oil) was replaced with fats with fatty acids of different chain lengths and saturation and the serum lipids were monitored for 150 days. Principal component (PC) analysis of serum lipid components were related to chain length and saturation using second order polynomial regression analysis. The combined effect of chain length and saturation on PC 1 scores were evaluated by multiple regression analysis. Variation of lipid parameters cannot be well-explained by chain length or saturation alone. Consistent with the formation of large amounts of lipid droplets in the liver, expression of sterol regulatory element binding protein -2 (SREBP2) and peroxisome proliferator-activated receptors (PPARα) involved in hepatic lipid metabolism showed significant (Pgroup compared to the control group. Average chain length of fatty acids in triglycerides has a higher influence on the quality of serum lipid parameters than the average degree of saturation of fatty acids.</div

Antioxidant and Nutritional Properties of Domestic and Commercial Coconut Milk Preparations

The aqueous extract of scraped coconut kernel is known as coconut milk. Coconut milk preparations are also commercially available in the form of desiccated powders or liquids. While these various coconut milk preparations are heavily used in cooking in the Asian countries as a major source of dietary fat, limited studies have been conducted on their chemical and nutritional composition. In this study, we have determined the chemical composition and nutritional effects of both domestic preparations of coconut milk and the commercially available counterparts. The results indicate that the phenolic compounds of all coconut milk preparations provide protection against oxidative damage on lipids and inhibit oxidative damage of both proteins and DNA. The lipid profiles are not significantly affected by the consumption of the three coconut milk preparations despite their different fat contents

Expression of Nitric Oxide Synthase and Nitric Oxide Levels in Peripheral Blood Cells and Oxidized Low-Density Lipoprotein Levels in Saliva as Early Markers of Severe Dengue

Background. Severe dengue (SD), experienced by only a fraction of dengue patients, can be lethal. Due to the lack of early markers that can predict the evolution of SD, all dengue patients have to be monitored under hospital care. We discovered early oxidative stress markers of SD to identify patients who can benefit from early intervention before the symptoms appear. Methods. The expression of inducible nitric oxide synthase (iNOS) in peripheral blood cells (PBC), nitric oxide (NO), and oxidized low-density lipoprotein (oxLDL) levels in plasma and saliva collected at early stages of dengue infection from 20 nonsevere dengue fever (DF) patients and 20 patients who later developed SD were analyzed in a retrospective nested case-control study. Results. The expression of iNOS is significantly (P<0.05) lower in patients who developed SD than in DF patients at admission within 4 days from fever onset. Median plasma NO concentration within 4 days from fever onset is also significantly (P<0.05) lower in patients who developed SD (17.9±1.6 μmol/L) than DF (23.0±2.1 μmol/L). Median oxLDL levels in plasma within 3 days from fever onset is significantly (P<0.05) lower in patients who developed SD (509.4±224.1 ng/mL) than DF (740.0±300.0 ng/mL). Median salivary oxLDL levels are also significantly (P<0.05) lower in patients who developed SD (0.8±0.5 ng/mL) than DF (3.6±2.6 ng/mL) within 4 days from fever onset. Conclusions. These findings suggest that the expression of iNOS (73% sensitivity, 86% specificity) and plasma NO (96% sensitivity, 61% specificity at 22.3 μmol/L; P<0.05) may serve as early markers of SD within 3 days from fever onset. Salivary oxLDL levels may serve as early noninvasive markers of SD with a sensitivity and specificity, respectively, of 57% and 91% at 0.9 ng/mL; 76% and 55% at 2.3 ng/mL; and 100% and 50% at 4.6 ng/mL (P<0.05) within 4 days from fever onset

Improvement of Oxidative Stability and Microbial Shelf Life of Vanilla Cake by Coconut Oil Meal and Sesame Oil Meal Phenolic Extracts

Phenolic extracts of coconut oil meal (CME) and sesame oil meal (SME) were compared with synthetic antioxidants for the potential of improving shelf life of vanilla cake. CME maintained hexanal (product of chemical spoilage) levels below 0.3 mg/kg in cake up to 14 days. BHT- and SME-added cakes maintained hexanal levels below 2 mg/kg while control cake with no added antioxidants exceeded this level by day 14. Both CME and SME extended the microbial shelf life up to 13 days while control and BHT-added cake exceeded the maximum allowed colony count by day 7 and day 11 respectively. The results indicate that the onset of microbial spoilage of vanilla cake is faster than the chemical spoilage and addition of CME and SME extend both microbiological and chemical stability of cakes beyond day 7 during storage. Over 90% of the antioxidant activity of CME and SME retained after heating at 180 °C for 2 h. CME and SME are ideal thermally stable natural alternatives for synthetic antioxidants in vanilla cake. </p

Comparison of the Basic Nutritional Characteristics of the First Extract and Second Extract of Coconut Milk

ABSTRACT: Coconut milk is the aqueous extract of grated coconut kernel. In traditional cooking in the South Asian region, grated coconut kernel is hand-pressed with water to obtain a viscous white coconut milk known as first extract (FE). The coconut kernel remaining after the first extraction is further extracted with a fresh portion of water to obtain second extract (SE), which is less viscous. In the present study, the nutritional composition and the effect of FE and SE on the serum lipid profiles was evaluated. The results indicate that the lipid and protein contents of SE is equivalent to a 3 fold diluted solution of FE. However, the levels of sugars and phenolic contents of the SE cannot be achieved by the same fold ofdilution of FE. There is no significant difference (p &lt; 0.05)in the lipid profiles of the rats fed with SE after 21 days

Transport percentages of caffeic acid and lucifer yellow after 1 hr of transport through a Caco-2 cell monolayer.

<p>Transport percentages of caffeic acid and lucifer yellow after 1 hr of transport through a Caco-2 cell monolayer.</p

Ferric reducing antioxidant power (reducing power %) of plasma.

<p>Ferric reducing antioxidant power of Soybean oil and caffeic acid treated group and the Olive oil and caffeic acid treated group were significantly lower compared to the Coconut oil and caffeic acid treated group up to 1 hr after treatment (p<0.05). n = 6.</p