Plasma deoxysphingolipids: a novel class of biomarkers for the metabolic syndrome?

AIMS/HYPOTHESIS: Sphingolipid synthesis is typically initiated by the conjugation of L-serine and palmitoyl-CoA, a reaction catalysed by serine palmitoyltransferase (SPT). SPT can also metabolise other acyl-CoAs (C(12) to C(18)) and other amino acids such as L-alanine and glycine, giving rise to a spectrum of atypical sphingolipids. Here, we aimed to identify changes in plasma levels of these atypical sphingolipids to explore their potential as biomarkers in the metabolic syndrome and diabetes. METHODS: We compared the plasma profiles of ten sphingoid bases in healthy individuals with those of patients with the metabolic syndrome but not diabetes, and diabetic patients (n = 25 per group). The results were verified in a streptozotocin (STZ) rat model. Univariate and multivariate statistical analyses were used. RESULTS: Deoxysphingolipids (dSLs) were significantly elevated (p = 5 × 10⁻6) in patients with the metabolic syndrome (0.11 ± 0.04 µmol/l) compared with controls (0.06 ± 0.02 µmol/l) but did not differ between the metabolic syndrome and diabetes groups. Levels of C(16)-sphingosine-based sphingolipids were significantly lowered in diabetic patients but not in patients with the metabolic syndrome but without diabetes (p = 0.008). Significantly elevated dSL levels were also found in the plasma and liver of STZ rats. A principal component analysis revealed a similar or even closer association of dSLs with diabetes and the metabolic syndrome in comparison with the established biomarkers. CONCLUSIONS/INTERPRETATION: We showed that dSLs are significantly elevated in patients with type 2 diabetes mellitus and non-diabetic metabolic syndrome compared with healthy controls. They may, therefore, be useful novel biomarkers to improve risk prediction and therapy monitoring in these patients.

Dataset on the optimization by response surface methodology for the synthesis of silver nanoparticles using Laxitextum bicolor mushroom.

Silver nanoparticles (AgNP) are important materials in developing novel devices owing to their unique physical and chemical properties. It attracted much interest because it exhibits a prominent Surface Plasmon Resonance (SPR) property that is dependent on its nanodimension and nanostructure. Its green synthesis using biological extracts offers a cheap and benign process to afford AgNPs. However, natural extracts contain thousands of metabolites that affect the formation of the desired AgNP. Other factors such as temperature, pH, time, and volume also influence the formation of the nanometal hence, optimization is always carried out to afford sufficient amounts of the nanometals. To eliminate further trials and errors, this work reports the optimization of AgNP using the aqueous extract from Laxitextum bicolor, a wild type of mushroom from the family of Stereacea. Using central composite design (CCD) under Response Surface Methodology (RSM), five levels from each of the five independent parameters (pH, temperature, time, volume of extract, and volume of AgNO3) in a single-block mode afforded 32 experimental runs where SPR at 420 nm of the formed AgNP was measured as the dependent variable. ANOVA evaluation revealed that the p-value of the refined model is significant (p-value = 0.00) and the p-value of lack-of-fit is insignificant (LoF = 0.223). Model statistics displayed acceptable goodness of fit (R2 = 98.54%, adjusted R2 = 97.34, predicted R2 = 92.50%). The predicted optimal condition to synthesize AgNP from aqueous extract of L. bicolor were determined to be pH = 10, Temperature = 55 °C, Time = 180 min, Vol. Ext = 1.5 mL, and Vol. AgNO3 = 20 mL. To check the accuracy and repeatability of predicted optimal synthesis conditions, the UV-Vis analysis was employed. It showed that the peak intensity has a narrow peak with an absorbance of 3.40 at around 420 nm, which was the set criteria for choosing the optimal synthesis condition.

Dataset on photocatalytic degradation of Levofloxacin using hydroxyapatite photocatalyst: Optimization by response surface methodology.

The upsurge of antibiotic usage in the 20th century has resulted in increasing levels of pharmaceutical compounds in bodies of water. A particular antibiotic, levofloxacin, is a third-generation quinolone known to target Gram-positive organisms like atypical pathogens. Chronic toxic effects of levofloxacin to some microorganisms lead to the disruption of marine ecosystems. Unfortunately, a relatively low concentration of levofloxacin in water bodies discourages researchers from exploring potential risk assessment and removal in wastewater treatment plants. In this article, aqueous levofloxacin was degraded using hydroxyapatite catalyst under UV-irradiation. Response Surface Methodology (Box Behnken Model) was used to model and optimize the degradation efficiency parameter. The response was fitted into a 2-factor interaction equation revealing a satisfactory ANOVA evaluation (R2=97.08%, adjusted R2= 94.89, predicted R2=91.1%). An optimal photodegradation efficiency was determined to attain the following conditions: 1.5 g/L catalyst dose, 4 ppm levofloxacin, and a pH level of 10. The model predicted a value of 71.6% degradation efficiency, which is very close to 70.6% generated experimentally.

Persistent lipid abnormalities in statin-treated patients with diabetes mellitus in Europe and Canada: results of the Dyslipidaemia International Study.

AIM: To assess the prevalence of persistent lipid abnormalities in statin-treated patients with diabetes with and without the metabolic syndrome. METHODS: This was a cross-sectional study of 22,063 statin-treated outpatients consecutively recruited by clinicians in Canada and 11 European countries. Patient cardiovascular risk factors, risk level, lipid measurements and lipid-modifying medication regimens were recorded. RESULTS: Of the 20,129 subjects who had documented diabetes and/or metabolic syndrome status, 41% had diabetes (of whom 86.8% also had the metabolic syndrome). Of those with diabetes, 48.1% were not at total cholesterol target compared with 58% of those without diabetes. Amongst those with diabetes, 41.6 and 41.3% of those with and without the metabolic syndrome, respectively, were not at their LDL cholesterol goal relative to 54.2% of those with metabolic syndrome and without diabetes, and 52% of those with neither condition. Twenty per cent of people with diabetes but without the metabolic syndrome were not at the optimal HDL cholesterol level compared with 9% of those with neither condition. Of people with diabetes and the metabolic syndrome, 49.9% were not at optimal triglyceride level relative to 13.5% of people with neither diabetes nor the metabolic syndrome. Simvastatin was the most commonly prescribed statin (>45%) and the most common statin potency was 20-40 mg/day (simvastatin equivalent). Approximately 14% of patients were taking ezetimibe alone or in combination with a statin. CONCLUSIONS: Despite evidence supporting the benefits of lipid modification and international guideline recommendations, statin-treated patients with diabetes had a high prevalence of persistent lipid abnormalities. There is frequently room to optimize therapy through statin dose up-titration and/or addition of other lipid-modifying therapies.

Hypoxia induces apelin expression in human adipocytes.

Adipokines play a central role in the development of diseases associated with insulin resistance and obesity. Hypoxia in adipose tissue leads to a dysregulation of the expression of adipokines. The effect of hypoxia on the more recently identified adipokine apelin in human adipocytes is unclear. Therefore, we aimed at investigating the role of hypoxia on the expression of the adipokine apelin. Differentiated human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes were cultured under hypoxic conditions for varying time periods. A modular incubator chamber was used to create a hypoxic tissue culture environment (defined as 1% O(2), 94% N, and 5% CO(2)). In addition, hypoxic conditions were mimicked by using CoCl(2). The effect of hypoxia on the expression of the investigated adipokines was measured by real-time PCR and the secretion of apelin was quantified by ELISA. Induction of hypoxia significantly induced mRNA expression of leptin and apelin in differentiated SGBS adipocytes compared with the normoxic control condition. Expression of adiponectin was significantly decreased by hypoxia. In addition, the amount of secreted apelin protein in response to hypoxia was elevated compared to untreated cells. Furthermore, we could demonstrate that the observed hypoxia-induced induction of apelin mRNA expression is in the first phase dependent on HIF-1α. In our study, we could demonstrate for the first time that apelin expression and secretion by human adipocytes are strongly induced under hypoxic conditions and that the early response on hypoxia with apelin induction is dependent on HIF-1α.

Designing hydrophobic bacterial cellulose film composites assisted by sound waves.

Bacterial cellulose (BC) is a promising material for new technologies, but the range of application is limited due to its hydrophilicity. This work aims to design a hydrophobic material derived from BC, which may find use in a broad range of applications such as packaging, sensing, construction, and electronics. We report that ultrasonic treatment of BC increased the degree of material impregnation into the fiber network that altered the hydrophobic properties of the BC-based composite films. Measurements in XTM revealed that sonication enhanced the porosity of BC films from 5.77% to 22.54%. Materials such as magnesium hydroxide (MH), graphene oxide (GO), and stearic acid (SA) were impregnated into the BC films. FTIR analysis and SEM-EDS confirmed the absorption of these molecules into the BC fibers. The water contact angle (WCA) of BC films impregnated with these functional materials showed a three to four-fold increase in hydrophobicity. The incorporation of 0.3% GO in sonicated BC afforded WCA at 137.20°, which is way better than the commercial water repellant (114.90°). The sonicated BC film afforded better tensile strength and Young's modulus, up to 229.67 MPa and 6.85 GPa, respectively. This work has shown that ultrasonic treatment improved the absorption capability of BC towards hydrophobic functionalization.

Impact of ultrasonic treatment on rice starch and grain functional properties: A review.

As a green, nonthermal, and innovative technology, ultrasonication generates acoustic cavitation in an aqueous medium, developing physical forces that affect the starch chemistry and rice grain characteristics. This review describes the current information on the effect of ultrasonication on the morphological, textural, and physicochemical properties of rice starch and grain. In a biphasic system, ultrasonication introduced fissures and cracks, which facilitated higher uptake of water and altered the rice starch characteristics impacting textural properties. In wholegrain rice, ultrasonic treatment stimulated the production of health-related metabolites, facilitated the higher uptake of micronutrient fortificants, and enhanced the palatability by softening the rice texture. This review provides insights into the future direction on the utilization of ultrasonication for the applications towards the improvement of rice functional properties.

Cytotoxic and Apoptotic Activity of Aglaforbesin Derivative Isolated from Aglaia loheri Merr. on HCT116 Human Colorectal Cancer Cells.

BACKGROUND: The genus Aglaia (Meliaceae) is an established source of many anticancer compounds. The study evaluated the leaf extracts of Aglaia loheri, a tree native to the Philippines, as potential source of anticancer compounds. METHODS: Using bioassay-guided fractionation, A. loheri leaf extract was subjected to various chromatographic techniques and step-wise application of MTT assay on human colorectal carcinoma cells, HCT116, to determine the cytotoxic fractions. The most cytotoxic HPLC isolate was structurally identified using 1D and 2D NMR and its apoptotic effect was assessed by JC-1 staining, caspase 3/7 assay and TUNEL assay. RESULTS: After stepwise chromatography fractionation, an HPLC isolate, structurally identified as aglaforbesin derivative (AFD), demonstrated potent cytotoxicity against HCT116. AFD exhibited strong toxicity (IC50 = 1.13 ±0.07 µg/mL) and high selectivity on HCT116 than normal human kidney cells (HK-2). AFD-induced toxicity to HCT116 is possibly through the stimulation of the apoptotic signaling pathway via caspase 3/7 activation and DNA fragmentation independent of mitochondrial membrane depolarization. CONCLUSION: AFD exhibited selective cytotoxicity and apoptotic activity to HCT116 and could be further developed as anticancer drug lead.

Ultrasound-assisted depolymerization of kappa-carrageenan and characterization of degradation product.

Degradation of polysaccharides to afford low-molecular-weight oligosaccharides have been shown to produce new bioactivities that are not present in the starting material. The simplicity of ultrasonic treatment in the degradation of a polysaccharide, such as κ-carrageenan, offers practical advantage in producing degraded products with lower molecular weight that may have new interesting potential activities. This study embarked on investigating the effects in molecular weights and structural changes of κ-carrageenan under varying ultrasonic conditions. Molecular weight (MW) monitoring of ultrasonically-treated κ-carrageenan at various conditions were done by gel permeation chromatography. The product formed using the optimized condition was characterized using FTIR and NMR. The decrease in MW has been shown to be dependent on low concentration (5.0 mg mL-1), high amplitude (85%), and long treatment time (180 mins) to afford a degraded κ-carrageenan with average molecular weight (AMW) of 41,864 Da, which is a 96.33% reduction from the raw sample with initial AMW of 1,139,927 Da. Structural analysis reveals that most of the peaks of the raw κ-carrageenan was retained with minor change. 1D and 2D NMR analyses showed that the sonic process afforded a product where the sulfate group at the G4S-4 position was cleaved forming a methylene in the G4S ring. The results would be useful in the structure-activity relationship of κ-carrageenan oligosaccharides and in understanding the effect in the various potential applications of degraded κ-carrageenan.

Efficient fortification of folic acid in rice through ultrasonic treatment and absorption.

Folate deficiencies are prevalent in countries with insufficient food diversity. Rice fortification is seen as a viable way to improve the daily intake of folates. This work reports an efficient process of rice fortification involving ultrasonic treatment and absorption of the folic acid fortificant. Increased porosity due to sonication allowed the efficient absorption of folic acid into the brown rice kernel up to 5.195 × 104 µg/100 g, a 1,982-fold increase from its inherent content. The absorbed folic acid in brown rice has 93.53% retention after washing and cooking. Fortification of ultrasound-treated milled rice with folic acid was also efficient affording 6.559 × 104 µg/100 g, a 4,054-fold increase from its basal content. The effect of fortification caused a decrease in the thermal and pasting temperatures. The fortification also caused yellow coloration, decrease in hardness, and increase in the adhesiveness of the rice. The resulting fortified brown rice showed improved textural properties favorable for consumers.

Low bone mineral density is not associated with angiographically determined coronary atherosclerosis in men.

UNLABELLED: This study for the first time investigates the association of bone mineral density (BMD) with angiographically determined coronary atherosclerosis in men. Our data show that the prevalence of low BMD is very high in men undergoing coronary angiography. However, neither osteopenia nor osteoporosis is associated with an increased prevalence of angiographically determined coronary atherosclerosis. INTRODUCTION: The association of low BMD with angiographically determined coronary atherosclerosis in men is unknown. METHODS: We enrolled 623 consecutive men undergoing coronary angiography for the evaluation of established or suspected coronary artery disease (CAD). BMD was assessed by dual X-ray absorptiometry. CAD was diagnosed in the presence of any coronary artery lumen narrowing at angiography; coronary stenoses with lumen narrowing > or =50% were considered significant. RESULTS: From the total study cohort (mean age of 64 +/- 11 years), 207 patients (33.2%) had osteopenia and 65 (10.4%) had osteoporosis; at angiography, CAD was diagnosed in 558 patients (89.6%) and 403 (64.7%) had significant coronary stenoses. In multivariate logistic regression analysis neither osteopenia nor osteoporosis was associated with an increased prevalence of CAD (adjusted odds ratios (ORs) = 0.71 [95% confidence interval 0.40-1.23]; p = 0.222 and 1.03 [0.38-2.80]; p = 0.955, respectively) or with significant coronary stenoses (OR 0.74 [0.52-1.07], p = 0.112 and 0.72 [0.41-1.26]; p = 0.251, respectively). Also, as a continuous variable, BMD was not associated with angiographically diagnosed CAD. CONCLUSIONS: The prevalence of low BMD is very high in men undergoing coronary angiography. However, low BMD is not associated with angiographically determined coronary atherosclerosis in men.

[High-dose statin therapy for high-risk patients]. / Hochdosierte Statintherapie für kardiovaskuläre Risikopatienten.

Lowering LDL cholesterol (LDL-C) with statins decreases cardiovascular risk; therefore LDL-C is the primary target in lipid therapy. The amount of risk reduction is the greater, the lower the LDL-C values achieved by statin therapy are. Current guidelines therefore require an LDL-C as low as < 70 mg/dl in patients who are at a very high risk of cardiovascular events. This stringent treatment goal depending on the baseline LDL-C values typically can only be obtained with higher doses of potent statins. Randomised trials demonstrate the efficacy of high-dose therapy with atorvastatin 80 mg/day with regard to the prevention of cardiovascular events in patients after acute coronary syndromes (PROVE-IT TIMI 22 trial), in patients with stable coronary artery disease (TNT trial), and in patients after stroke or TIA (SPARCL trial). Moreover, potent statin treatment reduces the progression of coronary atherosclerosis (REVERSAL and ASTEROID trials). Furthermore, large meta-analyses of the efficacy of high-dose statin therapy confirm its safety; in particular, muscle-related adverse events are not more frequent than with standard statin doses. It is recommended that evidence-based statin doses be used in clinical practice; the dosages used in clinical trials should be given rather than titrating patients to LDL-C targets by increasing statin doses in a stepwise manner. Whether the strong LDL-C lowering combination of simvastatin plus ezetimibe will reduce cardiovascular events over and above simvastatin monotherapy is currently being tested in the ongoing IMPROVE-IT trial. Importantly, despite the large body of evidence in favour of high-dose statin therapy for patients at high cardiovascular risk, high-dose statin therapy is still underused and LDL-C goals are still not met in the majority of these patients.

Dataset on the folic acid uptake and the effect of sonication-based fortification on the color, pasting and textural properties of brown and milled rice.

The data included in this article are related to research paper entitled "Efficient fortification of folic acid in rice through ultrasonic treatment and absorption". These datasets compile the folic acid uptake expressed in concentration and the effects of folic acid fortification on the physical properties of brown and milled rice. We reported the folic acid uptake of rice in increasing fortificant concentration through soaking, one-step, and stepwise fortification protocols. In addition, the data on the effects of fortification on the color, pasting, and textural properties of brown and milled rice were also presented.

Sonication increases the porosity of uncooked rice kernels affording softer textural properties, loss of intrinsic nutrients and increased uptake capacity during fortification.

This work investigates the effect of sonication on brown and milled rice grains of both waxy and non-waxy varieties. We report herein the microstructural analysis of uncooked rice kernels under sonication and its effect on the textural properties. X-ray computed tomography results showed the formation of microporous surfaces and the creation of cracks and fissures. Sonication increased the % porosity of the rice samples allowing for easy penetration of water during the cooking process and promotes softer texture. Moreover, the effect of sonication in brown rice resulted to the decrease in endogenous iron and phosphorus contents but increased its capacity for iron uptake through fortification when sonicated rice is soaked in the mineral solution.

Encapsulation of folic acid in copper-alginate hydrogels and it's slow in vitro release in physiological pH condition.

Folic acid (FA) is an essential micronutrient but its delivery and bioavailability is a problem due to its inherent instability at various conditions. A robust protective encapsulation system for folic acid is highly desirable. This work reports the use of the divalent copper in complex with alginate as a strong encapsulation system for folic acid. Using gel spherification technique, hydrogels were formed upon dropwise addition of sodium alginate solution in a copper bath. In the presence of folic acid, encapsulation was achieved as evidenced by the yellow coloration, intact surface morphology (SEM), the presence of nitrogen (23.08% N; EDX), and thermal gravimetric degradation for folic acid (28% FA; TGA). The spherical hydrogels do not burst upon 2 m-drop test and remain intact at pH 1.2 with no evident release of folic acid indicating stability of the encapsulation system at the abdominal gastric condition. The copper alginate acted as gastro-resistant material and slow release of folic acid occurs only at pH > 5 especially at simulated intestinal conditions (pH 8.2). The study indicates the potential of copper alginates as a protective encapsulant to ensure stability and slow release of FA in simulated physiological pH conditions.

Metabolic and anti-inflammatory benefits of eccentric endurance exercise - a pilot study.

BACKGROUND: Eccentric endurance exercise (e.g. hiking downwards) is less strenuous than concentric exercise (e.g. hiking upwards) but its potential to reduce cardiovascular risk is unknown. MATERIALS AND METHODS: We randomly allocated 45 healthy sedentary individuals (16 men and 29 women, mean age 48 years) to one of two groups, one beginning with two months of hiking upwards, the other with two months of hiking downwards the same route, with a crossover for a further two months. For the opposite way, a cable car was used where compliance was recorded electronically. The difference in altitude was 540 metres; the distance was covered three to five times a week. Fasting and postprandial metabolic profiles were obtained at baseline and after the two month periods of eccentric and concentric exercise, respectively. RESULTS: Forty-two of the 45 participants completed the study; the compliance rate was therefore 93%. Compared with baseline, eccentric exercise lowered total cholesterol (by 4.1%; P = 0.026), low-density lipoprotein (LDL) cholesterol (by 8.4%, P = 0.001), Apolipoprotein B/Apolipoprotein A1 ratio (by 10.9%, P < 0.001), homeostasis model assessment of insulin resistance scores (by 26.2%, P = 0.017) and C-reactive protein (by 30.0%; P = 0.007); the magnitude of these changes was comparable to that of concentric exercise. Eccentric exercise improved glucose tolerance (by 6.2%, P = 0.023), whereas concentric exercise improved triglyceride tolerance (by 14.9%, P = 0.022). CONCLUSIONS: Eccentric endurance exercise is a promising new exercise modality with favourable metabolic and anti-inflammatory effects and is well applicable to sedentary individuals.

Characteristics of unique HBr-hydrolyzed cellulose nanocrystals from freshwater green algae (Cladophora rupestris) and its reinforcement in starch-based film.

Cellulose nanocrystals (CNCs) are promising materials that are readily extracted from plants and other cellulose-containing organisms. In this study, CNCs were isolated from freshwater green algae (Cladophora rupestris) thriving in a volcanic lake, using hydrobromic acid (HBr) hydrolysis. Morphological and structural studies revealed highly crystalline CNCs (94.0% crystallinity index) with preferred orientation to [100] lattice plane as shown by XRD measurements and have an average diameter of 20.0 (±4.4)nm as shown by TEM. Thermal studies showed increased temperature for thermal decomposition of CNCs (381.6°C), which is a result of HBr hydrolysis for CNCs isolation. The isolated CNCs were reinforced into starch based biocomposites via solution casting and evaporation method. Mechanical strength was improved as high as 78% upon addition of 1% cellulose nanocrystals in the films. The produced films are promising materials for their high mechanical strength, biodegradability and availability of raw materials.

Gender differences in the effects of cardiovascular drugs.

Although sex-specific differences in cardiovascular medicine are well known, the exact influences of sex on the effect of cardiovascular drugs remain unclear. Women and men differ in body composition and physiology (hormonal influences during the menstrual cycle, menopause, and pregnancy) and they present differences in drug pharmacokinetics (absorption, distribution, metabolism, and excretion) and pharmacodynamics, so that is not rare that they may respond differently to cardiovascular drugs. Furthermore, women are also less often treated with evidence-based drugs thereby preventing optimization of therapeutics for women of all ages, experience more relevant adverse drug reactions than men, and remain underrepresented in most clinical trials. Thus, current guidelines for prevention, diagnosis, and medical treatment for cardiovascular diseases are based on trials conducted predominantly in middle-aged men. A better understanding of these sex-related differences is fundamental to improve the safety and efficacy of cardiovascular drugs and for developing proper individualized cardiovascular therapeutic strategies both in men and women. This review briefly summarizes gender differences in the pharmacokinetics and pharmacodynamics of cardiovascular drugs and provides recommendations to close the gaps in our understanding of sex-specific differences in drug efficacy and safety.