Search results for: lipid

Authors: Myung Kwon Cho, Seul Ki Min, Gwang Heum Yoon, Jung Hyun Joo, Sang Jun Sim, Hwa Sung Shin

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Mechanotransduction is a mechanism that external mechanical stimulation is converted to biochemical activity in the cell. When applying this mechanism to the unicellular green algae Chlamydomonas reinhardtii, the dramatic result that the accumulation of intracellular lipid was up to 60% of dry weight basis occurred. Furthermore, various variations in cellular physiology occurred, but there is a lack of the development of the system and related research for applying that technology to control the mechanical stress and facilitate molecular analyses. In this study, applying a mechanical stress to microalgae, the microfluidic device system that finely induced direct membrane distortion of microalgae. Cellular membrane distortion led to deflagellation, calcium influx and lipid accumulation in microalgae. In conclusion, cytological studies such as mechanotransduction can be actualized by using this system and membrane distortion is a promising inducer for biodiesel production.

Keywords: mechanotransduction, microalgae, membrane distortion, biodiesel

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Authors: Khalil Abdullah Ahmed Khalil, Elsadig Mohamed Ahmed

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Ginger is one of the most important medicinal plants, which is widely used in folk medicine. This study was designed to go further step and evaluate the hypoglycemic and hypolipidaemic effects of the aqueous ginger root extract in normal and alloxan diabetic rabbits. Results revealed that the aqueous ginger has a significant hypoglycemic effect (P<0.05) in diabetic rabbits but a non-significant hypoglycemic effect (P>0.05) in normal rabbits. There were also significant decreases in the concentrations (P<0.05) in serum cholesterol, triglycerides and LDL – cholesterol in both normal and diabetic rabbits. Although there was an elevation in serum HDL- cholesterol in both normal and diabetic rabbits, these elevations were non-significant (P>0.05). Our data suggest the aqueous ginger has a hypoglycemic effect in diabetic rabbits and lipid-lowering properties in both normal and diabetic rabbits.

Keywords: aqueous extract of ginger root (AEGR), hypoglycemic, cholesterol, triglyceride

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Authors: Oluwatosin Adetola Arojojoye, Olajumoke Olufunlayo Alao, Philip Odigili

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This study investigated the extent of pollution in Eleyele River in Oyo State, Nigeria by investigating the antioxidant status and malondialdehyde levels (index of lipid peroxidation) in the organs of African Catfish, Clarias gariepinus from the river. Clarias gariepinus weighing between 250g-400g were collected from Eleyele River (a suspected polluted river) and Clarias gariepinus from a clean fish farm (Durantee fisheries) were used as the control. Levels of malondialdehyde, glutathione concentration (GSH) and activities of antioxidant enzymes - superoxide dismutase, catalase and glutathione-S-transferase (GST) were evaluated in the post-mitochondrial fractions of the liver, kidney and gills of the fishes. From the results, there were increases in malondialdehyde level and GSH concentration in the liver, kidney and gills of Clarias gariepinus from Eleyele River when compared with control. Glutathione-S-transferase activity was induced in the liver and kidney of Clarias gariepinus from Eleyele River when compared with control. However, the activity of this enzyme was depleted in the gills of fishes from Eleyele River compared with control. Also there was an induction in SOD activity in the liver of Clarias gariepinus from Eleyele River when compared with control but there was a decrease in the activity of this enzyme in the kidney and gills of fishes from Eleyele River compared with control. Increase in lipid peroxidation and alterations in antioxidant system in Clarias gariepinus from Eleyele River show that the fishes were under oxidative stress. These suggest that the river is polluted probably as a result of industrial, domestic and agricultural wastes frequently discharged into the river. This could pose serious health risks to consumers of water and aquatic organisms from the river.

Keywords: antioxidant, lipid peroxidation, Clarias gariepinus, Eleyele River

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Authors: N. Uchegbu Nneka

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This study was conducted to investigate the effect of the antioxidant activity of germinated African Yam Bean (AYB) on oxidative stress markers in alloxan-induced diabetic rat. Rats were randomized into three groups; control, diabetic and germinated AYB–treated diabetic rats. The Total phenol and flavonoid content and DPPH radical scavenging activity before and after germination were investigated. The glucose level, lipid peroxidation and reduced glutathione of the animals were also determined using the standard technique for four weeks. Germination increased the total phenol, flavonoid and antioxidant activity of AYB extract by 19.14%, 32.28%, and 57.25% respectively. The diabetic rats placed on germinated AYB diet had a significant decrease in the blood glucose and lipid peroxidation with a corresponding increase in glutathione (p<0.05). These results demonstrate that consumption of germinated AYB can be a good dietary supplement in inhibiting hyperglycemia/hyperlipidemia and the prevention of diabetic complication associated with oxidative stress.

Keywords: African yam bean, antioxidant, diabetes, total phenol

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Authors: Turan Yaman, Zabit Yener, Ismail Celik

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The aim of this study was to investigate the antioxidant properties and protective role of honey, considered a part of traditional medicine, against carcinogen chemical aflatoxin (AF) exposure in rats, which were evaluated by histopathological changes in liver and kidney, measuring level of serum marker enzymes [aspartate aminotransferase (AST), alanin aminotransferase (ALT), gamma glutamil transpeptidase (GGT)], antioxidant defense systems [Reduced glutathione (GSH), glutathione reductase (GR), superoxide dismutase (SOD), glutathione-S-transferase (GST) and catalase (CAT)], and lipid peroxidation content in liver, erythrocyte, brain, kidney, heart and lungs. For this purpose, a total of eighteen healthy Sprague-Dawley rats were randomly allocated into three experimental groups: A (Control), B (AF-treated) and C (AF+honey-treated). While rats in group A were fed with a diet without AF, B, and C groups received 25 µg of AF/rat/day, where C group additionally received 1 mL/kg of honey by gavage for 90 days. At the end of the 90-day experimental period, we found that the honey supplementation decreased the lipid peroxidation and the levels of enzyme associated with liver damage, increased enzymatic and non-enzymatic antioxidants in the AF+honey-treated rats. Hepatoprotective and nephroprotective effects of honey is further substantiated by showing almost normal histological architecture in AF+honey-treated group, compared to degenerative changes in the liver and kidney of AF-treated rats. Additionally, honey supplementation ameliorated antioxidant defense systems and lipid peroxidation content in other tissues of AF+honey-treated rats. In conclusion, the present study indicates that honey has a hepatoprotective and nephroprotective effect in rats with experimental aflatoxicosis due to its antioxidant activity.

Keywords: aflatoxicosis, honey, histopathology, malondialdehyde, antioxidant, rat

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Authors: Raj Kumar, Prem Felix Siril

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The poor aqueous solubility of many pharmaceutical drugs and potential drug candidates is a big challenge in drug development. Nanoformulation of such candidates is one of the major solutions for the delivery of such drugs. We initially developed the evaporation assisted solvent-antisolvent interaction (EASAI) method. EASAI method is use full to prepared nanoparticles of poor water soluble drugs with spherical morphology and particles size below 100 nm. However, to further improve the effect formulation to reduce number of dose and side effect it is important to control the delivery of drugs. However, many drug delivery systems are available. Among the many nano-drug carrier systems, solid lipid nanoparticles (SLNs) have many advantages over the others such as high biocompatibility, stability, non-toxicity and ability to achieve controlled release of drugs and drug targeting. SLNs can be administered through all existing routes due to high biocompatibility of lipids. SLNs are usually composed of lipid, surfactant and drug were encapsulated in lipid matrix. A number of non-steroidal anti-inflammatory drugs (NSAIDs) have poor bioavailability resulting from their poor aqueous solubility. In the present work, SLNs loaded with NSAIDs such as Nabumetone (NBT), Ketoprofen (KP) and Ibuprofen (IBP) were successfully prepared using different lipids and surfactants. We studied and optimized experimental parameters using a number of lipids, surfactants and NSAIDs. The effect of different experimental parameters such as lipid to surfactant ratio, volume of water, temperature, drug concentration and sonication time on the particles size of SLNs during the preparation using hot-melt sonication was studied. It was found that particles size was directly proportional to drug concentration and inversely proportional to surfactant concentration, volume of water added and temperature of water. SLNs prepared at optimized condition were characterized thoroughly by using different techniques such as dynamic light scattering (DLS), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), X-ray diffraction (XRD) and differential scanning calorimetry and Fourier transform infrared spectroscopy (FTIR). We successfully prepared the SLN of below 220 nm using different lipids and surfactants combination. The drugs KP, NBT and IBP showed 74%, 69% and 53% percentage of entrapment efficiency with drug loading of 2%, 7% and 6% respectively in SLNs of Campul GMS 50K and Gelucire 50/13. In-vitro drug release profile of drug loaded SLNs is shown that nearly 100% of drug was release in 6 h.

Keywords: nanoparticles, delivery, solid lipid nanoparticles, hot-melt sonication, poor water soluble drugs, solubility, bioavailability

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Authors: Spandana Ramisetty, Mandan Chidambaram, Ramesh Bhujade

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Algal biomass is not only a potential source for biocrude but also for high value chemicals like carotenoids, fatty acids, proteins, polysaccharides, vitamins etc. Astaxanthin is one such high value vital carotenoid which has extensive applications in pharmaceutical, aquaculture, poultry and cosmetic industries and expanding as dietary supplement to humans. Green microalgae Haematococcus pluvialis is identified as the richest natural source of astaxanthin and is the key source of commercial astaxanthin. Several extraction processes from wet and dry Haematococcus pluvialis biomass have been explored by researchers. Extraction with supercritical CO₂ and various physical disruption techniques like mortar and pestle, homogenization, ultrasonication and ball mill from dried algae are widely used extraction methods. However, these processes require energy intensive drying of biomass that escalates overall costs notably. From the process economics perspective, it is vital to utilize wet processing technology in order to eliminate drying costs. Hydrothermal liquefaction (HTL) is a thermo-chemical conversion process that converts wet biomass containing over 80% water to bio-products under high temperature and high pressure conditions. Astaxanthin is a lipid soluble pigment and is usually extracted along with lipid component. Mild HTL at 200°C and 60 bar has been demonstrated by researchers in a microfluidic platform achieving near complete extraction of astaxanthin from wet biomass. There is very limited work done in this field. An integrated approach of sequential HTL offers cost-effective option to extract astaxanthin/lipid from wet algal biomass without drying algae and also recovering water, minerals and nutrients. This paper reviews past work and evaluates the astaxanthin extraction processes with focus on hydrothermal extraction.

Keywords: astaxanthin, extraction, high value chemicals, hydrothermal liquefaction

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Authors: Ammaarah Gamieldien

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Depression is a very common and serious mental illness that has a significant impact on both the social and economic aspects of sufferers worldwide. This study aimed to investigate the association between body mass index (BMI), blood pressure, and lipid profiles with mental health symptoms in university students. Secondary objectives included the associations between the variables (BMI, blood pressure, and lipids) with themselves, as they are key factors in cardiometabolic disease. Sixty-three (63) students participated in the study. Thirty-two (32) were assigned to the control group (minimal-mild depressive symptoms), while 31 were assigned to the depressive group (moderate to severe depressive symptoms). Montgomery-Asberg Depression Rating Scale (MADRS) and Beck Depression Inventory (BDI) were used to assess depressive scores. Anthropometric measurements such as weight (kg), height (m), waist circumference (WC), and hip circumference were measured. Body mass index (BMI) and ratios such as waist-to-hip ratio (WHR) and waist-to-height ratio (WtHR) were also calculated. Blood pressure was measured using an automated AfriMedics blood pressure machine, while lipids were measured using a CardioChek plus analyzer machine. Statistics were analyzed via the SPSS statistics program. There were no significant associations between anthropometric measurements and depressive scores (p > 0.05). There were no significant correlations between lipid profiles and depression when running a Spearman’s rho correlation (P > 0.05). However, total cholesterol and LDL-C were negatively associated with depression, and triglycerides were positively associated with depression after running a point-biserial correlation (P < 0.05). Overall, there were no significant associations between blood pressure measurements and depression (P > 0.05). However, there was a significant moderate positive correlation between systolic blood pressure and MADRS scores in males (P < 0.05). Depressive scores positively and strongly correlated to how long it takes participants to fall asleep. There were also significant associations with regard to the secondary objectives. This study indicates the importance of determining the prevalence of depression among university students in South Africa. If the prevalence and factors associated with depression are addressed, depressive symptoms in university students may be improved.

Keywords: depression, blood pressure, body mass index, lipid profiles, mental health symptoms

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Authors: Rayhana Begum, HongBin Wang, Nur Alam Siddiquee, Md.Yasin Ahmed

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Biotin treatment has significant effects on blood glucose, and pharmacological doses of biotin improve hyperglycemia. The present study was aimed to investigate the efficacy and safety of biotin in combination with canagliflozin in improving glycemic control on High Fat Diet-induced diabetes in Rats. Thirty male rats were divided into five groups (six rats /group): control, high fat diet (HFD), canagliflozin (CAG), biotin (BIO), and CAG + BIO. The treatments with CAG and /or BIO significantly reduced the body weight gain, blood glucose and HbA1c levels, whereas CAG in combination with BIO revealed greater glycemic improvement than CAG monotherapy. The treatment with CAG and /or BIO causes significant change in lipid profile and CK level while the treatment with CAG in combination with BIO showed better results as compared with CAG monotherapy. Furthermore, combination of biotin with CAG improved the pancreatic and cardiac damage when compared with other treated groups.

Keywords: canagliflozin, biotin, HbA1c, lipid profile

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Authors: Ifeoma C. Afiaenyi, Elizabeth K. Ngwu, Rufina N. B. Ayogu

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Diabetes has crept into the rural areas of Nigeria, causing devastating effects on its sufferers; most of them could not afford diabetic medications. Moringa oleifera has been used extensively in animal models to demonstrate its antilipidaemic and haematinic qualities; however, there is a scarcity of data on the effect of graded levels of Moringa oleifera leaves on the lipid profile and hematological parameters in human diabetic subjects. The study determined the effect of Moringa oleifera leaves on the lipid profile and hematological parameters of type 2 diabetic subjects in Ukehe, a rural Nigerian community. Twenty-four adult male and female diabetic subjects were purposively selected for the study. These subjects were shared into four groups of six subjects each. The diets used in the study were isocaloric. A control group (diabetics, group 1) was fed diets without Moringa oleifera leaves. Experimental groups 2, 3 and 4 received 20g, 40g and 60g of Moringa oleifera leaves daily, respectively, in addition to the diets. The subjects' lipid profile and hematological parameters were measured prior to the feeding trial and at the end of the feeding trial. The feeding trial lasted for fourteen days. The data obtained were analyzed using the computer program Statistical Product for Service Solution (SPSS) for windows version 21. A Paired-samples t-test was used to compare the means of values collected before and after the feeding trial within the groups and significance was accepted at p < 0.05. There was a non-significant (p > 0.05) decrease in the mean total cholesterol of the subjects in groups 1, 2 and 3 after the feeding trial. There was a non-significant (p > 0.05) decrease in the mean triglyceride levels of the subjects in group 1 after the feeding trial. Groups 1 and 3 subjects had a non-significant (p > 0.05) decrease in their mean low-density lipoprotein (LDL) cholesterol after the feeding trial. Groups 1, 2 and 4 had a significant (p < 0.05) increase in their mean high-density lipoprotein (HDL) cholesterol after the feeding trial. A significant (p < 0.05) decrease in the mean hemoglobin level was observed only in group 4 subjects. Similarly, there was a significant (p < 0.05) decrease in the mean packed cell volume of group 4 subjects. It was only in group 4 that a significant (p < 0.05) decrease in the mean white blood cells of the subjects was also observed. The changes observed in the parameters assessed were not dose-dependent. Therefore, a similar study of longer duration and more samples is imperative to authenticate these results.

Keywords: anemia, diabetic subjects, lipid profile, moringa oleifera

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Authors: Abdolamir Allameh, Shahnaz Esmaeili, Mina Allameh, Safoura Khajeniazi

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Stem cells with therapeutic applications can be isolated from human placenta/umblical cord blood (UCB) as well as the cord tissue (UC). Stem cells in culture are vulnerable to oxidative stress, particularly when subjected to differentiation process. The aim of this study was to examine the chnages in the rate of oxidation that occurs to cellular macromolecules during hepatic differentiation of mononuclear cells (MSCs). In addition, the impact of the hepatic differentiation process of MSC on cellular and biological activity of the cells will be undertaken. For this purpose, first mononuclear cells (MNCs) were isolated from human UCB which was obtained from a healthy full-term infant. The cells were cultured at a density of 3×10⁵ cells/cm² in DMEM- low-glucose culture media supplemented with 20% FBS, 2 mM L-glutamine, 100 μg/ml streptomycin and 100 U/ml penicillin. Cell cultures were then incubated at 37°C in a humidified 5% CO₂ incubator. After removing non-adherent cells by replacing culture medium, fibroblast-like adherent cells were resuspended in 0.25% trypsin-EDTA and plated in 25 cm² flasks (1×10⁴/ml). Characterization of the MSCs was routinely done by observing their morphology and growth curve. MSCs were subjected to a 2-step hepatocyte differentiation protocol in presence of hepatocyte growth factor (HGF), dexamethazone (DEX) and oncostatin M (OSM). The hepatocyte-like cells derived from MSCs were checked every week for 3 weeks for changes in lipid peroxidation, protein carbonyl formation and DNA oxidation i.e., 8-hydroxy-2'-deoxyguanosine (8-OH-dG) assay. During the 3-week differentiation process of MSCs to hepatocyte-like cells we found that expression liver-specific markers such as albumin, was associated with increased levels of lipid peroxidation and protein carbonyl formation. Whereas, undifferentiated MSCs has relatively low levels of lipid peroxidation products. There was a significant increase ( p < 0.05) in lipid peroxidation products in hepatocytes on days 7, 14, and 21 of differentiation. Likewise, the level of protein carbonyls in the cells was elevated during the differentiation. The level of protein carbonyls measured in hepatocyte-like cells obtained 3 weeks after differentiation induction was estimated to be ~6 fold higher compared to cells recovered on day 7 of differentiation. On the contrary, there was a small but significant decrease in DNA damage marker (8-OH-dG) in hepatocytes recovered 3 weeks after differentiation onset. The level of 8-OHdG which was in consistent with formation of reactive oxygen species (ROS). In conclusion, this data suggest that despite the elevation in oxidation of lipid and protein molecules during hepatocyte development, the cells were normal in terms of DNA integrity, morphology, and biologically activity.

Keywords: adult stem cells, DNA integrity, free radicals, hepatic differentiation

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Authors: Mustafa Kucukoduk, Evren Yildiztugay, A. Hediye Sekmen, Ismail Turkan, Yavuz Bagci

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In this study, physiological and biochemical responses of Centaurea tuzgoluensis, a Turkish endemic halophyte, to salinity were studied. Therefore, the changes in shoot growth, leaf relative water content (RWC), ion concentrations, lipid peroxidation, hydroxyl (OH.) radical scavenging activity, proline (Pro) content, and antioxidant system [superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX) and glutathione reductase (GR)] were investigated. The 60 days (d) old C. tuzgoluensis seedlings were subjected to 0, 150 and 300 mM NaCl for 7 d and 14 d. The relative shoot growth was generally did not change in the 150 mM NaCl, but reduced with 300 mM NaCl stress at 7 d and 14 d. RWC was higher in 150 mM NaCl-treated leaves than that of 300 mM NaCl. Salinity decreased K+/Na+ ratio, but increased Na+, Cl, Ca+2 and Na+/Cl ratio in the leaves. On the other hand, it did not change or increase the K+ content at 150 and 300 mM NaCl, respectively. MDA content in the 150 and 300 mM NaCl-treated leaves remained close to control at 7 d. This was related to enhanced activities of SOD, CAT, APX and GR enzymes, and their isoenzymes especially Fe-SOD in the leaves. On the other hand, the higher sensitivity to 300 mM NaCl at 14 d was associated with inadequate increase in antioxidant enzymes and the decreased OH radical scavenging activity. All these results suggest that C. tuzgoluensis has different antioxidant metabolisms between short- (7 d) and long-term (14 d) salt treatments and salinity tolerance of C. tuzgoluensis might be closely related to increased capacity of antioxidative system to scavenge reactive oxygen species (ROS) and accumulation of osmoprotectant proline under salinity conditions.

Keywords: antioxidant enzymes, endemic halophyte, ion exchange, lipid peroxidation, antioxidant, enzymes, endemic halophyte, ion exchange, lipid peroxidation, proline, Centaurea tuzgoluensis

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Authors: Ehsan Etesami, Mostafa Noroozi

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Thalassiosira weissflogii with proper size and nutrition value specially PUFA n-3 has been widely used in bivalve shellfish larviculture and shrimp industries. This diatom was isolated from Caspian Sea and identified with morphology and molecular characters. T. weissflogii was cultivated in normal and nitrogen deficiency F2 medium during 18 to 30 days, in addition, the growth indices, total lipid, and EPA-DHA content were elucidated. The growth indices of the cells decreased during the stress experiments while the total lipid levels increased during prolonged culturing (30 days). The maximum level of C20:5 was calculated as 8.8 (%TFA) in normal condition during 30 days; however, the combination of N- deficiency condition with prolonged culturing led to the increase of the level of C22:6 from 3.5 to 12.63 (%TFA). The concept of N-deficiency along with prolonged culturing of Thalassiosira weissflogii can improve PUFA n-3 content in order to use in shellfish and shrimp industries.

Keywords: DHA, Thalassiosira weissflogii, nitrogen deficiency, EPA, fatty acids, aquafeed

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Authors: Vladimir M. Tomović, Branislav V. Šojić, Predrag M. Ikonić, Ljiljana S. Petrović, Anamarija I. Mandić, Natalija R. Džinić, Snežana B. Škaljac, Tatjana A. Tasić, Marija R. Jokanović

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In this paper influence of packaging method (vacuum and modified atmosphere packaging) on lipid oxidative stability and sensory properties of odor and taste of the traditional sausage Petrovská klobása were examined. These parameters were examined during storage period (7 months). In the end of storage period, vacuum packed sausage showed better oxidative stability. Propanal content was significantly lower (P<0.05) in vacuum packed sausage compared to these values in unpacked and modified atmosphere packaging sausage. Hexanal content in vacuum packed sausage was 1.85 µg/g, in MAP sausage 2.98 µg/g and in unpacked sausage 4.94 µg/g. After 2 and 7 months of storage, sausages packed in vacuum had the highest grades for sensory properties of odor and taste.

Keywords: lipid oxidation, MAP, sensory properties, traditional sausage, vacuum

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Authors: Zineb Taidirt, Fathia Sebahi, Mohamed Karim Guarchani, Anissa Berkane, Noureddine Smail, Ouahiba Hadjoudj

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Cardiovascular diseases are one of the most important causes of death in Algeria. Several risk factors are responsible for this, including the consumption of foods containing saturated fat and trans fatty acids TFAs. This brief presents the results of a descriptive study of the lipid composition of 251 food products marketed in Algeria. The objective of the study is to describe the nature and composition of lipids and to verify the compliance of saturated and trans fatty acids intakes with the regulations. The study is based on data from the nutrition labelling of marketed food products. The results showed that the lipids in foodstuffs are diverse in nature and of varying amounts, but their nature is not specified on all products. In addition, the required content of saturated fatty acids is mentioned only in 29.48% of the products; 21.62% of them do not comply with the standard. Hydrogenation of fats, which produced Trans fatty acids, is common: 19.92% of products contain hydrogenated fats, and 74.89% may contain them according to the aspect of the lipid (solid fat). However, the trans fatty acid content is only mentioned in 5.18% of the products. The latter is above the limits set by Algerian regulations in 50% of the butter samples studied. The composition of lipids in mono- and polyunsaturated fatty acids essential for the body is insufficient: only 13.94% of the products inform their contents on their labels. It is necessary to adopt mandatory restriction of trans fatty acids, to ban the use of partially-hydrogenated oils, and to require required mandatory labeling of the TFAs and the other fatty acids on packaged foods, and to conduct more studies in order to appreciate the intake of TFAs and saturated fat and appreciate their effects on the Algerian population and to get more informed about the composition of the lipid in packaged foods.

Keywords: cardiovascular diseases, lipids, nutrition labelling, lipids, trans fatty acids

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Authors: Wael M. El-Deeb

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The aim of this study was to assess the pathophysiological importance of lipid profile, acute phase proteins, proinflammatory cytokines and oxidative stress markers in sheep with pneumonic pasteurellosis. Blood samples were collected from 36 Pasteurellamultocida-infected sheep, together with 20 healthy controls. Samples for bacteriological examination (nasal swabs, bronchoalveolar lavage) were collected from all animals and subjected to bacteriological examinations. Moreover, heart blood and lung samples were collected from the dead pneumonic sheep and subjected also to bacteriological examinations. A lipid profile was determined, along with a blood picture and other biochemical parameters. The acute phase proteins (fibrinogen, haptoglobin, serum amyloid A), the proinflammatory cytokine tumour necrosis factor-alpha, interleukins (IL-1α, IL-1β, IL-6), interferon-gamma and the oxidative stress markers malondialdehyde, super oxide dismutase, glutathione and catalase were also measured. The examined biochemical parameters were increased in the pneumonic sheep, except for cholesterol and high-density lipoprotein cholesterol (HDL-c), which were significantly lower than control group. Acute phase proteins and cytokines were significantly higher in the pneumonic sheep when compared to the healthy sheep. There was a significant increase in the levels of malondialdehyde; however, a significant decrease in the levels of super oxide dismutase, glutathione and catalase was observed. The present study shed the light on the possible pathphysiological role of lipid profile, acute phase proteins (APPs), proinflammatory cytokines and oxidative stress markers in pneumonic pasteurelosis in sheep.

Keywords: acute phase proteins, sheep, pasteurella, interleukins, stress

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Authors: F. Pires, V. Geraldo, O. N. Oliveira Jr., M. Raposo

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Catechins are powerful antioxidants which have attractive properties useful for tumor therapy. Considering their antioxidant activity, these molecules can act as a scavenger of the reactive oxygen species (ROS), alleviating the damage of cell membrane induced by oxidative stress. The complexity and dynamic nature of the cell membrane compromise the analysis of the biophysical interactions between drug and cell membrane and restricts the transport or uptake of the drug by intracellular targets. To avoid the cell membrane complexity, we used biomimetic systems as liposomes and Langmuir monolayers to study the interaction between catechin and membranes at the molecular level. Liposomes were formed after the dispersion of anionic 1,2-dipalmitoyl-sn-glycero-3-[phospho-rac-(1-glycerol)(sodium salt) (DPPG) phospholipids in an aqueous solution, which mimic the arrangement of lipids in natural cell membranes and allows the entrapment of catechins. Langmuir monolayers were formed after dropping amphiphilic molecules, DPPG phospholipids, dissolved in an organic solvent onto the water surface. In this work, we mixed epigallocatechin-3-gallate (EGCG) with DPPG liposomes and exposed them to ultra-violet radiation in order to evaluate the antioxidant potential of these molecules against oxidative stress induced by radiation. The presence of EGCG in the mixture decreased the rate of lipid peroxidation, proving that EGCG protects membranes through the quenching of the reactive oxygen species. Considering the high amount of hydroxyl groups (OH groups) on structure of EGCG, a possible mechanism to these molecules interact with membrane is through hydrogen bonding. We also investigated the effect of EGCG at various concentrations on DPPG Langmuir monolayers. The surface pressure isotherms and infrared reflection-absorption spectroscopy (PM-IRRAS) results corroborate with absorbance results preformed on liposome-model, showing that EGCG interacts with polar heads of the monolayers. This study elucidates the physiological action of EGCG which can be incorporated in lipid membrane. These results are also relevant for the improvement of the current protocols used to incorporate catechins in drug delivery systems.

Keywords: catechins, lipid membrane, anticancer agent, molecular interactions

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Authors: H. Jeries, N. Volkova, C. G. Iglesias, M. Najjar, M. Rosenblat, M. Aviram, T. Hayek

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Background: Synthetic forms of glucocorticoids (e.g., prednisone, prednisolone) are anti-inflammatory drugs which are widely used in clinical practice. The role of glucocorticoids (GCs) in cardiovascular diseases including atherosclerosis is highly controversial, and their impact on macrophage foam cell formation is still unknown. Our aim was to investigate the effects of prednisone or its active metabolite, prednisolone, on macrophage oxidative stress and lipid metabolism using in-vivo, ex-vivo and in-vitro systems. Methods: The in-vivo study included C57BL/6 mice which were intraperitoneally injected with prednisone or prednisolone (5mg/kg) for 4 weeks, followed by lipid metabolism analyses in the mice aorta, and in peritoneal macrophages (MPM). In the ex-vivo study, we analyzed the effect of serum samples obtained from 9 healthy volunteers before or after treatment with oral prednisone (20mg for 5 days), on J774A.1 macrophage atherogenicity. In-vitro studies were conducted using J774A.1 macrophages, human monocyte derived macrophages (HMDM) and fibroblasts. Cells were incubated with increasing concentrations (0-200 ng/ml) of prednisone or prednisolone, followed by determination of cellular oxidative status, triglyceride and cholesterol metabolism. Results: Prednisone or prednisolone treatment resulted in a significant reduction in triglycerides and mainly in cholesterol cellular accumulation in MPM or in J774A.1 macrophages incubated with human serum. Similar resulted were noted in HMDM or in J774A.1 macrophages which were directly incubated with the GCs. These effects were associated with GCs inhibitory effect on triglycerides and cholesterol biosynthesis rates, throughout downregulation of diacylglycerol acyltransferase1 (DGAT1) expression, and of the sterol regulatory element binding protein (SREBP2) and HMGCR expression, respectively. In parallel to prednisone or prednisolone induced reduction in macrophage triglyceride content, paraoxonase 2 (PON2) expression was significantly upregulated. GCs-induced reduction of cellular triglyceride and cholesterol mass was mediated by the GCs receptors on macrophages since the GCs receptor antagonist (RU 486) abolished these effects. In fibroblasts, unlike macrophages, prednisone or prednisolone showed no anti-atherogenic effects. Conclusions: Prednisone or prednisolone are anti-atherogenic since they protected macrophages from lipid accumulation and foam cell formation.

Keywords: atherosclerosis, cholesterol, foam cell, macrophage, prednisone, prednisolone, triglycerides

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Authors: Nalan Hakime Nogay

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Childhood obesity is a significant health issue that is currently on the rise all over the world. In recent years, the relationship between childhood obesity and cardiovascular disease risk has been pointed out. The purpose of this study is to evaluate the relationship between some of the anthropometric indicators and blood lipid levels in adolescents. The present study has been conducted on a total of 252 adolescents -200 girls and 52 boys- within an age group of 12 to 18 years. Blood was drawn from each participant in the morning -after having fasted for 10 hours from the day before- to analyze their total cholesterol, HDL, LDL and triglyceride levels. Their body weight, height, waist circumference, subscapular skinfold thicknesses and triceps skinfold thicknesses measurements were taken and their individual waist/height ratios, BMI and body fat ratios were calculated. The blood lipid levels of the participants were categorized as acceptable, borderline and high in accordance with the 2011 Expert Panel Integrated Guidelines. The body fat ratios, total blood cholesterol and HDL levels of the girls were significantly higher than the boys whereas their waist circumference values were lower. The triglyceride levels, total cholesterol/HDL, LDL/HDL, triglyceride/HDL ratios of the group with the BMI ≥ 95 percentile ratio (the obese group) were higher than the groups that were considered to be overweight and normal weight as per their respective BMI values, while the HDL level of the obese group was lower; a fact that was found to be statistically significant. No significant relationship could be established, however, between the total blood cholesterol and LDL levels with their anthropometric measurements. The BMI, waist circumference, waist/height ratio, body fat ratio and triglyceride level of the group with the higher triglyceride level ( ≥ 130mg/dl) were found to be significantly higher compared to borderline (90-129 mg/dl) and the normal group (< 90 mg/dl). The BMI, waist circumference, waist/height ratio values of the group with the lower HDL level ( < 40 mg/dl) were significantly higher than the normal ( > 45 mg/dl) and borderline (40-45 mg/dl) groups. All of the anthropometric measurements of the group with the higher triglyceride/HDL ratio ( ≥ 3) were found to be significantly higher than that of the group with the lower ratio (< 3). Having a high BMI, waist/height ratio and waist circumference is related to low HDL and high blood triglyceride and triglyceride/HDL ratio. A high body fat ratio, on the other hand, is associated with a low HDL and high triglyceride/HDL ratio. Tackling childhood and adolescent obesity are important in terms of preventing cardiovascular diseases.

Keywords: adolescent, body fat, body mass index, lipid profile

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Authors: Hasmik V. Zanginyan, Gayane S. Ghazaryan, Laura M. Hovsepyan

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Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating disease of the central nervous system that is induced in laboratory animals by developing an immune response against myelin epitopes. The typical clinical course is ascending palsy, which correlates with inflammation and tissue damage in the thoracolumbar spinal cord, although the optic nerves and brain (especially the subpial white matter and brainstem) are also often affected. With multiple sclerosis, there is a violation of lipid metabolism in myelin. When membrane lipids (glycosphingolipids, phospholipids) are disturbed, metabolites not only play a structural role in membranes but are also sources of secondary mediators that transmit multiple cellular signals. The purpose of this study was to investigate the effect of ganglioside as a therapeutic agent in experimental multiple sclerosis. The biological activity of a ganglioside-containing medicinal preparation (Cronassial) was evaluated in an experimental model of multiple sclerosis in laboratory animals. An experimental model of multiple sclerosis in rats was obtained by immunization with myelin basic protein (MBP), as well as homogenization of the spinal cord or brain. EAE was induced by administering a mixture of an encephalitogenic mixture (EGM) with Complete Freund’s Adjuvant. Mitochondrial fraction was isolated in a medium containing 0,25 M saccharose and 0, 01 M tris buffer, pH - 7,4, by a method of differential centrifugation on a K-24 centrifuge. Glutathione peroxidase activity was assessed by reduction reactions of hydrogen peroxide (H₂O₂) and lipid hydroperoxides (ROOH) in the presence of GSH. LPO activity was assessed by the amount of malondialdehyde (MDA) in the total homogenate and mitochondrial fraction of the spinal cord and brain of control and experimental autoimmune encephalomyelitis rats. MDA was assessed by a reaction with Thiobarbituric acid. For statistical data analysis on PNP, SPSS (Statistical Package for Social Science) package was used. The nature of the distribution of the obtained data was determined by the Kolmogorov-Smirnov criterion. The comparative analysis was performed using a nonparametric Mann-Whitney test. The differences were statistically significant when р ≤ 0,05 or р ≤ 0,01. Correlational analysis was conducted using a nonparametric Spearman test. In the work, refrigeratory centrifuge, spectrophotometer LKB Biochrom ULTROSPECII (Sweden), pH-meter PL-600 mrc (Israel), guanosine, and ATP (Sigma). The study of the process of lipid peroxidation in the total homogenate of the brain and spinal cord in experimental animals revealed an increase in the content of malonic dialdehyde. When applied, Cronassial observed normalization of lipid peroxidation processes. Reactive oxygen species, causing lipid peroxidation processes, can be toxic both for neurons and for oligodendrocytes that form myelin, causing a violation of their lipid composition. The high content of lipids in the brain and the uniqueness of their structure determines the nature of the development of LPO processes. The lipid layer of cellular and intracellular membranes performs two main functions -barrier and matrix (structural). Damage to the barrier leads to dysregulation of intracellular processes and severe disorders of cellular functions.

Keywords: experimental autoimmune encephalomyelitis, multiple sclerosis, neuroinflammation, therapy

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Authors: Faheema Khan

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We have investigated the effects of salt stress on the stability of plant growth, water relations, photosynthetic variables, lipid peroxidation and antioxidant system in salt-tolerant (PK-327) and salt-sensitive (PK-471) soybean genotypes. Ten-day-old salt-tolerant and salt-sensitive soybean plants were subjected to 0-150 mM NaCl for 15 days. While the growth of genotype PK-327 was not affected significantly up to 75 mM NaCl treatment, the growth of the PK-471 was reduced significantly beyond 25 mM NaCl treatments. Salt stress caused severe impairments in photosynthetic variables like photosynthetic rate, chlorophyll fluorescence and chlorophyll content, being more pronounced in salt-sensitive genotype than in salt-tolerant.The activities of antioxidant enzymes (superoxide dismutase, catalase, ascorbate peroxidase and glutathione reductase) were higher in PK-327 than in PK-471 at various levels of salt treatments.It is concluded that tolerance capacity of PK-327 against salinity can be associated with the ability of this genotype in keeping an active photosynthetic system and strong antioxidant defence system.

Keywords: salt stress, soybean, antioxidant, photosynthesis

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Authors: Carolina N. França, Jônatas B. do Amaral, Maria C.O. Izar, Ighor L. Teixeira, Francisco A. Fonseca

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Introduction: Atherosclerosis is a progressive disease, characterized by lipid and fibrotic element deposition in large-caliber arteries. Conditions related to the development of atherosclerosis, as dyslipidemia, hypertension, diabetes, and smoking are associated with endothelial dysfunction. There is a frequent recurrence of cardiovascular outcomes after acute myocardial infarction and, at this sense, cycles of mobilization of monocyte subtypes (classical, intermediate and nonclassical) secondary to myocardial infarction may determine the colonization of atherosclerotic plaques in different stages of the development, contributing to early recurrence of ischemic events. The recruitment of different monocyte subsets during inflammatory process requires the expression of chemokine receptors CCR2, CCR5, and CX3CR1, to promote the migration of monocytes to the inflammatory site. The aim of this study was to evaluate the effect of lipid-lowering treatment by six months in the monocyte phenotype and chemokine receptor levels of patients after Acute Myocardial Infarction (AMI). Methods: This is a PROBE (prospective, randomized, open-label trial with blinded endpoints) study (ClinicalTrials.gov Identifier: NCT02428374). Adult patients (n=147) of both genders, ageing 18-75 years, were randomized in a 2x2 factorial design for treatment with rosuvastatin 20 mg/day or simvastatin 40 mg/day plus ezetimibe 10 mg/day as well as ticagrelor 90 mg 2x/day and clopidogrel 75 mg, in addition to conventional AMI therapy. Blood samples were collected at baseline, after one month and six months of treatment. Monocyte subtypes (classical - inflammatory, intermediate - phagocytic and nonclassical – anti-inflammatory) were identified, quantified and characterized by flow cytometry, as well as the expressions of the chemokine receptors (CCR2, CCR5 and CX3CR1) were also evaluated in the mononuclear cells. Results: After six months of treatment, there was an increase in the percentage of classical monocytes and reduction in the nonclassical monocytes (p=0.038 and p < 0.0001 Friedman Test), without differences for intermediate monocytes. Besides, classical monocytes had higher expressions of CCR5 and CX3CR1 after treatment, without differences related to CCR2 (p < 0.0001 for CCR5 and CX3CR1; p=0.175 for CCR2). Intermediate monocytes had higher expressions of CCR5 and CX3CR1 and lower expression of CCR2 (p = 0.003; p < 0.0001 and p = 0.011, respectively). Nonclassical monocytes had lower expressions of CCR2 and CCR5, without differences for CX3CR1 (p < 0.0001; p = 0.009 and p = 0.138, respectively). There were no differences after the comparison between the four treatment arms. Conclusion: The data suggest a time-dependent modulation of classical and nonclassical monocytes and chemokine receptor levels. The higher percentage of classical monocytes (inflammatory cells) suggest a residual inflammatory risk, even under preconized treatments to AMI. Indeed, these changes do not seem to be affected by choice of the lipid-lowering strategy.

Keywords: acute myocardial infarction, chemokine receptors, lipid-lowering treatment, monocyte subtypes

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Authors: Linda A. O’Higgins, Astrid Wingler, Jorge Oliveira

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The growth of Chlorella vulgaris was characterized as a function of irradiance in a laboratory turbidostat (1 L) and compared to batch growth in sunlit modules (5–25 L) of the commercial Phytobag photobioreactor. The effects of variable sunlight and culture density were deconvoluted by a mathematical model. The analysis showed that algal growth was light-limited due to shading by external construction elements and due to light attenuation within the algal bags. The model was also used to predict maximum biomass productivity. The manipulative experiments and the model predictions were confronted with data from a production season of a 10m2 pilot-scale photobioreactor, Phytobag (10,000 L). The analysis confirmed light limitation in all three photobioreactors. An additional limitation of biomass productivity was caused by the nitrogen starvation that was used to induce lipid accumulation. Reduction of shading and separation of biomass and lipid production are proposed for future optimization.

Keywords: microalgae, batch cultivation, Chlorella vulgaris, Mathematical model, photobioreactor, scale-up

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Authors: Seema Dhariwal, Kiran Maan, Ruchi Baghel, Apoorva Sharma, Poonam Rana

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Introduction: Traumatic brain injury (TBI) is defined as the temporary or permanent alteration in brain function and pathology caused by an external mechanical force. It represents the leading cause of mortality and morbidity among children and youth individuals. Various models of TBI in rodents have been developed in the laboratory to mimic the scenario of injury. Blast overpressure injury is common among civilians and military personnel, followed by accidents or explosive devices. In addition to this, the lateral Controlled cortical impact (CCI) model mimics the blunt, penetrating injury. Method: In the present study, we have developed two different mild TBI models using blast and CCI injury. In the blast model, helium gas was used to create an overpressure of 130 kPa (±5) via a shock tube, and CCI injury was induced with an impact depth of 1.5mm to create diffusive and focal injury, respectively. C57BL/6J male mice (10-12 weeks) were divided into three groups: (1) control, (2) Blast treated, (3) CCI treated, and were exposed to different injury models. Serum was collected on Day1 and day7, followed by biphasic extraction using MTBE/Methanol/Water. Prepared samples were separated on Charged Surface Hybrid (CSH) C18 column and acquired on UHPLC-Q-TOF-MS using ESI probe with inhouse optimized parameters and method. MS peak list was generated using Markerview TM. Data were normalized, Pareto-scaled, and log-transformed, followed by multivariate and univariate analysis in metaboanalyst. Result and discussion: Untargeted profiling of lipids generated extensive data features, which were annotated through LIPID MAPS® based on their m/z and were further confirmed based on their fragment pattern by LipidBlast. There is the final annotation of 269 features in the positive and 182 features in the negative mode of ionization. PCA and PLS-DA score plots showed clear segregation of injury groups to controls. Among various lipids in mild blast and CCI, five lipids (Glycerophospholipids {PC 30:2, PE O-33:3, PG 28:3;O3 and PS 36:1 } and fatty acyl { FA 21:3;O2}) were significantly altered in both injury groups at Day 1 and Day 7, and also had VIP score >1. Pathway analysis by Biopan has also shown hampered synthesis of Glycerolipids and Glycerophospholipiods, which coincides with earlier reports. It could be a direct result of alteration in the Acetylcholine signaling pathway in response to TBI. Understanding the role of a specific class of lipid metabolism, regulation and transport could be beneficial to TBI research since it could provide new targets and determine the best therapeutic intervention. This study demonstrates the potential lipid biomarkers which can be used for injury severity diagnosis and identification irrespective of injury type (diffusive or focal).

Keywords: LipidBlast, lipidomic biomarker, LIPID MAPS®, TBI

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Authors: Jeanne Leblond, Warren Viricel, Amira Mbarek

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Although several products have reached the market, gene therapeutics are still in their first stages and require optimization. It is possible to improve their lacking efficiency by the use of carefully engineered vectors, able to carry the genetic material through each of the biological barriers they need to cross. In particular, getting inside the cell is a major challenge, because these hydrophilic nucleic acids have to cross the lipid-rich plasmatic and/or endosomal membrane, before being degraded into lysosomes. It takes less than one hour for newly endocytosed liposomes to reach highly acidic lysosomes, meaning that the degradation of the carried gene occurs rapidly, thus limiting the transfection efficiency. We propose to use a new pH-sensitive lipid able to change its conformation upon protonation at endosomal pH values, leading to the disruption of the lipidic bilayer and thus to the fast release of the nucleic acids into the cytosol. It is expected that this new pH-sensitive mechanism promote endosomal escape of the gene, thereby its transfection efficiency. The main challenge of this work was to design a preparation presenting fast-responding lipidic bilayer destabilization properties at endosomal pH 5 while remaining stable at blood pH value and during storage. A series of pH-sensitive lipids able to perform a conformational switch upon acidification were designed and synthesized. Liposomes containing these switchable lipids, as well as co-lipids were prepared and characterized. The liposomes were stable at 4°C and pH 7.4 for several months. Incubation with siRNA led to the full entrapment of nucleic acids as soon as the positive/negative charge ratio was superior to 2. The best liposomal formulation demonstrated a silencing efficiency up to 10% on HeLa cells, very similar to a commercial agent, with a lowest toxicity than the commercial agent. Using flow cytometry and microscopy assays, we demonstrated that drop of pH was required for the transfection efficiency, since bafilomycin blocked the transfection efficiency. Additional evidence was brought by the synthesis of a negative control lipid, which was unable to switch its conformation, and consequently exhibited no transfection ability. Mechanistic studies revealed that the uptake was mediated through endocytosis, by clathrin and caveolae pathways, as reported for previous lipid nanoparticle systems. This potent system was used for the treatment of hypercholesterolemia. The switchable lipids were able to knockdown PCSK9 expression on human hepatocytes (Huh-7). Its efficiency is currently evaluated on in vivo mice model of PCSK9 KO mice. In summary, we designed and optimized a new cationic pH-sensitive lipid for gene delivery. Its transfection efficiency is similar to the best available commercial agent, without the usually associated toxicity. The promising results lead to its use for the treatment of hypercholesterolemia on a mice model. Anticancer applications and pulmonary chronic disease are also currently investigated.

Keywords: liposomes, siRNA, pH-sensitive, molecular switch

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Authors: Nabila N. El-Maraghy, Amany Essa, Yousra Abdel–Mottaleb, Nada Ismail

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The use of combination of chemotherapy and natural products to influence the cell death with low doses of chemotherapeutic agents and few side effects has recently emerged as a new method of cancer therapy. Aim: Evaluation the modulatory effect of Thymoquinone on HepG2 cells treated with Sorafenib. Methods: Hepatocellular Carcinoma HepG2 cell line was treated with Sorafenib and TQ individually and in combination. The effect of these treatments on cell viability (MTT assay), apoptosis (Expression of Caspase-3) and oxidative markers (GSH content and extent of lipid peroxidation) was determined. Results: When compared the effect of both agents alone and the combination of the IC50 of Sorafenib and the IC50 TQ, the combination resulted in reduction of cell inhibition and apoptosis and antagonize their actions on GSH content and extent of lipid peroxidation which are increased. This study showed potent anti-tumor activity of both TQ and Sorafenib separately on HepG2 but upon combination surprisingly they interacted and give antagonistic effect. Conclusion: Co-treatment resulted in antagonistic interaction between Sorafenib and Thymoquinone.

Keywords: antagonism, hepatocellular carcinoma, sorafenib, thymoquinone

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Authors: Weiam Daear, Patrick Lai, Elmar Prenner

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The human body offers many avenues that could be used for drug delivery. The pulmonary route, which is delivered through the lungs, presents many advantages that have sparked interested in the field. These advantages include; 1) direct access to the lungs and the large surface area it provides, and 2) close proximity to the blood circulation. The air-blood barrier of the alveoli is about 500 nm thick. The air-blood barrier consist of a monolayer of lipids and few proteins called the lung surfactant and cells. This monolayer consists of ~90% lipids and ~10% proteins that are produced by the alveolar epithelial cells. The two major lipid classes constitutes of various saturation and chain length of phosphatidylcholine (PC) and phosphatidylglycerol (PG) representing 80% of total lipid component. The major role of the lung surfactant monolayer is to reduce surface tension experienced during breathing cycles in order to prevent lung collapse. In terms of the pulmonary drug delivery route, drugs pass through various parts of the respiratory system before reaching the alveoli. It is at this location that the lung surfactant functions as the air-blood barrier for drugs. As the field of nanomedicine advances, the use of nanoparticles (NPs) as drug delivery vehicles is becoming very important. This is due to the advantages NPs provide with their large surface area and potential specific targeting. Therefore, studying the interaction of NPs with lung surfactant and whether they affect its stability becomes very essential. The aim of this research is to develop a biomimetic model of the human lung surfactant followed by a biophysical analysis of the interaction of polymeric NPs. This biomimetic model will function as a fast initial mode of testing for whether NPs affect the stability of the human lung surfactant. The model developed thus far is an 8-component lipid system that contains major PC and PG lipids. Recently, a custom made 16:0/16:1 PC and PG lipids were added to the model system. In the human lung surfactant, these lipids constitute 16% of the total lipid component. According to the author’s knowledge, there is not much monolayer data on the biophysical analysis of the 16:0/16:1 lipids, therefore more analysis will be discussed here. Biophysical techniques such as the Langmuir Trough is used for stability measurements which monitors changes to a monolayer's surface pressure upon NP interaction. Furthermore, Brewster Angle Microscopy (BAM) employed to visualize changes to the lateral domain organization. Results show preferential interactions of NPs with different lipid groups that is also dependent on the monolayer fluidity. Furthermore, results show that the film stability upon compression is unaffected, but there are significant changes in the lateral domain organization of the lung surfactant upon NP addition. This research is significant in the field of pulmonary drug delivery. It is shown that NPs within a certain size range are safe for the pulmonary route, but little is known about the mode of interaction of those polymeric NPs. Moreover, this work will provide additional information about the nanotoxicology of NPs tested.

Keywords: Brewster angle microscopy, lipids, lung surfactant, nanoparticles

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Authors: Pedro Cabrales, Scott Caroen, Tony R. Reid, Bryan Oronsky

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Introduction and Purpose RRx-001 is an NLRP3 inhibitor and Nrf2 agonist in Phase 3 trials for the treatment of cancer. The purpose of this study was to examine whether treatment with RRx-001, given itsanti-inflammatory and antioxidant properties, improvedexercise and skeletal muscle oxidative capacity in mice on the generalpremiss that better health outcomes correlatewith more activity. Material and Methods Male and female adult mice (n=6 per group) were subjected to an endurance exercise capacity (EEC)test until exhaustion on a motorized treadmill after 3 once weekly doses of either RRx-001 5 mg/kg, RRx-001 2 mg/kg, or vehicle. The EEC protocol consisted of a treadmill velocity of 30meters per min at an uphill inclination (slope of 10%) until the mice reached fatigue, which was defined as the inability of the mice to maintain the appropriate pace despitecontinuous hand stimulation for 1 min. The concentration of malondialdehyde (MDA), an indicator of lipid peroxidation, and creatine kinase (CK), an indicator of muscle damage, in the blood samples collected immediately after the acute exercise was determined with a commercial ELISA assay kit. ResultsThe exhaustive exercise times of the RRx-001 groups were significantly longer than that of the vehicle group (p<0.05) by weeks 2 and 3. In addition, MDA levels in the gastrocnemius, soleus, and extensor digitorum longus muscles were significantly lower than those of the vehicle group were (p<0.05), as were the serum CK levels(p<0.05). ConclusionsIn conclusion, this study found that RRx-001 has anti-fatigue properties, as evidenced by an increase in exercise capacity with RRx-001 treatment, and protects against strenuous exercise-induced muscle damage and lipid peroxidation. This data potentially supports the use of RRx-001 in the clinic to improve exercise performance and reduce physical fatigue.

Keywords: RRx-001, anti-fatigue, muscle protection, increased exercise tolerance, lipid peroxidation

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Authors: U. P. Rathnakar, Sejpal Jaykumar, Shenoy K. Ashok

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The effect of Shilajit was investigated for lipid lowering activity and its effect on weight gain in Wistar albino rats. Shilajit, semi-hard brownish black resin formed through long-term humidification of several plant types, mainly bryophytes, can be obtained from steep rocks of the Himalayas at altitudes between 1000 to 5000 meters. Hyperlipidemia was produced by feeding the rats with the cholesterol-rich high-fat diet (HFD) for 2 months. This diet contained deoxycholic acid, cholesterol and warm coconut oil in powdered rat chow diet. At the end of study, Shilajit treated rats showed significant decrease in serum LDL, triglyceride and total cholesterol level as well as increase in serum HDL level, in comparison to rats fed on high-fat diet with no treatment. Also during study period, increase in weight in Shilajit treated group was significantly less than in the other group of rats fed on high-fat diet with no treatment. Thus, Shilajit has significantly controlled the development of hyperlipidemia and weight gain in high-fat diet fed rats in the present study.

Keywords: Shilajit, hyperlipidemia, weight control, cholesterol-rich high-fat diet

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Authors: Marcela Parra-Vargas, Ana Sandoval-Rodriguez, Roberto Rodriguez-Echevarria, Jose Dominguez-Rosales, Juan Armendariz-Borunda

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Non-alcoholic fatty liver disease (NAFLD) is characterized by an excess of hepatic lipids, and it is to author’s best knowledge, the most prevalent chronic liver disorder. Anthocyanin-rich food consumption is linked to health benefits in metabolic disorders associated with obesity and NAFLD, although the precise functional role of anthocyanidin delphinidin (Dp) has yet to be established. The aim of this study was to investigate the effect of the Dp in NAFLD metabolic alterations by evaluating prevention or amelioration of hepatic lipid accumulation, as well as molecular mechanisms in two experimental obesity-related models of NALFD. In vitro: HepG2 cells were incubated with sodium palmitate (PA, 1 mM) to induce lipotoxic damage, and concomitantly treated with Dp (180 uM) for 24 h. Subsequently, total lipid accumulation was measured by colorimetric staining with Oil Red O, and total intrahepatic triglycerides were determined by an enzymatic assay. To assess molecular mechanisms, cells were pre-treated with PA for 24 h and then exposed to Dp for 1 h. In vivo: four-week-old male C57BL/6Nhsd mice were allocated in two main groups. Mice were fed with standard diet (control) or high-fat and high-carbohydrate diet (45% fat, HFD) for 16 wk to induce NAFLD. Then HFD was divided into subgroups: one treated orally with Dp (15 mg/kg bw, HFD-Dp) every day for 4 wk, while HFD group treated with vehicle (DMSO). Weight and fasting glucose were recorded weekly, while dietary ingestion was measured daily. Insulin tolerance test was performed at the end of treatment. Liver histology was evaluated with H&E and Masson’s trichrome stain. RT-PCR was used to evaluate gene expression and Western Blot to determine levels of protein in both experimental models. Parametric data were analyzed with one-way ANOVA and Tukey’s post-hoc test. Kruskal-Wallis and Mann-Whitney U test for non-parametric data, and P < 0.5 were considered significant. Dp prevented hepatic lipid accumulation by PA in HepG2 hepatocytes. Furthermore, Dp down-regulated gene expression of SREBP1c, FAS, and CPT1a without modifying AMPK phosphorylation levels. In vivo, Dp oral administration did not ameliorate lipid metabolic alterations raised by HFD. Adiposity, dietary ingestion, fasting glucose, and insulin sensitivity after Dp treatment remained similar to HFD group. Histological analysis showed hepatic damage in HFD groups and no differences between HFD and HFD-Dp groups were found. Hepatic gene expression of ACC and FAS were not altered by HFD. SREBP1c was similar in both HFD and HFD-Dp groups. No significant changes were observed in SREBP1c, ACC, and FAS adipose tissue gene expression by HFD or Dp treatment. Additionally, immunoblotting analysis revealed no changes in pathway SIRT1-LKB-AMPK and PPAR alpha by both HFD groups compared to control. In conclusion, the antioxidant Dp may provoke beneficial effects in the prevention of hepatic lipid accumulation. Nevertheless, the oral dose administrated in mice that simulated the total intake of anthocyanins consumed daily by humans has no effect as a treatment on hepatic lipid metabolic alterations and histological abnormalities associated with exposure to chronic HFD. A healthy lifestyle with regular intake of antioxidants such as anthocyanins may prevent metabolic alterations in NAFLD.

Keywords: anthocyanins, antioxidants, delphinidin, non-alcoholic fatty liver disease, obesity

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