Supercritical CO2 extraction increases the recovery levels of omega-3 fatty acids in Tetraselmis chuii extracts.

Tetraselmis chuii is a microalgae marketed as ingredient meeting the acceptance criteria for novel foods established by the European Union and can be an important source of healthy fatty acids (FA). The aim of this research was to characterize the FA profile of T. chuii fractions obtained by supercritical carbon dioxide (SCCO2) extraction operating with two sequential co-solvents and to evaluate the effect of biomass pretreatment (freeze/thaw cycles followed by ultrasounds). T. chuii biomass was confirmed to be an important source of omega-3 FA, mainly due to the abundance of α-linolenic acid, and pre-treatment significantly improved the lipid yield. Other omega-3 FA, such as 16:3, 16:4, 18:4, 18:5, 20:3 and 20:5, were also detected in different proportions. When SCCO2 extraction of pretreated and un-pretreated T. chuii was compared with conventional solvent extraction, the nutritional quality indices of the extracts were improved by the use of SCCO2.

Unveiling the Probiotic Potential of Streptococcus thermophilus MCC0200: Insights from In Vitro Studies Corroborated with Genome Analysis.

Streptococcus thermophilus is widely used as a starter culture in the dairy industry and has garnered attention as a beneficial bacterium owing to its health-promoting functionalities in humans. In this study, the probiotic potential of S. thermophilus MCC0200 isolated from a dairy product was investigated through a combinatorial approach of in vitro and in silico studies. MCC0200 demonstrated the ability to survive harsh gastrointestinal (GI) transit, adhere to intestinal mucosa and exert health-promoting traits in in vitro studies. These findings were corroborated with in silico evidence, wherein, MCC0200 genome harboured genes associated with tolerance to GI conditions, intestinal adhesion and colonization. Genome mapping also highlighted the ability of MCC0200 to produce compounds advantageous for the host (folate, bacteriocins), to release antioxidant enzymes that can quench the free radicals (superoxide dismutase, NADH peroxidase), and to metabolize food components that can be harmful to sensitive people (lactose). MCC0200 also demonstrated a positive effect on reducing cholesterol levels, proving to be a potential candidate for food and pharmaceutical applications. The absence of transmissible antibiotic resistance genes and virulence genes underscored the generally regarded as safe (GRAS) nature of MCC0200. This study explored the potential of Streptococcus thermophilus for its probable applications as a probiotic beyond the dairy industry.

INFLUENCE OF CHOLESTEROL ENRICHED DIET ON GENES EXPRESSION ENCODING BONE MORPHOGENETIC PROTEIN-2 AND OSTEOCALCIN IN MOUSE MANDIBLE.

OBJECTIVE: The aim: To evaluate the mRNA expression of the key regulators of osteogenesis - osteocalcin and BMP-2 in the mouse embryos mandible (17th day of pregnancy) which were borne by females on high-cholesterol diet for 30 days before fertilization and throughout pregnancy. PATIENTS AND METHODS: Materials and methods: Experimental hypercholesterolemia (2%) was simulated by adding Cholesterol to the diet for 60 days. In experiment were used 40 mature female white mice that were randomly divided to control and experimental groups. The control group were fed with standard chow diet, the experimental group with diet with cholesterol enriched diet (with addition of 2 grams of Cholesterol per 100 grams of standard chow). The mandibles of mouse embryos (E-17) were examined by using molecular genetic methods. RESULTS: Results: In control group the relative level of BMP-2 mRNA / actin mRNA was 27.0«2.82, the relative level of and osteocalcin mRNA / actin mRNA was 30.5«6,28. In the jaws of animals in the experimental group with cholesterol enriched diet, the expression relative level of BMP-2 was 30.9«5.81 that is by 14,4% higher than in control group. Therefore, the expression level of оsteocalcin, on the contrary, decreased by 22.3% and was 23.7+5.31. CONCLUSION: Conclusions: Our study report influence of the cholesterol enriched diet (2%) on mRNA expression of BMP-2 and osteocalcin encoding genes. The embryos from mouse on cholesterol enriched diet (2%) had increased level of BMP-2 gene expression, however significantly decreased level of osteocalcin gene expression.

Oxidized Low-density Lipoproteins and Lipopolysaccharides Augment Carotid Artery Plaque Vulnerability in Hypercholesterolemic Microswine.

Atherosclerosis is a chronic inflammatory disease and hypercholesterolemia is a risk factor. This study aims to compare the potency of lipopolysaccharide (LPS) and oxidized low-density lipoproteins (oxLDL) to induce plaque formation and increase plaque vulnerability in the carotid artery of hypercholesterolemic Yucatan microswine. Atherosclerotic lesions at the common carotid artery junction and ascending pharyngeal artery were induced in hypercholesterolemic Yucatan microswine at 5-6 months of age with balloon angioplasty. LPS or oxLDL were administered intraluminally at the site of injury after occluding the arterial flow temporarily. Pre-intervention ultrasound (US), angiography, and optical coherence tomography (OCT) were done at baseline and just before euthanasia to assess post-op parameters. The images from the US, OCT, and angiography in the LPS and the oxLDL-treated group showed increased plaque formation with features suggestive of unstable plaque, including necrotic core, thin fibrous caps, and a signal poor region more with oxLDL compared to LPS. Histomorphology of the carotid artery tissue near the injury corroborated the presence of severe lesions in both LPS and oxLDL-treated pigs but more in the oxLDL group. Vascular smooth muscle and endothelial cells treated with LPS and oxLDL showed increased folds changes in mRNA transcripts of the biomarkers of inflammation and plaque vulnerability compared to untreated cells. Collectively, the results suggest that angioplasty-mediated intimal injury of the carotid arteries in atherosclerotic swine with local administration of LPS or ox-LDL induces vulnerable plaques compared to angioplasty alone and oxLDL is relatively more potent than LPS in inducing vulnerable plaque.

Therapeutic Applications and Effects of Lupinus angustifolius (Blue Lupin) and Its Components: A Systematic Review and Meta-Analysis.

Lupinus angustifolius has a unique nutrient profile among legumes and may have beneficial health effects when included in the diet. The aim of this study was to investigate the biological properties of blue lupin (Lupinus angustifolius), its chemical components, and their relevance for monitoring biological and anthropometric health markers, including triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), BMI, weight, and glycemia, compared with control groups with other kinds of diets. PubMed, Web of Science, and Scopus databases, updated to December 2023, were searched. Out of the 194 studies identified, a total of 7 randomized controlled trials (RCTs) comprising 302 participants met the eligibility criteria. The results of our study indicated that the blue lupin diet has a direct relationship with parameters such as blood glucose, weight, and LDL-C but not with TGs or BMI. In conclusion, the research described in this review clearly indicates that L. angustifolius may play an important role in the dietary prevention of hyperlipidemia and hypertension. Therefore, it would be highly advisable to increase its consumption in diets. However, further studies, ideally in humans, are required to truly establish L. angustifolius's health-promoting properties.

Intratumoral Restoration of miR-137 Plus Cholesterol Favors Homeostasis of the miR-137/Coactivator p160/AR Axis and Negatively Modulates Tumor Progression in Advanced Prostate Cancer.

MicroRNAs (miRNAs) have gained a prominent role as biomarkers in prostate cancer (PCa). Our study aimed to evaluate the potential suppressive effect of miR-137 in a model of advanced PCa with and without diet-induced hypercholesterolemia. In vitro, PC-3 cells were treated with 50 pmol of mimic miR-137 for 24 h, and gene and protein expression levels of SRC-1, SRC-2, SRC-3, and AR were evaluated by qPCR and immunofluorescence. We also assessed migration rate, invasion, colony-forming ability, and flow cytometry assays (apoptosis and cell cycle) after 24 h of miRNA treatment. For in vivo experiments, 16 male NOD/SCID mice were used to evaluate the effect of restoring miR-137 expression together with cholesterol. The animals were fed a standard (SD) or hypercholesterolemic (HCOL) diet for 21 days. After this, we xenografted PC-3 LUC-MC6 cells into their subcutaneous tissue. Tumor volume and bioluminescence intensity were measured weekly. After the tumors reached 50 mm3, we started intratumor treatments with a miR-137 mimic, at a dose of 6 µg weekly for four weeks. Ultimately, the animals were killed, and the xenografts were resected and analyzed for gene and protein expression. The animals' serum was collected to evaluate the lipid profile. The in vitro results showed that miR-137 could inhibit the transcription and translation of the p160 family, SRC-1, SRC-2, and SRC-3, and indirectly reduce the expression of AR. After these analyses, it was determined that increased miR-137 inhibits cell migration and invasion and impacts reduced proliferation and increased apoptosis rates. The in vivo results demonstrated that tumor growth was arrested after the intratumoral restoration of miR-137, and proliferation levels were reduced in the SD and HCOL groups. Interestingly, the tumor growth retention response was more significant in the HCOL group. We conclude that miR-137 is a potential therapeutic miRNA that, in association with androgen precursors, can restore and reinstate the AR-mediated axis of transcription and transactivation of androgenic pathway homeostasis. Further studies involving the miR-137/coregulator/AR/cholesterol axis should be conducted to evaluate this miR in a clinical context.

Perspective: Hepatocyte-Directed Base Editing as Novel Treatment for Human Dyslipidemia-Current Status and Remaining Challenges.

Hyperlipidemia is a major risk factor for the development of atherosclerotic cardiovascular disease. Lipid-lowering drug therapies therefore still form the heart of the ongoing battle against the occurrence of cardiovascular events. However, in light of the important improvements in gene interference and editing that have been made during the last 2 decades, gene therapy-the genetic modification of cells to produce a permanent therapeutic effect-is currently employed to relief hypercholesterolemic subjects from their potential (chronic) cardiovascular disease burden. In this perspective, we review the current status regarding hepatocyte-directed base editing to treat human dyslipidemia and provide suggestions for further technological improvement.

Fatty Acids in Waste Tissues: The Nutraceutical Value of Gonads and Livers from the Moroccan Hypophthalmichthys molitrix and Cyprinus carpio Fishes.

Fishes are an important component of human nutrition, mainly acting as source of essential fatty acids in the prevention of cardiovascular disorders. The increase in their consumption has led to a growth of fishes waste; therefore, the disposal and recycling of waste has become a key issue to address, in accordance with circular economy principles. The Moroccan Hypophthalmichthys molitrix and Cyprinus carpio fishes, living in freshwater and marine environments, were collected at mature and immature stages. The fatty acid (FA) profiles of liver and ovary tissues were investigated by GC-MS and compared with edible fillet tissues. The gonadosomatic index, the hypocholesterolemic/hypercholesterolemic ratio, and the atherogenicity and thrombogenicity indexes were measured. Polyunsaturated fatty acids were found to be abundant in the mature ovary and fillet of both species, with a polyunsaturated fatty acids/saturated fatty acids ratio ranging from 0.40 to 1.06 and a monounsaturated fatty acids/polyunsaturated fatty acids ratio between 0.64 and 1.84. Saturated fatty acids were found to be highly abundant in the liver and gonads of both species (range 30-54%), as well as monounsaturated fatty acids (range 35-58%). The results suggested that the exploitation of fish wastes, such as the liver and ovary, may represent a sustainable strategy for the achievement of high value-added molecules with nutraceutical potential.

Cucumis melo seed oil: agro-food by-product with natural anti-hyperlipidemic potential.

BACKGROUND: Sweet melon (Cucumis melo) seed is generally considered as agro-waste, however, the current study aimed to use this waste as a valuable oil source. The seed oil extracted by two different extraction techniques (cold press and solvent extraction) was investigated for its anti-hyperlipidemic potential. Hyperlipidemic rabbits were fed on the diet supplemented with sweet melon seed oil for 6 weeks (42 days) and thoroughly examined for the change in their lipid profile. RESULTS: The blood lipid profile indicated a significant decrease in total cholesterol triglyceride and low-density lipoprotein (LDL) contents of blood in hyperlipidemic rabbits fed on the diet supplemented with sweet melon seed oils while high-density lipoprotein (HDL) contents showed a noteworthy increase during the study period. CONCLUSION: Cucumis melo seed oil can be used to control hyperlipidemia without restricting the intake of lipids in diet. Solvent extraction provided better results regarding extraction yield and product functionality than cold press method. © 2022 Society of Chemical Industry.

Cholesterol Triggers Nuclear Co-Association of Androgen Receptor, p160 Steroid Coactivators, and p300/CBP-Associated Factor Leading to Androgenic Axis Transactivation in Castration-Resistant Prostate Cancer.

BACKGROUND/AIMS: Cholesterol modulates intratumoral androgenic signaling in prostate cancer; however, the molecular mechanisms underlying these changes in castration-resistant prostate cancer (CRPC) are not fully elucidated. Herein, we investigated the effect of cholesterol on androgen receptor (AR) coactivators expression and tumorigenesis in vitro and in vivo. METHODS: Herein, we monitored the expression of AR coactivators (SRC-1, 2, 3 and PCAF) genes in PC-3 cells exposed to 2µg/mL of cholesterol for 8 hours by qPCR. We also performed cell migration at 0, 8, 24, 48 and 72h and flow cytometry assays (viability, apoptosis, and cell cycle) after a 24h exposure. Immunofluorescence assay was performed to evaluate the protein expression of the AR coactivators. Additionally, in vivo experiments were conducted using 22 male NOD/SCID mice. Mice were fed a standard (Control) or hypercholesterolemic (HCOL) diet for 21 days and then subcutaneously implanted with PC-3 cells. The tumor volume was calculated every two days, and after four weeks, the tumors were resected, weighed, and the serum lipid profile was measured. We also measured the intratumoral lipid profile and AR coactivators gene and protein expression by qPCR and Western Blot, respectively. Intratumor testosterone and dihydrotestosterone (DHT) concentrations were determined using ELISA. RESULTS: Cholesterol up-regulated the gene expression of coactivators SRC-1, SRC-2, SRC-3and PCAF, increasing AR expression in PC-3 cells. Next, cholesterol-supplemented PC-3 cells exhibited increased cell migration and altered cell cycle phases, leading to changes in proliferation and reduced apoptosis. We found that SRC-1, SRC-2, SRC-3 and PCAF proteins co-localized in the nucleus of cholesterol-supplemented cells and co-associate with AR. In the in vivo model, the hypercholesterolemic (HCOL) group displayed higher serum total and intratumoral cholesterol levels, increased testosterone and dihydrotestosterone concentrations, and up-regulated AR coactivator expression. The tumor volume of the HCOL group was significantly higher than the control group. CONCLUSION: Our findings revealed that increased nuclear translocation of the coactivators leads to up-regulated AR gene and protein expression, potentially influencing tumor progression. Studies targeting cholesterol-modulated changes in AR coactivator expression may provide insights into the molecular mechanisms associated with the CRPC phenotype.

Evaluation of the Nutritional and Health Values of Selected Polish Mushrooms Considering Fatty Acid Profiles and Lipid Indices.

Imleria badia, Boletus edulis, and Cantharellus cibarius are popular mushrooms of economic importance in Poland. Since physical and mental development of a person and the maintenance of good health entail providing the body with adequate nutrients, including plant and animal fats, the aim of this study was to determine the fatty acid profiles of three mushroom species from Poland and to assess their nutritional and health values using lipid indices. Studied mushrooms have a favorable fatty acid composition due to the high percentage of polyunsaturated fatty acids. Low values of the atherohenic index (AI) and the thrombogenic index (TI) prove that the consumption of the fungi may decrease the risk of coronary heart disease. Products with a high hypocholesterolemic/hypercholesterolemic ratio (H/H) and health-promoting index value are assumed to be more beneficial to human health, granting the possibility for using mushrooms in the nutrition of people with hypertension and in the prevention of cardiovascular diseases.

Fatty Acid and Tocopherol Composition of Pomace and Seed Oil from Five Grape Varieties Southern Spain.

Grape pomace and seeds are important winemaking by-products. Their oils are rich in bioactive compounds such as fatty acids and tocopherols. We have characterized oils from both by-products from five Spanish grape varieties (Palomino Fino, Pedro Ximénez, Muscat of Alexandria, Tempranillo and Tintilla de Rota). A high content of UFAs was found in all the analyzed samples. Grape pomace oils generally had the same oleic acid (PUFAω-6) content as seed oils, and lower PUFA contents; they also had a markedly higher linolenic acid (PUFAω-3) content, improving the PUFAω-6/PUFAω-3 ratio. All the oil studied show good indicators of nutritional quality: low values of the atherogenicity (0.112-0.157 for pomace, 0.097-0.112 for seed) and thrombogenicity indices (0.30-0.35 for pomace, 0.28-0.31 for seed) and high values of the relationship between hypo- and hypercholesterolemic fatty acids (6.93-9.45 for pomace, 9.11-10.54 for seed). Three tocopherols were determined: α-, γ- and δ-tocopherol. Pomace oils have higher relative contents of α- and δ-tocopherol, whereas seed oils have higher relative contents of γ-tocopherol. A significantly higher content of total tocopherols has been found in pomace oil; it is higher in the oils from red varieties of pomace (628.2 and 706.6 mg/kg by-product), and in the oils from pomace containing stems (1686.4 mg/kg by-product). All the oils obtained can be considered as a source of vitamin E, and their consumption is beneficial for health.

The Effect of Different Nutritional Education Models on Reducing Cardiovascular Disease Risk Factors by Improving Dietary Fat Quality in Hemodialysis Patients.

Cardiovascular disease (CVD) is the most common complication in hemodialysis patients. Nutritional education provided by dietitians could improve overall dietary quality and dietary fat quality to reduce the risk of CVD. However, no studies have investigated the relationship between dietary fat quality (using the hypocholesterolemic/hypercholesterolemic ratio, or the h/H) and CVD risk factors in hemodialysis patients. The aim of this study was to examine the association between the h/H and CVD risk factors, and further explore how nutritional education intervention models could improve dietary fat quality and CVD risk factors in hemodialysis patients. A quasi-experimental design was conducted from May 2019 to April 2021 on four groups, including 'no course for patients and nurses' as the non-C group, a "course for nurses" as the CN group, a "course for patients" as the CP group, and a "course for patients and nurses" as the CPN group. Nutritional education booklets based on a healthy eating index for hemodialysis patients were developed and provided to patients and nurses. Data of 119 patients were collected at baseline, intervention, and follow-up periods, including patients' basic information, blood biochemical data, dietary content, and calculated h/H. The results showed that the h/H was negatively correlated with body mass index (BMI) and positively correlated with high-density lipoprotein cholesterol (HDL-C). Compared with the non-C group, the CPN group was significantly higher in the h/H as well as HDL-C, and significantly lower in serum total cholesterol. In conclusion, the h/H was found to predict CVD risk factors, which helps in improving dyslipidemia. Nutritional education for both patients and nurses showed a beneficial impact on reducing CVD risks in hemodialysis patients.

Recapsoma®: A Novel Mixture Based on Bergamot, Ipomoea Batatas, Policosanol Extracts and Liposomal Berberine for the Treatment of Hypercholesterolemia.

Cardiovascular disease (CVD) is considered one of the major causes of mortality worldwide. Epidemiological studies have shown that regular consumption of phenols is inversely associated with cardiovascular disease, and the use of nutraceuticals and functional foods can provide protective, preventive, and possibly curative effects in CVD. A novel mixture of different natural substances named Recapsoma® (bergamot, liposomal berberine, Ipomoea batatas, oleuropein, polycosanols, and vitamin E) has been produced, and its anti-dyslipidaemic efficacy has been tested, specifically studying the in vitro effects on the mechanisms of action underlying cholesterol synthesis, triglycerides, and LDL-cholesterol oxidation. The work has demonstrated the ability of this herbal extract mixture to inhibit the action of PCSK, ACAT, PAP, and HMGR and to increase the LDL receptor (LDLR), underlying the synergistic effect of the mixture over the single components. Such results suggest that the Recapsoma® mixture could be used as a tool for controlling hypercholesterolemia, and an alternative to statins, especially for those patients with metabolic syndrome.

Gamma-Irradiation-Induced Degradation of the Water-Soluble Polysaccharide from Auricularia polytricha and Its Anti-Hypercholesterolemic Activity.

The water-soluble polysaccharides (APPs) isolated from the edible mushroom Auricularia polytricha were irradiated by γ-ray at doses of 10, 100, and 1000 kGy. The effect of gamma irradiation on the degradation of the polysaccharide was investigated. After irradiation treatment, the viscosity and molecular weight of APPs decreased with the increase in the irradiation dose. The changes in the enthalpy of APPs after irradiation treatment were observed. Meanwhile, SEM showed that R-APPs were crushed into fragments and the surfaces became smooth and wrinkled after irradiation. In further spectrum analysis, it was found that the glycoside bonds of the polysaccharides were broken and accompanied by the formation of double bonds. This suggested that gamma irradiation could cause the depolymerization and oxidation of polysaccharides. In addition, irradiated APPs could reduce the body weight of hyperlipidemia mice. The levels of serum and liver TC, TG, and serum LDH-c significantly decreased in hyperlipidemia mice after treatment by irradiated APPs. It indicated that gamma irradiation significantly improved the anti-hypolipidemic activity of APPs. The relationship between the physicochemical properties and hypolipidemic activity of polysaccharides was interpreted, which provides a theoretical basis for the further development of APP products. Gamma irradiation is a viable technology for macromolecular modification for degradation.

An evaluation of the effects of Pistacia atlantica gum hydro-alcoholic extract on the phagocytosis ability of macrophages and atherosclerosis development in hypercholesteremic rats.

BACKGROUND: Atherosclerosis is an inflammatory disease that various factors affect the onset and its progression, including free radicals, hypertension, diabetes, genetic changes, hypercholesterolemia, and even some microorganisms such as herpes viruses and chlamydia. Therefore, compounds that can be effective in any of the above cases may be considered as a useful therapeutic agent in the process of atherosclerosis. The aim of the present study was to evaluate the effects of Pistacia atlantica gum hydro-alcoholic extract on macrophage phagocytosis ability and development of atherosclerosis in hypercholesterolemic rats. METHODS: The statistical population of the present study consisted of 25 rats that were randomly divided into 5 groups (one control group under standard diet, 4 treatment groups under high-fat diet). After consumption of high-fat food for 45 days, the treatment groups orally received 100, 200, and 400 mg/kg of Pistacia atlantica gum hydro-alcoholic extract for 30 days. Then, peritoneal macrophages were isolated and blood samples were collected to measure the level of nitroblue tetrazolium (NBT), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG). P ˂ 0.05 was considered significant in all evaluations. RESULTS: The level of cholesterol (503.66 ± 17.15), TG (436.66 ± 16.80), LDL-C (343.66 ± 11.59), HDL-C (54.33 ± 7.02), and NBT (0.64 ± 0.02) decreased in the treatment groups. Besides, exactly in a concentration-dependent manner, plant extract significantly reduced the level of respiratory potential level in macrophages. CONCLUSION: Hydro-alcoholic extract of Pistacia atlantica gum could effectively decrease hypercholesterolemia and increase phagocytic ability of macrophages. Therefore, it can be suggested for more investigation as a blockage of atherosclerosis.

Synthesis and In Vivo Hypolipidemic Effect of Some N-(Benzoylphenyl)-Carboxamide Derivatives in Triton WR-1339-Induced Hyperlipidemic Rats

A series of N-(benzoylphenyl)-carboxamide derivatives (2a, 2b, 3a, 3b, 4a, 4b, 5a, 5b, 6a and 6b) was prepared with good yields by reacting the corresponding carbonyl chlorides with aminobenzophenones at room temperature. This was followed by evaluating the hypotriglyceridemic and hypocholesterolemic effects of 3b, 5a and 5b. Triton WR-1339 (300 mg/kg) was intraperitoneally administered to overnight-fasted rats to induce hyperlipidemia. Rats were divided into six groups: control, hyperlipidemic, hyperlipidemic plus compounds 3b, 5a and 5b and hyperlipidemic plus bezafibrate. Results showed that after 18 h of treatment at a dose of 15 mg/kg body weight of each of the test compounds, the elevated plasma levels of triglycerides (TG) and total cholesterol (TC) were significantly lowered by compounds 5b and 3b (p < 0.001) and by 5a (p < 0.0001), compared to the hyperlipidemic control group. Compounds 3b and 5a significantly increased levels of high-density lipoprotein cholesterol (HDL-C) by 58 and 71%, respectively. In addition, compounds 3b and 5a caused significant reduction (p < 0.0001) of low-density lipoprotein cholesterol (LDL-C) levels compared to the control group. These results suggest a promising potential for compounds 3b, 5a and 5b as lipid-lowering agents, which may contribute to reducing the risk of atherosclerosis and cardiovascular disease

Characterization of atherosclerotic plaques in blood vessels with low oxygenated blood and blood pressure (Pulmonary trunk): role of growth differentiation factor-15 (GDF-15).

BACKGROUND: Growth differentiation factor (GDF)-15 is linked to inflammation, cancer, and atherosclerosis. GDF-15 is expressed in most tissues but is extremely induced under pathological conditions. Elevated serum levels are suggested as a risk factor and a marker for cardiovascular diseases. However, the cellular sources and the effects of GDF-15 on the cardiovascular system have not been completely elucidated including progression, and morphology of atherosclerotic plaques. Thus, this work aimed to characterize the influence of GDF-15 deficiency on the morphology of atherosclerotic plaques in blood vessels with low-oxygen blood and low blood pressure as the pulmonary trunk (PT), in hypercholesterolemic ApoE-/- mice. METHODS: GDF-15-/- ApoE-/- mice were generated by crossbreeding of ApoE-/-- and GDF-15-/- mice. After feeding a cholesterol-enriched diet (CED) for 20 weeks, samples of the brachiocephalic trunk (BT) and PT were dissected and lumen stenosis (LS) was measured. Furthermore, changes in the cellularity of the PT, amounts of apoptosis-, autophagy-, inflammation- and proliferation-relevant proteins were immunohisto-morphometrically analyzed. Additionally, we examined an atherosclerotic plaque in a human post mortem sample of the pulmonary artery. RESULTS: After CED the body weight of GDF-15-/-ApoE-/- was 22.9% higher than ApoE-/-. Double knockout mice showed also an 35.3% increase of plasma triglyceride levels, whereas plasma cholesterol was similar in both genotypes. LS in the BT and PT of GDF-15-/-ApoE-/- mice was significantly reduced by 19.0% and by 6.7% compared to ApoE-/-. Comparing LS in PT and BT of the same genotype revealed a significant 38.8% (ApoE-/-) or 26.4% (GDF-15-/-ApoE-/-) lower LS in the PT. Immunohistomorphometry of atherosclerotic lesions in PT of GDF-15-/-ApoE-/- revealed significantly increased levels (39.8% and 7.3%) of CD68 + macrophages (MΦ) and α-actin + smooth muscle cells than in ApoE-/-. The density of TUNEL + , apoptotic cells was significantly (32.9%) higher in plaques of PT of GDF-15-/-ApoE-/- than in ApoE-/-. Analysis of atherosclerotic lesion of a human pulmonary artery showed sm-α-actin, CD68+, TUNEL+, Ki67+, and APG5L/ATG+ cells as observed in PT. COX-2+ and IL-6+ immunoreactivities were predominantly located in endothelial cells and subendothelial space. In BT and PT of GDF15-/-ApoE-/- mice the necrotic area was 10% and 6.5% lower than in ApoE-/-. In BT and PT of GDF15-/-ApoE-/- we found 40% and 57% less unstable plaques than ApoE-/- mice. CONCLUSIONS: Atherosclerotic lesions occur in both, BT and PT, however, the size is smaller in PT, possibly due to the effect of the low-oxygen blood and/or lower blood pressure. GDF-15 is involved in atherosclerotic processes in BT and PT, although different mechanisms (e.g. apoptosis) in these two vessels seem to exist.

Bioactive Sugarcane Lipids in a Circular Economy Context.

Most of the global sugar and ethanol supply trade comes from the harvesting of Saccharum officinarum (i.e., sugarcane). Its industrial processing results in numerous by-products and waste streams, such as tops, straw, filter cake, molasses and bagasse. The recovery of lipids (i.e., octacosanol, phytosterols, long-chain aldehydes and triterpenoids) from these residues is an excellent starting point for the development of new products for various application fields, such as health and well-being, representing an important feature of the circular economy. By selecting green scalable extraction procedures, industry can reduce its environmental impact. Refluxed ethanol extraction methods have been demonstrated to meet these characteristics. On the other hand, effective non-solvent methodologies such as molecular distillation and supercritical CO2 extraction can fractionate lipids based on high temperature and pressure application with similar yields. Sugarcane lipophilic extracts are usually analyzed through gas chromatography (GC) and liquid chromatography (LC) techniques. In many cases, the identification of such compounds involves the development of high-temperature GC-MS/FID techniques. On the other hand, for the identification and quantification of thermolabile lipids, LC-MS techniques are suitable for the separation and identification of major lipid classes. Generically, its composition includes terpenes, phytosterols, tocopherol, free fatty acids, fatty alcohols, wax esters, triglycerides, diglycerides and monoglycerides. These compounds are already known for their interesting application in various fields such as pharma and cosmetics due to their anti-hypercholesterolemic, anti-hyperglycemic, antioxidant and anti-inflammatory properties.

α-globulin-rich rice cultivar, low glutelin content-1 (LGC-1), decreases serum cholesterol concentration in exogenously hypercholesterolemic rats.

BACKGROUND: Rice α-globulin has been reported to have serum cholesterol-lowering activity in rats. However, it is still unclear whether α-globulin exerts this effect when taken as one of the dietary components. In the present study, we investigated the effect of two cultivars of rice, low glutelin content (LGC)-1 and LGC-Jun, on reducing serum cholesterol in exogenously hypercholesterolemic (ExHC) rats. LGC-1 is enriched in α-globulin (10.6 mg g-1 rice flour, which is an approximately 1.5 times higher α-globulin content than in Koshihikari a predominant rice cultivar in Japan), whereas LGC-Jun is a globulin-negative cultivar. METHODS: ExHC rats, the model strain of diet-induced hypercholesterolemia, were fed 50% LGC-1 or LGC-Jun and 0.5% cholesterol-containing diets for 2 weeks, followed by measurement of cholesterol metabolism parameters in serum and tissues. RESULTS: Serum cholesterol and non-high-density lipoprotein cholesterol levels were significantly lower in the LGC-1 group compared to the LGC-Jun group. Cholesterol intestinal absorption markers, hepatic and serum levels of campesterol and ß-sitosterol, and lymphatic cholesterol transport were not different between the two groups. Levels of 7α-hydroxycholesterol, an intermediate of bile acid synthesis, showed a downward trend in the livers of rats that were fed LGC-1 (P = 0.098). There was a significant decrease in the hepatic mRNA expression of Cyp7a1 (a synthetic enzyme for 7α-hydroxycholesterol) in the LGC-1 group compared to the LGC-Jun group. CONCLUSION: Dietary LGC-1 significantly decreased serum cholesterol levels in ExHC rats. The possible mechanism for the cholesterol-lowering activity of LGC-1 is partial inhibition of bile acid and cholesterol synthesis in the liver. © 2021 Society of Chemical Industry.