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BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a respiratory disorder of obscure etiology and limited treatment options, possibly linked to dysregulation in lipid metabolism. While several observational studies suggest that lipid-lowering agents may decrease the risk of IPF, the evidence is inconsistent. The present Mendelian randomization (MR) study aims to determine the association between circulating lipid traits and IPF and to assess the potential influence of lipid-modifying medications for IPF. METHODS: Summary statistics of 5 lipid traits (high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, apolipoprotein A, and apolipoprotein B) and IPF were sourced from the UK Biobank and FinnGen Project Round 10. The study's focus on lipid-regulatory genes encompassed PCSK9, NPC1L1, ABCG5, ABCG8, HMGCR, APOB, LDLR, CETP, ANGPTL3, APOC3, LPL, and PPARA. The primary effect estimates were determined using the inverse-variance-weighted method, with additional analyses employing the contamination mixture method, robust adjusted profile score, the weighted median, weighted mode methods, and MR-Egger. Summary-data-based Mendelian randomization (SMR) was used to confirm significant lipid-modifying drug targets, leveraging data on expressed quantitative trait loci in relevant tissues. Sensitivity analyses included assessments of heterogeneity, horizontal pleiotropy, and leave-one-out methods. RESULTS: There was no significant effect of blood lipid traits on IPF risk (all Pï¼0.05). Drug-target MR analysis indicated that genetic mimicry for inhibitor of NPC1L1, PCSK9, ABCG5, ABCG8, and APOC3 were associated with increased IPF risks, with odds ratios (ORs) and 95% confidence intervals (CIs) as follows: 2.74 (1.05-7.12, P = 0.039), 1.36 (1.02-1.82, P = 0.037), 1.66 (1.12-2.45, P = 0.011), 1.68 (1.14-2.48, P = 0.009), and 1.42 (1.20-1.67, P = 3.17×10-5), respectively. The SMR method identified a significant association between PCSK9 gene expression in whole blood and reduced IPF risk (OR = 0.71, 95% CI: 0.50-0.99, P = 0.043). Sensitivity analyses showed no evidence of bias. CONCLUSIONS: Serum lipid traits did not significantly affect the risk of idiopathic pulmonary fibrosis. Drug targets MR studies examining 12 lipid-modifying drugs indicated that PCSK9 inhibitors could dramatically increase IPF risk, a mechanism that may differ from their lipid-lowering actions and thus warrants further investigation.
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HDL-Colesterol , LDL-Colesterol , Fibrose Pulmonar Idiopática , Análise da Randomização Mendeliana , Pró-Proteína Convertase 9 , Triglicerídeos , Humanos , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/sangue , Pró-Proteína Convertase 9/genética , Triglicerídeos/sangue , LDL-Colesterol/sangue , HDL-Colesterol/sangue , Apolipoproteínas B/genética , Apolipoproteínas B/sangue , Membro 8 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Membro 5 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Proteínas de Membrana Transportadoras/genética , Hipolipemiantes/uso terapêutico , Proteínas Semelhantes a Angiopoietina/genética , Proteína 3 Semelhante a Angiopoietina , Proteínas de Transferência de Ésteres de Colesterol/genética , Polimorfismo de Nucleotídeo Único , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Feminino , Lipase Lipoproteica , Apolipoproteína B-100 , Hidroximetilglutaril-CoA Redutases , Receptores de LDL , Apolipoproteína C-IIIRESUMO
BACKGROUND: Fruit consumption has been associated with a lower cardiovascular disease (CVD) risk but the underlying mechanisms are unclear. We investigated the cross-sectional and prospective associations of fruit consumption with markers of adiposity, blood pressure, lipids, low-grade inflammation, glycaemia, and oxidative stress. METHODS: The main analyses included 365 534 middle-aged adults from the UK Biobank at baseline, of whom 11 510, and 38 988 were included in the first and second follow-up respectively, free from CVD and cancer at baseline. Fruit consumption frequency at baseline was assessed using a questionnaire. We assessed the cross-sectional and prospective associations of fruit with adiposity (body mass index, waist circumference and %body fat), systolic and diastolic blood pressure, lipids (low-density and high-density lipoproteins, triglycerides and apolipoprotein B), glycaemia (haemoglobin A1c), low-grade inflammation (C-reactive protein) and oxidative stress (gamma-glutamyl-transferase) using linear regression models adjusted for socioeconomic and lifestyle factors. Analyses were repeated in a subset with two to five complete 24-h dietary assessments (n = 26 596) allowing for adjustment for total energy intake. RESULTS: Fruit consumption at baseline generally showed weak inverse associations with adiposity and biomarkers at baseline. Most of these relationships did not persist through follow-up, except for inverse associations with diastolic blood pressure, C-reactive protein, gamma-glutamyl transferase and adiposity. However, for most mechanisms, mean levels varied by less than 0.1 standard deviations (SD) between high and low fruit consumption (> 3 vs < 1 servings/day) in further adjusted models (while the difference was < 0.2 SD for all of them). For example, waist circumference and diastolic blood pressure were 1 cm and 1 mmHg lower in high compared to low fruit intake at the first follow-up (95% confidence interval: -1.8, -0.1 and -1.8, -0.3, respectively). Analyses in the 24-h dietary assessment subset showed overall similar associations. CONCLUSIONS: We observed very small differences in adiposity and cardiometabolic biomarkers between those who reported high fruit consumption vs low, most of which did not persist over follow-up. Future studies on other mechanisms and detailed assessment of confounding might further elucidate the relevance of fruit to cardiovascular disease.
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Adiposidade , Biomarcadores , Frutas , Humanos , Masculino , Reino Unido/epidemiologia , Feminino , Pessoa de Meia-Idade , Biomarcadores/sangue , Estudos Transversais , Estudos Prospectivos , Bancos de Espécimes Biológicos , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/epidemiologia , Fatores de Risco Cardiometabólico , Dieta/estatística & dados numéricos , Adulto , Estresse Oxidativo/fisiologia , Lipídeos/sangue , Biobanco do Reino UnidoRESUMO
This work evaluated structured lipids (SLs) through chemical and enzymatic interesterification (CSLs and ESLs). Blends of soybean oil and peanut oil 1:1 wt% were used, with gradual addition of fully hydrogenated crambe to obtain a final behenic acid concentration of 6, 12, 18, and 24 %. Chemical catalysis used sodium methoxide (0.4 wt%) at 100 °C for 30 min, while enzymatic catalysis used Lipozyme TL IM (5 wt%) at 60 °C for 6 h. Major fatty acids identified were C16:0, C18:0, and C22:0. It was observed that with gradual increase of hard fat, the CSLs showed high concentrations of reaction intermediates, indicating further a steric hindrance, unlike ESLs. Increased hard fat also altered crystallization profile and triacylglycerols composition and ESLs showed lower solid fat, unlike CSLs. Both methods effectively produced SLs as an alternative to trans and palm fats, view to potential future applications in food products.
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Óleo de Palmeira , Óleo de Soja , Óleo de Palmeira/química , Óleo de Soja/química , Esterificação , Óleo de Amendoim/química , Ácidos Graxos trans/química , Ácidos Graxos trans/análise , Ácidos Graxos/química , Lipídeos/química , Triglicerídeos/química , Manipulação de Alimentos/métodos , Lipase/química , Lipase/metabolismo , HidrogenaçãoRESUMO
In critical illness the regulation of inflammation and oxidative stress can improve patient outcomes, and thus omega-3 polyunsaturated fatty acids (PUFAs) have been used as part of parenteral nutrition (PN) owing to their potential anti-inflammatory effects. The international lipids in PN Summit, encompassed discussions and the production of consensus guidelines concerning PN intravenous lipid emulsion (ILE) use in critical care. The Lipid Summit participants agreed that the inclusion of fish oil in ILEs is associated with meaningful clinical benefits without signals of harm, based on a strong biological rationale and current clinical evidence. Decisions concerning ILE choice should be made based on current evidence, thus addressing clinical requirements for guidance, particularly as further definitive evidence seems unlikely to occur. In addition, a future of individualized ICU care is envisioned, yielding better clinical outcomes. This approach will require the greater use of intelligent study designs incorporating the use of biomarkers of omega-3 derivatives, inflammatory-resolving processes, and/or muscle protein breakdown.
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Cuidados Críticos , Emulsões Gordurosas Intravenosas , Ácidos Graxos Ômega-3 , Humanos , Ácidos Graxos Ômega-3/uso terapêutico , Ácidos Graxos Ômega-3/administração & dosagem , Emulsões Gordurosas Intravenosas/uso terapêutico , Emulsões Gordurosas Intravenosas/administração & dosagem , Cuidados Críticos/métodos , Nutrição Parenteral/métodos , Nutrição Parenteral/normas , Estado Terminal/terapia , Óleos de Peixe/uso terapêutico , Óleos de Peixe/administração & dosagem , Cirurgia de Cuidados CríticosRESUMO
Background: High lipoprotein (a) [Lp(a)] is associated with adverse limb events in patients undergoing lower extremity revascularization. Lp(a) levels are genetically pre-determined, with LPA gene encoding for two apolipoprotein (a) [apo(a)] isoforms. Isoform size variations are driven by the number of kringle IV type 2 (KIV-2) repeats. Lp(a) levels are inversely correlated with isoform size. In this study, we examined the role of Lp(a) levels, apo(a) size, and inflammatory markers with lower extremity revascularization outcomes. Methods: Twenty-five subjects with chronic peripheral arterial disease (PAD) underwent open or endovascular lower extremity revascularization (mean age, 66.7 ± 9.7 years; Female = 12; Male = 13; Black = 8; Hispanic = 5; and White = 12). Pre- and postoperative medical history, self-reported symptoms, ankle-brachial indices (ABIs), and lower extremity duplex ultrasounds were obtained. Plasma Lp(a), apoB100, lipid panel, and pro-inflammatory markers (IL-6, IL-18, hs-CRP, TNFα) were assayed preoperatively. Isoform size was estimated using gel electrophoresis and weighted isoform size (wIS) calculated based on % isoform expression. Firth logistic regression was used to examine the relationship between Lp(a) levels and wIS with procedural outcomes: symptoms (better/worse), early primary patency at 2 to 4 weeks, ABIs, and reintervention within 3 to 6 months. We controlled for age, sex, history of diabetes, smoking, statin, antiplatelet, and anticoagulation use. Results: Median plasma Lp(a) level was 108 (interrquartile range, 44-301) nmol/L. The mean apoB100 level was 168.0 ± 65.8 mg/dL. These values were not statistically different among races. We found no association between Lp(a) levels and wIS with measured plasma pro-inflammatory markers. However, smaller apo(a) wIS was associated with occlusion of the treated lesion(s) in the postoperative period (odds ratio, 1.97; 95% confidence interval, 1.01-3.86; P < .05). The relationship of smaller apo(a) wIS with reintervention was not as strong (odds ratio, 1.57; 95% confidence interval, 0.96-2.56; P = .07). We observed no association between wIS with patient reported symptoms or change in ABIs. Conclusions: In this small study, subjects with smaller apo(a) isoform size undergoing peripheral arterial revascularization were more likely to experience occlusion in the postoperative period and/or require reintervention. Larger cohort studies identifying the mechanism and validating these preliminary data are needed to improve understanding of long-term peripheral vascular outcomes.
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Sulfur-containing amino acids have been proposed as drugs for lipid oxidation associated with diseases for a long time, but the molecular-level mechanism on the effectiveness of sulfur-containing amino acids against lipid oxidation remains elusive. In this work, with the interfacial sensitivity mass spectrometry method, oxidation of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylglycerol (POPG), a widely used model lipid, was significantly inhibited on hung droplet surface in presence of sulfur-containing amino acids, such as cysteine (Cys) and methionine (Met). Both the Cys and Met showed a self-sacrificing protection. The amino acids with -S-R tails (R referring to methyl or t-butyl group) showed more effective against POPG oxidation than those with -SH tails, and this process was not related to the conformations of amino acids. The low effectiveness of Cys during the interfacial chemistry was proved to arise from the formation of disulfide bond. This study extends the current understanding of chemistry of sulfur-containing amino acids and provides insights to aid the sulfur-containing amino acids against cell oxidation.
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One of the reasons to suggest olive oil consumption for a healthy life is its potential to induce robust lipidomic remodeling through membrane modification by dietary lipids. This remodeling might, in turn, modulate essential lipid-protein interactions while maintaining accurate transmembrane protein/domain orientation. Oleic acid, the primary compound in olive oil, has been suggested as a modulator of ion channel function. In this study, we explored whether this lipid could rescue the trafficking of mutated transmembrane proteins. In our initial approach, we supplemented the cell culture medium of HEK-293 cells expressing cyclic nucleotide channels tagged using green fluorescent protein (CNG-GFP) with olive oil or oleic acid. In addition to wild-type channels, we also expressed R272Q and R278W mutant channels, two non-functional intracellularly retained channels related to retinopathies. We used fluorescence microscopy and patch-clamp in the inside-out configuration to assess changes in the cell localization and function of the tested channels. Our results demonstrated that olive oil and oleic acid facilitated the transport of cyclic nucleotide-gated R272Q mutant channels towards the plasma membrane, rendering them electrophysiologically functional. Thus, our findings reveal a novel property of olive oil as a membrane protein traffic inductor.
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BACKGROUND: Cross-sectional studies revealed that risk factor exposure increases with age but after reaching its peak decreases. This decline may be attributed to higher mortality among exposed individuals, lifestyle, or natural physiological changes related to age. Only prospective observations at the individual level provide credible insights of exposure during the transition from middle to old age. This study addresses changes in cardiovascular risk factors among older urban residents in Poland over an 18-year period. METHODS: The study analyzed data from the Polish arm of the Health, Alcohol and Psychosocial factors In Eastern Europe (HAPIEE) project, a prospective cohort study investigating cardiovascular disease determinants. The sample included 312 participants (46-69 years). Data on demographic characteristics, blood lipids, blood pressure, body mass index (BMI), fasting glucose, and smoking status were collected at baseline and during re-examination. RESULTS: The analysis yielded a decrease in diastolic blood pressure, total cholesterol, LDL-cholesterol, and non-HDL cholesterol concentrations. However, BMI and fasting glucose levels increased. The decrease in blood pressure was mainly attributed to treatment effects, while the reduction in lipid concentrations was observed regardless of treatment. In addition, smoking prevalence decreased over the course of 18 years. CONCLUSIONS: The results of the prospective nearly 20 year observation at the individual level confirm findings from repeated cross-sectional studies on decrease in lipid concentrations, blood pressure and prevalence of smoking in older individuals.
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Acquired drug resistance is the major cause for disease recurrence in cancer patients, and this is particularly true for patients with metastatic melanoma that carry a BRAF V600E mutation. To address this problem, we investigated cyclic membrane-active peptides as an alternative therapeutic modality to kill drug-tolerant and resistant melanoma cells to avoid acquired drug resistance. We selected two stable cyclic peptides (cTI and cGm), previously shown to have anti-melanoma properties, and compared them with dabrafenib, a drug used to treat cancer patients with the BRAF V600E mutation. The peptides act via a fast membrane-permeabilizing mechanism and kill metastatic melanoma cells that are sensitive, tolerant, or resistant to dabrafenib. Melanoma cells do not become resistant to long-term treatment with cTI, nor do they evolve their lipid membrane composition, as measured by lipidomic and proteomic studies. In vivo studies in mice demonstrated that the combination treatment of cTI and dabrafenib resulted in fewer metastases and improved overall survival. Such cyclic membrane-active peptides are thus well suited as templates to design new anticancer therapeutic strategies.
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OBJECTIVE: Omega-3 polyunsaturated fatty acids (PUFAs) play a critical role in regulating inflammation and lipid metabolism. This study sought to ascertain the frequency of omega-3 deficiency in patients with SLE and investigate whether supplementation with krill oil concentrate (KOC) could replenish omega-3 levels and decrease SLE disease activity. METHODS: A multicentre, randomised, double-blind, placebo-controlled trial was conducted in adult patients with active SLE. Eligible patients were randomised to receive 4 g/day KOC or placebo (vegetable oil mixture) for the first 24 weeks, and thereafter patients could opt to enter an open-label extension. The primary end point was improvement of the red blood cell Omega-3 Index from baseline to week 24. Changes in clinical features, including SLE Disease Activity Index 2000 (SLEDAI-2K) disease activity scores, were also monitored. RESULTS: Seventy-eight patients met eligibility criteria and were randomised to a treatment group (n=39 per group). The baseline Omega-3 Index in the total SLE cohort was a mean 4.43% (±SD 1.04%). After 4 weeks of KOC treatment, the Omega-3 Index rapidly increased to 7.17%±1.48% (n=38) and after 24 weeks to 8.05%±1.79% (n=25) (each p<0.001 vs baseline), whereas no significant change from baseline was noted in patients receiving placebo. Increases in the Omega-3 Index in KOC-treated patients persisted through week 48. After patients switched from placebo to KOC at 24 weeks, the mean Omega-3 Index showed a rapid and significant increase (from 4.63%±1.39% at week 24 (n=26) to 7.50%±1.75% at week 48 (n=12); p<0.001). Although there were no changes in disease activity in the study population overall, SLEDAI-2K scores decreased significantly in the KOC group during the 24-week randomised period among those who had high disease activity at baseline (SLEDAI-2K ≥9) (p=0.04, p=0.02 and p=0.01 vs placebo at 4, 8 and 16 weeks, respectively; n=9 per group). KOC was well-tolerated, with no significant safety concerns. CONCLUSION: KOC corrected omega-3 deficiency in patients with SLE. Supplementation with KOC was safe and decreased disease activity in those with more active disease. These findings warrant further evaluation of omega-3 fatty acid supplementation with KOC in the management of SLE. TRIAL REGISTRATION NUMBER: NCT03626311.
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Suplementos Nutricionais , Euphausiacea , Ácidos Graxos Ômega-3 , Lúpus Eritematoso Sistêmico , Humanos , Método Duplo-Cego , Feminino , Ácidos Graxos Ômega-3/uso terapêutico , Masculino , Adulto , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/complicações , Pessoa de Meia-Idade , Animais , Resultado do Tratamento , Índice de Gravidade de DoençaRESUMO
In this study, the effects of sea buckthorn oil (SBO), fish oil (FO) and an enzymatically synthesized structured lipid (SL) on serum, short-chain fatty acids (SCFAs) and intestinal microbiota in Sprague-Dawley (SD) rats were investigated. The results demonstrated that FO, SBO, and SL effectively reduced the levels of high-density lipoprotein cholesterol and low-density lipoprotein cholesterol in the serum of SD rats. SBO increased serum triglyceride levels, while FO elevated total cholesterol levels. Furthermore, all three dietary lipids decreased short-chain fatty acid production and enhanced intestinal microbiota diversity. FO increased the abundance of intestinal microbiota including Romboutsia, Lactobacillus, Escherichia-Shigella, and Lachnospiraceae_NK4A136_group. Conversely, all three dietary lipids reduced the abundance of Klebsiella and Blautia. These findings provide a foundation for understanding the functionality of SBO and FO as well as their potential application in synthesizing novel SLs to regulate intestinal microbiota.
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Angiogenesis is a physiological process of forming new blood vessels that has pathological importance in seemingly unrelated illnesses like cancer, diabetes, and various inflammatory diseases. Treatment targeting angiogenesis has shown promise for these types of diseases, but current anti-angiogenic agents have critical limitations in delivery and side-effects. This necessitates exploration of alternative approaches like biomolecule-based drugs. Proteins, lipids, and oligonucleotides have recently become popular in biomedicine, specifically as biocompatible components of therapeutic drugs. Their excellent bioavailability and potential bioactive and immunogenic properties make them prime candidates for drug discovery or drug delivery systems. Lipid-based liposomes have become standard vehicles for targeted nanoparticle (NP) delivery, while protein and nucleotide NPs show promise for environment-sensitive delivery as smart NPs. Their therapeutic applications have initially been hampered by short circulation times and difficulty of fabrication but recent developments in nanofabrication and NP engineering have found ways to circumvent these disadvantages, vastly improving the practicality of biomolecular NPs. In this review, we are going to briefly discuss how biomolecule-based NPs have improved anti-angiogenesis-based therapy.
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Inibidores da Angiogênese , Neovascularização Patológica , Nanomedicina Teranóstica , Humanos , Inibidores da Angiogênese/química , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/administração & dosagem , Nanomedicina Teranóstica/métodos , Neovascularização Patológica/tratamento farmacológico , Animais , Lipossomos/química , Nanoestruturas/química , Neoplasias/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Oligonucleotídeos/química , Oligonucleotídeos/administração & dosagem , Oligonucleotídeos/farmacocinética , Oligonucleotídeos/farmacologia , Proteínas/química , Proteínas/administração & dosagem , Lipídeos/química , Nanopartículas/químicaRESUMO
Objective: To evaluate the effects of surgical treatment of deep endometriosis on the metabolic profile, quality of life and psychological aspects. Methods: Prospective observational study, carried out with women of reproductive age diagnosed with deep endometriosis, treated in a specialized outpatient clinic, from October/2020 to September/2022, at a University Hospital in Fortaleza - Brazil. Standardized questionnaires were applied to collect data on quality of life and mental health, in addition to laboratory tests to evaluate dyslipidemia and dysglycemia, at two moments, preoperatively and six months after surgery. The results were presented using tables, averages and percentages. Results: Thirty women with an average age of 38.5 years were evaluated. Seven quality of life domains showed improved scores: pain, control and impotence, well-being, social support, self-image, work life and sexual relations after surgery (ES ≥ 0.80). There was an improvement in mental health status with a significant reduction in anxiety and depression postoperatively. With the metabolic profile, all average levels were lower after surgery: total cholesterol 8.2% lower, LDL 12.8% lower, triglycerides 10.9% lower, and fasting blood glucose 7.3% lower (p < 0.001). Conclusion: Surgical treatment of deep endometriosis improved the quality of life and psychological aspects of patients. The lipid profile of patients after laparoscopy was favorable when compared to the preoperative lipid profile.
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Endometriose , Qualidade de Vida , Humanos , Feminino , Endometriose/cirurgia , Endometriose/psicologia , Adulto , Estudos Prospectivos , Pessoa de Meia-Idade , Adulto Jovem , Metaboloma , Saúde MentalRESUMO
Background: Hyperlipidemia has been demonstrated to be an autonomous predictor of numerous cardiovascular and cerebrovascular ailments, and research indicates that polyphenols have preventive and therapeutic effects on hyperlipidemia. Nevertheless, the impact of polyphenol-rich foods on blood lipids and oxidative stress status in patients with hyperlipidemia remains inconclusive. Objective: To examine the impact of polyphenol-rich foods on lipid levels and oxidative stress in individuals with hyperlipidemia. Methods: To retrieve papers published from the establishment of the database through October 9, 2023, eight databases were searched: the Chinese National Knowledge Infrastructure, the China Biomedical Literature Database, the Wanfang Database, the China Science and Technology Journal Database, PubMed, the Cochrane Library, Embase, and the Web of Science. The quality of include studies was assessed using the Cochrane Risk of Bias in Randomized Trials tool, v2. Results: The study involved 13 surveys encompassing 640 patients diagnosed with hyperlipidemia. The scope of the food surveys included 12 commonly consumed food groups and medicinal and food homologous substances. All 13 studies reported the effects of polyphenol-rich foods on blood lipids, with significant improvements observed in blood lipid levels for 9 types of foods. Eight studies examined the impact on oxidative stress, and six foods demonstrated a significant reduction in oxidative stress levels. The observed effects were found to be influenced by factors such as dosage, duration of intervention, and gender. Conclusion: Foods abundant in polyphenols play a crucial role in the prevention and treatment of hyperlipidemia by counteracting oxidative stress and regulating metabolic disorders. The confirmation of certain positive effects by several studies notwithstanding, discrepancies in results arise from various factors, necessitating further large-scale, prospective, well-designed randomized controlled studies to address this issue.
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Arrhythmogenic cardiomyopathy (ACM) is a familial heart disease characterized by cardiac dysfunction, arrhythmias, and myocardial inflammation. Exercise and stress can influence the disease's progression. Thus, an investigation of whether a high-fat diet (HFD) contributes to ACM pathogenesis is warranted. In a robust ACM mouse model, 8-week-old Desmoglein-2 mutant (Dsg2mut/mut) mice were fed either an HFD or rodent chow for 8 weeks. Chow-fed wildtype (WT) mice served as controls. Echo- and electrocardiography images pre- and post-dietary intervention were obtained, and the lipid burden, inflammatory markers, and myocardial fibrosis were assessed at the study endpoint. HFD-fed Dsg2mut/mut mice showed numerous P-wave perturbations, reduced R-amplitude, left ventricle (LV) remodeling, and reduced ejection fraction (%LVEF). Notable elevations in plasma high-density lipoprotein (HDL) were observed, which correlated with the %LVEF. The myocardial inflammatory adipokines, adiponectin (AdipoQ) and fibroblast growth factor-1, were substantially elevated in HFD-fed Dsg2mut/mut mice, albeit no compounding effect was observed in cardiac fibrosis. The HFD not only potentiated cardiac dysfunction but additionally promoted adverse cardiac remodeling. Further investigation is warranted, particularly given elevated AdipoQ levels and the positive correlation of HDL with the %LVEF, which may suggest a protective effect. Altogether, the HFD worsened some, but not all, disease phenotypes in Dsg2mut/mut mice. Notwithstanding, diet may be a modifiable environmental factor in ACM disease progression.
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Dieta Hiperlipídica , Animais , Dieta Hiperlipídica/efeitos adversos , Camundongos , Modelos Animais de Doenças , Miocárdio/patologia , Miocárdio/metabolismo , Fibrose , Masculino , Remodelação Ventricular , Desmogleína 2/genética , Miocardite/etiologia , Miocardite/fisiopatologia , Camundongos Endogâmicos C57BL , Displasia Arritmogênica Ventricular Direita/etiologia , Displasia Arritmogênica Ventricular Direita/fisiopatologia , Adiponectina/sangue , Inflamação , Cardiomiopatias/etiologia , Cardiomiopatias/fisiopatologiaRESUMO
Marine sponges represent a good source of natural metabolites for biotechnological applications in the pharmacological, cosmeceutical, and nutraceutical fields. In the present work, we analyzed the biotechnological potential of the alien species Haliclona (Halichoclona) vansoesti de Weerdt, de Kluijver & Gomez, 1999, previously collected in the Mediterranean Sea (Faro Lake, Sicily). The bioactivity and chemical content of this species has never been investigated, and information in the literature on its Caribbean counterpart is scarce. We show that an enriched extract of H. vansoesti induced cell death in human melanoma cells with an IC50 value of 36.36 µg mL-1, by (i) triggering a pro-inflammatory response, (ii) activating extrinsic apoptosis mediated by tumor necrosis factor receptors triggering the mitochondrial apoptosis via the involvement of Bcl-2 proteins and caspase 9, and (iii) inducing a significant reduction in several proteins promoting human angiogenesis. Through orthogonal SPE fractionations, we identified two active sphingoid-based lipid classes, also characterized by nuclear magnetic resonance and mass spectrometry, as the main components of two active fractions. Overall, our findings provide the first evaluation of the anti-cancer potential of polar lipids isolated from the marine sponge H. (Halichoclona) vansoesti, which may lead to new lead compounds with biotechnological applications in the pharmaceutical field.
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Antineoplásicos , Apoptose , Haliclona , Lipídeos , Melanoma , Animais , Haliclona/química , Humanos , Melanoma/patologia , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Poríferos/químicaRESUMO
This review explores the evolution of lipid-based nanoparticles (LBNPs) for drug delivery (DD). Herein, LBNPs are classified into liposomes and cell membrane-based nanoparticles (CMNPs), each with unique advantages and challenges. Conventional LBNPs possess drawbacks such as poor targeting, quick clearance, and limited biocompatibility. One of the possible alternatives to overcome these challenges is surface modification of nanoparticles (NPs) with materials such as polyethylene glycol (PEG), aptamers, antibody fragments, peptides, CD44, hyaluronic acid, folic acid, palmitic acid, and lactoferrin. Thus, the main focus of this review will be on the different surface modifications that enable LBNPs to have beneficial properties for DD, such as enhancing mass transport properties, immune evasion, improved stability, and targeting. Moreover, various CMNPs are explored used for DD derived from cells such as red blood cells (RBCs), platelets, leukocytes, cancer cells, and stem cells, highlighting their unique natural properties (e.g., biocompatibility and ability to evade the immune system). This discussion extends to the biomimicking of hybrid NPs accomplished through the surface coating of synthetic (mainly polymeric) NPs with different cell membranes. This review aims to provide a comprehensive resource for researchers on recent advances in the field of surface modification of LBNPs and CMNPs. Overall, this review provides valuable insights into the dynamic field of lipid-based DD systems.
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Chlorella sorokiniana, isolated from a pond adjacent to a cement plant, was cultured using flue gas collected directly from kiln emissions using 20 L and 25000 L photobioreactors. Lipids, proteins, and polysaccharides were analyzed to understand their overall composition for potential applications. The lipid content ranged from 17.97% to 21.54% of the dry biomass, with carotenoid concentrations between 8.4 and 9.2 mg/g. Lutein accounted for 55% of the total carotenoids. LC/MS analysis led to the identification of 71 intact triacylglycerols, 8 lysophosphatidylcholines, 10 phosphatidylcholines, 9 monogalactosyldiacylglycerols, 12 digalactosyldiacylglycerols, and 1 sulfoquinovosyl diacylglycerol. Palmitic acid, oleic acid, linoleic acid, and α-linolenic acid were the main fatty acids. Polyunsaturated fatty acid covers ≥ 56% of total fatty acids. Protein isolates and polysaccharides were also extracted. Protein purity was determined to be ≥75% by amino acid analysis, with all essential amino acids present. Monomer analysis of polysaccharides suggested that they are composed of mainly D-(+)-mannose, D-(+)-galactose, and D-(+)-glucose. The results demonstrate that there is no adverse effect on the metabolite profile of C. sorokiniana biomass cultured using flue gas as the primary carbon source, revealing the possibility of utilizing such algal biomass in industrial applications such as animal feed, sources of cosmeceuticals, and as biofuel.
Assuntos
Biomassa , Carbono , Chlorella , Ácidos Graxos , Chlorella/metabolismo , Chlorella/crescimento & desenvolvimento , Chlorella/química , Ácidos Graxos/análise , Ácidos Graxos/metabolismo , Carbono/química , Polissacarídeos/química , Polissacarídeos/análise , Ácido alfa-Linolênico/análise , Ácido alfa-Linolênico/metabolismo , Gases/química , Ácido Linoleico/análise , Ácido Linoleico/metabolismo , Lipídeos/análise , Lipídeos/química , Galactolipídeos/análise , Galactolipídeos/metabolismo , Carotenoides/análise , Carotenoides/metabolismo , Ácido Oleico/análiseRESUMO
The objective of the current study was to evaluate the effects of soybean oil inclusion in diets on feeding behaviour, digestibility, performance, and blood metabolites of feedlot lambs. Forty non-castrated Santa Inês lambs with a mean age of 5 months and initial body weight of 34.88 ± 3.19 kg were used in a 40-day feeding trial. The lambs were distributed in five experimental diets with the inclusion of increasing soybean oil (SO) levels: 0, 30, 60, 90, and 120 g/kg DM. The SO inclusion promoted a linear reduction in DM intake (p < 0.001), crude protein (CP, p < 0.001), non-fibrous carbohydrates (NFC, p < 0.001), and total digestible nutrients (TDN, p = 0.004). There was an increasing quadratic effect on the intake of ether extract (EE; p = 0.002) and decreasing for neutral detergent fiber (p = 0.005). The soybean oil inclusion promoted the greater apparent digestibility of CP (p = 0.016), EE (p = 0.005), NDFom (p < 0.001), and TDN (p < 0.001); on the other hand, the apparent digestibility of NFC (p = 0.005) was decreased. The average daily gain decreased (p < 0.001) with SO inclusion. The SO inclusion increased feeding time (p = 0.004), reduced the efficiency of DM rumination (p = 0.001), and reduced the concentration of blood N-ureic (p < 0.001). Considering the productive parameters, SO can be included in diets and it is recommended that we include SO of up to 41 g/kg DM in diets for fattening lambs as the ideal maximum level. The strategy implemented to adapt lambs to increasing levels of high-fat diet mitigated the detrimental effects of lipids on the rumen, with high-density energy intake being the constraining factor on performance.
RESUMO
BACKGROUND: High incidence of cardiovascular disease (CVD) in South Asia is linked to genetic predisposition and diets high in saturated fatty acids (SFAs). Increased CVD prevalence correlates with rising palm oil consumption in some South Asian countries, where coconut oil and palm olein oil are primary SFA sources. OBJECTIVE: Compare the effects of coconut oil and palm olein oil on serum lipoprotein lipids and biochemical parameters in healthy adults. METHODS: A sequential feeding crossover clinical trial with two feeding periods of 8 weeks each was conducted among 40 healthy adults. Participants were provided palm olein oil in the first feeding period followed by coconut oil with a 16-week washout period in between. The outcomes measured were the difference in serum low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C), TC/HDL-C ratio, triglycerides (TG), very-low-density lipoprotein cholesterol (VLDL-C), fasting plasma glucose (FPG), and liver enzymes. RESULTS: Thirty-seven participants completed the study. LDL-C decreased by 13.0 % with palm olein oil (p < 0.001) and increased by 5.6 % with coconut oil (p = 0.044), showing a significant difference (p < 0.001). TC decreased by 9.9 % with palm olein oil (p < 0.001) and increased by 4.0 % with coconut oil (p = 0.044). CONCLUSION: Palm olein oil consumption resulted in more favorable changes in lipid-related CVD risk factors (TC, LDL-C, TC:HDL-C, and FPG) compared to coconut oil. Clinical Trial Registry number and website where it was obtained: (SLCTR/2019/034); https://slctr.lk/trials/slctr-2019-034.