High Cholesterol Concentrations Research Articles

To invest or not to invest, that is the question: Male presence and genetic relatedness as modulators of female reproductive effort in a shrimp

The present work was aimed at evaluating whether females of a freshwater shrimp, Neocaridina davidi (Bouvier, 1904), allocate differentially to reproduction when reared in the presence of males and in the presence of brothers/non-brothers. Ovarian growth was evaluated in three consecutive maturation cycles. The composition of biochemical reserves was determined in the eggs (i.e., embryos) laid at the end of the first cycle, in 20-day-old juveniles produced at the end of the second cycle, and in the mature ovary of females at the end of the third cycle. When reared in the absence of males, females took longer to mature the ovaries and stored less proteins, triglycerides and cholesterol in the mature ovary. Females reared with brothers took longer to mature the ovaries than females reared with non-brothers, with no differences in the biochemical composition of their mature ovaries. The eggs produced by females mated to brothers showed a lower carotenoid content, higher cholesterol content and a tendency towards lower energy content than those produced by females mated to non-brothers. These results suggest that females are capable of recognizing kin and modulate primary reproductive effort, in terms of ovarian and egg biochemical composition, according to male presence and genetic relatedness.

Cardiovascular outcomes in patients with homozygous familial hypercholesterolaemia on lipoprotein apheresis initiated during childhood: long-term follow-up of an international cohort from two registries

Homozygous familial hypercholesterolaemia (HoFH) is a rare genetic disease characterised by extremely high plasma LDL cholesterol from birth, causing atherosclerotic cardiovascular disease at a young age. Lipoprotein apheresis in combination with lipid-lowering drugs effectively reduce LDL cholesterol, but long-term health outcomes of such treatment are unknown. We aimed to investigate the long-term cardiovascular outcomes associated with lipoprotein apheresis initiated in childhood or adolescence. In this cohort study, data were drawn from the HoFH International Clinical Collaboration (HICC) and the international registry for Children with Homozygous Hypercholesterolemia on Lipoprotein Apheresis (CHAIN). An overall cohort included patients diagnosed with HoFH aged 0-18 years who were alive and in follow-up between Jan 1, 2010, and Nov 8, 2021, and whose high plasma LDL cholesterol concentrations made them eligible for lipoprotein apheresis. To compare cardiovascular outcomes, patients who initiated lipoprotein apheresis in childhood (lipoprotein apheresis group) and patients who only received lipid-lowering drugs (pharmacotherapy-only group) were matched by sex and untreated plasma LDL cholesterol concentrations. The primary outcome was a composite of cardiovascular death, myocardial infarction, ischaemic stroke, percutaneous coronary intervention, coronary artery bypass grafting, aortic valve replacement, peripheral artery disease, carotid endarterectomy, angina pectoris, and supra-aortic or aortic stenosis (collectively referred to as atherosclerotic cardiovascular disease), for which survival analyses were performed in the matched cohort. Cox regression analyses were used to compare disease-free survival between cohorts and to calculate hazard ratio (HR) and 95% CI adjusted for sex, age at diagnosis, untreated plasma LDL cholesterol concentration, and number of lipid-lowering therapies other than lipoprotein apheresis. The overall cohort included 404 patients with a median age at diagnosis of 6·0 years (IQR 3·0-9·5) and median untreated plasma LDL cholesterol of 17·8 mmol/L (14·7-20·8). The matched cohorts included 250 patients (125 patients per group), with a median untreated LDL cholesterol of 17·2 mmol/L (14·8-19·7). Mean reduction in plasma LDL cholesterol concentrations between baseline and final follow-up was greater in the lipoprotein apheresis group (-55% [95% CI -60 to -51] vs -31% [-36 to -25]; p<0·0001). Patients in the lipoprotein apheresis group had longer atherosclerotic cardiovascular disease-free survival (adjusted HR 0·52 [95% CI 0·32-0·85]) and longer cardiovascular death-free survival (0·0301 [0·0021-0·4295]). Cardiovascular death was more common in the pharmacotherapy-only group than in the lipoprotein apheresis group (ten [8%] vs one [1%]; p=0·010), whereas median age at coronary artery bypass grafting was lower in the lipoprotein apheresis group than in the pharmacotherapy-only group (15·0 years [IQR 12·0-24·0] vs 30·5 years [19·0-33·8]; p=0·037). Among patients with HoFH, lipoprotein apheresis initiated during childhood and adolescence is associated with reduced long-term risk of atherosclerotic cardiovascular disease and death, and clear benefits of early initiation of high-frequency treatment on reducing plasma cholesterol were found. Consensus recommendations are now needed to guide more widespread and timely use of lipoprotein apheresis for children with HoFH, and research is required to further optimise treatment and ensure benefits of early and aggressive treatment delivery are balanced against effects on quality of life. Amsterdam University Medical Centers, Location Academic Medical Center; Perelman School of Medicine at the University of Pennsylvania; European Atherosclerosis Society; and the US National Heart, Lung, and Blood Institute, National Institutes of Health.

Liver X receptor activation in chronic myelogenous leukemia cells yields distinct mass fingerprints by whole cell MALDI-TOF MS, which correspond to changes in cell viability, gene expression, and differentiation markers

Liver X receptor (LXR) agonists, including synthetic ligands or naturally-occurring oxysterols, exert promising lipid-modulating, anti-inflammatory, and anti-tumor effects. Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) whole cell mass spectrometry (MS) shows promise in chronic disease and food science research, clinical diagnostics of cancer cells and bacterial pathogens, and drug/nutraceutical discovery due to its relatively low-cost, rapid, reliable, and high-throughput ability to identify unique cell phenotypes and differentiation states of immune cells that play essential roles in chronic metabolic and inflammatory disease pathophysiology. However, optimization of whole cell MALDI-TOF MS-based methods to assess cellular changes in response to pharmaceutical and/or nutraceutical treatment warrants further study. Thus, we investigated whether whole cell MALDI-TOF MS could detect cellular phenotype changes of human stem-like erythroleukemia K562 cells – a model for chronic myelogenous leukemia (CML) – induced by the LXR agonist TO-901317, a synthetic ligand that mimics effects of naturally-occurring oxysterols, which are oxidized cholesterol derivatives formed under conditions of high cellular cholesterol concentrations and in food products. TO-901317 dose- and time-dependently altered mRNA expression of cholesterol flux genes, including ATP-binding cassette transporter A1 (ABCA1), LDL-receptor (LDLR), HMG-CoA reductase (HMGCR), and reduced cellular cholesterol content by 22.9% at 24 h. TO-901317 additionally dose- and time-dependently impacted K562 cell viability, number, size, and reduced mRNA expression of the anti-apoptotic gene BCL2L1 by 43.3%. These effects corresponded to induced gene expression of erythroid markers and hemoglobin content, suggesting that LXR activation may promote erythroid lineage differentiation. Whole cell MALDI-TOF MS mass fingerprinting revealed distinct proteomic phenotypes between TO-901317 vs. untreated cells, and identified histone 2 A and histone H4 as uniquely expressed proteins. These findings not only elucidate a novel role for LXR agonists in a model of CML, but demonstrate that mass fingerprints obtained by whole cell MALDI-TOF mass spectrometry effectively distinguish between treatment-induced cell phenotypes.

Biomarker signatures associated with ageing free of major chronic diseases: results from a population-based sample of the EPIC-Potsdam cohort.

A number of biomarkers denoting various pathophysiological pathways have been implicated in the aetiology and risk of age-related diseases. Hence, the combined impact of multiple biomarkers in relation to ageing free of major chronic diseases, such as cancer, cardiovascular disease and type 2 diabetes, has not been sufficiently explored. We measured concentrations of 13 biomarkers in a random subcohort of 2,500 participants in the European Prospective Investigation into Cancer and Nutrition Potsdam study. Chronic disease-free ageing was defined as reaching the age of 70years within study follow-up without major chronic diseases, including cardiovascular disease, type 2 diabetes or cancer. Using a novel machine-learning technique, we aimed to identify biomarker clusters and explore their association with chronic disease-free ageing in multivariable-adjusted logistic regression analysis taking socio-demographic, lifestyle and anthropometric factors into account. Of the participants who reached the age of 70years, 321 met our criteria for chronic-disease free ageing. Machine learning analysis identified three distinct biomarker clusters, among which a signature characterised by high concentrations of high-density lipoprotein cholesterol, adiponectin and insulin-like growth factor-binding protein 2 and low concentrations of triglycerides was associated with highest odds for ageing free of major chronic diseases. After multivariable adjustment, the association was attenuated by socio-demographic, lifestyle and adiposity indicators, pointing to the relative importance of these factors as determinants of healthy ageing. These data underline the importance of exploring combinations of biomarkers rather than single molecules in understanding complex biological pathways underpinning healthy ageing.

Dyslipidemia among adult HIV patients on antiretroviral therapy and its association with age and body mass index in Ethiopia: A systematic review and meta-analysis.

Dyslipidemia is a common public health problem in people living with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy and increases the risk of cardiovascular disease. Although evidence indicates that the prevalence of dyslipidemia is high, estimated pooled data are not well documented. Therefore, we aimed to estimate the pooled prevalence of dyslipidemia in adult people living with HIV receiving antiretroviral therapy in Ethiopia. We conducted a systematic review and meta-analysis of the literature. The following databases and grey literature were searched: PubMed, WorldCat, ScienceDirect, DOAG, African Journals Online, Google Scholar, and African Index Medicine. We included all comparative epidemiological studies that reported the prevalence of high concentration of total cholesterol, triglycerides, and low density lipoprotein, and low concentration of high density lipoprotein cholesterol that were published between January 2003 and July 2023. The random effects model was used to pool the outcome of interest. Additionally, subgrouping, sensitivity analyses, and funnel plots were performed. R software Version 4.2.1 was used for statistical analysis. Seventeen studies with a total of 3929 participants were included in the meta-analysis. The pooled prevalence of dyslipidemia, high total cholesterol, high triglyceride, elevated level of low density lipoprotein and low level of high density lipoprotein cholesterol were 69.32% (95% CI: 63.33, 74.72), 39.78% (95%CI: 32.12, 47.96), 40.32% (95%CI: 34.56, 46.36), 28.58% (95%CI: 21.81, 36.46), and 36.17% (95%CI: 28.82, 44.24), respectively. Age and body mass index were associated with high total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels. The authors concluded that the prevalence of dyslipidemia in Ethiopia is high in people living with HIV receiving antiretroviral therapy. Early detection of dyslipidemia and its integration into treatment are essential for preventing cardiovascular disease. Protocol registered with PROSPERO (CRD42023440125).

GROWTH PERFORMANCE AND LIPID PROFILE OF ARCHACHATINA MARGINATA (GIANT AFRICAN LAND SNAIL) FED VARYING LEVELS OF RIPE EGGPLANT FRUITS BASED DIETS

The performance of African giant land snails (Archachatina marginata) fed ripe eggplant fruits was studied using eighty-four (84) juvenile (four months old) Archachatina marginata for eight (8) weeks. The study evaluated the snails' growth performance and lipid profile (total cholesterol, low-density lipoprotein, high-density lipoprotein and triglycerides). The snails were divided into four treatment groups, with twenty-one (21) snails per group in a completely randomized design (CRD). Treatments 1, 2, 3 and 4 had varying levels of ripe eggplant fruits at 0%, 5%, 10% and 15% inclusion levels respectively. Isocaloric and isonitrogenous feeds and water were provided ad libitum, while other management practices were strictly adhered to. The results showed no significant differences (P&gt;0.05) in growth performance across treatments. The results also revealed that total cholesterol decreased (P&lt;0.05) significantly as the levels of ripe eggplant fruits increased across treatments. There were no significant differences (P&gt;0.05) in low-density lipoprotein and triglycerides, while high-density lipoprotein differed (P&lt;0.05) significantly across treatments. The result also showed a linear increase in high-density lipoprotein ("good" cholesterol) as the levels of ripe eggplant fruits increased across treatments. Therefore, a 15% inclusion level of ripe eggplant fruits in the diet of Archachatina marginata reduces total cholesterol levels and increases high-density lipoprotein without any adverse effect on growth. The study recommends using ripe eggplant fruits to formulate diets for animals with high cholesterol content and high levels of low-density lipoprotein in their meat.

Influence of lipid bilayer on the structure of the muscle-type nicotinic acetylcholine receptor

The muscle-type nicotinic acetylcholine receptor is a transmitter-gated ion channel residing in the plasma membrane of electrocytes and striated muscle cells. It is present predominantly at synaptic junctions, where it effects rapid depolarization of the postsynaptic membrane in response to acetylcholine released into the synaptic cleft. Previously, cryo-EM of intact membrane from Torpedo revealed that the lipid bilayer surrounding the junctional receptor has a uniquely asymmetric and ordered structure, due to a high concentration of cholesterol. It is now shown that this special lipid environment influences the transmembrane (TM) folding of the protein. All five submembrane MX helices of the membrane-intact junctional receptor align parallel to the surface of the cholesterol-ordered lipids in the inner leaflet of the bilayer; also, the TM helices in the outer leaflet are splayed apart. However in the structure obtained from the same protein after extraction and incorporation in nanodiscs, the MX helices do not align to a planar surface, and the TM helices arrange compactly in the outer leaflet. Realignment of the MX helices of the nanodisc-solved structure to a planar surface converts their adjoining TM helices into an obligatory splayed configuration, characteristic of the junctional receptor. Thus, the form of the receptor sustained by the special lipid environment of the synaptic junction is the one that mediates fast synaptic transmission; whereas, the nanodisc-embedded protein may be like the extrajunctional form, existing in a disordered lipid environment.

Electroformation of Giant Unilamellar Vesicles from Damp Lipid Films with a Focus on Vesicles with High Cholesterol Content.

Giant unilamellar vesicles (GUVs) are membrane models used to study membrane properties. Electroformation is one of the methods used to produce GUVs. During electroformation protocol, dry lipid film is formed. The drying of the lipid film induces the cholesterol (Chol) demixing artifact, in which Chol forms anhydrous crystals which do not participate in the formation of vesicles. This leads to a lower Chol concentration in the vesicle bilayers compared to the Chol concentration in the initial lipid solution. To address this problem, we propose a novel electroformation protocol that includes rapid solvent exchange (RSE), plasma cleaning, and spin-coating methods to produce GUVs. We tested the protocol, focusing on vesicles with a high Chol content using different spin-coating durations and vesicle type deposition. Additionally, we compared the novel protocol using completely dry lipid film. The optimal spin-coating duration for vesicles created from the phosphatidylcholine/Chol mixture was 30 s. Multilamellar vesicles (MLVs), large unilamellar vesicles (LUVs) obtained by the extrusion of MLVs through 100 nm membrane pores and LUVs obtained by extrusion of previously obtained LUVs through 50 nm membrane pores, were deposited on an electrode for 1.5/1 Chol/phosphatidylcholine (POPC) lipid mixture, and the results were compared. Electroformation using all three deposited vesicle types resulted in a high GUV yield, but the deposition of LUVs obtained by the extrusion of MLVs through 100 nm membrane pores provided the most reproducible results. Using the deposition of these LUVs, we produced high yield GUVs for six different Chol concentrations (from 0% to 71.4%). Using a protocol that included dry lipid film GUVs resulted in lower yields and induced the Chol demixing artifact, proving that the lipid film should never be subjected to drying when the Chol content is high.

Shrimp Lipids Inhibit Migration, Epithelial-Mesenchymal Transition, and Cancer Stem Cells via Akt/mTOR/c-Myc Pathway Suppression.

Shrimp is a rich source of bioactive molecules that provide health benefits. However, the high cholesterol content in shrimp oil may pose a risk. We utilized the cholesterol elimination method to obtain cholesterol-free shrimp lipids (CLs) and investigated their anticancer potential, focusing on cancer stem cells (CSCs) and epithelial-to-mesenchymal transition (EMT). Our study focused on CSCs and EMT, as these factors are known to contribute to cancer metastasis. The results showed that treatment with CLs at doses ranging from 0 to 500 µg/mL significantly suppressed the cell migration ability of human lung cancer (H460 and H292) cells, indicating its potential to inhibit cancer metastasis. The CLs at such concentrations did not cause cytotoxicity to normal human keratinocytes. Additionally, CL treatment was found to significantly reduce the levels of Snail, Slug, and Vimentin, which are markers of EMT. Furthermore, we investigated the effect of CLs on CSC-like phenotypes and found that CLs could significantly suppress the formation of a three-dimensional (3D) tumor spheroid in lung cancer cells. Furthermore, CLs induced apoptosis in the CSC-rich population and significantly depleted the levels of CSC markers CD133, CD44, and Sox2. A mechanistic investigation demonstrated that exposing lung cancer cells to CLs downregulated the phosphorylation of Akt and mTOR, as well as c-Myc expression. Based on these findings, we believe that CLs may have beneficial effects on health as they potentially suppress EMT and CSCs, as well as the cancer-potentiating pathway of Akt/mTOR/c-Myc.

GROWTH PERFORMANCE, CARCASS TRAITS, MEAT QUALITY AND HISTOCHEMICAL CHARACTERISTICS OF MUSCLE FIBERS IN MEXICAN HAIRLESS FINISHING PIGS SUPPLEMENTED WITH ORGANIC COPPER

&lt;p&gt;&lt;strong&gt;Background:&lt;/strong&gt; Pork meat is related to cardiovascular diseases, due to its high content of saturated fatty acids and cholesterol. But it has been shown that dietary supplementation of pigs with organic minerals benefits growth qualities and improves carcass and meat quality characteristics. &lt;strong&gt;Objective:&lt;/strong&gt; The objective was to evaluate the effect of Cu proteinate supplementation of finishing Mexican Hairless pigs (MHP) on growth, carcass characteristics, meat quality and muscle fiber composition. &lt;strong&gt;Methodology:&lt;/strong&gt; Twenty-eight castrated male MHP (62±5.2 kg BW) were randomly assigned to four levels of Cu in the diet (0, 75, 150, and 225 mg kg&lt;sup&gt;-1&lt;/sup&gt; DM) for 46 d. The DMI, DWG, FC and FE were measured. At the end of fattening, the pigs were slaughtered and the characteristics of the carcass were evaluated. Tissue samples of &lt;em&gt;Longissiumus thoracis&lt;/em&gt; (LT) were obtained and muscle fibers, pH, color, temperature and drip loss were evaluated. &lt;strong&gt;Results:&lt;/strong&gt; The DMI was reduced linearly (&lt;em&gt;P&lt;/em&gt;≤0.05) as Cu level supplementation increased in the diet. Growth performance was modified quadratically as Cu level supplementation was increased in the diet, as well as the highest DWG and the lowest FC values were found in barrows supplemented with 75 mg Cu kg&lt;sup&gt;-1&lt;/sup&gt; DM. Pigs supplemented with 75 and 150 mg Cu kg&lt;sup&gt;-1&lt;/sup&gt; DM had the highest (&lt;em&gt;P≤&lt;/em&gt;0.05) CW and LEA compared with the other treatments. BFT and DL decreased linearly (&lt;em&gt;P&lt;/em&gt;≤0.05) as Cu supplementation increased in the diet. The Cu supplementation affected (&lt;em&gt;P&lt;/em&gt;≤0.05) the color index &lt;em&gt;b&lt;/em&gt; and &lt;em&gt;h&lt;/em&gt; after 48h. The Cu affected (&lt;em&gt;P≤&lt;/em&gt;0.05) the number, composition and relative area of the type I, IIA and BII fibers of the LT. &lt;strong&gt;Implications: &lt;/strong&gt;Organic Cu supplementation in the diet of Mexican Hairless pigs benefits growth efficiency, carcass yield and backfat reduction; however, its effect on content, FA profile, and oxidative stability of IF meat should be analyzed. &lt;strong&gt;Conclusions:&lt;/strong&gt; It is concluded that Cu supplementation effected quadratically the values of Final BW, DWG, CW and LEA, and linearly Cu affected the values of DMI, FC, CCD, BFT, DL, pH, the color index &lt;em&gt;b&lt;/em&gt; and &lt;em&gt;h&lt;/em&gt; after 48h; treatments with Cu also influenced linearly or quadratically the number, composition and relative area of the type I, IIA and BII fibers of the LT post slaughter muscle metabolism and it may influence the parameters of quality of meat in finishing Mexican Hairless pigs. The production of MHP meat in an intensive fattening system is profitable and can be improved with the inclusion of Cu proteinate in the diet. &lt;/p&gt;

Dietary Energy Density Is Associated with Biomarkers of Chronic Diseases—A Cross-Sectional Study of School-Aged Children in Rural Mexico

BackgroundDietary energy density (DED) is associated with chronic disease markers in adults. However, results in children are still controversial. ObjectiveTo evaluate the DED of children and its association with obesity and biomarkers of chronic disease. MethodsIn this cross-sectional study, we recruited 284 children (6–10 y) from rural Mexico. Dietary intake was assessed using three 24-h recalls. DED was calculated for “foods only” (DEDfo) and for “foods and beverages” (DEDfb). Weight, height, and body fat percent (dual-energy X-ray absorptiometry) were measured. Inflammatory cytokines, lipid profile, leptin, and insulin resistance were determined from a fasting blood sample. ResultsDEDfo was 1.91 ± 0.36 kcal/g and DEDfb was 1.36 ± 0.31 kcal/g. Higher DEDfo and DEDfb were associated with higher risk to have insulin resistance [odds ratio (OR) = 3.92, 95% confidence interval (CI): 1.66, 9.22, P < 0.01; OR = 3.51, 95% CI: 1.25, 9.87, P = 0.02, respectively]. Higher DEDfo was associated with higher risk of higher leptin levels (OR = 3.17, 95% CI: 1.01, 10.23). Also, DEDfo and DEDfb were associated with higher concentrations of cholesterol (β = 11.67, 95% CI: 1.81, 19.53, P = 0.03; and β = 11.74, 95% CI: 2.69, 20.74 P = 0.01, respectively) and higher odds of having high insulin concentrations (OR = 2.52, 95% CI: 1.26, 5.06, P = 0.01; and OR = 2.95, 95% CI: 1.30, 6.70, P = 0.01). DEDfo and DEDfb were not associated with any measure of obesity and inflammatory cytokines in the adjusted models. ConclusionsDED was associated with higher leptin and cholesterol concentrations, and having insulin resistance, but not with any measure of obesity or inflammation. Reducing DED may reduce risk of cardiovascular disease and improve insulin sensitivity in school-aged children.

Associations of the triglyceride-glucose index and remnant cholesterol with coronary artery disease: a retrospective study

BackgroundRemnant cholesterol (RC) represents a low-cost and readily measured lipid index that contributes significantly to residual cardiovascular disease risk. The triglyceride-glucose (TyG) index exhibits a significant correlation with cardiovascular disease occurrence. However, RC and the TyG index have rarely been examined for their potentials in predicting coronary artery disease (CAD). Accordingly, the study was designed to validate the correlations of these two biomarkers with CAD and to compare the forecasted values of these two biomarkers for newly diagnosed CAD.MethodsTotally 570 subjects firstly administered coronary angiography were enrolled, including 431 newly diagnosed CAD cases and 139 individuals without CAD. The individuals were classified into two groups according to CAD diagnosis. RC was derived as total cholesterol content (mmol/L) – (high density lipoprotein cholesterol content + low density lipoprotein cholesterol content; both in mmol/L). The TyG index was determined as ln (fasting triglyceride level [mg/dL] × fasting plasma glucose level [mg/dL])/2.ResultsBaseline feature analysis revealed significant differences in RC and the TyG index between the CAD and non-CAD groups (both P < 0.001). RC and the TyG index were independent risk factors for CAD in accordance with logistic regression analysis (both P < 0.05). Moreover, spearman correlation analysis elucidated CAD had a more remarkable correlation with the TyG index compared with RC (both P < 0.001). Furthermore, according to receiver operating characteristic curve analysis, the TyG index was better than RC in predicting CAD.ConclusionsThe TyG index and RC have significant associations with CAD. Compared with RC, the TyG index possesses a closer correlation with CAD and a higher predictive value for CAD.

Eggs - a scoping review for Nordic Nutrition Recommendations 2023.

Cardiovascular diseases (CVD), type 2 diabetes (T2D), and cancer are a significant public health burden in the Nordic and Baltic countries. High intake of eggs, mainly due to its high cholesterol content, has been suggested to have adverse health effects. The purpose of this scoping review is to describe the evidence related to the impact of egg intake on health. A literature search identified 38 systematic reviews and meta-analyses on egg consumption in relation to health outcomes published between 2011 and 30 April 2022. Overall, current evidence from systematic reviews of randomized clinical trials indicates that higher egg intake may increase serum total cholesterol concentration and the ratio of low-density lipoprotein to high-density lipoprotein cholesterol, but with substantial heterogeneity in the response. However, recent evidence from observational studies does not provide strong support for a detrimental role of moderate egg consumption (up to one egg/day) on the risk of CVD, especially in the European studies. The overall evidence from observational studies indicates that egg consumption is not associated with increased risk of mortality or T2D in European study populations. There is also little support for a role of egg consumption in cancer development, although a weak association with higher risk of certain cancers has been found in some studies, mainly case-control studies. Again, no associations with cancer risk have been observed in European studies. Systematic reviews and meta-analyses of egg consumption in relation to other health-related outcomes are scarce. There are also limited data available on the associations between the consumption of more than one egg/day and risk of diseases. Based on the available evidence, one egg/day is unlikely to adversely affect overall disease risk.

Clustering of risk behaviours and associations between risk behaviours and cardio-metabolic risk factors in adult individuals with type 1 diabetes

AimsTo assess clustering of risk behaviours and their health determinants. MethodsCross-sectional health behaviour and health data were collected from individuals with type 1 diabetes, in the FinnDiane Study. Clustering of risk behaviours was assessed and associations between behaviours and health variables were investigated. ResultsData were available from 956 participants (40 % men, mean age 46 years). Altogether, 4.3 % individuals reported no risk behaviours, while 25.7 %, 37.4 %, 24.7 %, 6.8 %, and 1.0 % reported 1, 2, 3, 4, and 5 risk behaviours, respectively. Reporting ≥4 risk behaviours occurred more frequently than expected by chance. Dietary non-adherence was most frequently reported (84.4 %), followed by low LTPA (54.4 %), poor sleep (41.9 %), high alcohol consumption (15.2 %), and smoking (11.2 %). Adjusted for confounders, relative to ≤1 risk behaviour, reporting ≥2 risk behaviours was associated with higher BMI, waist circumference, and diastolic blood pressure. Having ≥3 risk behaviours was associated with larger waist-hip ratio, and higher HbA1c and triglyceride concentration; ≥4 risk behaviours was associated with higher cholesterol concentration. Of the health behaviours, low LTPA had the highest number of deleterious health associations. ConclusionsAccumulation of risk behaviors increases negative health outcomes. Exhibiting ≥2 risk behaviours or low LTPA was associated with multiple adverse outcomes.

Applications of phase-separating multi-bilayers in protein-membrane domain interactions.

Synthetic model membranes are important tools to elucidate lipid domain and protein interactions due to predefined lipid compositions and characterizable biophysical properties. Here, we introduce a model membrane with multiple lipid bilayers (multi-bilayers) stacked on a mica substrate that is prepared through a spin-coating technique. The spin-coated multi-bilayersare useful in the study of phase separated membranes with a high cholesterol content, mobile lipids, microscopic and reversible phase separation, and easy conjugation with proteins, which make them a good model to study interactions between proteins and membrane domains.

Enhanced sensitivity in Staphylococcus aureus detection: Unveiling the impact of lipid composition on the performance of carboxyfluorescein (CF)-Loaded liposome-based assay

Liposomes have emerged as versatile nanocarriers, finding applications not only in drug delivery but also in pathogen detection and diagnostics. This study aimed to enhance the sensitivity of liposomes to Staphylococcus aureus by investigating the impact of lipid composition on liposomes loaded with 5(6)-carboxyfluorescein (CF). Liposomes were fabricated using various concentrations of cholesterol (10–40 mol%) combined with saturated phospholipids. Dynamic light scattering results revealed that higher cholesterol concentrations led to reduced liposome size, CF release (%), and entrapment efficiency (%). Liposome sensitivity towards S. aureus was evaluated by using CF-loaded liposomes with and without aptamer insertion. Liposomes with a higher cholesterol content (40 mol%) exhibited a strong ability to detect low bacterial concentrations down to 5 × 102 CFU/mL without relying solely on specific receptor-ligand recognition. However, functionalizing the liposome with an aptamer further improved the specificity and sensitivity of S. aureus detection at even lower concentrations, down to 80 CFU/mL, in the wide range of 80–107 CFU/mL. This study highlights the potential for optimizing the lipid composition of liposomes to improve their sensitivity for pathogen detection, particularly when combined with aptamer-based strategies.

Familial hypercholesterolemia and its manifestations: Practical considerations for general practitioners.

Familial hypercholesterolemia (FH) is the most common genetic disorder of lipid metabolism, affecting almost 1 in 250 individuals worldwide. It is usually inherited via the autosomal dominant way and is characterized by aberrantly high total and low-density lipoprotein cholesterol (LDL-C) concentrations from early childhood, predisposing to increased risk of premature atherosclerotic cardiovascular disease (ASCVD), mostly coronary heart disease (CHD). Despite its high prevalence in the general population and the high ASCVD risk, FH is often underdiagnosed and undertreated. Genetic diagnosis is not always necessary, since specific criteria, taking into account the patient's individual and family history, clinical signs and untreated LDL-C concentrations, may be used for prompt diagnosis. Except for CHD, which may be already evident at diagnosis, leading to increased mortality, other non-CHD morbidities, such as stroke, peripheral artery disease, carotid artery stenosis and aortic valve calcification may be also present, substantiating the need for prompt intervention. Statins constitute the mainstay of treatment both in adults and children >8 years old. In cases of statin intolerance or not achieving the LDL-C target despite maximal tolerated statin dose, ezetimibe and/or proprotein convertase subtilisin-kexin type 9 inhibitors may be used. The advent of the recently approved medications, such as inclisiran and bempedoic acid, either as monotherapy or as add-on-therapy to statins, has further enhanced the therapeutic armamentarium in patients with FH. The purpose of this narrative review is to provide practical considerations regarding the diagnostic and therapeutic approach of patients with FH.

Self-Association of Von Willebrand Factor (VWF) into Prothrombotic Fibers Is Most Potently Enhanced By the Highly Atherogenic Small, Dense Fraction of Low-Density Lipoprotein (sd-LDL)

We recently demonstrated that plasma lipoproteins play a major role in regulating the function of the hemostatic system by either inhibiting or promoting the self-association of von Willebrand factor (VWF) into large fibers and bundles that are hyperadhesive for platelets. Such fibers can form on the surface of activated endothelium such as during thrombotic microangiopathies. We showed that high-density lipoprotein (HDL) attenuates VWF self-association and reduces the formation of VWF-platelet thrombi, both in vitro and in mice (PMID:26552698). By contrast, low-density lipoprotein (LDL) enhances VWF self-association and promotes the formation of VWF-platelet thrombi ( Blood, in press). Consequently, wild-type mice with elevated plasma LDL display intense and prolonged VWF-platelet thrombosis in stimulated mesenteric microvessels, exceeding even the thrombosis observed in ADAMTS13-deficient mice with normal LDL levels. All the lipoproteins of low density carry apolipoprotein (apo) B100 and comprise fractions of very low density (VLDL), intermediate density (IDL), and low density (LDL). The LDL fraction comprises two subfractions: small-dense (sd) LDL and large-buoyant (lb) LDL. Epidemiologic studies suggest that sd-LDL is the most atherogenic subfraction (PMID:33586462). Another atherogenic lipoprotein also carries apoB-100, Lp(a), in which the apoB-100 is complexed with apo(a). Here, we sought to determine the effect of LDL subfraction(s) on VWF self-association. We isolated LDL, sd-LDL and lb-LDL from healthy donor plasma by sequential KBr density centrifugation. Lp(a) was purified from patients with high circulating Lp(a) (&amp;gt;50 mg/dL) as described by Mueller et al. (PMID:35650291). We first tested these lipoproteins in microfluidic devices adapted from the design of Herbig and Diamond (PMID:26178390). In these devices, high shear stress and flow acceleration are generated around a 30-um-wide pillar within a 60-um-wide flow channel and induce the attachment and self-association of VWF into fibers on and around the pillar. We quantified VWF fiber accumulation from differential interference contrast (DIC) images. Of all the lipoprotein fractions, sd-LDL was the most potent in accelerating VWF strand accumulation (see figure). The effect of lipoproteins in this device correlated with their impact on microvascular thrombosis in vivo. We infused apoB100-containing lipoproteins into wild-type mice (3-4 weeks old) before inducing VWF-platelet thrombi deposition in the mesenteric microvasculature with ionophore. All the apoB100 lipoproteins enhanced microvascular thrombosis [we did not test Lp(a), which had no effect in the microfluidic channel], but sd-LDL was by far the most potent; the treated mice had twice the number of large thrombi (&amp;gt;30-um diameter) as the mice treated with an equivalent quantity of lb-LDL. The effect also persisted for much longer before returning to baseline with the sd-LDL. We have explored possible reasons why sd-LDL is so much more potent. Compared to the other apoB-containing lipoproteins, sd-LDL is smaller and denser, with a greater surface curvature. Whether this fact changes accessibility to sites on apoB100 is not known. We also compared the lipidomes and proteomes of sd-LDL and lb-LDL for clues to the difference. Compared to lb-LDL, sd-LDL contained a much higher content of cholesterol and cholesterol esters per particle. The proteomes of the two particles were also different, with several proteins being more abundant in lb-LDL, in particular apoC-III, apoE, apoA-IV, and apoC-II. Only apoF was significantly more abundant in sd-LDL. We are currently testing to determine if any of these difference accounts for the differences between the two LDL subfractions in promoting VWF self-association. In summary, we show that the lipoprotein associated with the greatest atherosclerotic burden and most cardiovascular disease is also the one with the most potent effect in promoting a prothrombotic state by enhancing VWF self-association. These findings have important implications for the development of the atherosclerotic lesion, the formation of the thrombus after the lesion ruptures, and for the microvascular dysfunction often observed after revascularization.

Comparative analysis, potential benefits, and safety of milk from five commercially milk-producing mammals

Milk production is a key feature of the Mammalia class. This study summarizes the characteristics of milk produced by the main dairy industry mammals: cows, buffalo, goats, sheep, and camels. The study compares their physical and chemical constituents, therapeutic benefits, and allergenicity and safety. The optimal milk for different situations can be identified using nutritional, medicinal, and safety studies.Cow milk is the most widely produced globally, accounting for more than eighty percent of the milk produced. Buffalo and sheep milk contain significantly more lactose than cow and goat milk. Bovine and bison milk have the highest cholesterol concentration. Goat milk has a higher fat content, while camel milk has fewer adverse effects.Consumption of cow or buffalo milk may induce minor allergic reactions; however, milk can also ease certain allergy problems. Sheep milk can benefit those with eczema and asthma. This research can help achieve a balanced utilization of varied milk varieties. The study aids consumers in choosing the right milk by investigating and comparing their commercial viability to cellular milk and other types of commercially accessible milk.In conclusion, the study highlights the advantages and disadvantages of different types of milk produced by the main dairy industry mammals. The choice of milk can depend on various factors such as nutritional content, allergenicity, and safety concerns. This research can help consumers make an informed choice regarding the optimal milk for different situations, which can aid in achieving a balanced utilization of varied milk varieties.

Lipids, lipoproteins, and apolipoproteins during the first year of life: a prospective cohort study

Abstract Background/Introduction Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally, and treatment of well-established lifestyle risk factors are cornerstones in CVD prevention. An atherogenic lipid profile with high concentrations of low-density lipoprotein (LDL) cholesterol and other apolipoprotein B containing lipoproteins is a driving force in the pathogenesis of atherosclerotic CVD (ASCVD). The lifelong atherosclerotic process is proportional to concentrations of apolipoprotein B-containing lipoproteins, hence risk of developing ASCVD is cumulative over time. The higher the baseline concentrations, the sooner the threshold for increased risk of ASCVD will be reached. It is therefore crucial to implement changes as early as possible and prevent risk factors in occurring – so-called primordial prevention. Childhood has been described as a "window of opportunity" for preventing risk factors in occurring and thus avoiding ASCVD. Whether concentrations of atherogenic lipoproteins at birth can predict future concentrations in early childhood and thus may indicate increased risk of dyslipidemia later in life remains unknown. Purpose The aim of the present study was to investigate atherogenic lipid traits during the first year of life, to identify influential factors for lipid concentrations, and to determine whether concentrations at birth can predict future lipid concentrations in early childhood. Methods For this purpose, we used the Copenhagen Baby Heart Study comprising more than 13,000 umbilical cord blood samples and parallel venous blood samples from children and parents at birth (n=444), at two months (n=363), and at 14-16 months (n=158). Lipid traits were determined in all samples. Results Concentrations of low-density lipoprotein (LDL) cholesterol, non-high-density lipoprotein (HDL) cholesterol, and apolipoprotein B increased during the first year of life. Girls had higher concentrations at birth and at two months compared with boys. Children born preterm had higher cord blood concentrations than children born at term. A linear mixed model showed that high concentrations of LDL cholesterol, non-HDL cholesterol and apolipoprotein B at birth predicted high concentrations at two months and at 14-16 months. Multivariable adjusted odds ratios (95% CI) for having high concentrations at two months when children had high concentrations at birth were 1.95 (1.01-3.79) for LDL cholesterol, 1.36 (0.69-2.67) for non-HDL cholesterol and 1.90 (1.02-3.53) for apolipoprotein B. Conclusion The lipid profile change during the first year of life and sex and gestational age influence concentrations. Children with high concentrations of LDL cholesterol, non-HDL cholesterol and apolipoprotein B at birth had higher levels at two and at 14-16 months. Concentrations at birth may thus be used to identify children at risk of dyslipidemia in later life.