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Chronic feeding of a high fat diet (HFD) in preclinical species induces broad metabolic dysfunction characterized by body weight gain, hyperinsulinemia, dyslipidemia and impaired insulin sensitivity. The plasma lipidome is not well characterized in dogs with HFD-induced metabolic dysfunction. We therefore aimed to describe the alterations that occur in the plasma lipid composition of dogs that are fed a HFD and examine the association of these changes with the clinical signs of metabolic dysfunction. Dogs were fed a normal diet (ND) or HFD for 12 weeks. Insulin sensitivity (SI) and beta cell compensation (AIRG) were assessed through an intravenous glucose tolerance test (IVGTT) and serum biochemistry was analyzed before the introduction of HFD and again after 12 weeks of continued ND or HFD feeding. Plasma lipidomics were conducted prior to the introduction of HFD and again at week 8 in both ND and HFD-fed dogs. 12 weeks of HFD feeding resulted in impaired insulin sensitivity and increased beta cell compensation measured by SI (ND mean: 11.5 [mU/l]–1 min–1, HFD mean: 4.7 [mU/l]–1 min–1) and AIRG (ND mean: 167.0 [mU/l]min, HFD mean: 260.2 [mU/l]min), respectively, compared to dogs fed ND over the same duration. Chronic HFD feeding increased concentrations of plasma lipid species and deleterious fatty acids compared to dogs fed a ND. Saturated fatty acid (SFA) concentrations were significantly associated with fasting insulin (R2 = 0.29), SI (R2 = 0.49) and AIRG (R2 = 0.37) in all dogs after 12 weeks, irrespective of diet. Our results demonstrate that chronic HFD feeding leads to significant changes in plasma lipid composition and fatty acid concentrations associated with metabolic dysfunction. High SFA concentrations may be predictive of deteriorated insulin sensitivity in dogs. [ABSTRACT FROM AUTHOR]

Objective: Statin treatment compliance and achieving target levels differ between populations. This study aimed to determine the status of achieving the lipid targets and evaluate patients' compliance to statin treatment in type 2 diabetic patients with dyslipidemia. Method: This cross-sectional study included type 2 diabetes mellitus (T2DM) patients with dyslipidemia who applied for treatment at our polyclinics. Statin compliance was evaluated using the Modified Morisky Adherence Scale (MMAS-8) through a face-to-face interview. Cardiovascular (CV) risk was calculated according to the 2019 ESC (European Society of Cardiology) criteria by evaluating the patients' individual risk factors. LDL targets were determined according to risk categories with the same criteria. Results: A total of 504 patients (F/M: 274/230) were included. The serum LDL levels were 102.6 ± 39.2 mg/dL. Of the patients, 56.1% were under statin treatment. CV risk was very high in 73.6% of patients. LDL levels were significantly lower in users than in non-users (91.2 ± 26.0, 117.3 ± 38.4, p < 0.0001). The rate of reaching the LDL target was 14.8% in statin users. Treatment compliance was low for 40.6% of statin users. Discontinuation of statin treatment due to side effects was 15.7% (n = 14). N = 49 patients willingly discontinued statin treatment. They reported that 40.8% considered the treatment unnecessary. Conclusion: It was observed that 56.1% of type 2 diabetic patients were on statin therapy. A small percentage of them 14.8% (n = 42) reached the LDL target. Statin non-compliance and a lack of awareness of the statin treatment are the main reasons for high LDL levels in type 2 diabetic patients. [ABSTRACT FROM AUTHOR]

Whole-body vibration (WBV), a training method based on the stimulation of muscle contraction by mechanical vibration generated in a vibrating platform, is claimed to be effective in diabetes management. This meta-analysis evaluated WBV effects against other exercises, placebo, or no intervention in type-2 diabetes. Medline, Scopus, and Web of Science databases were systematically searched through June 2023. Randomized controlled trials reported the effect of WBV on glucose (hemoglobin A1C and fasting blood glucose), and lipid profiles (total cholesterol, triglycerides, high, and low-density lipoprotein) were included. Two researchers independently extracted the characteristics of the studies, participants, WBV intervention and comparisons, and the outcomes from the included articles. The Physiotherapy Evidence Database (PEDro) scale assessed trial quality. In this review, all articles had no high risk of bias according to the PEDro scale, with studies achieving optimal, excellent, and good scores. Network meta-analysis revealed that WBV was effective for reducing hemoglobin A1C when compared with conventional (mean difference: − 1.58%, 95%CrI: − 2.51, − 0.47) and resistance exercise (mean difference: − 1.32%, 95%CrI: − 1.96, − 0.33). WBV had also a desirable but insignificant effect on hemoglobin A1C compared to stretching and balance exercises, placebo, and no intervention. The current pairwise meta-analysis did not show that WBV favors fasting blood glucose and lipids. WBV may have potential advantages for glycemic control in type-2 diabetes. However, uncertainties in the findings remain due to the limited number of studies and their heterogeneity. [ABSTRACT FROM AUTHOR]

Diosgenin (DG), a well-known steroidal sapogenin, is abundantly found in the plants of the Dioscoreaceae family and exhibits diverse pharmacological properties. In our previous study, we demonstrated that DG supplementation protected Caenorhabditis elegans from high glucose-induced lipid deposition, oxidative damage, and lifespan reduction. Nevertheless, the precise biological mechanisms underlying the beneficial effects of DG have not yet been described. In this context, the present study aims to elucidate how DG reduces molecular and cellular declines induced by high glucose, using the powerful genetics of the C. elegans model. Treatment with DG significantly (p < 0.01) prevented fat accumulation and extended lifespan under high-glucose conditions without affecting physiological functions. DG-induced lifespan extension was found to rely on longevity genes daf-2, daf-16, skn-1, glp-1, eat-2, let-363, and pha-4. Specifically, DG regulates lipophagy, the autophagy-mediated degradation of lipid droplets, in C. elegans, thereby inhibiting fat accumulation. Furthermore, DG treatment did not alter the triglyceride levels in the fat-6 and fat-7 single mutants and fat-6;fat-7 double mutants, indicating the significant role of stearoyl-CoA desaturase genes in mediating the reduction of fat deposition by DG. Our results provide new insight into the fat-reducing mechanisms of DG, which might develop into a multitarget drug for preventing obesity and associated health complications; however, preclinical studies are required to investigate the effect of DG on higher models. [ABSTRACT FROM AUTHOR]

Calcification of aortic valve leaflets is a growing mortality threat for the 18 million human lives claimed globally each year by heart disease. Extensive research has focused on the cellular and molecular pathophysiology associated with calcification, yet the detailed composition, structure, distribution and etiological history of mineral deposition remains unknown. Here transdisciplinary geology, biology and medicine (GeoBioMed) approaches prove that leaflet calcification is driven by amorphous calcium phosphate (ACP), ACP at the threshold of transformation toward hydroxyapatite (HAP) and cholesterol biomineralization. A paragenetic sequence of events is observed that includes: (1) original formation of unaltered leaflet tissues: (2) individual and coalescing 100’s nm- to 1 μm-scale ACP spherules and cholesterol crystals biomineralizing collagen fibers and smooth muscle cell myofilaments; (3) osteopontin coatings that stabilize ACP and collagen containment of nodules preventing exposure to the solution chemistry and water content of pumping blood, which combine to slow transformation to HAP; (4) mm-scale nodule growth via ACP spherule coalescence, diagenetic incorporation of altered collagen and aggregation with other ACP nodules; and (5) leaflet diastole and systole flexure causing nodules to twist, fold their encasing collagen fibers and increase stiffness. These in vivo mechanisms combine to slow leaflet calcification and establish previously unexplored hypotheses for testing novel drug therapies and clinical interventions as viable alternatives to current reliance on surgical/percutaneous valve implants. [ABSTRACT FROM AUTHOR]

Nesfatin-1 (NESF-1) has been shown to modulate lipid metabolism. We have identified a nesfatin-1-like-peptide (NLP) processed from a related precursor nucleobindin 1 (NUCB1). Here we determined if NLP, like NESF-1, regulates lipid accumulation in vitro, and tested if the disruption of nucb1 gene affects hepatic lipid metabolism genes in mice. Hepatocytes (HepG2/C3A cells) express NLP and NESF-1 and both peptides significantly reduced lipogenic enzyme mRNAs and enhanced beta-oxidation enzyme mRNAs. Lipid contents in oleic acid induced HepG2/C3A cells were attenuated by NESF-1 and NLP. The inhibitory effect on cellular lipid content was blocked by compound C, an inhibitor of AMPK. The disruption of nucb1 gene affected lipid metabolism-related enzyme mRNAs, endogenous nucb2 mRNA and AMPK phosphorylation. The lipid-lowering effects identified here highlights the potential of nucleobindins and peptides processed from them to address lipid disorders, and its possible benefits in metabolic disease management. Nesfatin-1 and nesfatin-1-like peptide reduced lipid content in oleic acid-induced HepG2/C3A cells, an effect that was blocked by an AMPK inhibitor compound C. This highlights the therapeutic potential for nesfatin-1 and NLP in lipid disorders. [ABSTRACT FROM AUTHOR]

The use of new materials in the field of biofuel production has been represented as a step in the development of remarkable catalysts. The use of lipases in the production of biodiesel is often seen as a cost-limiting step, as the operating expenses in recovering such catalysts can lead to unfeasible market expectations. In this study, hydroxyapatite (HAp) particles were evaluated as a support to immobilize commercial lipase, following application in ethyl ester synthesis. First, hydroxyapatite was synthesized through the co-precipitation method at constant pH and selected as a support to be used in enzyme immobilization. The characterization of the biocatalyst support materials produced was carried out using DRX, BET, FTIR, TGA, and SEM analysis. The lipase from Thermomyces lanuginosus was then immobilized in the matrices, and, subsequently, there was transesterification of the vegetable oil deodorization distillate (VODD). The biodiesel samples generated showed that they were within commercial standards, achieving ester conversion greater than 96.5%. Other properties such as density (0.87 g.cm−3) and viscosity (4.36 mm2.s−1) meet the specifications required by ASTM to be used as a biofuel. In the experiment planning technique, the results revealed an experimental trend and a defined behavior: a higher lipase loading in the immobilization and the use of temperatures in the range of 40–50 °C favor high conversions of ethyl esters. Thus, this confirms that the enzymatic chemical catalyst was able to form the main fatty acid esters even using a residual lipid raw material. [ABSTRACT FROM AUTHOR]

Lipid nanoparticles (LNPs) have emerged as promising platforms for efficient in vivo mRNA delivery owing to advancements in ionizable lipids. However, maintaining the thermostability of mRNA/LNP systems remains challenging. While the importance of only a small amount of lipid impurities on mRNA inactivation is clear, a fundamental solution has not yet been proposed. In this study, we investigate an approach to limit the generation of aldehyde impurities that react with mRNA nucleosides through the chemical engineering of lipids. We demonstrated that piperidine-based lipids improve the long-term storage stability of mRNA/LNPs at refrigeration temperature as a liquid formulation. High-performance liquid chromatography analysis and additional lipid synthesis revealed that amine moieties of ionizable lipids play a vital role in limiting reactive aldehyde generation, mRNA–lipid adduct formation, and loss of mRNA function during mRNA/LNP storage. These findings highlight the importance of lipid design and help enhance the shelf-life of mRNA/LNP systems. Piperidine-based ionizable lipids avoid the formation of mRNA–lipid adduct that is responsible for the loss-of-function of mRNA and contribute to the long-term storage stability of mRNA/LNPs as a wet preparation. [ABSTRACT FROM AUTHOR]

Breast cancer, a leading cause of female mortality due to delayed detection owing to asymptomatic nature and limited early diagnostic tools, was investigated using a multi-modal approach. Plasma-derived small EVs from breast cancer patients (BrCa, n = 74) and healthy controls (HC, n = 30) were analyzed. Small EVs (n = 104), isolated through chemical precipitation, underwent characterization via transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Validation involved antibody-based tests (TSG101, CD9, CD81, CD63). Infrared spectra of small EVs were obtained, revealing significant differences in lipid acyl chains, particularly in the C–H stretching of CH3. The study focused on the lipid region (3050–2900 cm−1), identifying peaks (3015 cm−1, 2960 cm−1, 2929 cm−1) as distinctive lipid characteristics. Spectroscopic lipid-to-lipid ratios [(I3015/I2929), (I2960/I2929)] emerged as prominent breast cancer markers. Exploration of protein, nucleic acid, and carbohydrate ratios indicated variations in alpha helices, asymmetric C–H stretching vibrations, and C–O stretching at 1033 cm−1. Principal component analysis (PCA) successfully differentiated BrCa and HC small EVs, and heatmap analysis and receiver operating characteristic (ROC) curve evaluations underscored the discriminatory power of lipid ratios. Notably, (I2960/I2929) exhibited 100% sensitivity and specificity, highlighting its potential as a robust BrCa sEV marker for breast cancer detection. [ABSTRACT FROM AUTHOR]

Human pharmaceuticals represent a major challenge in natural environment. A better knowledge on their mechanisms of action and adverse effects on cellular pathways is fundamental to predict long-term consequences for marine wildlife. The FTIRI Imaging (FTIRI) spectroscopy represents a vibrational technique allowing to map specific areas of non-homogeneous biological samples, providing a unique biochemical and ultrastructural fingerprint of the tissue. In this study, FTIRI technique has been applied, for the first time, to characterize (i) the chemical building blocks of digestive glands of Mytilus galloprovincialis, (ii) alterations and (iii) resilience of macromolecular composition, after a 14-days exposure to 0.5 µg/L of carbamazepine (CBZ), valsartan (VAL) and their mixture, followed by a 14-days recovery period. Spectral features of mussels digestive glands provided insights on composition and topographical distribution of main groups of biological macromolecules, such as proteins, lipids, and glycosylated compounds. Pharmaceuticals caused an increase in the total amount of protein and a significant decrease of lipids levels. Changes in macromolecular features reflected the modulation of specific molecular and biochemical pathways thus supporting our knowledge on mechanisms of action of such emerging pollutants. Overall, the applied approach could represent an added value within integrated strategies for the effects-based evaluation of environmental contaminants. [ABSTRACT FROM AUTHOR]

Lipid oxidation in emulsions is hypothesised to increase with decreasing droplet size, as this increases the specific oil–water interfacial area, where lipid oxidation is expected to be initiated. In literature, however, contradictory results have been reported, which can be caused by confounding factors such as the oil droplet polydispersity and the distribution of components between the available phases. In this work, monodisperse surfactant-stabilised emulsions with highly controlled droplet sizes of 4.7, 9.1, and 26 µm were produced by microfluidic emulsification. We show that lipid oxidation increases with decreasing droplet size, which we ascribe to the increased contact area between lipids and continuous phase prooxidants. Besides, a significant amount of oxygen was consumed by oxidation of the surfactant itself (Tween 20), an effect that also increased with decreasing droplet size. These insights substantiate the importance of controlling droplet size for improving the oxidative stability of emulsions. [ABSTRACT FROM AUTHOR]

The ability of the Torpedo nicotinic acetylcholine receptor (nAChR) to undergo agonist-induced conformational transitions requires the presence of cholesterol and/or anionic lipids. Here we use recently solved structures along with multiscale molecular dynamics simulations to examine lipid binding to the nAChR in bilayers that have defined effects on nAChR function. We examine how phosphatidic acid and cholesterol, lipids that support conformational transitions, individually compete for binding with phosphatidylcholine, a lipid that does not. We also examine how the two lipids work synergistically to stabilize an agonist-responsive nAChR. We identify rapidly exchanging lipid binding sites, including both phospholipid sites with a high affinity for phosphatidic acid and promiscuous cholesterol binding sites in the grooves between adjacent transmembrane α-helices. A high affinity cholesterol site is confirmed in the inner leaflet framed by a key tryptophan residue on the MX α-helix. Our data provide insight into the dynamic nature of lipid-nAChR interactions and set the stage for a detailed understanding of the mechanisms by which lipids facilitate nAChR function at the neuromuscular junction. Multiscale molecular dynamics simulations reveal rapidly exchanging lipid binding sites on the nicotinic acetylcholine receptor, including sites with high affinity for phosphatidic acid and promiscuous cholesterol sites in inter-α-helix grooves. [ABSTRACT FROM AUTHOR]

Drosophila melanogaster is unique among animal models because it has a fully defined synthetic diet available to study nutrient-gene interactions. However, use of this diet is limited to adult studies due to impaired larval development and survival. Here, we provide an adjusted formula that reduces the developmental period, restores fat levels, enhances body mass, and fully rescues survivorship without compromise to adult lifespan. To demonstrate an application of this formula, we explored pre-adult diet compositions of therapeutic potential in a model of an inherited metabolic disorder affecting the metabolism of branched-chain amino acids. We reveal rapid, specific, and predictable nutrient effects on the disease state consistent with observations from mouse and patient studies. Together, our diet provides a powerful means with which to examine the interplay between diet and metabolism across all life stages in an animal model. [ABSTRACT FROM AUTHOR]

Trace metals are naturally occurring metals found in very small concentrations in the environment. In the context of fish flesh, metals such as copper, calcium, potassium, sodium, zinc, iron, and manganese are absorbed by fish and play vital roles in various physiological functions. However, if these metals exceed the recommended limits set by WHO/FAO, they are termed 'toxic metals' due to their harmful impacts on both the fish and its consumers. Therefore, the present study aims to analyze the levels of protein, lipids, and certain metals—Aluminum (Al), Sodium (Na), Zinc (Zn), Titanium (Ti), Iron (Fe), Copper (Cu), Potassium (K), and Calcium (Ca) in three commercially important marine fishes i.e. Rastrelliger kanagurta, Sardinella abella, and Otolithes ruber. The study also aims to assess their potential impact on human health. The macro-Kjeldhal method and Soxhlet apparatus were used to estimate protein and lipid contents, while atomic absorption spectroscopy (AAS) was used to estimate trace metals found in fishes. The study found that these fish species are valuable sources of protein, lipids, and certain essential minerals. The protein content (CP) in these three species ranged from 63.35 to 86.57%, while lipid content was from 21.05 to 23.86%. The overall results of the trace metal concentrations analyzed in the present study revealed that Aluminum (Al), Sodium (Na), Zinc (Zn), Titanium (Ti), Copper (Cu), Potassium (K), and Calcium (Ca) were found in low concentration or traces and also within suitable ranges as set by WHO/FAO. However, Iron (Fe) was absent in all three species. Moreover, both copper and potassium were found in all three species, while Zinc was present in Rastrelliger kanagurta and Sardinella abella, calcium in Sardinella abella, and sodium in Otolithes ruber only. Titanium was recorded for the first time in S. abella. However, the total health risk assessment associated with these fish food consumption was measured by THQ and TTHQ and found to be less than 1, which shows no potential risk related to trace metals found in these fishes on human health upon their consumption. In conclusion, these commercially important marine fish species were found valuable sources of protein, lipids, and essential trace minerals that are necessary for human health. Thus, the current study provides useful information for the local population to make informed decisions about their daily diets and highlights the importance of sustainable fishing practices to maintain these valuable marine resources by periodical monitoring of their ecosystem. [ABSTRACT FROM AUTHOR]

Previous studies found lipid levels, especially triglycerides (TG), are associated with acute pancreatitis, but their causalities and bi-directions were not fully examined. We determined whether abnormal levels of TG, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) are precursors and/or consequences of acute pancreatitis using bidirectional two-sample Mendelian randomization (MR) with two non-overlapping genome-wide association study (GWAS) summary statistics for lipid levels and acute pancreatitis. We found phenotypic associations that both higher TG levels and lower HDL-C levels contributed to increased risk of acute pancreatitis. Our GWAS meta-analysis of acute pancreatitis identified seven independent signals. Genetically predicted TG was positively associated with acute pancreatitis when using the variants specifically associated with TG using univariable MR [Odds ratio (OR), 95% CI 2.02, 1.22–3.31], but the reversed direction from acute pancreatitis to TG was not observed (mean difference = 0.003, SE = 0.002, P-value = 0.138). However, a bidirectional relationship of HDL-C and acute pancreatitis was observed: A 1-SD increment of genetically predicted HDL-C was associated with lower risk of acute pancreatitis (OR, 95% CI 0.84, 0.76–0.92) and genetically predisposed individuals with acute pancreatitis have, on average, 0.005 SD lower HDL-C (mean difference = − 0.005, SE = 0.002, P-value = 0.004). Our MR analysis confirms the evidence of TG as a risk factor of acute pancreatitis but not a consequence. A potential bidirectional relationship of HDL-C and acute pancreatitis occurs and raises the prospect of HDL-C modulation in the acute pancreatitis prevention and treatment. [ABSTRACT FROM AUTHOR]

Microalgae-derived biochemicals and biofuels offer a sustainable alternative to petroleum-based products, with algal lipids being highly valuable due to their energy content and renewable characteristics. In this study, the lipid production potential and growth and lipid production kinetics of Leptolyngbya subtilis JUCHE1 under photo-heterotrophic conditions have been investigated using glycerol as a carbon source. The concentration of glycerol was systematically varied from 0.04 g/L to 0.15 g/L (Equivalent to C-concentrations for different inlet-CO2 concentrations in the gas phase i.e. 5-20%v/v). The growth behaviour of L. subtilis JUCHE1, including the values of biomass concentration and specific growth rate were found to be 0.81 g/L and 0.71 d−1 respectively. The findings demonstrate that L. subtilis JUCHE1, a power plant blue-green alga, shows adaptability to utilize an organic carbon source (glycerol) instead of its usual substrate i.e. inorganic carbon source (CO2). The incorporation of glycerol enhances the growth and lipid yields of L. subtilis JUCHE1, offering a cost-effective and environmentally friendly approach. The kinetics follow both the Monod model and Luong type power law model in uninhibited (up to 0.11g/L glycerol) and inhibited growth regimes respectively having µmax, KS, and KI values of 0.88 d−1, 0.03 g/L, and 0.49 g/L. The lipid generation is growth-associated and kinetics follow the Luedeking Piret model. The characterization of lipids produced by Leptolyngbya subtilis JUCHE1 under heterotrophic conditions shows the presence of many valuable biochemical like Eicosenoic acid, Hexadecenoic acid, Glycidol, Palmitoleic acid, and Oleic acid to name a few. [ABSTRACT FROM AUTHOR]

Objective: Diabetes mellitus is a chronic metabolic disease often associated with hyperlipidemia. High low-density lipoprotein cholesterol (LDLc), high triglyceride, and low high-density lipoprotein cholesterol (HDLc) form the atherogenic lipoprotein profile. In this study, we examined how exenatide, a glucagon-like peptide 1 (GLP-1) analog, affects lipid profile and atherogenic indices in patients with diabetes. Methods: 100 patients diagnosed with type 2 diabetes mellitus (T2DM) participated in this retrospective study. Clinical and laboratory data of the patients were obtained before exenatide treatment and at the 12th week. From the lipid profile, Atherogenicity Plasma Index (AIP), Castelli Risk Index I (CRI-I), Castelli Risk Index II (CRI-II), Atherogenic Coefficient (AC), triglyceride (TG)/HDLc, TG- Glucose index (TyG) and TyG-Body Mass Index (BMI) data were calculated. Results: There was a significant improvement in body weight (BW), BMI, fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), and conventional lipid profile after exenatide treatment. Statistically, significant decreases were observed in atherogenicity indices TyG index, TyG-BMI index, CRI-I, CRI-II, AIP, and AC indices (p < 0.05). This improvement in TG/HDLc, TyG index, CRI-I, CRI-II, AIP and AC indices was independent of HbA1c and BMI. Especially in patients with BMI ≥ 40 kg/m2, TyG-BMI index (p:0.01), a statistically significant decrease was observed in TyG index, TyG-BMI index, CRI-I, and AIP values in patients with HbA1c ≥8% (p:0.001, p:0.016, p:0.047, p:0.008). Conclusion: In addition to its commonly known effects such as lowering FPG levels and weight loss, exenatide has been observed to have a positive effect on traditional lipid profiles and atherogenicity-related indices. In addition to its antidiabetic effect, it should be considered in diabetic patients in treatment options for atherosclerotic cardiovascular prevention. [ABSTRACT FROM AUTHOR]

Deregulation of lipid composition in adipose tissue adjacent to breast tumour is observed in ex vivo and animal models. Novel non-invasive magnetic resonance imaging (MRI) allows rapid lipid mapping of the human whole breast. We set out to elucidate the spatial heterogeneity of peri-tumoural lipid composition in postmenopausal patients with oestrogen receptor positive (ER +) breast cancer. Thirteen participants (mean age, 62 ± [SD] 6 years) with ER + breast cancer and 13 age-matched postmenopausal healthy controls were scanned on MRI. The number of double bonds in triglycerides was computed from MRI images to derive lipid composition maps of monounsaturated, polyunsaturated, and saturated fatty acids (MUFA, PUFA, SFA). The spatial heterogeneity measures (mean, median, skewness, entropy and kurtosis) of lipid composition in the peri-tumoural region and the whole breast of participants and in the whole breast of controls were computed. The Ki-67 proliferative activity marker and CD163 antibody on tumour-associated macrophages were assessed histologically. Mann Whitney U or Wilcoxon tests and Spearman's coefficients were used to assess group differences and correlations, respectively. For comparison against the whole breast in participants, peri-tumoural MUFA had a lower mean (median (IQR), 0.40 (0.02), p <.001), lower median (0.42 (0.02), p <.001), a negative skewness with lower magnitude (− 1.65 (0.77), p =.001), higher entropy (4.35 (0.64), p =.007) and lower kurtosis (5.13 (3.99), p =.001). Peri-tumoural PUFA had a lower mean (p <.001), lower median (p <.001), a positive skewness with higher magnitude (p =.005) and lower entropy (p =.002). Peri-tumoural SFA had a higher mean (p <.001), higher median (p <.001), a positive skewness with lower magnitude (p <.001) and lower entropy (p =.012). For comparison against the whole breast in controls, peri-tumoural MUFA had a negative skewness with lower magnitude (p =.01) and lower kurtosis (p =.009), however there was no difference in PUFA or SFA. CD163 moderately correlated with peri-tumoural MUFA skewness (rs = −.64), PUFA entropy (rs =.63) and SFA skewness (rs =.59). There was a lower MUFA and PUFA while a higher SFA, and a higher heterogeneity of MUFA while a lower heterogeneity of PUFA and SFA, in the peri-tumoural region in comparison with the whole breast tissue. The degree of lipid deregulation was associated with inflammation as indicated by CD163 antibody on macrophages, serving as potential marker for early diagnosis and response to therapy. [ABSTRACT FROM AUTHOR]

Deregulation of lipid composition in adipose tissue adjacent to breast tumour is observed in ex vivo and animal models. Novel non-invasive magnetic resonance imaging (MRI) allows rapid lipid mapping of the human whole breast. We set out to elucidate the spatial heterogeneity of peri-tumoural lipid composition in postmenopausal patients with oestrogen receptor positive (ER +) breast cancer. Thirteen participants (mean age, 62 ± [SD] 6 years) with ER + breast cancer and 13 age-matched postmenopausal healthy controls were scanned on MRI. The number of double bonds in triglycerides was computed from MRI images to derive lipid composition maps of monounsaturated, polyunsaturated, and saturated fatty acids (MUFA, PUFA, SFA). The spatial heterogeneity measures (mean, median, skewness, entropy and kurtosis) of lipid composition in the peri-tumoural region and the whole breast of participants and in the whole breast of controls were computed. The Ki-67 proliferative activity marker and CD163 antibody on tumour-associated macrophages were assessed histologically. Mann Whitney U or Wilcoxon tests and Spearman's coefficients were used to assess group differences and correlations, respectively. For comparison against the whole breast in participants, peri-tumoural MUFA had a lower mean (median (IQR), 0.40 (0.02), p <.001), lower median (0.42 (0.02), p <.001), a negative skewness with lower magnitude (− 1.65 (0.77), p =.001), higher entropy (4.35 (0.64), p =.007) and lower kurtosis (5.13 (3.99), p =.001). Peri-tumoural PUFA had a lower mean (p <.001), lower median (p <.001), a positive skewness with higher magnitude (p =.005) and lower entropy (p =.002). Peri-tumoural SFA had a higher mean (p <.001), higher median (p <.001), a positive skewness with lower magnitude (p <.001) and lower entropy (p =.012). For comparison against the whole breast in controls, peri-tumoural MUFA had a negative skewness with lower magnitude (p =.01) and lower kurtosis (p =.009), however there was no difference in PUFA or SFA. CD163 moderately correlated with peri-tumoural MUFA skewness (rs = −.64), PUFA entropy (rs =.63) and SFA skewness (rs =.59). There was a lower MUFA and PUFA while a higher SFA, and a higher heterogeneity of MUFA while a lower heterogeneity of PUFA and SFA, in the peri-tumoural region in comparison with the whole breast tissue. The degree of lipid deregulation was associated with inflammation as indicated by CD163 antibody on macrophages, serving as potential marker for early diagnosis and response to therapy. [ABSTRACT FROM AUTHOR]

Plant sterols are used as a supplement or an additive to reduce LDL cholesterol. The poor dispersibility and instability of phytosterols are the main limitations of their application. So, we tried to overcome these problems through nanoencapsulation of them with colloidal natural RSs (SLNs) using an effective approach to achieve higher efficiency and less intrinsic coagulation. Phytosterols extracted from flax seeds oil with caffeine by a new method were encapsulated with a stable colloid of sheep fat and ostrich oil (1:2), soy lecithin, and glucose through co-sonicated coacervation. Characterization of the obtained SLNs was conducted using FTIR, UV–Vis, SEM, DLS, and GC analysis. The three–factor three–level Behnken design (BBD) was used to prioritize the factors affecting the coacervation process to optimize particle size and loading capacity of SLNs. Operational conditions were examined, revealing that the size of SLNs was below 100 nm, with a phytosterols content (EE %) of 85.46% with high positive zeta potential. The nanocapsules' anti-microbial activity and drug-release behavior were then evaluated using the CFU count method and Beer-Lambert's law, respectively. The controlled release of nanocapsules (below 20%) at ambient temperature has been tested. The stability of nano-encapsulated phytosterols was investigated for six months. All results show that this green optimal coacervation is a better way than conventional methods to produce stable SLNs for the nanoencapsulation of phytosterols. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is a type of cancer that affects the colon or rectum and occurs in individuals over the age of 50, although it can affect people of all ages. Quercetin is a flavonoid, which is a type of plant pigment with antioxidant and anti-inflammatory properties. Some studies have explored the potential of quercetin as an adjuvant therapy to enhance the effectiveness of chemotherapy or radiation therapy. Methodology: In the proposed work, the nano-biomaterials of solid lipids such as stearic acid (SA) and tripalmitin (TpN) as well as the surfactants tween 80 and span 80 were used to prepare novel quercetin (QuR)-loaded-solid lipid nanoparticles (QuR-SLNs) for medical applications in colorectal cancer (CRC). The resulting bio-nano SLNs' mean entrapment efficiency (EE) and particle size (PS) were optimized by Box–Behnken design (BBD) approach based on the response-like surface methodology (RSM). The variables include lipid ratio (X1), surfactant ratio (X2), QuR-to-lipid ratio (X3), the sonication time (X4), and the homogenization time (X5). Requirements on the maximum EE (%) and minimum PS (nm) were optimized for the preparation of QuR-SLN. Differential scanning calorimetry (DSC), X-ray diffraction (XRD) analysis, and scanning electron microscopy (SEM) were then used to analyze the optimized SLN and to find the crystalline state of QuR with lipid relationship. In addition, on the Caco-2 cells, at IC50 (49 µM/mL), in vitro cytotoxicity was attained. Results: The optimized QuR-SLN had practically spherical shapes, with % EE and a PS of 97.8 ± 1.16% and 132.16 ± 4.1 nm, respectively. In aqueous media, the degree of lipid crystallinity and the lipid modification was investigated, and the QuR incorporation and release patterns showed high correlations with both. The results showed that over 41.12 ± 1.6% of the bio-nano QuR-SLNs was released gradually over the course of 48 h, demonstrating effective QuR delayed release. Results on apoptotic observations indicate that apoptosis accounts for the majority of cell death, while necrosis, a type of cell death, constitutes a very minor portion. In conclusion, the prepared bio-nano QuR-SLNs might improve cytotoxicity and can act as an ideal carrier for the delivery of QuR and this preparation is used in the treatment of CRC. [ABSTRACT FROM AUTHOR]

To develop artificial cell models that mimic living cells, cell-sized lipid vesicles encapsulating cell-free protein synthesis (CFPS) systems are useful for protein expressions or artificial gene circuits for vesicle–vesicle communications. Therefore, investigating the transcriptional and translational properties of CFPS systems in lipid vesicles is important for maximizing the synthesis and functions of proteins. Although transcription and translation using CFPS systems inside lipid vesicles are more important than that outside lipid vesicles, the former processes are not investigated by changing the lipid composition of lipid vesicles. Herein, we investigated changes in transcription and translation using CFPS systems inside giant lipid vesicles (approximately 5–20 μm in diameter) caused by changing the lipid composition of lipid vesicles containing neutral, positively, and negatively charged lipids. After incubating for 30 min, 1 h, 2 h, and 4 h, the transcriptional and translational activities in these lipid vesicles were determined by detecting the fluorescence intensities of the fluorogenic RNA aptamer on the 3′-untranslated region of mRNA (transcription) and the fluorescent protein sfCherry (translation), respectively. The results revealed that transcriptional and translational activities in a lipid vesicle containing positively charged lipids were high when the protein was synthesized using the CFPS system inside the lipid vesicle. Thus, the present study provides an experimental basis for constructing complex artificial cell models using bottom-up approaches. [ABSTRACT FROM AUTHOR]

To evaluate the effect of yoga on the frequency of MetS and its impact on cardiovascular risk markers in climacteric women. We recruited 84 sedentary women between 40 and 65 years diagnosed with MetS. Participants were randomly assigned to a 24-week yoga intervention or control group. We evaluated the frequency of MetS and changes in the individual components of MetS at baseline and after 24 weeks. We also assessed the impact of yoga practices on cardiovascular risk through the following markers: High-sensitivity C-reactive Protein (hs-CRP), Lipid Accumulation Product (LAP), Visceral Adiposity Index (VAI), and Atherogenic Index of Plasma (AIP). The frequency of MetS reduced significantly after 24 weeks of yoga practice (− 34.1%; p < 0.001). Statistical analysis showed that the frequency of MetS was significantly lower in the yoga group (65.9%; n = 27) than in the control group (93.0%; n = 40) after 24 weeks (p = 0.002). Regarding the individual components of MetS, yoga practitioners had statistically lower waist circumference, systolic blood pressure, triglycerides, HDLc, and glucose serum concentrations than the control group after 24 weeks. Yoga practitioners also had a significant decrease in hs-CRP serum concentrations (3.27 ± 2.95 mg/L vs. 2.52 ± 2.14 mg/L; p = 0.040) and a lower frequency of moderate or high cardiovascular risk (48.8% vs. 34.1%; p = 0.001) after 24 weeks of practice. The yoga group had LAP values significantly lower than the control group after the intervention period (55.8 ± 38.04 vs. 73.9 ± 40.7; p = 0.039). Yoga practice demonstrated to be an effective therapeutic to manage MetS and reduce cardiovascular risk in climacteric women. [ABSTRACT FROM AUTHOR]

The main component of pulmonary surfactant is dipalmitoyl phosphatidylcholine (DPPC), which reduces the surface tension almost to zero when the lung surface is compressed, thus preventing the alveolus from collapse in the course of exhalation. In this work the methods of the surface rheology have been employed to determine the influence of six pulmonary lipids on the dynamic surface properties of a DPPC monolayer at different temperatures and in a wide range of surface tensions. Particular attention has been paid to the region of low surface tensions (lower than 25 mN/m) at temperatures of 25 and 35°С, with these conditions being close to the physiological state on the internal surface of lungs. The addition of lipids with similar molecular structures to DPPC does not affect significantly the dynamic surface properties at a temperature of 25°C. At the same time, the addition of these lipids increases the surface elasticity in the region of low surface tensions at 35°С. However, under these conditions, the presence of lipids with unsaturated hydrocarbon radicals in the surface layer leads to the opposite effect and hinders the achievement of low surface tensions during slow compression. The results obtained have shown the possibility to control the properties of the lipid/DPPC mixed monolayer, which can be considered which can be considered as a model of pulmonary surfactant. [ABSTRACT FROM AUTHOR]

Background Diversity of risk factors, namely, vitamin D and lipid panel abnormalities, are connected to multiple sclerosis (MS) etiology and may possess an influential role on disease course. In a cross-sectional study, we correlated the demographic, clinical and radiological characteristics of 111 relapsing-remitting MS (RRMS) patients with their serum levels of vitamin D and lipid profile to evaluate the consequences of their abnormalities on disease activity and/or its progression. Results In the study group, the mean serum level of vitamin D was 18.93 ± 9.85 ng/mL, over 80% had insufficient level (< 30 ng/mL) and significantly lower in females (P = 0.011). Insufficient vitamin D significantly associated with high relapse frequency (P = 0.005). Measurement the direction of this association showed that each 1 ng/mL increase in vitamin D was correlated with both decrease in annualized relapse rate (ARR) of 0.02 relapse/year (P = 0.017) and with decrease in number of relapses during last 2 years of 0.02 relapse (P = 0.045). Analysis of serum lipid panel showed a direct link between higher levels of TC and LDL to increased total number of relapses (P < 0.001 and 0.003, respectively) and EDSS (P = 0.001 and 0.022), also between higher TG and EDSS (P = 0.001). This link became indirect between HDL and both total number of relapse and EDSS (P = 0.001 and 0.001). Radiologically, positively linked confluent brain lesion to elevated TC and TG levels (P = 0.001 and 0.002, respectively) and cord lesions to elevated TC (P = 0.007). Longer disease duration positively associated with all lipids-related variables. As a direct effect on lipid metabolism, each 1 ng/mL increase in vitamin D was associated with reduction in serum TC of 1.48 mg/dL (P = 0.002) and rise in HDL of 0.35 mg/dL (P = 0.028). Conclusions Management of vitamin D insufficiency may decrease risk of higher ARR and the same for dyslipidemia in reduction of disability and confluent brain T2 lesion. Increasing vitamin D was positively correlated with HDL but negatively with TC. [ABSTRACT FROM AUTHOR]

Lipid oxidation in food products is a crucial problem that causes undesirable changes in the food's flavor, texture, and nutritional value. It should be carefully monitored as it can lead to the formation of potentially toxic compounds and in that way reduce the shelf life of the product. Liquid chromatography coupled to mass spectrometry is a powerful tool to monitor the formation of oxidized lipids. However, the presence of lipid species in both their non-oxidized and oxidized forms at distinctly different concentrations can hinder the detection and identification of the less abundant oxidized species, due to coelution. In this study, a flow injection mass spectrometry approach was used to selectively ionize oxidized triacylglycerols versus their non-oxidized precursors. Three mobile phase additives were investigated (ammonium formate, sodium acetate, and sodium iodide) at three different concentrations, and ion source settings (i.e., sheath gas temperature, capillary voltage, and nozzle voltage) were optimized. A fractional factorial design was conducted to examine not only the direct effect of the operating parameters on the selectivity of ionization for the oxidized lipid species, but also to assess their combined effect. Overall, selective ionization of oxidized versus non-oxidized lipid species was favored by the use of sodium-containing solvent additives. The application of specific ion source settings resulted in an increased ionization selectivity, with sheath gas temperature and capillary voltage having the most significant influence. A selectivity factor as high as 120 could be reached by combining 0.1 mg/mL sodium-containing additives, with 250 °C sheath gas temperature and 5000 V capillary voltage. These findings will contribute to future studies on fast detection and relative quantification of low abundant oxidized triacylglycerols and their possible impact on human health. [ABSTRACT FROM AUTHOR]

To explore the association between lipid markers and osteoarthritis (OA). First, the National Health and Nutrition Examination Survey (NHANES) database was used to screen participants with lipid markers, OA and relevant covariates, and logistic regression was used to analyze the association between lipid markers and OA; Then, under the theoretical framework of Mendelian randomization (MR), two-sample MR was performed using GWAS data of lipid markers and OA to explore the causal association between the two, which was analyzed by inverse variance weighting (IVW) method. Heterogeneity test, sensitivity analysis and pleiotropy analysis were also performed. The NHANES database screened a total of 3706 participants, of whom 836 had OA and 2870 did not have OA. When lipid markers were used as continuous variables, multivariate logistic results showed an association between HDL, LDL and OA (HDL, OR (95%):1.01 (1.00, 1.01); LDL, OR (95%):1.00 (0.99, 1.00)). When lipid markers were used as categorical variables, multivariate logistic results showed the fourth quartile result of 0.713 (0.513, 0.992) for LDL relative to the first quartile. In MR study, the results of the IVW method for TG, TL, HDL and LDL showed OR (95% CI) of 1.06 (0.97–1.16), 0.95 (0.85–1.06), 0.94 (0.86–1.02) and 0.89 (0.80–0.998) with P-values of 0.21, 0.37. 013, 0.046. The heterogeneity tests and multiplicity analyses showed P-values greater than 0.05, and sensitivity analyses showed no abnormal single nucleotide polymorphisms. Through NHANES database and MR analyses, LDL was found to be a protective factor for OA, while HDL still needs further study. Our results provide new biomarkers for preventive and therapeutic strategies for OA. [ABSTRACT FROM AUTHOR]

Membrane curvature is essential for many cellular structures and processes, and factors such as leaflet asymmetry, lipid composition, and proteins all play important roles. Cardiolipin is the signature lipid of mitochondrial membranes and is essential for maintaining the highly curved shapes of the inner mitochondrial membrane (IMM) and the spatial arrangement of membrane proteins. In this study, we investigate the partitioning behavior of various lipids present in the IMM using coarse-grained molecular dynamics simulations. This study explores curved bilayer systems containing phosphatidylcholine (PC), phosphatidylethanolamine (PE), and cardiolipin (CDL) in binary and ternary component mixtures. Curvature properties such as mean and Gaussian curvatures, as well as the distribution of lipids into the various curved regions of the cristae models, are quantified. Overall, this work represents an advance beyond previous studies on lipid curvature sensing by simulating these systems in a geometry that has the morphological features and scales of curvature consistent with regions of the IMM. We find that CDL has a stronger preference for accumulating in regions of negative curvature than PE lipids, in agreement with previous results. Furthermore, we find lipid partitioning propensity is dominated by sensitivity to mean curvature, while there is a weaker correlation with Gaussian curvature. Lipid dynamics are analyzed in a model for the mitochondrial inner membrane using coarse-grained molecular dynamics. The model displays biological scales of curvature where strong partitioning of cardiolipin to negative curvature regions is observed. [ABSTRACT FROM AUTHOR]

Viral infections, fertilization, neurotransmission, and many other fundamental biological processes rely on membrane fusion. Straightforward calculations based on the celebrated Canham–Helfrich elastic model predict a large topological energy barrier that prevents the fusion process from being thermally activated. While such high energy is in accordance with the physical barrier function of lipid membranes, it is difficult to reconcile with the biological mechanisms involved in fusion processes. In this work, we use a Ginzburg–Landau type of free energy that recovers the Canham–Helfrich model in the limit of small width-to-vesicle-extension ratio, with the additional ability to handle topological transitions. We show that a local modification of the Gaussian modulus in the merging region both dramatically lowers the elastic energy barrier and substantially changes the minimal energy pathway for fusion, in accordance with experimental evidence. Therefore, we discuss biological examples in which such a modification might play a crucial role. [ABSTRACT FROM AUTHOR]

Lipid droplets (LDs) are intracellular storage vesicles composed of a neutral lipid core surrounded by a glycerophospholipid membrane. LD accumulation is associated with different stages of cancer progression and stress responses resulting from chemotherapy. In previous work, a novel dual nano-electrospray ionization source and data-dependent acquisition method for measuring the relative abundances of lipid species between two extracts were described and validated. Here, this same source and method were used to determine if oxaliplatin-sensitive and resistant cells undergo similar lipid profile changes, with the goal of identifying potential signatures that could predict the effectiveness of an oxaliplatin-containing treatment. Oxaliplatin is commonly used in the treatment of colorectal cancer. When compared to a no-drug control, oxaliplatin dosing caused significant increases in triglyceride (TG) and cholesterol ester (CE) species. These increases were more pronounced in the oxaliplatin-sensitive cells than in oxaliplatin-resistant cells. The increased neutral lipid abundance correlated with LD formation, as confirmed by confocal micrographs of Nile Red–stained cells. Untargeted proteomic analyses also support LD formation after oxaliplatin treatment, with an increased abundance of LD-associated proteins in both the sensitive and resistant cells. [ABSTRACT FROM AUTHOR]

Background: The goal of current research work is to develop and optimize curcumin-encapsulated nanostructured lipid carriers and to enhance therapeutic effect of curcumin after oral administration. Method: Curcumin-loaded nanostructured lipid carriers were developed by a single-step one-pot microwave-assisted technique. The preparation of curcumin-loaded nanostructured lipid carriers was optimized by employing two factors and three levels central composite design (Design Expert® software) taking concentration of lipid blend and surfactant as independent variables and particle size, polydispersity index, and zeta potential as dependent variables, to investigate the effect of formulation ingredients on the physicochemical characteristics of nanostructured lipid carriers. The optimized batch was investigated by Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction, high-resolution transmission electron microscopy, in vitro drug release, stability studies, cytotoxicity, and in vivo anthelmintic studies. Results: The average particle size, polydispersity index, and zeta potential of the optimized batch were found to be 144 nm, 0.301, and − 33.2 mV, respectively, with an entrapment efficiency of 92.48%. The results of high-resolution transmission electron microscopy confirmed spherical shape of particles. In vivo antiparasitic studies included determining the duration of paralysis and eventual death of earthworms in the presence of test samples. The results of in vivo studies showed good anthelmintic potential for curcumin-loaded nanostructured lipid carriers as compared to albendazole in different concentrations. Cytotoxicity studies also confirmed the formulation to be nontoxic to Vero cells. In vitro drug release study showed 90.76 ± 0.01% release of curcumin in 24 h by following the Korsmeyer-Peppas model of release kinetics. Conclusion: The aforementioned results imply that microwave-developed nanostructured lipid carriers could be promising drug carriers and will aid in their fabrication for oral administration as a possible alternative for the treatment of other parasitic infections. Highlights: Curcumin-loaded nanostructured lipid carriers (Cr-NLCs) were prepared by a fast and easy single-step one-pot microwave-assisted technique. Implementation of 2 factors at 3 levels with central composite design (Design Expert® software) to investigate the influence of the formulation ingredients on the physicochemical properties of the NLCs. Optimized batch of Cr-NLC demonstrated nanosized particles with improved drug release characteristics, excellent entrapment efficiency and augmented physical stability. The anthelmintic potential of Cr-NLC was determined by a study on earthworms and was compared with albendazole. A cytotoxicity study was performed on Vero cells and evaluated in terms of IC50 value. [ABSTRACT FROM AUTHOR]

Circadian rhythms, which are governed by a circadian clock, regulate important biological processes associated with obesity. SNPs in circadian clock genes have been linked to energy and lipid homeostasis. The aim of our study was to evaluate the associations of CLOCK and REV-ERBα SNPs with BMI and plasma lipid levels in pre-pubertal boys and girls. The study sample population comprised 1268 children aged 6–8 years. Information regarding anthropometric parameters and plasma lipid concentrations was available. Genotyping of CLOCK SNPs rs1801260, rs4580704, rs3749474, rs3736544 and rs4864548 and REV-ERBα SNPs rs2017427, rs20711570 and rs2314339 was performed by RT-PCR. The CLOCK SNPs rs3749474 and rs4864548 were significantly associated with BMI in girls but no in boys. Female carriers of the minor alleles for these SNPs presented lower BMI compared to non-carriers. A significant association of the REV-ERBα SNP rs2071570 with plasma total cholesterol, LDL-cholesterol and Apo B in males was also observed. Male AA carriers showed lower plasma levels of total cholesterol, LDL-cholesterol and Apo B levels as compared with carriers of the C allele. No significant associations between any of the studied REV-ERBα SNPs and plasma lipid levels were observed in females. In summary, CLOCK and REV-ERBα SNPs were associated with BMI and plasma lipid levels respectively in a sex-dependent manner. Our findings suggest that sex-related factors may interact with Clock genes SNPs conditioning the effects of these polymorphisms on circadian alterations. [ABSTRACT FROM AUTHOR]

Introduction: Sleep patterns are more frequently interrupted in patients with Parkinson's disease (PD), and it is still unclear whether genetic factors are involved in PD-related sleep disorders. In this study, we hypothesize that PD-associated genetic risk affects lipid metabolism, which in turn contributes to different types of sleep disorders. Methods: We used a non-targeted lipidomics to explore the lipid composition of cerebrospinal fluid (CSF) exosomes derived from patients with PD carrying phospholipase A2 Group VI (PLA2G6) and sphingomyelin phosphodiesterase 1 (SMPD1) mutations. Results: PLA2G6 mutations (c.1966C > G, Leu656Val; c.2077C > G, Leu693Val; c.1791delC, His597fx69) significantly increase the exosomal content of glycerophospholipids and lysophospholipids, specifically phosphatidylcholine (PC) and lysophosphatidylcholine (LPC). Exosome surface presence of melatomin receptor 1A (MTNR1A) was detectable only in patients with PLA2G6 mutations. We have further shown that, in patients with PD carrying PLA2G6 mutations, sleep latency was significantly longer compared to those carrying WT PLA2G6, and we speculate that functional PLA2G6 mutations lead to structural changes and lipid deregulation of exosomes, which in turn alters exosomal cargo and affects PD-related sleep disorders. In SMPD1, G508R variant-carrying patients with PD abundance of sphingomyelins was significantly higher and had significantly shorter rapid eye movement sleep. Conclusions: Our study demonstrated that the disturbed composition and function of CSF-derived exosome lipidome during the pathological stage of PD may affect different types of sleep disorder in PD. [ABSTRACT FROM AUTHOR]

Background: Dyslipidemia is a crucial risk factor for atherosclerotic cardiovascular disease. However, there is limited data available on the differences in the prevalence of dyslipidemia between rural and urban populations in India. The aim of the present investigation is to describe the prevalence of dyslipidemia and the risk factors associated with adverse lipid profiles among adults residing in rural, sub-urban, and urban areas of India, and to assess its association with diabetes and hypertension. Methods: We enrolled adults over the age of 20 who lived in three distinct demographic areas in South India: rural, sub-urban, and urban. Data on demographics, lifestyle, disease history, family history, body weight, height, waist circumference, blood pressure, and clinical characteristics were collected for this study. We used chi-square tests and multivariable logistic regression to analyze demographic prevalence and risk factors related to lipid abnormalities among study participants. Results: This study enrolled 2976 randomly selected participants from rural, sub-urban, and urban communities in Tamil Nadu, India. Of these, 865 (29.1%) were rural residents, 1030 (34.6%) were sub-urban residents, and 1081 (36.3%) were urban residents. About 80% of women who lived in the suburban area had higher rates of low-HDL cholesterol. Compared to sub-urban (29.9%, 49%, and 21.1%) and rural (33.4%, 43.4%, and 24.1%) populations, urban populations had higher prevalence rates of hypercholesterolemia, hypertriglyceridemia, and elevated LDL-C (37.3%, 52.5%, and 38.6%), respectively. Men were more likely than women to develop dyslipidemia before the age of 40, but after that age, men showed a reduced risk of dyslipidemia than women, except for low HDL cholesterol. Age group, gender, current drinker, overweight, obesity, diabetes, and hypertension showed a significant association (p < 0.05) with dyslipidemia. Conclusions: The study found that more than 85% of the sub-urban and urban population had dyslipidemia (at least one lipid abnormality) compared to rural residents (78.5%). The prevalence rates were higher among those with diabetes and hypertension in urban residents. [ABSTRACT FROM AUTHOR]

Lipid nanoparticles (LNPs) have been used as a carrier for messenger RNA (mRNA) vaccines. Surface properties of LNPs are important to the stability and function of mRNA vaccines. Polyethylene-glycol (PEG) is a functional lipid at the surface of LNPs that improves colloidal stability, increases circulation time, and impacts cellular uptake. In this study, we explore in-depth lipid composition at the surface of mRNA-LNPs using high-field nuclear magnetic resonance (NMR) spectroscopy. Our results provide a unique surface lipid profile of intact LNPs identifying PEG chains and partial ionizable lipids are present with quantification capability. The surface PEG density is determined to reveal the brush-like conformation on the surface of mRNA-LNPs. Furthermore, we implement a diffusion NMR strategy for routine testing of formulated drug products during drug development. Comparative NMR analysis of different vaccine preparations and stability samples provides a global view of the mRNA-LNP surface structure for enhanced product knowledge. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19), which affects multiple organs, is causing an unprecedented global public health crisis. Most COVID-19 patients recover gradually upon appropriate interventions. Viruses were reported to utilize the small extracellular vesicles (sEVs), containing a cell-specific cargo of proteins, lipids, and nucleic acids, to escape the attack from the host's immune system. This study aimed to examine the sEVs lipid profile of plasma of recovered COVID-19 patients (RCs). Plasma sEVs were separated from 83 RCs 3 months after discharge without underlying diseases, including 18 recovered asymptomatic patients (RAs), 32 recovered moderate patients (RMs), and 33 recovered severe and critical patients (RSs), and 19 healthy controls (HCs) by Total Exosome Isolation Kit. Lipids were extracted from sEVs and then subjected to targeted liquid chromatography-mass spectrometry. The size, concentration, and distribution of sEVs did not differ in RCs and HCs as validated by transmission electron microscopy, nanoparticle tracking analysis, and immunoblot analysis. Fifteen subclasses of 508 lipids were detected in plasma sEVs from HCs, RAs, RMs, and RSs, such as phosphatidylcholines (PCs) and diacylglycerols (DAGs), etc. Total lipid intensity displayed downregulation in RCs compared with HCs. The relative abundance of DAGs gradually dropped, whereas PCs, lysophosphatidylcholines, and sphingomyelins were higher in RCs relative to HCs, especially in RSs. 88 lipids out of 241 in sEVs of RCs were significantly different and a conspicuous increase was revealed with disease status. The sEVs lipids alternations were found to be significantly correlated with the clinical indices in RCs and HCs, suggesting that the impact of COVID-19 on lipid metabolism lingered for a long time. The lipid abnormalities bore an intimate link with glycerophospholipid metabolism and glycosylphosphatidylinositol anchor biosynthesis. Furthermore, the lipidomic analysis showed that RCs were at higher risk of developing diabetes and sustaining hepatic impairment. The abnormality of immunomodulation in RCs might still exist. The study may offer new insights into the mechanism of organ dysfunction and help identify novel therapeutic targets in the RCs. [ABSTRACT FROM AUTHOR]

Honokiol (HNK), one of the main active components of Magnolia officinalis, has a positive effect on non-alcoholic steatohepatitis (NASH). However, the effects of HNK on the composition of serum lipids and bile acids (BAs) and gut microbiota (GM) of NASH mice are still unknown.C57BL/6 mice were fed with methionine-choline deficiency (MCD) diet and gavaged with HNK (20 mg/kg/d) for 8 weeks, then the serum lipids and BAs were detected by LC–MS, the composition of ileum microflora and the mRNA expression of hepatic BAs homeostasis related genes were analyzed by 16S rDNA sequencing and RT-qPCR, respectively. HNK treatment decreased the degree of hepatic lipid drops, inflammatory cell infiltration and fibrosis. Meantime, the serum levels of 34 lipids and 4 BAs in MCD mice were significantly altered by HNK treatment, as well as the increased abundance of Ruminococcaceae, Caulobacteraceae and Brevundimonas, and the decreased abundance of Firmicutes and Dubosiella. Besides, HNK treatment increased the hepatic mRNA expression of Oatp1b2 in MCD mice. The ameliorating effect of HNK on NASH may be partly related to its correction on the disorders of GM, serum lipids and BAs of MCD mice. [ABSTRACT FROM AUTHOR]

Partially defatted poppy seeds, a by-product of poppy oil cold pressing, could be an interesting dietary supplement for obesity management. The aim of this study was to compare the effects of dietary supplementation with a small amount of native or partially defatted poppy seeds on gastrointestinal function and lipid metabolism in rats fed a high-fat diet. The defatted poppy seeds had, among others, lower fat content and higher fibre and protein content than native poppy seeds. The rats fed with a high-fat diet were characterised by severe metabolic disorders, especially in the liver, and poppy seeds were unable to prevent them. However, depending on the seed form, dietary supplementation with poppy seeds differentially affected the microbial and endogenous lipid metabolism in rats. In the distal intestine, both dietary seed forms stimulated microbial acetate production, and the supplementation with partially defatted poppy seeds additionally inhibited isobutyrate and isovalerate formation, which indicates a reduction in putrefaction. Both dietary seed forms increased cholesterol accumulation in the liver. Only dietary supplementation with partially defatted poppy seeds attenuated visceral fat and hepatic triglyceride accumulations and lowered blood triglyceride concentrations, and at the transcriptional level, the inhibition of SREBP-1c, which upregulates genes responsible for de novo lipogenesis, was additionally observed in this organ. In conclusion, a low and regular consumption of partially defatted poppy seeds may be beneficial in managing obesity-related disorders. [ABSTRACT FROM AUTHOR]

Previously, we observed curcumin improves aging-associated memory impairment in d-galactose (D-gal) and normal-aged (NA) mice. Evidence showed that multiple agents can be used in managing aging-induced memory dysfunction, drawn by the contribution of several pathways. Curcumin and Epigallocatechin 3 gallate (EGCG) combination substantially reduced the oxidative stress that commonly mediates aging. This study examined the combined effect of EGCG and curcumin on memory improvement in two recognized models, D-gal and normal-aged (NA) mice. The co-administration of EGCG and curcumin significantly (p < 0.05) increased retention time detected by passive avoidance (PA) and freezing response determined in contextual fear conditioning (CFC) compared to the discrete administration of EGCG or curcumin. Biochemical studies revealed that the combination of EGCG and curcumin remarkably ameliorated the levels (p < 0.05) of glutathione, superoxide dismutase, catalase, advanced oxidation protein products, nitric oxide, and lipid peroxidation compared to the monotherapy of EGCG or curcumin in mice hippocampi. The behavioral and biochemical studies revealed that the combination of EGCG and curcumin showed better improvement in rescuing aging-associated memory disorders in mice. EGCG and curcumin combination could serve as a better choice in managing aging-related memory disorders. [ABSTRACT FROM AUTHOR]

Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging (MALDI-MSI) spatially resolves the chemical composition of tissues. Lipids are of particular interest, as they influence important biological processes in health and disease. However, the identification of lipids in MALDI-MSI remains a challenge due to the lack of chromatographic separation or untargeted tandem mass spectrometry. Recent studies have proposed the use of MALDI in-source fragmentation to infer structural information and aid identification. Here we present rMSIfragment, an open-source R package that exploits known adducts and fragmentation pathways to confidently annotate lipids in MALDI-MSI. The annotations are ranked using a novel score that demonstrates an area under the curve of 0.7 in ROC analyses using HPLC–MS and Target-Decoy validations. rMSIfragment applies to multiple MALDI-MSI sample types and experimental setups. Finally, we demonstrate that overlooking in-source fragments increases the number of incorrect annotations. Annotation workflows should consider in-source fragmentation tools such as rMSIfragment to increase annotation confidence and reduce the number of false positives. [ABSTRACT FROM AUTHOR]

Metabolic reprogramming is a hallmark of cancers, but pan-cancer level roles of lipid metabolism in cancer development are remains poorly understood. We investigated the possible roles of lipid metabolic genes (LMGs) in 14 cancer types. The results indicate that: (1) there is strong evidence for increased lipid metabolism in THCA and KICH. (2) Although the overall levels of lipid metabolic processes are down-regulated in some cancer types, fatty acid synthase activity and fatty acid elongation are moderately up-regulated in more than half of the cancer types. Cholesterol synthesis is up-regulated in five cancers including KICH, BLCA, COAD, BRCA, UCEC, and THCA. (3) The catabolism of cholesterols, triglycerides and fatty acids is repressed in most cancers, but a specific form of lipid degradation, lipophagy, is activated in THCA and KICH. (4) Lipid storage is enhanced in in kidney cancers and thyroid cancer. (5) Similarly to primary tumors, metastatic tumors tend to up-regulate biosynthetic processes of diverse lipids, but down-regulate lipid catabolic processes, except lipophagy. (6) The frequently mutated lipid metabolic genes are not key LMGs. (7) We established a LMG-based model for predicting cancer prognosis. Our results are helpful in expanding our understanding of the role of lipid metabolism in cancer. [ABSTRACT FROM AUTHOR]

This study aimed at investigating the association of acrylamide consumption with the incidence of type 2 diabetes (T2D) in adults. The 6022 subjects of the Tehran lipid and glucose study participants were selected. The acrylamide content of food items were summed and computed cumulatively across follow up surveys. Multivariable Cox proportional hazard regression analyses were performed to estimate the hazards ratio (HR) and 95% confidence interval (CI) of incident T2D. This study was done on men and women, respectively aged 41.5 ± 14.1 and 39.2 ± 13.0 years. The mean ± SD of dietary acrylamide intake was 57.0 ± 46.8 µg/day. Acrylamide intake was not associated with the incidence of T2D after adjusting for confounding variables. In women, a higher acrylamide intake was positively associated with T2D [HR (CI) for Q4: 1.13 (1.01–1.27), P trend: 0.03] after adjusting for confounding factors. Our results demonstrated that dietary intake of acrylamide was associated with an increased risk of T2D in women. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is characterized by an increase in hepatic lipid accumulation due to impaired lipid metabolism. Although a correlation was found between NAFLD and sphingosine-1-phosphate (S1P), the role of the sphingolipid remains controversial. The aim of this study was to investigate any involvement of S1P in steatosis using its analog FTY720P and HepG2 cells. Lipid accumulation was induced by incubating the cells in a mixture of oleic and palmitic acid, and was quantified using Oil Red O. The involvement of signaling mediators was studied using pharmacological inhibitors and western blot analysis. FTY720P increased lipid accumulation, but this increase wasn't maintained in the presence of inhibitors of S1PR3, Gq, SREBP, mTOR, PI3K, and PPARγ indicating their involvement in the process. The results revealed that FTY720P binds to S1PR3 which activates sequentially Gq, PI3K, and mTOR leading to an increase in SREBP expression and PPARγ activation. It was concluded that in presence of a high level of fatty acids, lipid accumulation is increased in hepatocytes by the exogenously added FTY720P. [ABSTRACT FROM AUTHOR]

Fisetin (FST) is a naturally occurring flavonol that has recently emerged as a bioactive phytochemical with an impressive array of biological activities. To the author knowledge, boosting the activity of FST against severe acute pancreatitis (SAP) through a nanostructured delivery system (Nanophytomedicine) has not been achieved before. Thereupon, FST-loaded lipid polymer hybrid nanoparticles (FST-loaded LPHNPs) were prepared through conjoined ultrasonication and double emulsion (w/o/w) techniques. Comprehensive in vitro and in vivo evaluations were conducted. The optimized nanoparticle formula displayed a high entrapment efficiency % of 61.76 ± 1.254%, high loading capacity % of 32.18 ± 0.734, low particle size of 125.39 ± 0.924 nm, low particle size distribution of 0.357 ± 0.012, high zeta potential of + 30.16 ± 1.416 mV, and high mucoadhesive strength of 35.64 ± 0.548%. In addition, it exhibited a sustained in vitro release pattern of FST. In the in vivo study, oral pre-treatment of FST-loaded LPHNPs protected against l-arginine induced SAP and multiple organ injuries in rats compared to both FST alone and plain LPHNPs, as well as the untreated group, proven by both biochemical studies, that included both amylase and lipase activities, and histochemical studies of pancreas, liver, kidney and lungs. Therefore, the study could conclude the potential efficacy of the novel phytopharmaceutical delivery system of FST as a prophylactic regimen for SAP and consequently, associated multiple organ injuries. [ABSTRACT FROM AUTHOR]

We studied diverse prenylated intrinsically disordered regions (PIDRs) of Ras and Rho family small GTPases using long timescale atomistic molecular dynamics simulations in an asymmetric model membrane of phosphatidylcholine (PC) and phosphatidylserine (PS) lipids. Here we show that conformational plasticity is a key determinant of lipid sorting by polybasic PIDRs and provide evidence for lipid sorting based on both headgroup and acyl chain structures. We further show that conformational ensemble-based lipid recognition is generalizable to all polybasic PIDRs, and that the sequence outside the polybasic domain (PBD) modulates the conformational plasticity, bilayer adsorption, and interactions of PIDRs with membrane lipids. Specifically, we find that palmitoylation, the ratio of basic to acidic residues, and the hydrophobic content of the sequence outside the PBD significantly impact the diversity of conformational substates and hence the extent of conformation-dependent lipid interactions. We thus propose that the PBD is required but not sufficient for the full realization of lipid sorting by prenylated PBD-containing membrane anchors, and that the membrane anchor is not only responsible for high affinity membrane binding but also directs the protein to the right target membrane where it participates in lipid sorting. Conformational plasticity is a key determinant of lipid sorting by polybasic prenylated intrinsically disordered regions and lipid sorting might be based on both headgroup and acyl chain structures. [ABSTRACT FROM AUTHOR]

Sphingolipids play crucial roles in cellular membranes, myelin stability, and signalling responses to physiological cues and stress. Among them, sphingosine 1-phosphate (S1P) has been recognized as a relevant biomarker for neurodegenerative diseases, and its analogue FTY-720 has been approved by the FDA for the treatment of relapsing–remitting multiple sclerosis. Focusing on these targets, we here report three novel polymeric capture phases for the selective extraction of the natural biomarker and its analogue drug. To enhance analytical performance, we employed different synthetic approaches using a cationic monomer and a hydrophobic copolymer of styrene-DVB. Results have demonstrated high affinity of the sorbents towards S1P and fingolimod phosphate (FTY-720-P, FP). This evidence proved that lipids containing phosphate diester moiety in their structures did not constitute obstacles for the interaction of phosphate monoester lipids when loaded into an SPE cartridge. Our suggested approach offers a valuable tool for developing efficient analytical procedures. [ABSTRACT FROM AUTHOR]

Lipid nanoparticles (LNPs) have been used as a carrier for messenger RNA (mRNA) vaccines. Surface properties of LNPs are important to the stability and function of mRNA vaccines. Polyethylene-glycol (PEG) is a functional lipid at the surface of LNPs that improves colloidal stability, increases circulation time, and impacts cellular uptake. In this study, we explore in-depth lipid composition at the surface of mRNA-LNPs using high-field nuclear magnetic resonance (NMR) spectroscopy. Our results provide a unique surface lipid profile of intact LNPs identifying PEG chains and partial ionizable lipids are present with quantification capability. The surface PEG density is determined to reveal the brush-like conformation on the surface of mRNA-LNPs. Furthermore, we implement a diffusion NMR strategy for routine testing of formulated drug products during drug development. Comparative NMR analysis of different vaccine preparations and stability samples provides a global view of the mRNA-LNP surface structure for enhanced product knowledge. [ABSTRACT FROM AUTHOR]

The incidence of osteoarthritis (OA) has been expected to increase due to an aging population, as well as an increased incidence of intra-articular (osteo-) chondral damage. Lipids have already been shown to be involved in the inflammatory process of OA. This study aims at revealing region-specific lipid profiles of the infrapatellar fat pad (IPFP) of OA or cartilage defect patients by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), which could be used as biomarkers for early OA detection. A higher presence of phospholipids was found in OA patients compared with cartilage defect patients. In addition, a higher abundance of ether-linked phosphatidylethanolamines (PE O-s) containing arachidonic acid was specifically found in OA patients compared with cartilage defect patients. These lipids were mainly found in the connective tissue of the IPFP. Specific lipid species were associated to OA patients compared with cartilage defect patients. PE O-s have been suggested as possible biomarkers for OA. As these were found more abundantly in the connective tissue, the IPFP's intra-tissue heterogeneity might play an important role in biomarker discovery, implying that the amount of fibrous tissue is associated with OA. [ABSTRACT FROM AUTHOR]

Recently, lipid nanoparticles have been intensively studied as carriers of lipophilic drugs. In this work, we have studied the stability of nanoemulsions with paraffin oil, solid lipid nanoparticles with stearic acid, and nanostructured lipid particles with paraffin oil and stearic acid in a mass ratio of 1 : 1. The obtained results have shown that all studied lipid systems stabilized with nonionic surfactants Tween 60 and Span 60 were stable to aggregation and subsequent sedimentation for more than 30 days. The incorporation of lutein into the lipid particles has almost no effect on their stability, while the size of solid lipid nanoparticles and nanostructured lipid nanoparticles decreases from 28–30 to 15–17 nm. The bioavailability of lutein loaded in lipid nanoparticles is evaluated from their effect on the restoration of blood flow velocity by simulating hemic hypoxia. Almost immediately after the application of lipid nanoparticles, the blood flow velocity ceases to decrease, and a tendency to its restoration is observed in 5–10 min. This shows that lipid nanoparticles with paraffin oil and stearic acid are promising candidates for the delivery of lipophilic drugs. [ABSTRACT FROM AUTHOR]

The development of new efficient methods for combating serious diseases, among which, oncological and infectious diseases hold a special place, remains to be an urgent challenge of biomedicine and biotechnology. Currently, the efforts of scientists are focused on the search for drug systems that provide high efficiency of treatment with minimal impacts on a human body. The development of this field has led to the creation of stimuli-responsive liposomes that can release an encapsulated drug under a specific stimulus, such as temperature, pH, electromagnetic field, light, etc. Being stimulated, lipid bilayer vesicles change their structure, size, surface charge, or phase state, thus leading to a controlled release of the drug in a specific place of the body, thereby resulting in a more accurate and efficient delivery. This review discusses the current trends in the development of liposome-based stimuli-responsive systems for the controlled delivery of biologically active substances. [ABSTRACT FROM AUTHOR]