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Objective: The aim of this study was to examine the correlation between maternal body composition during the second trimester and the occurrence of dyslipidemia in the third trimester. Methods: A cohort of 1508 pregnant women who underwent antenatal testing at Shanghai Sixth People's Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, were included in this study. Maternal body composition was assessed using bioimpedance analysis between 14 and 22 weeks of gestation. Results: Among the 1508 participants, a total of 1420 individuals (94.2%) were diagnosed with dyslipidemia. Notably, there were significant differences in body composition between the normal lipid group and the dyslipidemia group. Logistic regression analysis revealed that various factors including BMI, total body water (TBW), intra-cellular water (ICW), extra-cellular water (ECW), percent body fat (PBF), visceral fat area (VFA), fat-free mass (FFM) and arm circumference (AC) during the second trimester were all found to be associated with dyslipidemia in the third trimester. Conclusion: The present study found that maternal body composition was associated with dyslipidemia. The BMI, TBW, ICW, ECW, PBF, VFA, FFM and AC in second trimester were associated with dyslipidemia in third trimester. [ABSTRACT FROM AUTHOR]

Platelet hyperreactivity and hyperlipidaemia contribute significantly to atherosclerosis. Thus, it is desirable to review the platelet–hyperlipidaemia interplay and its impact on atherogenesis. Native low‐density lipoprotein (nLDL) and oxidized LDL (oxLDL) are the key proatherosclerotic components of hyperlipidaemia. nLDL binds to the platelet‐specific LDL receptor (LDLR) ApoE‐R2′, whereas oxLDL binds to the platelet‐expressed scavenger receptor CD36, lectin‐type oxidized LDLR 1 and scavenger receptor class A 1. Ligation of nLDL/oxLDL induces mild platelet activation and may prime platelets for other platelet agonists. Platelets, in turn, can modulate lipoprotein metabolisms. Platelets contribute to LDL oxidation by enhancing the production of reactive oxygen species and LDLR degradation via proprotein convertase subtilisin/kexin type 9 release. Platelet‐released platelet factor 4 and transforming growth factor β modulate LDL uptake and foam cell formation. Thus, platelet dysfunction and hyperlipidaemia work in concert to aggravate atherogenesis. Hypolipidemic drugs modulate platelet function, whereas antiplatelet drugs influence lipid metabolism. The research prospects of the platelet–hyperlipidaemia interplay in atherosclerosis are also discussed. [ABSTRACT FROM AUTHOR]

SCARF1 (scavenger receptor class F member 1, SREC-1 or SR-F1) is a type I transmembrane protein that recognizes multiple endogenous and exogenous ligands such as modified low-density lipoproteins (LDLs) and is important for maintaining homeostasis and immunity. But the structural information and the mechanisms of ligand recognition of SCARF1 are largely unavailable. Here, we solve the crystal structures of the N-terminal fragments of human SCARF1, which show that SCARF1 forms homodimers and its epidermal growth factor (EGF)-like domains adopt a long-curved conformation. Then, we examine the interactions of SCARF1 with lipoproteins and are able to identify a region on SCARF1 for recognizing modified LDLs. The mutagenesis data show that the positively charged residues in the region are crucial for the interaction of SCARF1 with modified LDLs, which is confirmed by making chimeric molecules of SCARF1 and SCARF2. In addition, teichoic acids, a cell wall polymer expressed on the surface of gram-positive bacteria, are able to inhibit the interactions of modified LDLs with SCARF1, suggesting the ligand binding sites of SCARF1 might be shared for some of its scavenging targets. Overall, these results provide mechanistic insights into SCARF1 and its interactions with the ligands, which are important for understanding its physiological roles in homeostasis and the related diseases.

Aim. The aim of this cross-sectional retrospective study was to study the effect of SARS-CoV-2 S1/S2 infection on population lipid parameters, which are leading risk factors for the development and progression of atherosclerosis, which can be significantly distorted in systemic inflammation and, in particular, during respiratory viral infections.Material and methods. We analyzed anonymized results of one-time, one-year studies of complete lipid profiles and related laboratory parameters performed in the Helix Laboratory Service from February 1, 2015 to December 30, 2020 in 238541 males and 384437 females aged from 22 to 83 years in 334 populated areas of the European Russia using Roche Cobas C502, C702 (Roche Diagnostics GmbH, Mannheim, Germany), LIAISON XL (DiaSorin S.p.A, Italy) analyzers.Statistical analysis included methods of descriptive statistics, distribution analysis, sample comparisons, and search for dependencies.Results. A dramatic change in the magnitude and nature of seasonal population fluctuations in low-density lipoprotein cholesterol and high-density lipoprotein cholesterol (HDL-C) during the COVID-19 spread has been identified.COVID-19 differentially affects the relationship between high-sensitivity C-reactive protein (hsCRP) and atherogenic and antiatherogenic lipoproteins. These relationships have sex differences, are nonlinear, and in relation to HDL-C are associated with the level of specific anti-SARS-CoV-2 S1/S2 antibodies.Up to a hsCRP level of 2,5 mg/l, there is a significant increase in population levels of low-density lipoprotein cholesterol with a correlation coefficient of 0,14 for women (p2,5 mg/l, the trend reverses. At the same time, HDL-C levels sharply decrease with a negative correlation of -0,23 (p

Atherosclerosis is a chronic inflammatory vascular disease caused by various risk factors, in particular smoking, obesity, high blood pressure, and dyslipidemia. In addition, such signaling pathways as NLRP3 inflammasome, toll-like receptors, proprotein convertase subtilisin/kexin type 9, Notch and Wnt, which are associated with the inflammatory response in the human body, are involved in the pathogenesis of atherosclerosis. Therapeutic targeting of inflammatory pathways, especially the NLRP3 inflammasome pathway and the cascade of reactions regulated by it leading to the production of inflammatory interleukin-1β, may represent a new avenue for the treatment of atherosclerotic diseases. This article summarizes knowledge of the cellular participants and key inflammatory signaling pathways in atherosclerosis, discusses preclinical studies targeting these key pathways in atherosclerosis, clinical trials that will target some of these processes, and the effects of suppressing inflammation and atherosclerosis.

Hokkaido University (Tsumita T, 2022) researchers found that endothelial cells accumulate low-density lipoproteins (LDL) in tumor blood vessels. At the same time, the endothelium carries out neutrophil chemotaxis, which perform an immunosuppressive function contributing to cancer progression.Aim. To search for the relationship between the white blood cell (WBC) count and some lipid profile parameters in cancer patients with myocardial infarction (MI).Material and methods. We examined 319 patients who were treated at Dzhanelidze Research Institute of Emergency Medicine in 2018-2023, which were divided into three groups: MI in combination with an active cancer — 132 patients (Group I), MI+cancer in history — 58 patients (Group II), MI without cancer — 129 patients (Group III). Following laboratory data used in routine practice were assessed: WBC count, relative neutrophil count, total cholesterol, low-density lipoproteins.Results. Cancer patients with MI are characterized by higher WBC and neutrophil count than in other samples However, the total cholesterol level was significantly lower in this sample, and the LDL level was not significantly different. Patients with MI and previous cancer occupied an intermediate position between groups I and III in terms of studied parameters.Conclusion. In general, data on the role of cholesterol levels in cancer patients are contradictory. In particular, some studies have shown that elevated cholesterol levels are a potential risk factor for cancer. In our study, as in a number of others, no significant associations were identified between elevated cholesterol levels and the presence of cancer. Our study is a step towards understanding the connection between the cholesterol concentration and the immune response in cancer patients with MI.

Abstract Background The accurate measurement of Low-density lipoprotein cholesterol (LDL-C) is critical in the decision to utilize the new lipid-lowering therapies like PCSK9-inhibitors (PCSK9i) for high-risk cardiovascular disease patients that do not achieve sufficiently low LDL-C on statin therapy. Objective To improve the estimation of low LDL-C by developing a new equation that includes apolipoprotein B (apoB) as an independent variable, along with the standard lipid panel test results. Methods Using β-quantification (BQ) as the reference method, which was performed on a large dyslipidemic population (N = 24,406), the following enhanced Sampson-NIH equation (eS LDL-C) was developed by least-square regression analysis: $$eS\,LDL-C= \frac{TC}{1.15}-\frac{HDL-C}{1.25}-\frac{TG}{6.99}-\frac{\left(TG\times NonHDL-C\right)}{1120}+\frac{{TG}^{2}}{8910}+\frac{\left(TG\times ApoB\right)}{1240}+\frac{ApoB}{4.54}-4.73$$ e S L D L - C = TC 1.15 - H D L - C 1.25 - TG 6.99 - T G × N o n H D L - C 1120 + TG 2 8910 + T G × A p o B 1240 + ApoB 4.54 - 4.73 Results The eS LDL-C equation was the most accurate equation for a broad range of LDL-C values based on regression related parameters and the mean absolute difference (mg/dL) from the BQ reference method (eS LDL-C: 4.51, Sampson-NIH equation [S LDL-C]: 6.07; extended Martin equation [eM LDL-C]: 6.64; Friedewald equation [F LDL-C]: 8.3). It also had the best area-under-the-curve accuracy score by Regression Error Characteristic plots for LDL-C

Introduction: Depression is one of the leading causes of morbidity worldwide. It can impact various biomarkers, including proteins, monoamines, and lipids. Lipids play a critical role in regulating cellular function by influencing transport, anchoring, and providing structural support. The present study aimed to explore any correlation between lipid profiles and depression. Aim: To investigate the correlation between different lipid profile parameters (serum triglycerides, total cholesterol, serum Highdensity Lipoproteins (HDL), and Low-density Lipoproteins (LDL) levels) and the severity of depression. Materials and Methods: A hospital-based, cross-sectional study was conducted at the Department of Psychiatry, Faculty of Medicine and Health Sciences, SGT University, Gurugram, Haryana, India, from June 2020 to June 2021. A total of 200 participants aged 18-65 years, diagnosed with depression according to the ICD-10 classification, were enrolled. Clinical assessments were conducted, and the Hamilton Depression Rating Scale (HAM-D) (17 items) and Beck's Depression Inventory II (BDI II) (21-item scale) were used. Lipid parameters were obtained from fasting blood samples. The Wilcoxon’sMann-Whitney U test was applied to assess the association between gender distribution and lipid profiles. Spearman's correlation test was used to analyse the correlation between HAM-D and BDI scores with lipid profiles. Statistical significance was set at a p-value ≤0.05. Results: The mean age of the participants was 36.05±11.24 years. Correlations between HAM-D levels and lipid profiles revealed that all lipid parameters, except for HDL (which showed a negative correlation), were positively associated with HAM-D scores. These correlations were statistically significant (p ≤0.05). Similarly, a positive correlation was observed between all lipid levels and BDI scores, except for HDL, which exhibited a negative correlation. These correlations were also statistically significant (p≤0.05). Conclusion: Higher levels of LDL cholesterol were found to be associated with elevated depression rating scale scores and increased susceptibility to depression. On the other hand, HDL cholesterol demonstrated protective effects against depression. Adopting a healthy lifestyle, implementing dietary measures, and addressing stressors promptly may help prevent depressive symptoms.

Oxidative stress is one of the primary instigators of the onset of various human ailments, including cancers, cardiovascular diseases, and dementia. Particularly, oxidative stress severely affects low-density lipid & protein (LDL) oxidation, leading to several detrimental health effects. Therefore, in this study, the effect of beeswax alcohol (BWA) was evaluated in the prevention of LDL oxidation, enhancement of paraoxonase 1 (PON-1) activity of high-density lipid & protein (HDL), and zebrafish embryo survivability. Furthermore, the implication of BWA consumption on the oxidative plasma variables was assessed by a preliminary clinical study on middle-aged and older human subjects (n = 50). Results support BWA augmentation of PON-1 activity in a dose-dependent manner (10–30 μM), which was significantly better than the effect exerted by coenzyme Q10 (CoQ10). Moreover, BWA significantly curtails LDL/apo-B oxidation evoked by CuSO4 (final 0.5 μM) and a causes a marked reduction in lipid peroxidation in LDL. The transmission electron microscopy (TEM) analysis revealed a healing effect of BWA towards the restoration of LDL morphology and size impaired by the exposure of Cu2+ ions (final 0.5 μM). Additionally, BWA counters the toxicity induced by carboxymethyllysine (CML, 500 ng) and rescues zebrafish embryos from development deformities and apoptotic cell death. A completely randomized, double-blinded, placebo-controlled preliminary clinical study on middle- and older-aged human subjects (n = 50) showed that 12 weeks of BWA (100 mg/day) supplementation efficiently diminished serum malondialdehyde (MDA) and total hydroperoxides and enhanced total antioxidant status by 25%, 27%, and 22%, respectively, compared to the placebo-control and baseline values. Furthermore, the consumption of BWA did not exhibit any noteworthy changes in physical variables, lipid profile, glucose levels, and biomarkers pertinent to kidney and liver function, thus confirming the safety of BWA for consumption. Conclusively, in vitro, BWA prevents LDL oxidation, enhances PON-1 activity in HDL, and positively influences oxidative variables in human subjects.

Background Childhood cancer survivors have increased risk of dyslipidemia and atherosclerotic cardiovascular disease (CVD). The aim of this study was to evaluate the prevalence and associated cardiovascular risks of specific lipid abnormalities among childhood cancer survivors. Methods Comprehensive lipid panel measurements were obtained from 4115 5-year survivors, with 3406 (mean age at evaluation = 35.2 years, SD = 10.4 years) not having previous dyslipidemia diagnosis, as well as 624 age, sex, and race and ethnicity matched community controls. Results Previously undiagnosed dyslipidemia with abnormal low-density lipoprotein (LDL) cholesterol (>160 mg/dL), non–high density lipoprotein (HDL) cholesterol (>190 mg/dL), HDL cholesterol (<40 mg/dL for men, <50 mg/dL for women), and triglycerides (>150 mg/dL) were identified in 4%, 6%, 30%, and 17%, respectively. Survivors without previous dyslipidemia diagnosis had higher LDL cholesterol and non-HDL cholesterol and lower HDL cholesterol than community controls. Cranial radiotherapy (relative risk [RR] = 2.2, 95% confidence interval [CI] = 1.6 to 3.0 for non-HDL cholesterol) and total body irradiation for hematopoietic cell transplantation (RR = 6.7, 95% CI = 3.5 to 13.0 for non-HDL cholesterol; RR = 9.9, 95% CI = 6.0 to 16.3 for triglycerides) were associated with greater risk of dyslipidemia. Diagnoses of low HDL cholesterol (hazard ratio [HR] = 2.9, 95% CI = 1.8 to 4.7) and elevated triglycerides (HR = 3.1, 95% CI = 1.9 to 5.1) were associated with increased risk for myocardial infarction, and diagnoses of high LDL cholesterol (HR = 2.2, 95% CI = 1.3 to 3.7), high non-HDL cholesterol (HR = 2.2, 95% CI = 1.3 to 3.7), low HDL cholesterol (HR = 3.9, 95% CI = 2.8 to 5.4), and elevated triglycerides (HR = 3.8, 95% CI = 2.7 to 5.5) were associated with increased risk for cardiomyopathy. Conclusions Previously undiagnosed dyslipidemia among childhood cancer survivors was associated with increased risk for myocardial infarction and cardiomyopathy. Comprehensive dyslipidemia evaluation and treatment are needed to reduce cardiovascular morbidity in this population. [ABSTRACT FROM AUTHOR]

Miniature Schnauzer dogs (MSs) are predisposed to both idiopathic hypertriglyceridemia (iHTG) and hypercortisolism (HCort). To our knowledge, the lipoprotein profiles of MSs with iHTG have not been compared to those with HCort. We analyzed cholesterol and triglyceride concentrations and lipoprotein fractions in 4 groups of MSs: normotriglyceridemia (NTG) without concurrent disease (Healthy-NTG), HCort and NTG (HCort-NTG), HCort and HTG (HCort-HTG), and iHTG. Lipoprotein fractions were assessed by lipoprotein electrophoresis and compared between groups. Fifty-one plasma samples were analyzed. Twenty-five dogs had NTG (16 Healthy-NTG, 9 HCort-NTG) and 26 dogs had HTG (7 iHTG, 19 HCort-HTG). Dogs with iHTG or HCort-HTG had significantly higher cholesterol concentrations than Healthy-NTG dogs. Dogs with HCort-HTG had higher cholesterol than HCort-NTG dogs. There was a significantly higher low-density lipoprotein (LDL) percentage in iHTG and HCort-HTG dogs than HCort-NTG dogs. HCort-HTG dogs also had lower high-density lipoproteins (HDL) than HCort-NTG dogs. It was not possible to readily distinguish MSs with iHTG from MSs with HCort-HTG or Healthy-NTG using lipoprotein electrophoresis fractions. The diagnosis of iHTG remains a diagnosis by exclusion. [ABSTRACT FROM AUTHOR]

Obesity and overweight, frequently caused by a lack of exercise, are associated with many metabolic diseases, such as hypertension, diabetes, and dyslipidemia. Aerobic exercise effectively increases the high-density lipoproteins-cholesterol (HDL-C) levels and alleviates the triglyceride (TG) levels. The consumption of Cuban policosanol (Raydel®) is also effective in enhancing the HDL-C quantity and HDL functionality to treat dyslipidemia and hypertension. On the other hand, no study has examined the effects of a combination of high-intensity exercise and policosanol consumption in obese subjects to improve metabolic disorders. In the current study, 17 obese subjects (average BMI 30.1 ± 1.1 kg/m2, eight male and nine female) were recruited to participate in a program combining exercise and policosanol (20 mg) consumption for 12 weeks. After completion, their BMI, waist circumference, total fat mass, systolic blood pressure (SBP), and diastolic blood pressure (DBP) reduced significantly up to around −15%, −13%, −33%, −11%, and −13%, respectively. In the serum lipid profile, at Week 12, a significant reduction was observed in the total cholesterol (TC) and triglyceride (TG) levels, up to −17% and −54% from the baseline, respectively. The serum HDL-C was elevated by approximately +12% from the baseline, as well as the percentage of HDL-C in TC, and HDL-C/TC (%), was enhanced by up to +32% at Week 12. The serum coenzyme Q10 (CoQ10) level was increased 1.2-fold from the baseline in all participants at Week 12. In particular, the male participants exhibited a 1.4-fold increase from the baseline. The larger rise in serum CoQ10 was correlated with the larger increase in the serum HDL-C (r = 0.621, p = 0.018). The hepatic function parameters were improved; the serum γ-glutamyl transferase decreased at Week 12 by up to −55% (p < 0.007), while the aspartate aminotransferase and alanine transaminase levels diminished within the normal range. In the lipoprotein level, the extent of oxidation and glycation were reduced significantly with the reduction in TG content. The antioxidant abilities of HDL, such as paraoxonase (PON) and ferric ion reduction ability (FRA), were enhanced significantly by up to 1.8-fold and 1.6-fold at Week 12. The particle size and number of HDL were elevated up to +10% during the 12 weeks, with a remarkable decline in the TG content, glycation extent, and oxidation. The improvements in HDL quality and functionality were linked to the higher survivability of adult zebrafish and their embryos, under the co-presence of carboxymethyllysine (CML), a pro-inflammatory molecule known to cause acute death. In conclusion, 12 weeks of Cuban policosanol (Raydel®, 20 mg) consumption with high-intensity exercise displayed a significant improvement in blood pressure, body fat mass, blood lipid profile without liver damage, CoQ10 metabolism, and renal impairment. [ABSTRACT FROM AUTHOR]

Introduction: Depression is one of the leading causes of morbidity worldwide. It can impact various biomarkers, including proteins, monoamines, and lipids. Lipids play a critical role in regulating cellular function by influencing transport, anchoring, and providing structural support. The present study aimed to explore any correlation between lipid profiles and depression. Aim: To investigate the correlation between different lipid profile parameters (serum triglycerides, total cholesterol, serum High-density Lipoproteins (HDL), and Low-density Lipoproteins (LDL) levels) and the severity of depression. Materials and Methods: A hospital-based, cross-sectional study was conducted at the Department of Psychiatry, Faculty of Medicine and Health Sciences, SGT University, Gurugram, Haryana, India, from June 2020 to June 2021. A total of 200 participants aged 18-65 years, diagnosed with depression according to the ICD-10 classification, were enrolled. Clinical assessments were conducted, and the Hamilton Depression Rating Scale (HAM-D) (17 items) and Beck's Depression Inventory II (BDI II) (21-item scale) were used. Lipid parameters were obtained from fasting blood samples. The Wilcoxon's-Mann-Whitney U test was applied to assess the association between gender distribution and lipid profiles. Spearman's correlation test was used to analyse the correlation between HAM-D and BDI scores with lipid profiles. Statistical significance was set at a p-value ≤0.05. Results: The mean age of the participants was 36.05±11.24 years. Correlations between HAM-D levels and lipid profiles revealed that all lipid parameters, except for HDL (which showed a negative correlation), were positively associated with HAM-D scores. These correlations were statistically significant (p ≤0.05). Similarly, a positive correlation was observed between all lipid levels and BDI scores, except for HDL, which exhibited a negative correlation. These correlations were also statistically significant (p≤0.05). Conclusion: Higher levels of LDL cholesterol were found to be associated with elevated depression rating scale scores and increased susceptibility to depression. On the other hand, HDL cholesterol demonstrated protective effects against depression. Adopting a healthy lifestyle, implementing dietary measures, and addressing stressors promptly may help prevent depressive symptoms. [ABSTRACT FROM AUTHOR]

A pilot randomized, double-blind placebo-controlled trial was conducted to assess the effects of orticumab, a monoclonal antibody that targets oxidized low-density lipoprotein (oxLDL), on coronary inflammation in patients with psoriasis. The study found that treatment with orticumab reduced the Fat Attenuation Index (FAI) score, a measure of coronary inflammation, in patients with high levels of inflammation but had no effect in those with low levels of inflammation. The study suggests that targeting oxLDL with orticumab may reduce coronary inflammation and potentially lower the risk of fatal cardiac events in patients with elevated inflammation. However, further research is needed to fully understand the mechanisms and clinical implications of this treatment. [Extracted from the article]

Obesity and overweight, frequently caused by a lack of exercise, are associated with many metabolic diseases, such as hypertension, diabetes, and dyslipidemia. Aerobic exercise effectively increases the high-density lipoproteins-cholesterol (HDL-C) levels and alleviates the triglyceride (TG) levels. The consumption of Cuban policosanol (Raydel®) is also effective in enhancing the HDL-C quantity and HDL functionality to treat dyslipidemia and hypertension. On the other hand, no study has examined the effects of a combination of high-intensity exercise and policosanol consumption in obese subjects to improve metabolic disorders. In the current study, 17 obese subjects (average BMI 30.1 ± 1.1 kg/m2, eight male and nine female) were recruited to participate in a program combining exercise and policosanol (20 mg) consumption for 12 weeks. After completion, their BMI, waist circumference, total fat mass, systolic blood pressure (SBP), and diastolic blood pressure (DBP) reduced significantly up to around −15%, −13%, −33%, −11%, and −13%, respectively. In the serum lipid profile, at Week 12, a significant reduction was observed in the total cholesterol (TC) and triglyceride (TG) levels, up to −17% and −54% from the baseline, respectively. The serum HDL-C was elevated by approximately +12% from the baseline, as well as the percentage of HDL-C in TC, and HDL-C/TC (%), was enhanced by up to +32% at Week 12. The serum coenzyme Q10 (CoQ10) level was increased 1.2-fold from the baseline in all participants at Week 12. In particular, the male participants exhibited a 1.4-fold increase from the baseline. The larger rise in serum CoQ10 was correlated with the larger increase in the serum HDL-C (r = 0.621, p = 0.018). The hepatic function parameters were improved; the serum γ-glutamyl transferase decreased at Week 12 by up to −55% (p < 0.007), while the aspartate aminotransferase and alanine transaminase levels diminished within the normal range. In the lipoprotein level, the extent of oxidation and glycation were reduced significantly with the reduction in TG content. The antioxidant abilities of HDL, such as paraoxonase (PON) and ferric ion reduction ability (FRA), were enhanced significantly by up to 1.8-fold and 1.6-fold at Week 12. The particle size and number of HDL were elevated up to +10% during the 12 weeks, with a remarkable decline in the TG content, glycation extent, and oxidation. The improvements in HDL quality and functionality were linked to the higher survivability of adult zebrafish and their embryos, under the co-presence of carboxymethyllysine (CML), a pro-inflammatory molecule known to cause acute death. In conclusion, 12 weeks of Cuban policosanol (Raydel®, 20 mg) consumption with high-intensity exercise displayed a significant improvement in blood pressure, body fat mass, blood lipid profile without liver damage, CoQ10 metabolism, and renal impairment.

SCARF1 (scavenger receptor class F member 1, SREC-1 or SR-F1) is a type I transmembrane protein that recognizes multiple endogenous and exogenous ligands such as modified low-density lipoproteins (LDLs) and is important for maintaining homeostasis and immunity. But the structural information and the mechanisms of ligand recognition of SCARF1 are largely unavailable. Here, we solve the crystal structures of the N-terminal fragments of human SCARF1, which show that SCARF1 forms homodimers and its epidermal growth factor (EGF)-like domains adopt a long-curved conformation. Then, we examine the interactions of SCARF1 with lipoproteins and are able to identify a region on SCARF1 for recognizing modified LDLs. The mutagenesis data show that the positively charged residues in the region are crucial for the interaction of SCARF1 with modified LDLs, which is confirmed by making chimeric molecules of SCARF1 and SCARF2. In addition, teichoic acids, a cell wall polymer expressed on the surface of gram-positive bacteria, are able to inhibit the interactions of modified LDLs with SCARF1, suggesting the ligand binding sites of SCARF1 might be shared for some of its scavenging targets. Overall, these results provide mechanistic insights into SCARF1 and its interactions with the ligands, which are important for understanding its physiological roles in homeostasis and the related diseases., Competing Interests: YW, FX, GL, CC, BY, ZZ, DK, FC, YL, ZF, LC, YY, YG, YH No competing interests declared, (© 2024, Wang, Xu, Li et al.)

Background and Aims: The criteria for the use of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) more restrictive than those approved were established in Catalonia by the Health System (CatSalut) to improve their efficiency, with different LDL-C values from which to start treatment according to risk factors. The aim of the study is to analyse adherence to these criteria and results., Methods: A retrospective study of patients treated with PCSK9i at Vall d'Hebron University Hospital between 2016 and 2021 was performed using data from the Registry of Patients and Treatments and medical records. The degree of agreement with the CatSalut criteria, LDL-C-responders (decrease ≥30%), cardiovascular events and discontinuations were analysed., Results: A total of 193 patients treated with PCSK9i were followed for a median of 27 months (IQR 23). The median age was 61 (IQR 15); 62.7% were men. Seventy percent of the patients had non-familial hypercholesterolemia. Treatment was for secondary prevention of cardiovascular disease in 82.4% of cases. The median LDL-C decreased from 139 (IQR 52) to 59 (IQR 45) mg/dL. The percentage of LDL-C reduction was 61.0% (IQR 30). In 72.5% of patients, all CatSalut criteria for starting treatment were met. The rate of responders was 85.4%. During follow-up, 19 patients (9.8%) had a cardiovascular event, and 15 (7.7%) discontinued treatment, in two cases due to toxicity., Conclusion: PCSK9i were used according to CatSalut criteria in three out of four cases. In this high-risk population, incidence of cardiovascular events was similar to that in clinical trials., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

[Display omitted] [ABSTRACT FROM AUTHOR]

Hypothyroidism, also known as underactive thyroid, is a condition where the thyroid gland does not produce enough thyroid hormone. Deficiency or lack of thyroid hormone causes patients to have a slower metabolism, which may lead to secondary medical issues such as weight gain, fatigue, depression, and increased cardiovascular risk. This systematic review aims to explore the effect of levothyroxine therapy on the lipid profile of hypothyroid patients. Through a comprehensive search, 3096 articles were retrieved using keywords such as Hypothyroidism, Levothyroxine, Lipid, Dyslipidemia, and Cholesterol from PubMed, PubMed Central, Google Scholar, and ScienceDirect databases. The Medical Subject Headings (MeSH) strategy was also leveraged to extensively search the PubMed database. Research articles that were published from the year 2020 until May 2024, including randomized control trials, observational studies, meta-analyses, systematic reviews, literature reviews, and case reports, were included in the research. Research papers published before 2020, written in languages other than English, and animal studies were excluded. The 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria were used in the design of the systematic review. Levothyroxine therapy is the treatment of choice in patients suffering from hypothyroidism, and based on our review, the treatment has a positive impact, leading to a significant decrease in total cholesterol, low-density lipoproteins, and triglyceride values in hypothyroid patients. The research highlights the importance of starting timely levothyroxine therapy in hypothyroid patients to maintain normal lipid levels and reduce the associated cardiovascular risk., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Nishat et al.)

Background: Atherosclerosis is a chronic disease characterized by the increased infiltration and retention of LDL particles in arterial walls. There are several mechanisms underlying atherogenesis, with the pro-atherogenic modifications of LDL playing a significant role. One such modification of native LDL is desialylation, which is characterized by the removal of terminal sialic acid from ApoB-100 glycans that induces critical changes in the overall functionality of the LDL particle., Aims: The aim of this study was to model the desialylation of native LDL in mice, resembling a phenomenon previously observed in atherosclerotic patients., Objective: LDL desialylation was induced in C57BL/6J mice via the injection of exogenous neuraminidase. The degree of LDL desialylation and its duration were assessed. The impact of LDL desialylation on blood lipid levels was evaluated. Furthermore, the morphological alterations in the aorta during LDL desialylation in the bloodstream were examined., Method: The control group of C57BL/6J mice received saline injections, while the experimental group underwent a single injection of IgG-conjugated Vibrio cholerae neuraminidase. The LDL sialic acid levels were assessed 1-7 days post-injection using the Warren method and normalized to total protein content measured via the Lowry method. A similar protocol was followed for the subchronic administration of the IgG-neuraminidase conjugate over a 6-week period. The blood lipid profiles were analyzed using commercial kits. The atherosclerotic plaque burden in the mouse aorta was quantified using Oil Red O and hematoxylin-eosin staining., Result: A single administration of 20 mU IgG-neuraminidase conjugate resulted in decreased LDL sialic acid levels for 5 days, gradually recovering by days 6-7. Subchronic administration maintained reduced LDL sialic acid levels for up to 2 months. Notably, sustained LDL desialylation was associated with elevated LDL cholesterol levels., Conclusion: A sustained desialylation of LDL in C57BL/6J mice was achieved through subchronic administration of IgG-conjugated neuraminidase. This study provides an approach for sustained LDL desialylation in mice. Further studies using apolipoprotein E knockout mice and LDL desialylation will reveal the role of this process in the occurrence and development of atherosclerosis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The amount of the low-density lipoprotein receptor (LDLR) on the surface of hepatocytes is the primary determinant of plasma low-density lipoprotein (LDL)-cholesterol level. Although the synthesis and cellular trafficking of the LDLR have been well-documented, there is growing evidence of additional post-translational mechanisms that regulate or fine tune the surface availability of the LDLR, thus modulating its ability to bind and internalise LDL-cholesterol. Proprotein convertase subtilisin/kexin type 9 and the asialoglycoprotein receptor 1 both independently interact with the LDLR and direct it towards the lysosome for degradation. While ubiquitination by the E3 ligase inducible degrader of the LDLR also targets the receptor for lysosomal degradation, ubiquitination of the LDLR by a different E3 ligase, RNF130, redistributes the receptor away from the plasma membrane. The activity of the LDLR is also regulated by proteolysis. Proteolytic cleavage of the transmembrane region of the LDLR by γ-secretase destabilises the receptor, directing it to the lysosome for degradation. Shedding of the extracellular domain of the receptor by membrane-type 1 matrix metalloprotease and cleavage of the receptor in its LDL-binding domain by bone morphogenetic protein-1 reduces the ability of the LDLR to bind and internalise LDL-cholesterol at the cell surface. A better understanding of how the activity of the LDLR is regulated will not only unravel the complex biological mechanisms controlling LDL-cholesterol metabolism but also could help inform the development of alternative pharmacological intervention strategies for the treatment of hypercholesterolaemia., (© 2024 The Author(s).)

Oxidative stress is one of the primary instigators of the onset of various human ailments, including cancers, cardiovascular diseases, and dementia. Particularly, oxidative stress severely affects low-density lipid & protein (LDL) oxidation, leading to several detrimental health effects. Therefore, in this study, the effect of beeswax alcohol (BWA) was evaluated in the prevention of LDL oxidation, enhancement of paraoxonase 1 (PON-1) activity of high-density lipid & protein (HDL), and zebrafish embryo survivability. Furthermore, the implication of BWA consumption on the oxidative plasma variables was assessed by a preliminary clinical study on middle-aged and older human subjects ( n = 50). Results support BWA augmentation of PON-1 activity in a dose-dependent manner (10-30 μM), which was significantly better than the effect exerted by coenzyme Q 10 (CoQ 10 ). Moreover, BWA significantly curtails LDL/apo-B oxidation evoked by CuSO 4 (final 0.5 μM) and a causes a marked reduction in lipid peroxidation in LDL. The transmission electron microscopy (TEM) analysis revealed a healing effect of BWA towards the restoration of LDL morphology and size impaired by the exposure of Cu 2+ ions (final 0.5 μM). Additionally, BWA counters the toxicity induced by carboxymethyllysine (CML, 500 ng) and rescues zebrafish embryos from development deformities and apoptotic cell death. A completely randomized, double-blinded, placebo-controlled preliminary clinical study on middle- and older-aged human subjects ( n = 50) showed that 12 weeks of BWA (100 mg/day) supplementation efficiently diminished serum malondialdehyde (MDA) and total hydroperoxides and enhanced total antioxidant status by 25%, 27%, and 22%, respectively, compared to the placebo-control and baseline values. Furthermore, the consumption of BWA did not exhibit any noteworthy changes in physical variables, lipid profile, glucose levels, and biomarkers pertinent to kidney and liver function, thus confirming the safety of BWA for consumption. Conclusively, in vitro, BWA prevents LDL oxidation, enhances PON-1 activity in HDL, and positively influences oxidative variables in human subjects.