CHOLESTEROL

We aimed to investigate and compare the performance of C-reactive protein-triglyceride glucose index (CTI) and remnant cholesterol inflammation index (RCII) in carotid atherosclerotic plaque (CAP) risk prediction. We conducted a case-control study (2,888 age- and sex-matched pairs) and a prospective cohort study of 4,418 participants without CAP (median follow-up: 767 days). Multivariable logistic and Cox regression were used to assess the associations of CTI and RCII with CAP. Receiver operating characteristic (ROC), net reclassification index (NRI) and integrated discrimination improvement (IDI) were calculated. In the case-control study, increased CTI (OR: 1.45, 95% CI: 1.16-1.80) and RCII (OR: 1.95, 95% CI: 1.66-2.29) were significantly associated with increased CAP risk. Similar associations with CAP were also observed in the cohort for CTI (HR: 1.79, 95% CI: 1.32-2.44) and RCII (HR: 2.02, 95% CI: 1.60-2.54). Moreover, adding CTI and RCII showed improvements in CAP risk prediction beyond the traditional model, with the area under the ROC curve of 0.681 for CTI, 0.704 for RCII and 0.702 for RCII+CTI (p < 0.05). RCII showed a superior ability to identify high-risk individuals with CAP compared with CTI, with a significant NRI of 0.119 (95% CI: 0.045-0.191) and IDI of 0.006 (95% CI: 0.002-0.011). Both CTI and RCII were significantly associated with increased risk of CAP, and RCII may be a superior biomarker to CTI in CAP risk prediction. Future large-scale cohort studies are needed to validate the predictive value of CTI and RCII for subclinical atherosclerosis. Not applicable.

Cardiovascular disease (CVD) is a leading threat to long-term health in cancer survivors. This study aimed to evaluate whether integrating genetic risk with the composite cardiovascular health metric, the Life's Essential 8 (LE8) score, can improve primary prevention and guide personalized survivorship care in this population. We conducted a retrospective cohort study including 21,751 cancer survivors and 87,004 matched non-cancer controls from the UK Biobank. For each participant, a LE8 score, encompassing eight CVD-related factors (diet, physical activity, nicotine exposure, sleep, body mass index, blood pressure, blood glucose, and non-high-density lipoprotein cholesterol), and a polygenic risk score (PRS) for coronary artery disease (CAD) were calculated. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident risk of CAD across LE8 (or individual LE8 components) and PRS levels and to examine their potential interactions. A higher LE8 score and a lower PRS were independently associated with reduced CAD risk in cancer survivors. Participants with a high LE8 score and low PRS had the lowest CAD risk (HR 0.22; 95% CI, 0.09 0.53) when compared with those with a low LE8 score and high PRS. Similar patterns were observed in matched controls who had a lower CAD incidence rate. Associations between optimal blood lipid levels (as defined in the LE8 score) seemed to be more pronounced in individuals with high PRS, although it did not reach statistical significance among cancer survivors (p for interaction with PRS = 0.14 and 0.011, respectively, in cancer survivors and matched controls). Subgroup analyses showed consistent associations between LE8 score and CAD risk in breast, prostate, colorectal, and malignant skin cancer survivors, but not in those with lymphoma or hematologic malignancies. Furthermore, the association between LE8 score and CAD risk was stronger 5-10 years after cancer diagnosis and among younger cancer survivors aged under 55 years. Both a higher LE8 score and lower PRS for CAD were independently associated with substantially reduced risk of incident CAD.

Porokeratosis is a disorder of keratinisation linked to mevalonate pathway defects and often resistant to conventional therapy. Topical statins, which target this pathway directly, represent a rational mechanism-based treatment. A 63-year-old woman with disseminated superficial actinic porokeratosis (DSAP), refractory to calcipotriol and 5-fluorouracil, was treated with compounded simvastatin 2% cream twice daily. After 6 months, erythema and scale were markedly reduced; thin papules flattened almost completely, whereas hyperkeratotic plaques improved only partially. Treatment was well tolerated without systemic adverse effects, and the patient was maintained on once-daily application to prevent relapse. Evidence from 10 representative reports - including one randomised controlled trial (RCT) and one controlled split-body study - shows reproducible benefit of topical statins across DSAP and selected other variants. Early inflammatory lesions often flatten fastest, whereas older hyperkeratotic plaques improve more slowly; relapse has been reported after discontinuation, supporting the use of maintenance therapy. Safety is favourable, largely mild local irritation, with rare events such as allergic contact dermatitis to simvastatin and transient creatine kinase elevation/myalgia. The role of cholesterol co-formulation remains uncertain: the RCT found no added benefit, while split-face and case reports suggest activity of cholesterol alone in limited contexts. Standardised formulations and larger controlled trials are needed. Topical statins are a promising, low-toxicity therapy for porokeratosis. Larger, controlled studies are needed to standardise formulations, optimise maintenance, and confirm long-term safety.

Targeted and efficient delivery of nucleic acid therapeutics (NATs) is one of the major challenges in the development of next generation vaccine formulations. Glycosylated lipid nanoparticles (LNPs) utilising mannose as an active targeting ligand have the potential to improve NAT based treatments owing to their ability to bind to carbohydrate-binding protein receptors associated with immune cells. Addressing these receptors specifically results in improved cellular uptake and therefore more efficient delivery of the RNA cargo. Glycomacromolecules (GMs) with defined valency and configuration can distinguish between receptors and enhance the functionality of LNP-based formulations by pinpointing different cell types and enabling specific uptake. Therefore, in this study a library of nine discrete mannosylated GMs with a distinct stereoconfiguration were synthesised and incorporated into LNP membranes via cholesterol anchors. Established LNP formulations based on C12-200 are equipped with these GMs on their surface and evaluated for their biological performance. Surface plasmon resonance spectrometry (SPR) has been employed to investigate their binding properties with a variety of human lectins, to elucidate the avidity of both the individual GMs and the LNPs to the receptors, revealing specific lectin interactions. Additionally, the successful delivery of self-amplifying RNA (saRNA) in the glycosylated LNPs is analysed for cellular transfection efficiency in cell lines such as HEK293T/17, THP-1 and BMDC, and transfection efficiency is also evaluated in an ex vivo human skin explant model.

Congenital lipoid adrenal hyperplasia (lipoid CAH) is caused by pathogenic variants in STAR. In 46,XX patients, gonadotropin-driven cholesterol ester accumulation leads to premature ovarian insufficiency, with approximately one-third developing large ovarian cysts or torsion often requiring surgical intervention. No preventive strategy is established. We report a 46,XX patient treated with a gonadotropin-releasing hormone (GnRH) analog followed by estrogen and progestin, with longitudinal ovarian monitoring. An 18-year-old Japanese female was diagnosed with lipoid CAH neonatally based on failure to thrive, skin hyperpigmentation, electrolyte abnormalities, and bilateral adrenal hyperplasia with low attenuation on CT. Compound heterozygous STAR variants (p.Gln258* and p.Glu218Val) were identified. After spontaneous breast development at age 10 years, leuprorelin acetate was administered from age 10 years 4 months to 15 years 7 months. Transdermal estradiol was started at age 14 years and norethindrone at 14 years 11 months. The right ovarian cyst (13 mm, exceeding +2 SD before leuprorelin therapy) decreased to 6 mm within 6 months, and ovarian volumes normalized within 12 months. At age 18 years, no cysts, hypertrophy, or torsion had developed. This is the first reported case of lipoid CAH managed with GnRH analog-mediated gonadotropin suppression followed by estrogen and progestin administration. Both ovarian cyst diameter and volume improved and remained within the normal range over 8 years. This staged approach may prevent ovarian complications, although long-term effects on bone health, uterine maturation, and fertility require evaluation.

Heat stress is a major environmental constraint compromising poultry productivity, welfare, and health in tropical regions. This study evaluated the adaptive responses of five duck genotypes, including local Rupali, a BLRI-improved common duck with white plumage; Pekin, an exotic duck; F1, a crossbred (two-way crossing: Pekin ♂ x Rupali ♀); Muscovy duck, an exotic and H1, the first hybrid (three-way crossing: Muscovy ♂ x Pekin ♂ x Rupali ♀) under heat stress in tropical Bangladesh. A total of 200 ducklings (40 ducklings/genotype) were used in the study and allocated into 4 replicate groups per genotype (10 ducklings/group) housed in individual pens. The ducklings were exposed to elevated temperature in a controlled environmental chamber for 21 days. Respiration and panting rate, skin and rectal temperature, plasma corticosterone, immunological Y and M (IgY, IgM), cholesterol, triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), hemoglobin (Hb), heterophil to lymphocyte ratio (H/L ratio), white and red blood cells (WBC and RBC) count parameters were assessed at baseline (day 21), during acute heat stress (day 35), and after prolonged heat stress (day 42) period. Significant genotypic differences were observed in heat tolerance. H1 hybrid ducks exhibited comparatively balanced physiological and biochemical responses relative to the exotic genotypes under heat stress. These findings suggest that heterosis in H1 ducks may support partial metabolic stability and adaptive responses under heat stress conditions. The results support the potential use of H1 hybrids to enhance sustainable duck production in tropical environments.

The present study investigates the effect of 1,8-cineole on improving lipid metabolism disorder by regulating oxidative stress and inflammation via the TLR4/MyD88/NF-κB pathway. 1,8-Cineole is a monoterpene compound widely found in the essential oils of many plants and has been reported to possess anti-inflammatory and antioxidant activities. However, its role in regulating lipid metabolism disorders remains unclear. This study aimed to investigate the effects of 1,8-cineole on lipid metabolism and explore the potential mechanisms related to oxidative stress and inflammation. Cell viability was assessed by MTT assay to determine the optimal PA concentration for inducing lipid accumulation and the non-cytotoxic range of 1,8-cineole in HepG2 and AML-12 cells. Lipid droplets were visualized by Oil Red O staining, while triglyceride (TG) and total cholesterol (TC) levels were quantified using enzymatic kits. Oxidative stress markers (ROS by DCFH-DA fluorescence; MDA by TBA method; CAT activity by ammonium molybdate method) and inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-18 by ELISA) were measured. Western blotting analyzed key proteins in the TLR4/MyD88/NF-κB pathway (TLR4, MyD88, p-P65, p-IκBα). Pathway-specific inhibitors were employed for mechanistic validation. 1,8-Cineole (up to 1000 μg/mL) showed no cytotoxicity. It significantly attenuated PA-induced lipid droplet accumulation, reduced TG and TC levels ( p < 0.05), and ameliorated oxidative stress by decreasing ROS and MDA while enhancing CAT activity in AML-12 cells ( p < 0.01). Furthermore, 1,8-cineole suppressed pro-inflammatory cytokine release (TNF-α, IL-6, and IL-1β; p < 0.01), whereas no significant effect was observed on IL-18 levels. Downregulated TLR4/MyD88/NF-κB pathway activation. Inhibition of TLR4 or NF-κB mirrored these protective effects. 1,8-Cineole alleviates PA-induced lipid metabolism disorders, oxidative stress, and inflammation in hepatocytes, likely through suppression of the TLR4/MyD88/NF-κB signaling pathway.

To maintain its barrier function, human skin requires lipids, including cholesterol, ceramides, free fatty acids, and wax esters. In contrast to other skin lipids, wax esters remain largely unexplored as metabolites of the skin microbiome. Recently, we discovered that Staphylococcus aureus utilises its lipase Lip2 to detoxify antimicrobial fatty acids (AFAs) by esterification with cholesterol. The observed promiscuity of Lip2 and the presence of similar lipases among skin staphylococci prompted the search for novel substrates and products. Here, we identify S. aureus Lip2 and Lip1, Staphylococcus simulans SsL, and Staphylococcus epidermidis GehD and GehC as lipases capable of metabolizing wax esters. These lipases degraded wax esters into AFAs and fatty alcohols, and, except for GehC, shared the ability to esterify AFAs with fatty alcohols, thereby generating wax esters. In monocultures of bacteria heterologously expressing staphylococcal lipases, synthesis of wax esters mirrored protection from AFAs by fatty alcohols in planktonic or biofilm settings. In pairwise cocultures, lipases secreted by lipase-proficient S. aureus, S. simulans, and S. epidermidis functioned as public goods, rescuing lipase-deficient mutants. In the absence of detoxifying substrates/lipases, S. simulans or S. epidermidis outcompeted S. aureus when exposed to AFAs. A skin-mimicking high-salt environment increased the resistance of S. aureus, but not S. simulans, to AFAs, enabling S. aureus to match or outcompete S. simulans in the presence of AFAs or AFAs plus fatty alcohols, respectively. Collectively, our findings suggest that commensal modulation of skin lipids determines whether niche-specific communities are resilient or permissive to pathogenic invasion by S. aureus.

A typical case of eruptive xanthomas secondary to untreated type 2 diabetes mellitus complicated with severe hyperlipidemia was reported. The patient had a history of acute pancreatitis one month before the onset of xanthomas. Laboratory tests revealed high levels of triglycerides, cholesterol, blood glucose, and acute inflammatory markers. Histopathological examination showed the foam cells in the dermis. After interventions, including a low-fat and low-carbohydrate diet, anti-diabetic therapy and lipid-lowering therapy, the patient's skin lesions partially resolved within two months. At the same time, all laboratory indicators improved. In addition, a comprehensive literature review was conducted on the pathophysiological mechanisms, key clinical diagnostic points, triglyceride level thresholds, and main treatment strategies of eruptive xanthomas. This study emphasizes that eruptive xanthomas and acute pancreatitis are clinical manifestations induced by severe hypertriglyceridemia. For dermatologists, the occurrence of eruptive xanthomas should be used as a trigger to screen for dyslipidemia to effectively prevent life-threatening severe complications.

In this work, the effects of two UV filters - avobenzone and oxybenzone - on the membranes of fibroblasts and keratinocytes in ex vivo model systems (Langmuir monolayers) and cell line experiments were examined. The goal of these studies was to analyze the significance of lipid structures in the mechanism of UV filter-induced toxicity to skin cells. Monolayers composed of lipids characteristic of mammalian cell membranes - namely phosphatidylcholine (SOPC), sphingomyelin (SM), cholesterol (Chol) and ceramides (Ceramide 22 and Ceramide 17) - were used as model systems. Both mixed monolayers mimicking fibroblast and keratinocyte membranes and one-component lipid films were investigated. The surface pressure/area measurements and penetration studies were done, and Brewster angle microscopy was applied to verify the morphology of the studied systems. It was found that avobenzone has a stronger impact on molecular organization of skin cell model membranes than oxybenzone; however, its effect is concentration-limited. Both UV filters exhibited stronger affinity to Chol, SM and SOPC monolayers than to ceramides, which are the lipids characteristic for skin cells. Therefore, it can be suggested that ceramides may hinder the penetration of UV filter molecules into the interior of skin cells. Cell line model studied with SEM microscopy suggested that UV filters alter the skin cell membrane. Finally, it was summarized that the mechanism of UV filter toxicity is complex, but one of its important elements is the impact on the organization of lipid structures.

Oral isotretinoin is an indispensable treatment for patients with resistant and severe acne vulgaris, both in South Africa (SA) and globally. While routine laboratory monitoring is often deemed unnecessary for young, healthy patients, it remains unclear whether this applies in the SA context. To assess the need for routine blood monitoring for acne vulgaris patients on isotretinoin treatment at Tygerberg Hospital, SA. Specifically, we wanted primarily to determine the prevalence of patients with acne vulgaris whose oral isotretinoin treatment was altered owing to blood result abnormalities, and secondarily, to determine the prevalence of adverse events and liver function and lipid profile abnormalities associated with isotretinoin. This was a retrospective cohort study of hospital records from patients with acne vulgaris treated with oral isotretinoin at the dermatology clinic at Tygerberg Hospital between 1 January 2020 and 31 December 2023. There were 89 eligible records extracted from the Tygerberg Hospital Enterprise Content Management system. Baseline and 6-week follow-up laboratory data, including liver function tests and lipid profile, were extracted retrospectively from the National Health Laboratory Service. The sample comprised 89 patient hospital records, 62% male and 38% female. Of the total, 53% were aged between 12 and 20 years. Blood result abnormalities led to alterations in treatment regimens for 2/89 (2.2%) patients: one patient required treatment termination, while another continued on low-dose isotretinoin instead of the planned dose increase. Two patients (2.2%) developed increased aspartate aminotransferase levels and five (5.6%) developed new alanine aminotransferase increases above the upper limit of the normal range. Elevated triglyceride levels occurred in two patients (2.2%), and elevated cholesterol levels in nine (10.1%). Adverse events resulting in the premature termination of treatment with isotretinoin included one case of severe chest pain, one patient with pseudotumour cerebri and one patient who developed exuberant granulation tissue. This single-centre retrospective review highlights the scarcity of blood result abnormalities due to isotretinoin in patients with acne vulgaris. There were only two patients (2.2%) who had their management altered owing to blood result abnormalities, and both had chronic conditions. This may suggest that routine monitoring is indicated in patients with comorbidities, but not in otherwise healthy young patients with acne. However, larger prospective studies are needed in SA before such conclusions can be drawn.

Abdominal obesity (AO) significantly contributes to cardiometabolic diseases and poses an increasing public health challenge. Composite lipid-derived indices have been proposed as simple indicators of atherogenic dyslipidemia, but their relative importance for identifying AO at the population level remains incompletely understood. This study aimed to evaluate the link between various atherogenic lipid indices and AO, identifying key lipid-related predictors through interpretable machine learning methods. This cross-sectional study analyzed 5,612 adults from a population-based survey in Guangdong Province, China. Atherogenic lipid indices encompass the atherogenic index of plasma (AIP), non-high-density lipoprotein cholesterol (non-HDL-C), atherogenic coefficient (AC), Castelli risk indices I and II (CRI-I and CRI-II), lipid composite index (LCI), and the triglyceride-to-high-density lipoprotein cholesterol ratio (TG/HDL-C). Feature selection was conducted using Boruta and Least Absolute Shrinkage and Selection Operator (LASSO) methods prior to machine learning modeling. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, and F1 score. SHapley Additive exPlanations (SHAP) analysis was applied to quantify feature importance. Individuals with AO were generally older and more likely to exhibit lower education levels, reduced physical activity, cardiometabolic comorbidities, and unfavorable metabolic profiles. Feature selection identified 15 key predictors. Logistic regression demonstrated the most stable performance (training AUC: 0.767; testing AUC: 0.768; accuracy: 0.712; F1 score: 0.667) with good calibration and clinical utility. SHAP analysis consistently identified AIP, sex, CRI-II, uric acid, and diastolic blood pressure as the most influential predictors of AO. Composite lipid indices, particularly AIP and CRI-II, are strongly associated with AO and may serve as practical indicators for identifying individuals at elevated metabolic risk. Because these indices are derived from routinely measured lipid parameters, they may support scalable approaches for metabolic risk screening and monitoring in both clinical and community health settings.