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Dyslipidemia is a major contributor to the development of atherosclerotic cardiovascular disease. Despite high level of physical activity, athletes are not immune from dyslipidemia, but longitudinal data on the variation of lipids are currently lacking. We sought to assess lipid profile changes over time in Olympic athletes practicing different sports disciplines (power, skills, endurance, and mixed). We enrolled 957 consecutive athletes evaluated from London 2012 to Beijing 2022 Olympic Games. Dyslipidemia was defined as low-density lipoprotein (LDL) ≥115 mg/dl, high-density lipoprotein (HDL) <40 mg/dl for males, or HDL <50 mg/dl for females. Hypertriglyceridemia was defined as triglycerides >150 mg/dl. At the follow-up, a variation of ±40 mg/dl for LDL, ±6 mg/dl for HDL, and ±50 mg/dl for triglycerides was considered relevant. Athletes with follow-up <10 months or taking lower lipid agents were excluded. Follow-up was completed in 717 athletes (74.9%), with a mean duration of 55.6 months. Mean age was 27.2 ± 4.8 years old, 54.6% were male (n = 392). Overall, 19.8% (n = 142) athletes were dyslipidemic at both blood tests, being older, practicing nonendurance sports, and predominantly male. In 69.3% (n = 129) of those with elevated LDL at t0, altered values were confirmed at follow-up, while the same occurred in 36.5% (n = 15) with hypo-HDL and 5.3% (n = 1) in those with elevated triglycerides. Weight and fat mass percentage modifications did not affect lipid profile variation. LDL hypercholesterolemia tends to persist over time especially among male, older, and nonendurance athletes. LDL hypercholesterolemia detection in athletes should prompt early preventive intervention to reduce the risk of future development of atherosclerotic disease. [ABSTRACT FROM AUTHOR]

Cholesterol (Chol) plays a crucial role in shaping the intricate physicochemical attributes of biomembranes, exerting a considerable influence on water molecules proximal to the membrane interface. In this study, we conducted molecular dynamics simulations on the bilayers of two lipid species, dipalmitoylphosphatidylcholine (DPPC) and palmitoyl sphingomyelin; they are distinct with respect to the structures of the hydrogen-bond (H-bond) acceptors. Our investigation focuses on the dynamic properties and H-bonds of water molecules in the lipid-membrane systems, with a particular emphasis on the influence of Chol at varying temperatures. Notably, in the gel phase at 303 K, the presence of Chol extends the lifetimes of H-bonds of the oxygen atoms acting as H-bond acceptors within DPPC with water molecules by a factor of 1.5–2.5. In the liquid-crystalline phase at 323 K, on the other hand, H-bonding dynamics with lipid membranes remain largely unaffected by Chol. This observed shift in H-bonding states serves as a crucial key to unraveling the subtle control mechanisms governing water dynamics in lipid-membrane systems. [ABSTRACT FROM AUTHOR]

Purpose: Previous literature has demonstrated the mediating role of adiposity in the association between cardiorespiratory fitness (CRF) and cardiometabolic risk as well as the potential role of CRF in attenuating the adverse consequences associated with excess weight. This study aimed to evaluate the mediating role of CRF and adiposity in the possible association with cardiometabolic risk. Method: Observational 3-year longitudinal study that included 420 children and adolescents (10.50 [2.05] y of age at baseline; 56.2% girls). Body mass index (BMI) was calculated, and CRF was evaluated using field assessments. A clustered cardiometabolic risk score (cMetS) was calculated from glucose, systolic blood pressure, total cholesterol/high-density lipoprotein cholesterol ratio, and triglycerides z scores. Analyses evaluated the mediating role of BMI in the association between CRF and cMetS as well as whether CRF mediated the association between BMI and cMetS. Results: BMI at baseline was directly associated with the cMetS at follow-up (0.102; 95% confidence interval, 0.020 to 0.181), independently of CRF, whereas CRF was only indirectly associated with cMetS at follow-up through BMI (−0.036; 95% confidence interval, −0.070 to −0.009), meaning that the association between CRF and cMetS was explained via the mediation role of BMI. Conclusions: BMI presented direct association with cMetS, whereas CRF exhibited indirect association with cMetS mediated via BMI. [ABSTRACT FROM AUTHOR]

The quest to reduce dependency on fish‐ or vegetable‐based oil resources has prompted aquaculture experts to intensify their search for a suitable and sustainable alternative for aquafeed production. Based on this reality, the current study was designed to evaluate the dietary influence of African palm weevil oil (PWO) on the growth performance, serum biochemistry, lipid peroxidation products, antioxidant enzyme response, and organ integrity of African catfish (Clarias gariepinus) juveniles. Four diets were formulated, wherein the control diet was prepared using soybean oil (SO) as the main dietary oil source and was replaced with PWO in the treatment diets at 50% (PWO‐50), 75% (PWO‐75), or 100% (PWO‐100). A total of 180 African catfish (average weight: 18.76 ± 0.043) were randomly stocked at 15 fish per 50‐L tank in triplicate and hand‐fed to apparent satiation twice daily for 45 days. The results showed that the highest weight gain (WG), specific growth rate (SGR), and thermal growth coefficient (TGC) were found in control (SO)‐fed fish, which is similar to the PWO 50% but differs significantly from others (p < 0.05). The feed conversion ratio (FCR) and protein productive value (PPV) showed linear and quadratic trends, with a significantly lowest and highest value recorded in fish‐fed control and PWO 50%, respectively, compared to other dietary groups (p < 0.05). The protein efficiency ratio (PER) value decreases linearly (p < 0.001) as the level of PWO increases. The highest total immunoglobulin (TIG) and superoxide dismutase (SOD) activity were recorded in fish fed PWO‐50%, while PWO‐75% registered the highest lysozyme activity (LA). There was no statistically significant difference (p > 0.05) in the physiological parameters such as total cholesterol (TC), triglyceride (TG), low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein cholesterol (HDL‐C), alanine aminotransferase (ALT), C‐reactive protein (CRP), and lipid peroxidation index (malondialdehyde [MDA]) among the groups. The fish fed PWO‐100% had the lowest recorded values of villus height, area of absorption, and cryptal depth (p < 0.05). In summary, the current finding shows that oil extracted from African palm weevils appears promising at a 50% dietary level without impairing the growth performance, liver, or intestinal health of African catfish. [ABSTRACT FROM AUTHOR]

Background: Alterations in factors involved in cholesterol homeostasis are critical in Alzheimer's disease (AD), but the stage of occurrence, their specific association, and a possible relationship with the APOE4 genotype are not clarified. Objective: We aimed to quantify and correlate specific lipid factors in patients with different degrees of cognitive decline, namely patients with AD and patients with mild cognitive impairment due to AD (MCI-AD), carriers or non-carriers of the APOE4 genotype. Methods: We evaluated Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9), cholesterol and the oxidative metabolites 24-, 25-, 27-hydroxycholesterol (HC) in the cerebrospinal fluid (CSF) and serum of AD (n = 28) and MCI-AD (n = 27) patients. Results: CSF and serum PCSK9 and lipids were similar, except for higher serum PCSK9 and triglycerides in MCI-AD compared to AD. In CSF, AD APOE4 carriers showed higher PCSK9 and 24-HC (+61.3%, p = 0.027 and +32.7%, p = 0.037), compared to non-carriers. There was a negative association between CSF PCSK9 and 27-HC in AD (r = −0.444, p = 0.049) and, exclusively among AD APOE4 carriers, a negative association between CSF PCSK9 and 24-HC (r = −0.786, p = 0.028). A positive correlation was observed between CSF and serum PCSK9 in AD (r = 0.520, p = 0.004), driven by APOE4 carriers (r = 0.544, p = 0.038), suggesting PCSK9 exchange between brain and periphery. A positive correlation was detected between serum and CSF 27-HC (r = 0.465, p = 0.039) in AD. None of these results were found in MCI-AD patients. Conclusions: PCSK9 and 24-HC might be specific markers of ApoE4-associated lipid alterations in AD, possibly contributing to clinical progression in the AD continuum. [ABSTRACT FROM AUTHOR]

Macrophages are unique immune cells attracting growing attention as a potential candidate for cell‐based therapy for infectious diseases and cancer. Strategies that can reprogramme or gene‐edit macrophages hold potential across a spectrum of acute and chronic conditions. Herein, lipid nanoparticles (LNPs) are developed containing the ionizable lipid SM‐102, helper lipid monoolein which is known for self‐assembly in aqueous solutions into the inverse cubic lyotropic liquid crystalline mesophase, and cholesterol as an mRNA nanocarrier. The immortalized alveolar macrophage cell line (MH‐S cells) is utilized to investigate how cholesterol concentration impacts on mRNA delivery which is further validated using primary mouse alveolar macrophages isolated from the bronchoalveolar compartment and human monocyte derived macrophages. By using high‐throughput synchrotron small angle X‐ray scattering (SAXS), an acidification‐induced non‐ordered to ordered internal nanostructure transition of the formulated LNPs is observed, following the transition sequence of inverse micellar to hexagonal to cubic mesophase in the pH range from 7 to 4. Cholesterol is identified as another crucial component for superior mRNA transfection in macrophages, contributing to nanostructure transition and protein corona variation. Successful ex vivo mRNA transfection is also achieved in primary macrophages, highlighting the prospectivity of reprogramming macrophages as a cell therapy for lung diseases. [ABSTRACT FROM AUTHOR]

Cholesterol is an essential membrane component, and the metabolites from cholesterol play important biological functions to intricately support cancer progression and dampen immune responses. Preclinical and clinical studies have demonstrated the role of cholesterol metabolism regulation on inhibiting tumor growth, remodeling the immunosuppressive tumor microenvironment (TME), and enhancing anti‐tumor immunity. In this minireview, we discuss complex cholesterol metabolism in tumors, its important role in cancer progression, and its influences on immune cells in the TME. We provide an overview of recent advances in cancer treatment through regulating cholesterol metabolism. We discuss the design of cholesterol‐altering multifunctional nanomaterials to regulate oxidative stress, modulate immune checkpoints, manipulate mechanical stress responses, and alter cholesterol metabolic pathways. Additionally, we examine the interactions between cholesterol metabolism regulation and established cancer treatments with the aim of identifying efficient strategies to disrupt cholesterol metabolism and synergistic combination therapies for effective cancer treatment. [ABSTRACT FROM AUTHOR]

Cholesterol is an essential membrane component, and the metabolites from cholesterol play important biological functions to intricately support cancer progression and dampen immune responses. Preclinical and clinical studies have demonstrated the role of cholesterol metabolism regulation on inhibiting tumor growth, remodeling the immunosuppressive tumor microenvironment (TME), and enhancing anti‐tumor immunity. In this minireview, we discuss complex cholesterol metabolism in tumors, its important role in cancer progression, and its influences on immune cells in the TME. We provide an overview of recent advances in cancer treatment through regulating cholesterol metabolism. We discuss the design of cholesterol‐altering multifunctional nanomaterials to regulate oxidative stress, modulate immune checkpoints, manipulate mechanical stress responses, and alter cholesterol metabolic pathways. Additionally, we examine the interactions between cholesterol metabolism regulation and established cancer treatments with the aim of identifying efficient strategies to disrupt cholesterol metabolism and synergistic combination therapies for effective cancer treatment. [ABSTRACT FROM AUTHOR]

Background: NAD(P)-dependent steroid dehydrogenase-like protein (NSDHL), which is involved in breast tumor growth and metastasis, has been implicated in the maintenance of cancer stem cells. However, its role in regulating breast cancer stem-like cells (BCSCs) remains unclear. We have previously reported the clinical significance of NSDHL in patients with estrogen receptor-positive (ER +) breast cancer. This study aimed to elucidate the molecular mechanisms by which NSDHL regulates the capacity of BCSCs in the ER + human breast cancer cell line, MCF-7. Methods: NSDHL knockdown suppressed tumor spheroid formation in MCF-7 human breast cancer cells grown on ultralow-attachment plates. RNA sequencing revealed that NSDHL knockdown induced widespread transcriptional changes in the MCF-7 spheroids. TGF-β signaling pathway was the most significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway (fold change ≥ 2, P ≤ 0.05) identified in NSDHL-knockdown MCF-7 spheroids compared with the control. In orthotopic tumor models injected with NSDHL-knockdown MCF-7 spheroids, tumor initiation and growth were strongly suppressed compared with those in the control. Results: BCSC populations with CD44+/CD24- and CD49f+/EpCAM + phenotypes and high ALDH activity were decreased in NSDHL-knockdown MCF-7 spheroids and xenograft tumors relative to controls, along with decreased secretion of TGF-β1 and 3, phosphorylation of Smad2/3, and expression of SOX2. In RNA-sequencing data from The (TCGA) database, a positive correlation between the expression of NSDHL and SOX2 was found in luminal-type breast cancer specimens (n = 998). Our findings revealed that NSDHL plays an important role in maintaining the BCSC population and tumor-initiating capacity of ER-positive MCF-7 spheroids, suggesting that NSDHL is an attractive therapeutic target for eliminating BCSCs, thus preventing breast cancer initiation and progression. Conclusions: Our findings suggest that NSDHL regulates the BCSC/tumor-initiating cell population in MCF-7 spheroids and xenograft tumors. [ABSTRACT FROM AUTHOR]

Background: The prevalence of steatotic liver disease (SLD) in patients with type 2 diabetes (T2DM) exceeds 50%. This study aimed to investigate the clinical characteristics of SLD and liver fibrosis in Chinese patients with T2DM. Methods: Inpatients from 2021 to 2023 were included in the study. Fatty liver index (FLI) and fibrosis-4 (FIB-4) were calculated to assess hepatic steatosis and fibrosis respectively. Statistical analysis was completed by SPSS v25 and GraphPad Prism v8.0.1. Results: Of the 1466 participants, about one-third of the patients in T2DM-SLD group were diagnosed with liver fibrosis (LF), and the percentage of patients over 50 years old was 85.9%. Patients with SLD had higher levels of BMI, blood pressure, liver enzymes, fasting blood glucose (FBG), HbA1c, C-peptide, total cholesterol (TC) and triglyceride (TG) (P<0.05 for all). Patients with liver fibrosis had lower TC, TG, hemoglobin (Hb), erythrocyte count (RBC), leukocyte count (WBC) and platelet (PLT) levels (P<0.05 for all). Compared with simple T2DM and SLD-NLF (non-liver fibrosis) groups, for patients over 50 years old, the prevalence of coronary heart disease, stroke, tumor, and diabetic nephropathy was higher in patients with liver fibrosis. Liver fibrosis might be the risk factor of arterial stiffness, stroke, coronary heart disease and numbness based on multivariable logistic regression analysis. Conclusion: Hepatic steatosis and fibrosis were common in patients with T2DM. Liver fibrosis was relevant to many macrovascular and microvascular diabetic complications. [ABSTRACT FROM AUTHOR]

Besides being an essential structural component of plasma membranes and the precursor of many functional compounds and signaling molecules, cholesterol was also proposed to play a role in the etiology and/or manifestation of Parkinson's disease (PD). However, so far systematic investigations on the role of cholesterol and its metabolites present in the brain for the etiology of PD are missing. Here, we investigate for the first time the association of PD with SNPs in the genes of four cytochromes P450 (P450), CYP46A1, CYP39A1, CYP27A1 and CYP7B1, which are critical for the degradation of cholesterol in the brain. Analyzing 1,349 individuals from the PPMI data base, we found 24 SNPs in these four genes, which are significantly over- or under-represented in patients suffering from idiopathic PD (IPD). Studying each of the 362 IPD patients individually, we found that most patients (45%) showed only one associated SNP in one of the four P450 genes, while 31% displayed two associated SNPs and 18% three associated SNPs. The occurrence of some associated SNPs is in the same order of magnitude as SNPs in the GBA (beta-glucocerebrosidase) and thus might reflect a genetic predisposition for PD. As all 24 SNPs were located in introns and 3′ untranslated regions, we evaluated the prospective regulatory impact of the surrounding genomic regions by using transcriptome and epigenome data from the Foundational Data Initiative for Parkinson Disease (FOUNDIN-PD). FOUNDIN-PD provides gene expression, open chromatin and DNA methylation data in a cohort of 89 induced pluripotent stem cell (iPSC) lines differentiated to dopaminergic (DA) neurons derived from people in the PPMI study. Indeed, two of the 24 SNPs, one in CYP7B1 (rs118111353) and the other one in CYP27A1 (rs74446825), were localized within a region of open chromatin in differentiated neurons. Interestingly, all iPSC lines with open chromatin in rs118111353 showed the reference allele. As all four P450, CYP46A1, CYP39A1, CYP27A1 and CYP7B1, are expressed in dopaminergic neurons, we discuss further functional studies to connect SNPs in regulatory regions with gene expression levels. Finally, potential possibilities for personalized therapeutic treatment of patients with SNPs in the four investigated P450 are discussed. [ABSTRACT FROM AUTHOR]

Background/Aims: Ursodeoxycholic acid (UDCA) is the only well-established and widely used agent for dissolving gallstones. Epidemiological and animal studies have suggested potential therapeutic benefits of n-3 polyunsaturated fatty acids (PUFA) for dissolving cholesterol gallstones. We evaluated whether adding PUFA to UDCA improves gallstone dissolution in patients with cholesterol gallstones. Methods: This randomized, prospective, preliminary clinical trial compared the efficacy and safety of UDCA plus PUFA combination therapy (combination group) with those of UDCA monotherapy (monotherapy group). The inclusion criteria were a gallstone diameter ≤15 mm on ultrasonography, radiolucent stones on plain X-ray, and no to mild symptoms. Gallstone dissolution rates, response rates, and adverse events were evaluated. Results: Of the 59 screened patients, 45 patients completed treatment (24 and 21 in the monotherapy and combination groups, respectively). The gallstone dissolution rate tended to be higher in the combination group than in the monotherapy group (45.7% vs 9.9%, p=0.070). The radiological response rate was also significantly higher in the combination group (90.5% vs 41.7%, p=0.007). In both groups, dissolution and response rates were higher in patients with gallbladder sludge than in those with distinct stones. Four adverse events (two in each group) were observed, none of which were study drug-related or led to drug discontinuation. The incidence of these adverse events was similar in both groups (combination vs monotherapy: 9.5% vs 8.3%, p=0.890). Conclusions: UDCA plus PUFA therapy dissolves cholesterol gallstones more effectively than UDCA monotherapy, without significant complications. Further prospective, large-scale studies of this combination therapy are warranted. [ABSTRACT FROM AUTHOR]

Objective: The objective is to describe the clinical features, treatments, and outcomes of a case series of patients with Onodi cell mucocele, with or without cholesterol granuloma (CG). Material and methods: We retrospectively reviewed the medical records of eight patients diagnosed with Onodi cell mucocele at a single tertiary care university hospital in Beijing, China, between January 2017 and September 2020. Data regarding nasal symptoms, ocular symptoms, sinus computed tomography findings, treatments, histopathological results, and clinical outcomes were extracted. Results: We identified eight patients (six men and two women) of an average age of 48.1 (range, 26–70) years. Four patients presented nasal symptoms. Three patients presented ocular symptoms. Among them, one patient experienced concurrent nasal and ocular symptoms. Two patients were diagnosed based on a physical examination in the absence of nasal or ocular symptoms. All patients underwent endoscopic sinus surgery. The pathological specimens showed mucocele in four cases and mucocele with CG in the other four cases. Among the four cases with CG, three cases presented with decreased vision. After endoscopic sinus surgery, one patient recovered completely, and two patients showed significant improvement. Conclusion: If Onodi cell opacity is observed, especially with optic neuropathy, mucocele and CG are important differential diagnoses. The combination of mucocele and CG is more likely to promote bone destruction and cause serious optic neuropathy than simple mucocele. Endoscopic sinus surgery is appropriate. Diagnoses, treatments, and follow-up should be performed by a multidisciplinary team. [ABSTRACT FROM AUTHOR]

Background: Fatty acids can be protected by changing their structure or form against microbial activity, and the different forms of fatty acids can modulate the ruminal biohydrogenation rate and contribute to the desired fatty acid profile in milk fat. Objectives: The study investigated the effects of perilla (Perilla frutescens) dietary supplementation in the diet in different technological forms (seed, oil and formaldehyde‐treated oil) on milk, plasma and ruminal fatty acid composition, and milk quality in lactating goats. Methods: The four dietary treatments consisted of (1) no supplementation, basal diet (CON); (2) perilla supplementation as seed at 44.7 g/kg (consisting of 20 g/kg oil (PS)); (3) perilla supplementation as oil at 20 g/kg (PO); (4) perilla supplementation as formaldehyde treated oil at 20 g/kg (protected perilla oil [PPO]). The experiment was implemented in a double 4 × 4 Latin square trial design, and sampling was carried out for 7 days after 21 days of adaptation. Results: Performance parameters were not affected by P. frutescens supplementation to the diet. PO decreased milk fat, whereas PPO increased milk fat. Milk cholesterol was not affected by P. frutescens dietary supplementation. Perilla oil supplementation in different forms to the diet did not affect ruminal pH, VFA and methane production. Perilla oil supplementation in different forms to the diet did not also affect the concentration of blood serum glucose, cholesterol and non‐esterified fatty acids. Perilla supplementation to the diet increased the milk conjugated linoleic acid (CLA), C18:3n‐3, C22:5n‐3, C20:5n‐3, C22:6n‐3 and polyunsaturated fatty acid (PUFA) concentrations, and PPO group showed the greatest values. Ruminal palmitic (C16:0) acid was decreased, and in perilla groups, stearic acid (C18:0) concentration had the lowest, and ruminal c‐9, t‐11 CLA concentration had the highest value in PPO. Conclusions: It has been found that the most effective form of perilla oil in increasing milk quality is that with formaldehyde treatment (protected form). Perilla oil, which is a rich source of omega 3 in the diet, can be used to increase milk quality in goats without adversely affecting performance, ruminal fermentation and blood parameters. [ABSTRACT FROM AUTHOR]

Niemann–Pick type C (NPC) disease is an autosomal recessive lysosomal storage disorder where 95% of the cases are caused by mutations in the Niemann–Pick C1 (NPC1) gene. Loss of function in NPC1 mutants trigger the accumulation of cholesterol in late endo-lysosomes and lysosomal dysfunction. The current study examined the potential of polyphenol-rich methanol extracts from Rosa canina L. (RCME) and two of its components, rutin and quercitrin, to enhance protein trafficking of NPC1 and restore cholesterol levels in fibroblasts derived from NPC patients, in comparison with miglustat, a drug approved in Europe for NPC treatment. Interestingly, RCME improved the trafficking of the compound heterozygous mutant NPC1I1061T/P887L, homozygous mutant NPC1R1266Q, and heterozygous mutant NPC1N1156S between the endoplasmic reticulum and the Golgi and significantly reduced the levels of cellular cholesterol in the cell lines examined. Miglustat did not affect the trafficking of the three NPC1 mutants individually nor in combination with RCME. Markedly, rutin and quercitrin exerted their effects on cholesterol, but not in the trafficking pathway of NPC1, indicating that other components in RCME are implicated in regulating the trafficking of NPC1 mutants. By virtue of its dual function in targeting the trafficking of mutants of NPC1 as well as the cholesterol contents, RCME is more beneficial than available drugs that target substrate reduction and should be therefore considered in further studies for its feasibility as a therapeutic agent for NPC patients. [ABSTRACT FROM AUTHOR]

Introduction. Physical activity is vital for preventing and managing lifestyle-related diseases, which pose significant health and socio-economic challenges. This study aimed to evaluate the effects of a six-month supervised physical activity program on health risk factors and body composition in middle-aged individuals with overweight or obesity. Methods. The study involved 166 men and women aged 30 to 65 years, with a body mass index (BMI) ranging from 26 to 35 and moderate to severe health risks. Participants of the study were engaged in a six-month physical activity training program designed in accordance with World Health Organization guidelines. Comprehensive assessments were performed at baseline and after the intervention, including measurements of various anthropometric and body composition parameters, as well as evaluations of functional performance. Fitness tests were also conducted to assess participants' physical capacity and to monitor improvements throughout the training period. Results. Baseline measures of body mass composition and age demonstrated a strong positive correlation with visceral fat rating (VFR) in both men (r = 0.364, p < 0.001) and women (r = 0.420, p = 0.002). Following the six-month training program, participants exhibited an average improvement of 30% (p < 0.001) in their Cooper endurance test results. The physical activity intervention positively impacted body mass index (BMI) and various body composition metrics, including fat mass, VFR, and muscle mass, across all participants and most subgroups (gender, BMI, and age). In males, training at higher maximum heart rate (HRmax) zones significantly contributed to a reduction in the percentage of fat mass (80–89% HRmax) and an increase in the percentage of muscle mass (70–79% and 80–89% HRmax). Conclusions. The study indicates that a six-month supervised physical activity program significantly improves health risk factors and body composition (visceral fat reduction and improvement in percent of fat and muscle mass) among middle-aged individuals with overweight or obesity. Therefore, we advocate for the integration of structured physical activity interventions into healthcare practices to effectively enhance health outcomes in this population. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated that ultraviolet B (UVB) irradiation impacts both skin and hepatic functions. In this study, we investigated the effects of UVB irradiation on cholesterol metabolism in the liver. Hairless mice were exposed to UVB (1.6 J/cm2) irradiation. Dorsal skin and liver samples were collected 24 h after exposure. Total RNA was extracted from the skin and liver tissues, and used for DNA microarray analysis and real‐time polymerase chain reaction (PCR). Hepatic mRNA expression of Cyp7a1 revealed a 4.4‐fold decrease in the UVB (+) group compared to that in the UVB (−) group. No differences were observed in the expression of the other genes related to cholesterol metabolism. Additionally, the level of hepatic total cholesterol in the UVB (+) group was significantly higher than in the UVB (−) group. These findings suggest that acute UVB irradiation increases total cholesterol levels and decreases Cyp7a1 expression in the liver. [ABSTRACT FROM AUTHOR]

Inflammation and oxidative stress are the key factors in the pathogenesis of both metabolic dysfunction‐associated steatohepatitis (MASH) and atherosclerosis. Obeticholic acid (OCA), a farnesoid X receptor (FXR) agonist, improves hepatic inflammation and fibrosis in patients with MASH. However, it also reduces HDL cholesterol, suggesting that OCA may increase cardiovascular disease (CVD) risk in patients with MASH. We assessed HDL cholesterol efflux function, antioxidant (paraoxonase and ceruloplasmin activity), pro‐inflammatory index, and particle sizes in a small group of patients with and without diabetes (n = 10/group) at baseline and after 18 months of OCA treatment. Patients on lipid‐lowering medications (statins, fibrates) were excluded. At baseline, ferritin levels were higher in patients with MASH without diabetes (336.5 [157.0, 451.0] vs. 83 [36.0, 151.0] ng/mL, p < 0.005). Markers of HDL functions were similar in both groups. OCA therapy significantly improved liver histology and liver enzymes but increased alkaline phosphatase levels in nondiabetic patients with MASH (p < 0.05). However, it did not have any significant effect on cholesterol efflux and the antioxidant paraoxonase functions. In nondiabetics, ceruloplasmin (CP) antioxidant activity decreased (p < 0.005) and the pro‐inflammatory index of HDL increased (p < 0.005) due to OCA therapy. In contrast, in diabetics, OCA increased levels of pre‐β‐HDL—the HDL particles enhanced protective capacity (p = 0.005) with no alteration in HDL functionality. In all patients, serum glucose levels were negatively correlated with OCA‐induced change in pro‐inflammatory function in HDL (p < 0.001), which was primarily due to diabetes (p = 0.05). These preliminary results suggest a distinct effect of OCA therapy on diabetic and nondiabetic patients with MASH and warrant a future large‐scale study. [ABSTRACT FROM AUTHOR]

This study investigated the physiological effects of incorporating animal protein into a plant protein-based diet for red seabream, Pagrus major. Four diets with different levels of protein ingredients were formulated and fed to the fish (initial body weight: 11.3 ± 0.1 g) over a 4-week trial: a fishmeal (FM)-based diet (FM diet); an FM-free high-plant/low-animal protein diet (HPLA diet); an FM-free medium-plant/medium-animal protein diet (MPMA diet); and an FM-free plant protein-based diet (P diet). Fish fed the P diet showed an inferior growth performance, abnormal hindgut morphology, increased cholesterol biosynthesis, suppressed bile acid synthesis, and stimulated glycine and glutathione metabolism. These unfavorable effects on cholesterol metabolism were also confirmed by comprehensive transcriptome analysis. In addition, fish fed the P diet showed an upregulated expression of the haptoglobin precursor, an indicator of red blood cell damage. All of these negative physiological effects were either partially or totally improved by supplementation of the diet with animal proteins. Expression levels of insulin-like growth factor binding protein 1, a negative indicator of growth, were higher in fish fed the HPLA and P diets compared to fish in the FM group, whereas those of fish fed the MPMA diet were comparable to those of fish in the FM group. These results suggest that an optimal combination of plant- and animal-protein sources could improve the physiological condition of red seabream. Optimization of the dietary levels of plant and animal protein ingredients would contribute to the development of a low fishmeal diet that is well suited to improving the physiological condition of aquaculture target species. [ABSTRACT FROM AUTHOR]

Aim: Geraniol is an acyclic monoterpenoid that is abundant in many plants, including rose, lemongrass, and lavender. As geraniol has various beneficial functions, rose oil rich in geraniol is not only used for aromatherapy but also as a supplement to promote health benefits. However, the beneficial effects of geraniol on age‐related pathologies are unknown. In this study, we aimed to clarify the effects of geraniol intake on age‐related pathologies. Methods: We orally administered geraniol to aged mice (age: 24–29 months) five times a week for 4 weeks and sampled their blood and various organs. We investigated age‐related changes in the blood and organ samples. Furthermore, we treated HepG2 cells with geraniol and examined the expression level of the ALB gene and the amount of secreted albumin in vitro. Results: Geraniol significantly increased blood albumin, total cholesterol, and red blood cell counts, indicating an improvement in nutritional markers in aged mice. Geraniol also transcriptionally increased the Alb gene expression in the liver of aged mice. Furthermore, treatment with geraniol significantly upregulated the ALB gene expression and the secretion of albumin in the conditioned medium of HepG2 cells. Conclusion: Geraniol increases serum albumin levels at the transcriptional level. Geraniol intake can be an effective strategy for age‐related malnutrition. Geriatr Gerontol Int 2024; 24: 1233–1240. [ABSTRACT FROM AUTHOR]

Cholesterol, an essential lipid of cell membranes, regulates G protein-gated inwardly rectifying potassium (GIRK) channel activity. Previous studies have shown that cholesterol activates GIRK2 homotetrameric channels, which are expressed in dopaminergic neurons of the brain. Deletion of GIRK2 channels affects both GIRK2 homo- and heterotetrames and can lead to abnormal neuronal excitability, including conditions such as epilepsy and addiction. A 3.5 Á cryo-EM structure of GIRK2 in complex with CHS (cholesteryl hemisuccinate) and PIP2 (phosphatidylinositol 4,5-bisphosphate) has been solved. This structure provides the opportunity to study GIRK2 channel gating dynamics regulated by cholesterol using gating molecular dynamics (GMD) simulations. In the present study, we conducted microsecond-long GMD simulations on the GIRK2 channel in its APO, PIP2, and PIP2/CHS bound states, followed by systematic analysis to gain molecular insights into how CHS modulates GIRK2 channel gating. We found that CHS binding facilitates GIRK2 channel opening, with 43 K+ ion permeation events observed, compared to 0 and 2 K+ ion permeation events for GIRK2-APO and GIRK2/PIP2, respectively. Binding of CHS to the GIRK2 channel enhances PIP2 and channel interactions, which is consistent with previous experimental results. The negatively charged PIP2 alters the internal electrostatic potential field in the channel and lowers the negative free energy barrier for K+ ion permeation. [ABSTRACT FROM AUTHOR]

Coenzyme Q10 (Q10) and cholesterol are end-products of the mevalonate pathway, which is an essential metabolic network in the cell. Q10 has an established role as an electron transporter in the mitochondrial electron transport system and antioxidant protection. Here we investigated the hypothesis that chronic supplementation of Q10 could lower the cholesterol blood level in patients suffering from lipid disorders and ischemic heart disease (IHD). We also determined whether Q10 could influence the course of IHD assessed with the Rose questionnaire for the intensity of stenocardia symptoms. The study was conducted on 13 patients with mixed hyperlipidemia consisting of total cholesterol (TC) >300 mg/dL and triglycerides >200 mg/dL who were divided into those receiving orally either 50 mg Q10 t.i.d. (7 patients) or matching placebo pills (6 patients) over three months. We assessed TC and its fractions at monthly intervals. The findings were that Q10 significantly decreased the level of TC and low-density lipoprotein cholesterol by about 20% either, with inappreciable changes in other lipid fractions. Q10 also had a beneficial effect on stenocardia symptoms, lowering the incidence of chest pain attacks and the number of nitrate pills ingested. We conclude that Q10 exerts anticholesterolemic effects and is a viable candidate for adjunct hypercholesterolemia prophylaxis. [ABSTRACT FROM AUTHOR]

Summary: Background: Dietary interventions and increased physical activity are the cornerstones for management of the paediatric non‐alcoholic fatty liver disease (NAFLD). Though, no specific diet has been proven superior, Indo‐Mediterranean diet (IMD) has shown promise in adult literature. Thus, we aimed to compare the effect of IMD and a standard calorie‐restricted diet (CRD) in Indian overweight children and adolescents with biopsy‐proven NAFLD. Methods: Thirty‐nine consecutive biopsy‐proven NAFLD children between the ages of 8 and 18 years were randomized into either IMD or CRD for 180 days, and various parameters were evaluated at baseline and then after 180 days (NCT05073588). Results: A total of 34 subjects (18 in IMD and 16 in CRD group) completed the study. There was a significantly higher decrease in controlled attenuation parameter (CAP) values (as a marker of hepatic steatosis; on transient elastography) (95% CI: 4.2–73.4, p = 0.042), weight (95% CI: 0.75–5.5, p = 0.046) and body mass index (BMI) (95% CI: 0.21–2.05, p = 0.014) (but not in Pediatric NAFLD Fibrosis Index or PNFI; as a marker of hepatic fibrosis) in IMD group compared to the CRD group. Liver stiffness measurement, serum cholesterol and low‐density lipoprotein levels and HOMA‐IR decreased only in the IMD group (p < 0.001). Our statistical model showed that delta‐Weight was the only independent variable associated with delta‐CAP. Conclusion: Both IMD and CRD can improve the various anthropometric, clinical, imaging and biochemical parameters but IMD was superior to CRD in terms of reducing CAP values and weight/BMI over 180 days in overweight/obese NAFLD children. [ABSTRACT FROM AUTHOR]

Egg yolk lipids are important components in egg yolk. Compared with proteins, minerals, vitamins and pigments in egg yolk, there is a lack of systematic research on extraction methods and characteristics of yolk lipid. Therefore, in this study, the extraction of egg yolk lipids by supercritical CO2 fluid extraction (SFE), subcritical propane extraction (SPE) and ethanol solvent extraction (SE) was studied, and the differences in composition and physicochemical properties of the three yolk lipids were analyzed. The egg yolk lipids extracted by SFE had the advantages of high unsaturated fatty acid content, low saponification value, acid value, peroxide value, and high content of neutral lipids such as triglyceride and cholesterol, but the polar phospholipids were completely retained in the yolk powder. The efficiency of lipid extraction of SPE was the highest among all the three methods, but the extraction capacity to the polar phospholipid was in the middle of the three methods. The efficiency of lipid extraction of SE was low, but the extraction capacity to the polar phospholipid was the highest. Suitable extraction methods could be selected based on the specific application requirements of egg yolk lipids and low-fat egg yolk powders. [ABSTRACT FROM AUTHOR]

Background: Intraoperative conversion to open surgery is an adverse event during minimally invasive distal pancreatectomy (MIDP), associated with poor postoperative outcomes. The aim of this study was to develop a model capable of predicting conversion in patients undergoing MIDP. Methods: A total of 352 patients who underwent MIPD were included in this retrospective analysis and randomly assigned to training and validation cohorts. Potential risk factors related to open conversion were identified through a literature review, and data on these factors in our cohort was collected accordingly. In the training cohort, multivariate logistic regression analysis was performed to adjust the impact of confounding factors to identify independent risk factors for model building. The constructed model was evaluated using the receiver operating characteristics curve, decision curve analysis (DCA), and calibration curves. Results: Following an extensive literature review, a total of ten preoperative risk factors were identified, including sex, BMI, albumin, smoker, size of lesion, tumor close to major vessels, type of pancreatic resection, surgical approach, MIDP experience, and suspicion of malignancy. Multivariate analysis revealed that sex, tumor close to major vessels, suspicion of malignancy, type of pancreatic resection (subtotal pancreatectomy or left pancreatectomy), and MIDP experience persisted as significant predictors for conversion to open surgery during MIDP. The constructed model offered superior discrimination ability compared to the existing model (area under the curve, training cohort: 0.921 vs. 0.757, P < 0.001; validation cohort: 0.834 vs. 0.716, P = 0.018). The DCA and the calibration curves revealed the clinical usefulness of the nomogram and a good consistency between the predicted and observed values. Conclusion: The evidence-based prediction model developed in this study outperformed the previous model in predicting conversions of MIDP. This model could contribute to decision-making processes surrounding the selection of surgical approaches and facilitate patient counseling on the conversion risk of MIDP. [ABSTRACT FROM AUTHOR]

Metastasis to the liver is a leading cause of death in patients with colorectal cancer. To investigate the characteristics of cancer cells prone to metastasis, we utilized an isogenic model of BALB/c and colon tumor 26 (C26) cells carrying an active KRAS mutation. Liver metastatic (LM) 1 cells were isolated from mice following intrasplenic transplantation of C26 cells. Subsequent injections of LM1 cells generated LM2 cells, and after four cycles, LM4 cells were obtained. In vitro, using a perfusable capillary network system, we found comparable extravasation frequencies between C26 and LM4 cells. Both cell lines showed similar growth rates in vitro. However, C26 cells showed higher glucose consumption, whereas LM4 cells incorporated more fluorescent fatty acids (FAs). Biochemical analysis revealed that LM4 cells had higher cholesterol levels than C26 cells. A correlation was observed between fluorescent FAs and cholesterol levels detected using filipin III. LM4 cells utilized FAs as a source for cholesterol synthesis through acetyl‐CoA metabolism. In cellular analysis, cholesterol accumulated in punctate regions, and upregulation of NLRP3 and STING proteins, but not mTOR, was observed in LM4 cells. Treatment with a cholesterol synthesis inhibitor (statin) induced LM4 cell death in vitro and suppressed LM4 cell growth in the livers of nude mice. These findings indicate that colorectal cancer cells prone to liver metastasis show cholesterol‐dependent growth and that statin therapy could help treat liver metastasis in immunocompromised patients. [ABSTRACT FROM AUTHOR]

This article examines the relationship between cholesterol levels and Alzheimer's disease (AD), beginning with the early observation that individuals who died from heart attacks often had brain amyloid deposition. Subsequent animal model research proved that high cholesterol could hasten amyloid accumulation. In contrast, cholesterol-lowering treatments appeared to counteract this effect. Human autopsy studies reinforced the cholesterol-AD connection, revealing that higher cholesterol levels during midlife significantly correlated with higher brain amyloid pathology. This effect was especially pronounced in individuals aged 40 to 55. Epidemiological data supported animal research and human tissue observations and suggested that managing cholesterol levels in midlife could reduce the risk of developing AD. We analyze the main observational studies and clinical trials on the efficacy of statins. While observational data often suggest a potential protective effect against AD, clinical trials have not consistently shown benefit. The failure of these trials to demonstrate a clear advantage is partially attributed to multiple factors, including the timing of statin therapy, the type of statin and the appropriate selection of patients for treatment. Many studies failed to target individuals who might benefit most from early intervention, such as high-risk patients like APOE4 carriers. The review addresses how cholesterol is implicated in AD through various biological pathways, the potential preventive role of cholesterol management as suggested by observational studies, and the difficulties encountered in clinical trials, particularly related to statin use. The paper highlights the need to explore alternate therapeutic targets and mechanisms that escape statin intervention. [ABSTRACT FROM AUTHOR]

Aim: To investigate whether cardiovascular health (CVH) is associated with periodontitis. Materials and Methods: We used data from the 2009 to 2014 National Health and Nutrition Examination Survey. We quantified CVH using Life's Essential 8, which includes four health behaviours (diet, smoking, physical activity and sleep) and four health factors (body mass index, blood cholesterol, glucose and pressure). We categorized scores as low (0–49), moderate (50–79) and high (80–100). We calculated subscores of health behaviours and factors and categorized them as low, moderate and high. We used logistic regression to assess the association of CVH with periodontitis, adjusting for age, gender, race/ethnicity, education, poverty index, marital status and health insurance. We computed odds ratios (ORs) and 95% confidence intervals (CIs). Results: This study included 9296 adults ≥30 years old. Multivariable‐adjusted models showed that subjects with moderate (OR, 0.62; 95% CI: 0.52–0.74) or high (OR, 0.43; 95% CI: 0.33–0.57) CVH had significantly lower odds of periodontitis compared to those with low CVH. These results were consistent in the health behaviours model, but the estimates in the health factors model were not significant. Conclusions: Improving CVH may help prevent periodontitis. Longitudinal studies are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Summary: Unhealthy dietary patterns are a major contributor to obesity worldwide, leading to various adverse metabolic effects such as elevated liver enzyme levels and increased cholesterol concentrations. This study investigates the potential of cascara kombucha as a functional beverage to provide health benefits in both in vitro and in vivo models. Our results indicate that kombucha fermentation enhances the bioactive compounds in cascara, including polyphenols and flavonoids. The in vitro study found that cascara kombucha effectively decreased free radicals (DPPH and ABTS) levels, α‐amylase, and lipase activity, suggesting its potential to act as an antioxidant and modulate carbohydrate and lipid metabolism. In a mouse model, oral administration of cascara kombucha at a dose of 300 mg/kg body weight for 28 days successfully decreased fasting blood glucose levels, improved liver health by reducing aspartate transaminase and alanine transaminase levels, and lowered serum cholesterol content induced by a fat‐enriched diet compared to the untreated group. The levels of superoxide dismutase and catalase, suppressed by the fat‐enriched diet, were restored to normal. Additionally, cascara kombucha downregulated genes associated with inflammation induced by a fat‐enriched diet, including tnf‐α, IL‐6, IL‐1β, and cox‐2. It also positively affected the balance of intestinal microflora in mice by reducing coliform density and enhancing probiotic populations. These findings highlight the potential of cascara kombucha as a promising approach to addressing health issues caused by poor dietary habits and metabolic imbalances. [ABSTRACT FROM AUTHOR]

Summary: Encapsulation efficiency (EE), structure, antioxidant and antimicrobial activities of liposomes loaded with chitooligosaccharide–gallic acid conjugate (COS–GAL) as affected by cholesterol (CHO) and ascorbyl palmitate (AP) as stabilisers were investigated. In addition, release kinetics and in vitro digestion of selected liposomes were also studied. The higher EE was obtained for liposome (AP/COS–GAL) stabilised by 0.50% AP, when used to encapsulate 0.10% COS–GAL conjugate. The highest EE was noticed for 0.25% CHO when used to encapsulate 1.00% conjugate (CHO/COS–GAL) as compared to the counterparts (P < 0.05). Almost similar antioxidant and antimicrobial activities were noticed for all COS–GAL liposomes and COS–GAL powder. Microstructure study suggested the formation of bilayer in liposomes. CHO/COS–GAL showed a lower release efficiency than the AP/COS–GAL. CHO/COS–GAL was also able to protect conjugate during the in vitro digestion. Therefore, liposomes could be used as a promising carrier of COS–GAL conjugate in both foods as well as medical systems. [ABSTRACT FROM AUTHOR]

Purpose: High-density lipoprotein cholesterol (HDL-c) plays an important role in tumorigenesis in several endocrine-related cancers. Few studies have shown the effect of non-HDL-c in malignant tumors. The present study aimed to identify the association between non-HDL-c and high-grade pancreatic neuroendocrine neoplasms (PNENs). Methods: A total of 197 PNEN patients who underwent surgery were analyzed retrospectively. Clinical and histopathological features, such as patients' age and sex, tumor location and size, tumor grade, the level of serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c) and fasting plasma-glucose levels were obtained. Non-HDL-c was calculated as total cholesterol - HDL-c. The relationships between those features and high-grade PNENs were identified using logistic regression analysis. Results: Among the 197 patients with PNENs, a lower HDL-c level was more common seen in patients with poorly differentiated PNENs than in those with well-differentiated PNENs (P < 0.05). The non-HDL-c/HDL-c ratio was greater in patients with poorly differentiated PNENs than in those with well-differentiated PNENs (P < 0.01). Similarly, a greater proportion of patients with a non-HDL-c/HDL-c ratio larger than 5 was found in patients with poorly differentiated PNENs than in those with well-differentiation PNENs (P < 0.01). Multivariate logistic analysis showed that the non-HDL-c/HDL-c ratio was positively associated with poorly differentiated PNENs (odds ratio (OR) = 1.45, 95% conference interval (CI):1.13–1.87). Similarly, the risk of poorly differentiated PNENs increased significantly in patients with a non-HDL-c/HDL-c greater than 5 (OR = 14.13, 95%CI: 2.98–66.89). The risk of high-grade PNENs increased in patients with a high non-HDL-c/HDL-c ratio (OR = 1.27, 95% CI: 1.04–1.55), and the risk also increased markedly when the ratio was greater than 5 (OR = 5.00, 95%CI: 1.28–19.49). Conclusions: A high ratio of non-HDL-c/HDL-c was associated with high-grade PNENs or poorly differentiated PNENs. [ABSTRACT FROM AUTHOR]

Background and aims: Cardiovascular diseases (CVD) risk factors include high cholesterol. Children with total cholesterol (TC) levels ≥ 170 mg/dL are usually considered hypercholesterolemic. This study aimed at investigating the awareness of TC levels in a large Italian paediatric population and at looking for a possible correlation between their TC and TC in their parents' blood. Methods and results: A survey was carried out in 46,309 subjects (mean age 9.7 ± 2.3 years; age range 6–14 years) to check the awareness of their own TC levels by using a personal and family medical history questionnaire. In 95.67% of the sample TC value was unknown. In 2.69% TC was < 170 mg/dL, whereas 1.64% were hypercholesterolemic (TC ≥ 170 mg/dL). A statistically significant correlation was found between children with normal TC values and physiological TC values in both parents (p < 0.0001). Again, a significant association between children with high TC and their parents with high TC was detected when parents were analysed separately (i.e. children with TC ≥ 170 mg/dl vs maternal TC ≥ 200 mg/dL: OR 2.01 (95% CI 1.61–2.49, p < 0.001); children with TC ≥ 200 mg/dl vs maternal TC ≥ 240 mg/dL: OR 3.14 (95% CI 2.14–4.6, p < 0.001); children with TC ≥ 170 mg/dl vs paternal TC ≥ 200 mg/dL: OR 2.39 (95% CI 1.91–2.98, p < 0.001); children with TC ≥ 200 mg/dl vs paternal TC ≥ 240 mg/dL: OR 3.85 (95% CI 2.70–5,.50, p < 0.001). Conclusion: Just a minority of the investigated young patients knew their TC. This is worrisome. Children with normal TC values are more likely to be born from healthy parents with physiological TC. In addition, high TC in the enrolled subjects is significantly associated with high TC in their parents. Overall, these findings seem to highlight the importance of health education and genetics in TC pathogenesis. [ABSTRACT FROM AUTHOR]

We conducted this study to evaluate the efficacy of Curcumin and vitamin E on hot flashes, lipid profile, blood glucose, and hepatic & renal biomarkers. Eighty-four postmenopausal women were randomly assigned into three groups to receive one Curcumin 500 milligram, vitamin E 200 IU, or placebo capsules twice/daily/eight weeks. In comparison with placebo, vitamin E significantly decreased the number of hot flashes (P = 0.002), serum triglyceride (P < 0.001), and aspartate aminotransferase (P = 0.007), while it increased high-density lipoprotein cholesterol (P = 0.005). Curcumin decreased significantly fasting blood glucose (P = 0.007), total cholesterol (P = 0.015), and triglyceride (P = 0.007) compared to placebo. We conclude that vitamin E reduced the incidence of hot flashes by nearly one-third of the base amount. It improved serum lipid profile and aspartate aminotransferase. Curcumin ameliorated fasting blood glucose and serum lipid profile. [ABSTRACT FROM AUTHOR]

Gallstone formation is one of the most severe human diseases, with regional differences in gallstone composition worldwide. The formation of gallstones inside the gallbladder is a complex process and is still under debate despite advances in instrumentation. This study was an in‐depth analysis of the chemical, structural, and elemental composition of cholesterol and pigment‐type gallstones using Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy–energy dispersive X‐ray spectroscopy (SEM–EDS). Thermal gravimetric and differential scanning calorimetry (TG‐DSC) analysis was also carried out on gallstones to predict their thermal behavior. FTIR spectroscopy was employed to distinguish the cholesterol and pigment gallstones. Using SEM, we performed the morphological studies of gallstone and EDS were carried out to analyze elemental distribution within the gallstones. Elemental imaging and mapping of the major and minor elements within the cholesterol and black pigment gallstones were carried out, revealing the stone's heterogeneous nature. The level of heavy and toxic elements was found to be higher in pigment stones than in cholesterol gallstones. The results obtained from TG‐DSC are well correlated and supported by the results from FTIR spectroscopy. [ABSTRACT FROM AUTHOR]

It has long been thought that exocytosis was driven exclusively by well-studied fusion proteins. Some decades ago, the role of lipids became evident and escalated interest in the field. Our laboratory chose a particular cell to face this issue: the human sperm. What makes this cell special? Sperm, as terminal cells, are characterized by their scarcity of organelles and the complete absence of transcriptional and translational activities. They are specialized for a singular membrane fusion occurrence: the exocytosis of the acrosome. This unique trait makes them invaluable for the study of exocytosis in isolation. We will discuss the lipids' role in human sperm acrosome exocytosis from various perspectives, with a primary emphasis on our contributions to the field. Sperm cells have a unique lipid composition, very rare and not observed in many cell types, comprising a high content of plasmalogens, long-chain, and very-long-chain polyunsaturated fatty acids that are particular constituents of some sphingolipids. This review endeavors to unravel the impact of membrane lipid composition on the proper functioning of the exocytic pathway in human sperm and how this lipid dynamic influences its fertilizing capability. Evidence from our and other laboratories allowed unveiling the role and importance of multiple lipids that drive exocytosis. This review highlights the role of cholesterol, diacylglycerol, and particular phospholipids like phosphatidic acid, phosphatidylinositol 4,5-bisphosphate, and sphingolipids in driving sperm acrosome exocytosis. Furthermore, we provide a comprehensive overview of the factors and enzymes that regulate lipid turnover during the exocytic course. A more thorough grasp of the role played by lipids transferred from sperm can provide insights into certain causes of male infertility. It may lead to enhancements in diagnosing infertility and techniques like assisted reproductive technology (ART). [ABSTRACT FROM AUTHOR]

Background: Persistent innate and adaptive immune responses in the brain contribute to the progression of Alzheimer's disease (AD). APOE4, the most important genetic risk factor for sporadic AD, encodes apolipoprotein E4, which by itself is a potent modulator of immune response. However, little is known about the immune hub that governs the crosstalk between the nervous and the adaptive immune systems. Transient receptor potential vanilloid type 1 (TRPV1) channel is a ligand-gated, nonselective cation channel with Ca2+ permeability, which has been proposed as a neuroprotective target in AD. Methods: Using Ca2+-sensitive dyes, dynamic changes of Ca2+ in microglia were measured, including exogenous Ca2+ uptake and endoplasmic reticulum Ca2+ release. The mRFP-GFP-tagged LC3 plasmid was expressed in microglia to characterize the role of TRPV1 in the autophagic flux. Transcriptomic analyses and flow cytometry were performed to investigate the effects of APOE4 on brain microglia and T cells from APOE-targeted replacement mice with microglia-specific TRPV1 gene deficiency. Results: Both APOE4 microglia derived from induced pluripotent stem cells of AD patients and APOE4-related tauopathy mouse model showed significantly increased cholesterol biosynthesis and accumulation compared to their APOE3 counterparts. Further, cholesterol dysregulation was associated with persistent activation of microglia and elevation of major histocompatibility complex II-dependent antigen presentation in microglia, subsequently accompanied by T cell infiltration. In addition, TRPV1-mediated transient Ca2+ influx mitigated cholesterol biosynthesis in microglia by suppressing the transcriptional activation of sterol regulatory element-binding protein 2, promoted autophagic activity and reduced lysosomal cholesterol accumulation, which were sufficient to resolve excessive immune response and neurodegeneration in APOE4-related tauopathy mouse model. Moreover, microglia-specific deficiency of TRPV1 gene accelerated glial inflammation, T cell response and associated neurodegeneration in an APOE4-related tauopathy mouse model. Conclusions: The findings provide new perspectives for the treatment of APOE4-dependent neurodegeneration including AD. [ABSTRACT FROM AUTHOR]

It has long been thought that exocytosis was driven exclusively by well-studied fusion proteins. Some decades ago, the role of lipids became evident and escalated interest in the field. Our laboratory chose a particular cell to face this issue: the human sperm. What makes this cell special? Sperm, as terminal cells, are characterized by their scarcity of organelles and the complete absence of transcriptional and translational activities. They are specialized for a singular membrane fusion occurrence: the exocytosis of the acrosome. This unique trait makes them invaluable for the study of exocytosis in isolation. We will discuss the lipids' role in human sperm acrosome exocytosis from various perspectives, with a primary emphasis on our contributions to the field. Sperm cells have a unique lipid composition, very rare and not observed in many cell types, comprising a high content of plasmalogens, long-chain, and very-long-chain polyunsaturated fatty acids that are particular constituents of some sphingolipids. This review endeavors to unravel the impact of membrane lipid composition on the proper functioning of the exocytic pathway in human sperm and how this lipid dynamic influences its fertilizing capability. Evidence from our and other laboratories allowed unveiling the role and importance of multiple lipids that drive exocytosis. This review highlights the role of cholesterol, diacylglycerol, and particular phospholipids like phosphatidic acid, phosphatidylinositol 4,5-bisphosphate, and sphingolipids in driving sperm acrosome exocytosis. Furthermore, we provide a comprehensive overview of the factors and enzymes that regulate lipid turnover during the exocytic course. A more thorough grasp of the role played by lipids transferred from sperm can provide insights into certain causes of male infertility. It may lead to enhancements in diagnosing infertility and techniques like assisted reproductive technology (ART). [ABSTRACT FROM AUTHOR]

Background: Quercetin is a promising phytochemical in treating abnormalities associated with metabolic syndrome (MetS). This study aimed to explore the morphometric, metabolic, transcriptomic, and nutrigenetic responses to quercetin supplementation using two genetically distinct MetS models that only differ in the variant of the MetS-related Zbtb16 gene (Zinc Finger And BTB Domain Containing 16). Results: Quercetin supplementation led to a significant reduction in the relative weight of retroperitoneal adipose tissue in both investigated strains. A decrease in visceral (epididymal) fat mass, accompanied by an increase in brown fat mass after quercetin treatment, was observed exclusively in the SHR strain. While the levels of serum triglycerides decreased within both strains, the free fatty acids levels decreased in SHR-Zbtb16-Q rats only. The total serum cholesterol levels were not affected by quercetin in either of the two tested strains. While there were no significant changes in brown adipose tissue transcriptome, quercetin supplementation led to a pronounced gene expression shift in white retroperitoneal adipose tissue, particularly in SHR-Zbtb16-Q. Conclusion: Quercetin administration ameliorates certain MetS-related features; however, the efficacy of the treatment exhibits subtle variations depending on the specific variant of the Zbtb16 gene. [ABSTRACT FROM AUTHOR]

The risk of atherosclerotic cardiovascular diseases (ASCVDs) can be reduced by lowering low-density lipoprotein cholesterol (LDL-C) concentrations. Nevertheless, ASCVDs still cause most deaths worldwide. Here, we discuss the prevention of ASCVD and the event risk with a focus on heart-healthy diets, i.e., low intakes of saturated and trans-fatty acids and cholesterol, and high intakes of unsaturated fatty acids, viscous fibre, and dietary phytostanols as fatty acid esters, according to international dyslipidaemia treatment guidelines. Calculations based on both FINRISK and Cholesterol Treatment Trialists' Collaborators regression equations indicate that heart-healthy diets combined with phytostanol ester reduce LDL-C concentrations to such an extent that the 10-year estimated reduction in the incidence of coronary artery disease would be 23%. This information can be used, in particular, to prevent the development of subclinical atherosclerosis in healthy middle-aged populations and the progression of atherosclerosis to ASCVD. The outcome of simple and feasible dietary changes, and, when needed, combined with statins, can be significant: reduced mortality, an increased number of healthy life-years, and reduced healthcare costs. [ABSTRACT FROM AUTHOR]

Background: Vitamin E, an essential micronutrient with antioxidant potential, can dramatically reduce the cardiovascular risk in individuals with haptoglobin (Hp) 2‐2 genotype diabetes; however, the underlying mechanism remains unclear. Objective: The objective of this study is to evaluate the effect of vitamin E supplementation on high‐density lipoprotein (HDL) levels and function in individuals with diabetes stratified by Hp genotype. Methods: All relevant studies published up to May 2023 were systematically reviewed using PubMed, Cochrane Library, Web of Science, Chinese Wanfang, China Science and Technology Journal, and Chinese National Knowledge Infrastructure databases. Randomized controlled trials that evaluated the effects of vitamin E supplementation on HDL levels were included. The outcomes assessed were changes in HDL concentrations, cholesterol efflux, and HDL‐associated lipid peroxides. Results: In total, 163 publications were selected. Based on inclusion and exclusion selection and quality assessment, five studies with 463 participants were included. Vitamin E supplementation did not exert any effect on HDL levels in individuals with diabetes with any Hp genotype. Three of the five studies revealed that vitamin E improved cholesterol efflux and HDL lipid peroxides in individuals with Hp2‐2 diabetes but did not positively impact HDL function in Hp1 carriers. Conclusions: Although vitamin E supplementation did not significantly impact HDL levels in individuals with diabetes of any Hp genotype, it may improve HDL function in individuals with Hp2‐2 diabetes. These findings indicate a pharmacogenetic interaction between vitamin E and the Hp genotype on HDL function. Moreover, vitamin E supplementation may be an effective strategy for specific individuals with diabetes. [ABSTRACT FROM AUTHOR]

Understanding the systemic biochemistry of early pregnancy in the mare is essential for developing new diagnostics and identifying causes for pregnancy loss. This study aimed to elucidate the dynamic lipidomic changes occurring during the initial stages of equine pregnancy, with a specific focus on days 7 and 14 post-ovulation. By analysing and comparing the plasma lipid profiles of pregnant and non-pregnant mares, the objective of this study was to identify potential biomarkers for pregnancy and gain insights into the biochemical adaptations essential for supporting maternal recognition of pregnancy and early embryonic development. Employing discovery lipidomics, we analysed plasma samples from pregnant and non-pregnant mares on days 7 and 14 post-conception using the SCIEX ZenoTOF 7600 system. This high-resolution mass spectrometry approach enabled us to comprehensively profile and compare the lipidomes across these critical early gestational timepoints. Our analysis revealed significant lipidomic alterations between pregnant and non-pregnant mares and between days 7 and 14 of pregnancy. Key findings include the upregulation of bile acids, sphingomyelins, phosphatidylinositols, and triglycerides in pregnant mares. These changes suggest enhanced lipid synthesis and mobilization, likely associated with the embryo's nutritional requirements and the establishment of embryo–maternal interactions. There were significant differences in lipid metabolism between pregnant and non-pregnant mares, with a notable increase in the sterol lipid BA 24:1;O5 in pregnant mares as early as day 7 of gestation, suggesting it as a sensitive biomarker for early pregnancy detection. Notably, the transition from day 7 to day 14 in pregnant mares is characterized by a shift towards lipids indicative of membrane biosynthesis, signalling activity, and preparation for implantation. The study demonstrates the profound lipidomic shifts that occur in early equine pregnancy, highlighting the critical role of lipid metabolism in supporting embryonic development. These findings provide valuable insights into the metabolic adaptations during these period and potential biomarkers for early pregnancy detection in mares. [ABSTRACT FROM AUTHOR]

Background: The presence of hypertension significantly increases the risk of diabetes, particularly type 2 diabetes. Recently, Visceral Adiposity Index (VAI) has been introduced as a straightforward and robust alternative indicator for early detection of metabolic syndrome, cardiovascular disease, and T2DM. Visceral adiposity, more dangerous than subcutaneous fat, is associated with metabolic syndrome and cardiovascular diseases. The VAI and Lipid Accumulation Product (LAP) are indices that quantify visceral fat and lipid overaccumulation, respectively. This study aims to explore the association between VAI, LAP, and type 2 diabetes mellitus (T2DM) in US adults with hypertension using NHANES data from 2005 to 2018. Methods: We analyzed data from 5,620 participants with hypertension in The National Health and Nutrition Examination Survey (NHANES). VAI and LAP were calculated using established formulas. The VAI is calculated based on a combination of waist circumference, body mass index (BMI), triglycerides, and high-density lipoprotein (HDL) cholesterol levels. Logistic regression models were applied to evaluate the association between these indices and T2DM, adjusting for potential confounders. Subgroup analyses by age and gender were also conducted to assess variations in risk. Results: In all, 5,620 participants were enrolled in our analysis, with 2,754 (49%) being female, and a mean (standard deviation, SD) age of 57 (15) years. The mean (SD) cumulative average VAI and LAP among all participants was 241 (2.71) and 75 (67), respectively. Totally, higher VAI and LAP indices were significantly associated with an increased risk of T2DM in individuals with hypertension. For VAI, the odds ratios (OR) for T2DM were higher in older adults (≥ 60 years) [95% confidence interval (CI): 1.37, 1.22–1.53, per 1 SD increase] and females [95% confidence interval (CI): 1.39, 1.27–1.52, per 1 SD increase], indicating age and gender differences in risk. Non-linear relationships were observed, suggesting thresholds beyond which the risk of T2DM escalates dramatically. Conclusions: Both VAI and LAP are reliable markers for assessing T2DM risk in individuals with hypertension. Incorporating these indices into clinical practice could enhance the identification of high-risk individuals and facilitate early intervention strategies. Future longitudinal studies are needed to confirm these associations and explore targeted interventions. [ABSTRACT FROM AUTHOR]

Background/Objectives: Growing evidence suggests that erythrocyte membrane lipids are subject to changes during their lifespan. Factors such as the type of dietary intake and its composition contribute to the changes in red blood cell (RBC) membranes. Due to the high antioxidant content of beer, we aimed to investigate the effect of moderate beer consumption on the lipid composition of RBCs membranes from healthy overweight individuals. Methods: We conducted a four-weeks, prospective two-arm longitudinal crossed-over study, where participants (n = 36) were randomly assigned to alcohol-free beer group or traditional beer group. The lipids of RBCs membranes were assessed at the beginning and the end of the intervention by thin-layer chromatography. Results: Four-weeks of alcohol-free beer promoted changes in fatty acids (FA), free cholesterol (FC), phosphatidylethanolamine (PE) and phosphatidylcholine (PC) (p < 0.05). Meanwhile, traditional beer intake led to changes in FA, FC, phospholipids (PL), PE and PC (p < 0.05). The observed alterations in membrane lipids were found to be independent of sex and BMI as influencing factors. Conclusions: The lipid composition of erythrocyte membranes is distinctly but mildly influenced by the consumption of both non-alcoholic and conventional beer, with no effects on RBC membrane fluidity. [ABSTRACT FROM AUTHOR]

Besides being an essential structural component of plasma membranes and the precursor of many functional compounds and signaling molecules, cholesterol was also proposed to play a role in the etiology and/or manifestation of Parkinson’s disease (PD). However, so far systematic investigations on the role of cholesterol and its metabolites present in the brain for the etiology of PD are missing. Here, we investigate for the first time the association of PD with SNPs in the genes of four cytochromes P450 (P450), CYP46A1, CYP39A1, CYP27A1 and CYP7B1, which are critical for the degradation of cholesterol in the brain. Analyzing 1,349 individuals from the PPMI data base, we found 24 SNPs in these four genes, which are significantly over- or under-represented in patients suffering from idiopathic PD (IPD). Studying each of the 362 IPD patients individually, we found that most patients (45%) showed only one associated SNP in one of the four P450 genes, while 31% displayed two associated SNPs and 18% three associated SNPs. The occurrence of some associated SNPs is in the same order of magnitude as SNPs in the GBA (betaglucocerebrosidase) and thus might reflect a genetic predisposition for PD. As all 24 SNPs were located in introns and 3′ untranslated regions, we evaluated the prospective regulatory impact of the surrounding genomic regions by using transcriptome and epigenome data from the Foundational Data Initiative for Parkinson Disease (FOUNDIN-PD). FOUNDIN-PD provides gene expression, open chromatin and DNA methylation data in a cohort of 89 induced pluripotent stem cell (iPSC) lines differentiated to dopaminergic (DA) neurons derived from people in the PPMI study. Indeed, two of the 24 SNPs, one in CYP7B1 (rs118111353) and the other one in CYP27A1 (rs74446825), were localized within a region of open chromatin in differentiated neurons. Interestingly, all iPSC lines with open chromatin in rs118111353 showed the reference allele. As all four P450, CYP46A1, CYP39A1, CYP27A1 and CYP7B1, are expressed in dopaminergic neurons, we discuss further functional studies to connect SNPs in regulatory regions with gene expression levels. Finally, potential possibilities for personalized therapeutic treatment of patients with SNPs in the four investigated P450 are discussed. [ABSTRACT FROM AUTHOR]

The properties and applications of soybean protein isolates (SPIs) have been extensively investigated. In this study, we determined the optimal conditions for the preparation of the DND358 soybean protein isolate (DND358-SPI), assessed its physicochemical and functional properties, and investigated its potential applications in the food industry. According to the results, the highest extraction rate of DND358-SPI was observed when the pH was 9.5, the temperature was 55 °C, the duration was 80 min, and the material-to-liquid ratio was 1:20 (w/v). With regard to the functional properties, the water-holding capacity (WHC) and oil-binding capacity (OBC) of DND358-SPI were higher than those of other varieties, reaching 4.73% and 11.04%, respectively. In addition, the hardness, adhesiveness, chewiness, and resilience of DND358-SPI were higher than those of other varieties, reaching 159.27 g, 186.07 g, 6.78 mj, and 1.88, respectively. These findings indicate that DND358-SPI can reduce cholesterol levels and may be used to produce cholesterol-lowering food products. [ABSTRACT FROM AUTHOR]

Astaxanthin (Ax) determines the flesh redness of a salmonid fish which is the most desirable quality indicator by consumers. Fish cannot synthesize Ax de novo, therefore, the only way to increase flesh redness is to increase dietary input or improve the absorption and retention rate of dietary Ax. As a hydrophobic carotenoid, the absorption of Ax can be modulated by other lipid molecules in the diet. The present study explored the effect of three lipids, cholesterol (CH), phytosterol (PS), and docosahexaenoic acid (DHA) on Ax absorption, transport, and retention in rainbow trout. Dietary CH significantly improved Ax absorption by elevating plasma Ax levels (p < 0.05); however, it had no effect on the whole body Ax or flesh color. Dietary PS appears to inhibit Ax absorption since fish had significantly (p < 0.05) reduced whole body Ax. Dietary DHA appeared to have no effect on Ax absorption or retention. By comparing intestinal transcriptomes, a low density lipoprotein receptor (ldlr) gene was significantly downregulated in fish fed the CH diet as compared to the control diet. Since LDLR protein plays a major role in plasma lipoprotein turnover, we hypothesized that the inhibition of ldlr gene by high dietary CH resulted in higher retention of plasma Ax. The elevation of plasma Ax was not reflected in higher flesh coloration, which suggested other limiting factors governing Ax retention in the muscle. On the other hand, the transcriptomic and proteomic analyses found no changes of genes or proteins involved in Ax absorption, transport, or excretion in fish fed PS or DHA diets as compared to the control diet. In conclusion, this study has suggested that CH promotes Ax absorption by regulating lipoprotein retention and provide evidence for improving Ax absorption via dietary modulation. [ABSTRACT FROM AUTHOR]

Simple Summary: Animal models are crucial for exploration of the causes of and potential treatments for squamous cell carcinoma, a common type of skin cancer. This study compared four different hairless mouse models to determine which is most suitable for studying skin cancer development when exposed to ultraviolet (UV) light. The models varied in their skin characteristics, such as the presence of melanin, cholesterol level, and immune system function. By monitoring various skin health parameters and analyzing proteasome activity, this study found that the SKH-hr2+ApoE and SKH-hr2 models were the most effective for further research into squamous cell carcinoma. In contrast, the SKH-hr1 model, despite its common use, was less suitable. These findings will help guide future research efforts in understanding and developing treatments for skin cancer. Background: In recent decades, a significant global increase in the incidence of non-melanoma skin cancer has been observed. To explore the pathogenesis of and potential therapeutic approaches for squamous cell carcinoma, various in vivo studies using mouse models have been conducted. However, investigations comparing different hairless mouse models, with or without melanin, as well as models with hypercholesterolemia and immunosuppression, in terms of their ability to induce squamous cell carcinoma have yet to be undertaken. Methods: Four mouse strains, namely SKH-hr1, SKH-hr2, SKH-hr2+ApoE, and immunodeficient Nude (Foxn1 knockout), were exposed to UVA and UVB radiation three times per week, initially to 1 Minimal Erythemal Dose (MED), incrementally increased weekly to a maximum dose of 3 MED. Clinical evaluation, photodocumentation, and biophysical parameters were monitored, along with proteasome protein activity and histopathological assessments. Results: The SKH-hr1 model primarily developed actinic keratosis without significant progression to invasive squamous cell carcinoma (SCC), while the SKH-hr2 and SKH-hr2+ApoE models exhibited a higher likelihood and intensity of papilloma and aggressive SCC formation, with the latter showing upregulated proteasome activity. Histopathological analysis confirmed the presence of poorly differentiated, invasive SCCs in the SKH-hr2 and SKH-hr2+ApoE models, contrasting with the less aggressive SCCs in the Nude mice and the mixed lesions observed in the SKH-hr1 mice. Conclusions: The SKH-hr2+ApoE and SKH-hr2 mice were identified as the most suitable for further exploration of squamous cell carcinogenesis. In contrast, the SKH-hr1 mice were found to be the least suitable, even though they are albino. Notably, proteasome analysis revealed a potential role of proteasome activity in squamous cell carcinogenesis. [ABSTRACT FROM AUTHOR]

Background Antiretroviral therapy (ART)-related weight gain is of particular concern in people with HIV (PWH). Although weight gain was observed among PWH receiving tenofovir alafenamide (TAF), little is known about the potential reversibility after TAF discontinuation. We evaluated weight and metabolic changes 12 months after TAF discontinuation in the Swiss HIV Cohort Study. Methods We included participants who received at least 6 months of TAF-containing ART between January 2016 and March 2023. Using multivariable mixed-effect models, changes in weight and lipid levels were compared between individuals who continued TAF and those who switched to one of the following TAF-free regimens: (1) tenofovir disoproxil fumarate (TDF)-based ART, (2) dolutegravir/lamivudine (DTG/3TC), or (3) long-acting cabotegravir/rilpivirine (CAB/RPV). Results Of 6555 participants (median age 54 years, 24.3% female, 13% Black), 5485 (83.7%) continued, and 1070 (16.3%) stopped TAF. Overall, discontinuing TAF was associated with an adjusted mean weight change of −0.54 kg (95% confidence interval [CI] −.98 to −.11) after 12 months. In stratified analyses, switching from TAF to TDF led to an adjusted mean weight decrease of −1.84 kg (95% CI −2.72 to −.97), and to a decrease in mean total cholesterol (−0.44 mmol/L) and triglycerides (−0.38 mmol/L) after 12 months. Switching from TAF-based ART to DTG/3TC (−0.17 kg, 95% CI −.82 to.48) or long-acting CAB/RPV (−0.64 kg, 95% CI −2.16 to.89) did not lead to reductions in weight. Conclusions Replacing TAF with TDF in PWH led to a decrease in body weight and an improved lipid profile within 1 year. Weight changes were not observed among individuals who switched to DTG/3TC or long-acting CAB/RPV. [ABSTRACT FROM AUTHOR]

Purpose: Altered lipid metabolism frequently occurs in patients with solid cancers and dyslipidemia has been associated with poorer outcomes in patients with colorectal cancer. This study sought to investigate whether cholesterol levels are associated with clinical outcomes and can serve as survival predictors. Methods: We conducted a retrospective cohort study with Danish patients diagnosed with colorectal cancer who had surgery with curative intent for UICC stages I to III between 2015 and 2020. Using propensity score adjustment, we matched patients in a 1:1 ratio to examine the impact of total cholesterol (TC) > 4 mmol/L vs. ≤ 4 mmol/L within 365 days prior to surgery on overall survival (OS) and disease-free survival (DFS). Results: A total of 3443 patients were included in the study. Median follow-up time was 3.8 years. Following propensity score matching, 1572 patients were included in the main analysis. There was no statistically significant difference in OS or DFS between patients with TC > 4 mmol/L compared with TC ≤ 4 mmol/L (HR: 0.82, 95% CI, 0.65–1.03, HR: 0.87, 95% CI, 0.68–1.12, respectively.). A subgroup analysis investigating TC > 4 mmol/L as well as low-density lipoprotein (LDL) > 3 mmol/L found a significant correlation with OS (HR: 0.74, 95% CI, 0.54–0.99). Conclusion: TC levels alone were not associated with OS or DFS in patients with colorectal cancer. Interestingly, higher TC and LDL levels were linked to better overall survival, suggesting the need for further exploration of cholesterol's role in colorectal cancer. Trial registration: Not applicable. [ABSTRACT FROM AUTHOR]

The reliable monitoring of metabolites in biofluids plays a pivotal role in the diagnosis, treatment, and long-term management of various diseases. Surface-enhanced Raman spectroscopy (SERS) is considered a promising tool for metabolite detection because of its unique advantages for detecting trace amounts of chemical and biological molecules without requiring extensive sample preprocessing. In this study, a SERS sensor is proposed, utilizing silver nanoshells in cooperation with enzymes and 4-mercaptobenzoic acid (4-MBA) as a bifunctional molecule, to monitor two distinct biological metabolites, lactate and cholesterol, at their respective levels. In our method, the enzymatic reactions between oxidases and their specific metabolites initiate a domino reaction, resulting in significant changes in the SERS signal of 4-MBA. Through systematic sensor optimization, the quantification of lactate (1.0 × 10–1 to 1.0 × 10–7 M) and cholesterol (1.0 × 10–2 to 1.0 × 10–6 M) in a buffer solution was successfully achieved using the SERS intensity as an indicator. The limits of detection for lactate and cholesterol were estimated to be 2.7 × 10–7 and 1.0 × 10–8 M, respectively. Our proposed SERS sensor precisely detected lactate concentrations in serum samples, with a high accuracy of over 91%, demonstrating high selectivity for compounds with similar structures and serum constituents. Our SERS sensor platform can be utilized as an efficient and versatile tool for measuring lactate concentrations in serum samples and is expected to have the potential to advance personalized healthcare solutions through rapid point-of-care testing. [ABSTRACT FROM AUTHOR]