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Background: Platycodin D (PD) has been reported to treat metabolic diseases, including non-alcoholic fatty liver disease. In addition, platycodin D has been reported to activate intestinal 5’AMP-activated protein kinase (AMPK) phosphorylation levels, thereby reducing lipid absorption. Therefore, the aim of this study is to explore whether PD activation of intestinal AMPK and reduced lipid absorption can improve non-alcoholic fatty liver disease. Methods: Clean-grade male C57/BL mice were fed a high-fat diet (HFD) (containing 60% calories) for 16 weeks, and oral PD (10 mg/kg/day) was administered at the same time. The liver and intestines were the collected, and the intestines were tested. The expressions of lipid absorption genes (CD36, NPC1L1, and ApoB), the serum total triglyceride (TG) and total cholesterol (TC) levels in the intestines and livers, the fecal free fatty acid (FFA) levels, and the expression of AMPK phosphorylated proteins in the intestines were examined using Western blot analyses. The lipid distribution in the livers, intestines, and fat was detected using Oil Red O and hematoxylin and eosin (H&E) staining. A colon cancer cell line (Caco2) was used to confirm the effect of PD on the cellular lipid uptake in vitro. In addition, serum inflammatory factors and liver enzymes were measured to clarify the impact of PD on the circulation of metabolic syndrome. Leptin-deficient mice (OB) were then used to further explore the improvement of PD on body weight and blood lipids. Results: PD had a very significant therapeutic or preventive effect on metabolic syndrome and fatty liver induced by a high-fat diet. PD improved body weight, insulin sensitivity, and glucose tolerance in mice fed a high-fat diet and also prevented non-alcoholic fatty liver disease, reduced blood lipid levels, and increased fecal lipid excretion. In addition, PD reduced lipid absorption by activating the intestinal AMPK protein, which may have involved the inhibition of the gene expression levels of intestinal lipid absorption genes (CD36, NPC1L1, and ApoB). The combined effect of these factors improved hepatic lipid accumulation and lipid accumulation in adipose tissue. It was further found that PD also improved the body weights and blood lipid levels of leptin-deficient mice (OB) mice. Conclusion: PD had a very strong therapeutic effect on mice under a high-fat diet. PD reduced high-fat diet-induced obesity and non-alcoholic fatty liver disease by inhibiting intestinal fat absorption. [ABSTRACT FROM AUTHOR]

Background: Previous observational studies have reported a possible association between circulating lipids and lipid-lowering drugs and male infertility (MIF), as well as the mediating role of circulating vitamin D. Then, due to issues such as bias, reverse causality, and residual confounding, inferring causal relationships from these studies may be challenging. Therefore, this study aims to explore the effects of circulating lipids and lipid-lowering drugs on MIF through Mendelian randomization (MR) analysis and evaluate the mediating role of vitamin D. Method: Genetic variations related to lipid traits and the lipid-lowering effect of lipid modification targets are extracted from the Global Alliance for Lipid Genetics Genome-Wide Association Study. The summary statistics for MIF are from the FinnGen 9th edition. Using quantitative expression feature loci data from relevant organizations to obtain genetic variations related to gene expression level, further to explore the relationship between these target gene expression levels and MIF risk. Two-step MR analysis is used to explore the mediating role of vitamin D. Multiple sensitivity analysis methods (co-localization analysis, Egger intercept test, Cochrane’s Q test, pleiotropy residuals and outliers (MR-PRESSO), and the leave-one-out method) are used to demonstrate the reliability of our results. Result: In our study, we observed that lipid modification of four lipid-lowering drug targets was associated with MIF risk, the LDLR activator (equivalent to a 1-SD decrease in LDL-C) (OR=1.94, 95% CI 1.14-3.28, FDR=0.040), LPL activator (equivalent to a 1-SD decrease in TG) (OR=1.86, 95% CI 1.25-2.76, FDR=0.022), and CETP inhibitor (equivalent to a 1-SD increase in HDL-C) (OR=1.28, 95% CI 1.07-1.53, FDR=0.035) were associated with a higher risk of MIF. The HMGCR inhibitor (equivalent to a 1-SD decrease in LDL-C) was associated with a lower risk of MIF (OR=0.38, 95% CI 0.17-0.83, FDR=0.39). Lipid-modifying effects of three targets were partially mediated by serum vitamin D levels. Mediation was 0.035 (LDLR activator), 0.012 (LPL activator), and 0.030 (CETP inhibitor), with mediation ratios of 5.34% (LDLR activator), 1.94% (LPL activator), and 12.2% (CETP inhibitor), respectively. In addition, there was no evidence that lipid properties and lipid modification effects of six other lipid-lowering drug targets were associated with MIF risk. Multiple sensitivity analysis methods revealed insignificant evidence of bias arising from pleiotropy or genetic confounding. Conclusion: This study did not support lipid traits (LDL-C, HDL-C, TG, Apo-A1, and Apo-B) as pathogenic risk factors for MIF. It emphasized that LPL, LDLR, CETP, and HMGCR were promising drug targets for improving male fertility. [ABSTRACT FROM AUTHOR]

Objective: To investigate the efficacy and safety of Shengjiang powder as a treatment for DKD. Methods: A comprehensive search was performed in eight databases from their inception to December 30, 2023, to identify relevant RCTs. The inclusion criteria were diagnosis of DKD and intervention including TCM that contained Shengjiang powder. Two researchers independently conducted literature screening and data extraction, utilizing the Rob2 tool and GRADE to assess the quality of the RCTs. Meta-analysis was carried out using RevMan 5.4.1 and Stata 15.0. Results: As a result of the search, 23 RCTs comprising 1,682 patients. The interventions resulted in significant reductions in all the assessed indicators: 24-h urinary protein, UAER, mALB, BUN, Scr, FBG, 2hPG, HbA1c, total cholesterol, and Triglycerides. Together the results showed that Shengjiang powder, in conjunction with conventional therapy, is an effective treatment of DKD. Subgroup analyses, considering duration, stage, blood glucose control levels, baseline blood glucose levels, and baseline Scr levels indicated that shorter duration treatment had a greater effect on UAER, 2hPG, and HbA1c. Additionally, Shengjiang powder was more effective in reducing 24-h urinary protein, Scr, and 2hPG in stage IV patients compared to corresponding values at other stages. However, with respect to FBG, the treatment was more effective in stage II/III. Shengjiang powder also, reduced Scr levels significantly in patients with higher baseline Scr and reduced urinary protein excretion with stricter blood glucose control. The interventions had additional lipid-regulating effects in cases with looser blood glucose control and led to a remarkable reduction in BUN and Scr levels in patients with FBG > 11.1 mmol/L. Conclusion: Shengjiang powder may supplement conventional therapy, thus benefiting DKD patients in terms of reducing urinary protein, stabilizing kidney function, and improving blood glucose and lipid metabolism. Considering the significant heterogeneity among studies and limited quality of some reports, our conclusions need to be further verified through analyses utilizing larger, multicenter samples of higher quality. [ABSTRACT FROM AUTHOR]

Garcinia kola Heckel seed is widely used in the African traditional medicine as a aphrodisiac and male fertility enhancer. Probiotics can reestablish glucose homeostasis and improve blood lipid profiles by altering the composition of the intestinal flora. The study was planned to assess the efficacy of co-administration of Garcinia kola seed aqueous infusion and probiotic yoghurt in the management of diabetes and associated male fertility-stimulating hormones abnormalities. G. kola seed infusion was prepared, assessed for radical scavenging capacity, total phenolic content and phenolic profile using HPLC. Fermented yoghurt was prepared and inoculated with probiotic mixture. Rats were given a high-fat diet for four weeks and received an intraperitoneal injection of streptozotocin (30 mg/kg) to induce type 2 diabetes. Diabetic rats were received 200 mg/kg freeze-dried infusion of G. kola seed, probiotics yoghurt, and probiotic yoghurt mixed with G. kola once a day for four weeks. The levels of glucose, insulin, testosterone, follicle-stimulating hormone, luteinizing hormone, inflammatory indicators, oxidative markers, lipid profiles and liver as well as kidney biochemical indicators were measured. The administration of G. kola seed, probiotic yoghurt, or their combination to diabetic rats demonstrated potential anti-diabetic effects as evidenced by the down-regulation in glucose, insulin, lipid profile, oxidative markers, and inflammatory markers simultaneously with an up-regulation in testosterone, FSH, and LH levels compared to diabetic rats. G. kola seed, probiotic yoghurt, or their combination increased testosterone, FSH, and LH levels and are thought to have therapeutic promise for T2DM and its related oxidative stress. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effect of Angelica gigas Nakai ethanol extract (AGNEX) on benign prostatic hyperplasia (BPH) models induced by castration and testosterone propionate (TP) injection. Methods: 30 rats were randomly divided into six groups of five rats each. One group was used as a normal control (CON) and the other groups were castrated and injected intraperitoneally with TP to induce BPH. Positive control group (PCON) was administered finasteride (5 mg/kg) for 4 weeks and BPH-induced group without treatment was used as negative control (NCON). Groups administered AGNEX (1.25 mg/kg (AG1.25), 5 mg/kg (AG5), or 10 mg/kg (AG10)) instead of finasteride were assigned as study groups. The complete blood cell and lipid profiles, liver and kidney function assays, serum 5α-reductase activity and DHT levels as well as the histological examination of prostate tissues were determined. Results: The prostate volume of AG10 group decreased by approximately 35 % compared to BPH induced group (NCON). The prostate weight ratio decreased by 10 % in BPH + finasteride group compared to NCON group, and by 24 and 22 % in the AG5 and AG10 groups, respectively. AG10 group exhibited the lowest levels of 5α-reductase and dihydrotestosterone. Histopathological observations of prostate tissue showed normal cell shapes and reduced intraluminal polyp formation in the control and AGNEX-administered groups. Conclusion: The administration of 10 mg/kg of AGNEX is optimal dose for protective effect against BPH. Therefore, AGNEX has potentials for further investigations as source of lead agents for BPH management. [ABSTRACT FROM AUTHOR]

Purpose: To determine the effect of ginsenoside R3 (Rg3) on non-alcoholic fatty liver disease (NAFLD), and the mechanism involved. Methods: High-fat diet (HFD) was used to establish an NAFLD mouse model. The mice were daily and intraperitoneally injected with Rg3 at a dose of 1 mg/kg. Blood lipid levels and levels of liver inflammatory markers were measured by enzyme-linked immunosorbent assay (ELISA) while liver pathological changes and lipid accumulation were assessed with hematoxylin-eosin (H&E) staining and oil red O staining, respectively. The mRNA and protein expressions of miR-103-3p and PPARγ were determined with quantitative real-time polymerase chain reaction (qPCR) and western blot assay, respectively. Furthermore, an in vitro hepatocyte NAFLD model was established, and Rg3 was used to treat the cells; PPARγ was overexpressed in the cells. Lipid accumulation, inflammatory factors, as well as PPARγ and miR-103-3p expressions were assessed as indicated for the in vivo studies above. Apoptosis was determined by flow cytometry. Results: Rg3 alleviated the NAFLD-induced decreases in liver function, reversed NAFLD-mediated pathological injury in liver tissue injury, and decreased hepatic lipid build-up and inflammatory lesions (p < 0.05). It also significantly reversed the upregulation of PPARγ and miR-103-3p in the liver tissue of NAFLD mice. At the cellular level, Rg3 significantly inhibited free fatty acid (FFA)-induced lipid accumulation, apoptosis and inflammatory factors in primary mouse hepatocytes. The PPARγ overexpression counteracted the inhibitory effect of Rg3 on hepatocyte apoptosis, and increased miR- 103-3p expression (p < 0.05). Conclusion: These data suggest that Rg3 mitigates NAFLD through regulation of the PPARγ/miR-103- 3p pathway. Therefore, Rg3 may be suitable for the treatment of NAFLD. However, clinical trials are required to ascertain the validity of this therapeutic strategy in clinical practice. [ABSTRACT FROM AUTHOR]

To investigate the effects of methadone maintenance therapy on body mass index (BMI) and some biochemical parameters, including fasting blood glucose, lipid profile, and liver function indices as indicators of the biochemical function of the body for 3 years. This interventional study was performed on 43 opioid use disorder patients who had been selected for methadone maintenance therapy from 2016 to 2020. The morphine test on blood samples was carried out monthly for all patients. Fasting blood glucose, lipid profile including triglyceride, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and liver function tests including alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST), and body mass index (BMI) were measured over 3 years. Data analysis was performed using SPSS software. FBS in second and third year of therapy increased by 15.57 mg/dL (p-value 0.01) and 21.87 mg/dL (p-value 0.009), respectively; none of lipid profile variables was significantly different over time (p-value > 0.05). Only mean ALP levels significantly decreased 21.51 IU/L (p-value 0.04), 21.02 IU/L (p-value 0.04), and 26.07 IU/L (p-value 0.01) in liver function tests. The mean BMI increases each years but not significantly. Methadone treatment affects some biochemical parameters such as blood sugar and liver activity, so changes in biochemical parameters should be considered. [ABSTRACT FROM AUTHOR]

This study aimed to investigate circadian rhythm manifestations in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients (including a subpopulation of long-COVID patients) and matched healthy controls while also exploring their association with cardiovascular health variables. Thirty-one ME/CFS patients (75% females), 23 individuals diagnosed with post-COVID ME/CFS (56% females) and 31 matched healthy controls (68% females) were enrolled in this study. Demographic and clinical characteristics were assessed using validated self-reported outcome measures. Actigraphy data, collected over one week, were used to analyze the 24-h profiles of wrist temperature, motor activity, and sleep circadian variables in the study participants. Associations between lipid profile with endothelial dysfunction biomarkers (such as endothelin-1, ICAM-1 and VCAM-1) and with sleep and circadian variables were also studied. No differences were found in these variables between the two group of patients. Patients showed lower activity and worse sleep quality than matched healthy controls, together with a worse lipid profile than controls, that was associated with disturbances in the circadian temperature rhythm. ICAM-1 levels were associated with plasma lipids in healthy controls, but not in patients, who showed higher levels of endothelin-1 and VCAM-1. These findings suggest that lipid profiles in ME/CFS are linked to disrupted circadian rhythms and sleep patterns, likely due to endothelial dysfunction. Furthermore, they highlight the intricate relationship between sleep, circadian rhythms, and cardiovascular health in this condition. [ABSTRACT FROM AUTHOR]

Background: Menopause is associated with elevated cardiovascular risk due to the loss of the cardioprotective effect of oestrogens. Postmenopausal women are often prescribed hormone replacement therapy (HRT) in order to control menopause symptoms and correct hormone imbalances; however, HRT can impact serum lipids' concentrations. At present, data on the effect of the administration of medroxyprogesterone acetate plus conjugated equine oestrogens (MPACEE) on the lipid profile in females are uncertain, as the investigations conducted so far have produced conflicting results. Thus, we aimed to clarify the impact of MPACEE prescription on the serum lipids' values in women by means of a systematic review and meta‐analysis of randomized controlled trials (RCTs). Methods: We employed a random‐effects model based on the DerSimonian and Laird method to determine the combined estimates of the intervention's impact on the lipid profile. The computation of the weighted mean difference (WMD) and its corresponding 95% confidence interval (CI) relied on the mean and standard deviation values from both the MPACEE and control group, respectively. Results: A total of 53 RCTs were included in the meta‐analysis with 68 RCT arms on total cholesterol (TC), 70 RCT arms on low‐density lipoprotein cholesterol (LDL‐C) and triglycerides (TG), and 69 RCT arms on high‐density lipoprotein cholesterol (HDL‐C). Administration of MPACEE resulted in a significant reduction of TC (WMD = −11.93 mg/dL; 95% CI: −13.42, −10.44; p <.001) and LDL‐C (WMD = −16.61 mg/dL; 95% CI: −17.97, −15.26; p <.001) levels, and a notable increase in HDL‐C (WMD = 3.40 mg/dL; 95% CI: 2.93, 3.86; p <.001) and TG (WMD = 10.28 mg/dL; 95% CI: 7.92, 12.64; p <.001) concentrations. Subgroup analysis revealed that changes in the lipid profile were influenced by several factors: body mass index (for TC, HDL‐C, TG), MPACEE dosages (for TC, LDL‐C, HDL‐C, TG), age (for TC, LDL‐C, HDL‐C, TG), durations of the intervention (for TC, LDL‐C, HDL‐C, TG), continuous/sequential administration of MPACEE (continuous for TC; sequential for LDL‐C, TG) administration of MPACEE and serum lipids' concentrations before enrolment in the RCT (for TC, LDL‐C, HDL‐C, TG). Conclusions: MPACEE administration can influence serum lipids' concentrations in females by raising HDL‐C and TG levels and reducing LDL‐C and TC values. Therefore, postmenopausal women who suffer from hypercholesterolaemia might benefit from this type of HRT. [ABSTRACT FROM AUTHOR]

Fatty acid transport protein (FATP)4 was thought to mediate intestinal lipid absorption, which was disputed by a study using keratinocyte-Fatp4-rescued Fatp4(/( mice. These knockouts when fed with a Western diet showed elevated intestinal triglyceride (TG) and fatty acid levels. To investigate a possible role of FATP4 on intestinal lipid processing, ent-Fatp4 (KO) mice were generated by Villin-Cre-specific inactivation of the Fatp4 gene. We aimed to measure circulating and intestinal lipids in control and KO mice after acute or chronic fat intake or during aging. Remarkably, ent-Fatp4 mice displayed an approximately 30% decrease in ileal behenic, lignoceric, and nervonic acids, ceramides containing these FA, as well as, ileal sphingomyelin, phosphatidylcholine, and phosphatidylinositol levels. Such decreases were concomitant with an increase in jejunal cholesterol ester. After a 2-wk recovery from high lipid overload by tyloxapol and oral-lipid treatment, ent-Fatp4 mice showed an increase in plasma TG and chylomicrons. Upon overnight fasting followed by an oral fat meal, ent-Fatp4 mice showed an increase in plasma TG-rich lipoproteins and the particle number of chylomicrons and very low-density lipoproteins. During aging or after feeding with a high-fat high-cholesterol (HFHC) diet, ent-Fatp4 mice showed an increase in plasma TG, fatty acids, glycerol, and lipoproteins as well as intestinal lipids. HFHC-fed KO mice displayed an increase in body weight, the number of lipid droplets with larger sizes in the ileum, concomitant with a decrease in ileal ceramides and phosphatidylcholine. Thus, enterocyte FATP4 deficiency led to a metabolic shift from polar to neutral lipids in distal intestine rendering an increase in plasma lipids and lipoproteins. NEW & NOTEWORTHY Enterocyte-specific Fatp4 deficiency in mice increased intestinal lipid absorption with elevation of blood lipids during fasting and aging, as well as after an acute oral fat-loading or chronic HFHC feeding. Lipidomics revealed that knockout mice displayed a shift from very long-chain to long-chain fatty acids, and from polar to neutral lipids, predominantly in the ileum. Thus, FATP4 may have a physiological function in the control of blood lipids via metabolic shifts in distal intestine. [ABSTRACT FROM AUTHOR]

Purpose: To test the hypothesis that central drusen location is strongly linked with known Age‐related Macular Degeneration (AMD) risk factors and risk of incident late AMD. Methods: The Alienor study is a prospective population‐based cohort study of residents of Bordeaux, France, followed from 2009 to 2017. On retinal photographs, we defined central drusen as at least one soft drusen (>63 μm) within 500 μm from fovea and pericentral drusen as at least one drusen 500–3000 μm from fovea, in the absence of any central drusen. Late AMD (atrophic and/or neovascular) was diagnosed using multimodal imaging. In total, 481 eyes were included in the analysis: 160 central and 321 pericentral. We investigated associations with systemic (age, sex, smoking, medical prescriptions, plasma concentrations of lipids and nutrients, UV exposure, blood pressure), ocular (retinal thickness, cataract extraction) and genetic risk scores (GRS). Results: In multivariate logistic regression central drusen were associated with smoking (OR, 2.95 for smoking more than 20 pack‐years, p = 0.02), HDL‐cholesterol (OR, 1.57 for 1 standard deviation (SD) increase, p = 0.0048), pulse pressure (OR, 0.77 for 1 SD increase, p = 0.04), Age‐Related Maculopathy Susceptibility 2 (ARMS2) GRS (OR, 1.42; 95% CI, 1.11–1.83) and complement GRS (OR, 1.55; 95% CI, 1.15–2.10). In Cox modelling, the central location of drusen (at baseline or during the follow‐up) was associated with a 4.41‐fold increased risk (95% CI,1.98–9.81) for an incident late AMD. Conclusion: Central drusen were strongly associated with AMD risk factors and incident late AMD, suggesting that it represents a key marker for AMD progression. [ABSTRACT FROM AUTHOR]

This study aimed to explore the effect of standardized nutrition nursing combined with low molecular weight heparin calcium in treating patients with hyperlipidemic pancreatitis. A total of 100 patients from Yancheng Third People's Hospital were randomly divided into the control group and treatment group using a random number table. The control group received basic treatment that included fasting, isotonic saline, Ibuprofen, gastrointestinal decompression, Fentanyl, Pantoprazole, octreotide, electrolyte balance maintenance, glucose control, and lipid-lowering drug + routine enteral nutrition nursing. On this basis, the treatment group received low molecular weight heparin calcium injection + standardized enteral nutrition nursing. The total effective rate of the treatment group was higher than that of the control group (94.00% versus 76.00%; P < 0.05). After intervention, compared with the control group, serum levels of prealbumin, albumin, and transferrin were significantly higher (P < 0.05), while serum levels of triglyceride, total cholesterol, and amylase were significantly lower (P < 0.05) in the treatment group. Furthermore, improvements in prothrombin time, thrombin time, fibrinogen level, and activated partial thrombokinase time in the treatment group were more obvious (P < 0.05), while serum levels of C-reactive protein, tumor necrosis factor-α, and interleukin-6 were significantly lower (P < 0.05) than those in the control group. No difference was found in the incidence of adverse reactions between the two groups (P > 0.05). Overall, standardized nutrition nursing combined with low molecular weight heparin calcium can reduce blood lipid levels and inflammatory responses, improve coagulation function, and promote the nutritional status of patients with hyperlipidemic pancreatitis. [ABSTRACT FROM AUTHOR]

Dysregulation of growth hormone (GH) signaling consistently leads to increased lifespan in laboratory rodents, yet the precise mechanisms driving this extension remain unclear. Understanding the molecular underpinnings of the beneficial effects associated with GH deficiency could unveil novel therapeutic targets for promoting healthy aging and longevity. In our pursuit of identifying metabolites implicated in aging, we conducted an unbiased lipidomic analysis of serum samples from growth hormone‐releasing hormone knockout (GHRH‐KO) female mice and their littermate controls. Employing a targeted lipidomic approach, we specifically investigated ceramide levels in GHRH‐KO mice, a well‐established model of enhanced longevity. While younger GHRH‐KO mice did not exhibit notable differences in serum lipids, older counterparts demonstrated significant reductions in over one‐third of the evaluated lipids. In employing the same analysis in liver tissue, GHRH‐KO mice showed pronounced downregulation of numerous ceramides and hexosylceramides, which have been shown to elicit many of the tissue defects that accompany aging (e.g., insulin resistance, oxidative stress, and cell death). Additionally, gene expression analysis in the liver tissue of adult GHRH‐KO mice identified substantial decreases in several ceramide synthesis genes, indicating that these alterations are, at least in part, attributed to GHRH‐KO‐induced transcriptional changes. These findings provide the first evidence of disrupted ceramide metabolism in a long‐lived mammal. This study sheds light on the intricate connections between GH deficiency, ceramide levels, and the molecular mechanisms influencing lifespan extension. [ABSTRACT FROM AUTHOR]

Background: Alterations in the serum lipid profile have been suspected in many psychiatric disorders, such as schizophrenia and depression. However, studies on lipid status in attention-deficit/hyperactivity disorder (ADHD) are sparse and inconsistent. Methods: Using the nationwide, population-based IQVIA Disease Analyzer database, this retrospective cohort study included 5367 outpatients from general practices in Germany aged ≥18 years with a documented first diagnosis of ADHD between January 2005 and December 2021 and 26,835 propensity score-matched individuals without ADHD. Study outcomes were the first diagnosis of lipid metabolism disorders as a function of ADHD within up to 10 years of the index date. The cumulative 10-year incidence was analyzed using Kaplan–Meier curves and compared using the log-rank test. In addition, univariate Cox regression analyses were performed. Results: In the regression analysis, there was no significant association between ADHD and subsequent lipid metabolism disorders in the total population (HR: 0.94; 95% CI: 0.83–1.08), among women (HR: 1.04; 95% CI: 0.84–1.28), and among men (HR: 0.89; 95% CI: 0.74–1.06). In addition, no significant association was observed in the disease-stratified analyses. Conclusions: The findings of this study indicate that ADHD does not exert an influence on lipid metabolism. However, further investigation is warranted, particularly with respect to pharmacological interventions. [ABSTRACT FROM AUTHOR]

Altered cholesterol, oxysterol, sphingolipid, and fatty acid concentrations are reported in blood, cerebrospinal fluid, and brain tissue of people with relapsing-remitting multiple sclerosis (RRMS) and are linked to disease progression and treatment responses. CD4 + T cells are pathogenic in RRMS, and defective T-cell function could be mediated in part by liver X receptors (LXRs)—nuclear receptors that regulate lipid homeostasis and immunity. RNA-sequencing and pathway analysis identified that genes within the 'lipid metabolism' and 'signalling of nuclear receptors' pathways were dysregulated in CD4 + T cells isolated from RRMS patients compared with healthy donors. While LXRB and genes associated with cholesterol metabolism were upregulated, other T-cell LXR-target genes, including genes involved in cellular lipid uptake (inducible degrader of the LDL receptor, IDOL), and the rate-limiting enzyme for glycosphingolipid biosynthesis (UDP-glucosylceramide synthase, UGCG) were downregulated in T cells from patients with RRMS compared to healthy donors. Correspondingly, plasma membrane glycosphingolipids were reduced, and cholesterol levels increased in RRMS CD4 + T cells, an effect partially recapitulated in healthy T cells by in vitro culture with T-cell receptor stimulation in the presence of serum from RRMS patients. Notably, stimulation with LXR-agonist GW3965 normalized membrane cholesterol levels, and reduced proliferation and IL17 cytokine production in RRMS CD4 + T-cells. Thus, LXR-mediated lipid metabolism pathways were dysregulated in T cells from patients with RRMS and could contribute to RRMS pathogenesis. Therapies that modify lipid metabolism could help restore immune cell function. Lipid metabolism was dysregulated in CD4 + T cells and serum from patients with relapsing-remitting multiple sclerosis compared to healthy controls, characterized by differential regulation of genes involved in cellular lipid uptake and lipid biosynthesis, altered T-cell plasma membrane lipid profiles and changes in serum lipoprotein expression. Alterations in T-cell plasma membrane lipids (lipid rafts) could be partially recapitulated in healthy T cells by in vitro culture with T-cell receptor stimulation in the presence of serum from RRMS patients. Conversely, co-stimulation of RRMS T cells with a liver X receptor (LXR)-agonist (a nuclear receptor important for lipid homeostasis), normalized membrane cholesterol levels, and reduced proliferation and IL17 cytokine production, suggesting that defects in LXR-mediated lipid metabolism pathways could contribute to RRMS pathogenesis. Graphical Abstract [ABSTRACT FROM AUTHOR]

The effect of the lipid extract isolated from the tunic of the marine hydrobiont Halocynthia aurantium was studied. Its administration during hypothermia, hyperthermia, muscle load, introduction of hexenal, and the vertical fixation by the dorsal neck fold, as well as its embryotoxic and teratogenic effects, was evaluated. The impact of stress (vertical fixation of rats by the dorsal neck fold) was accompanied by an increase in the plasma levels of total lipids, total cholesterol, cholesterol/phospholipid ratios, and a decrease in the total phospholipids, as well as by a change in the quantitative characteristics of classes of neutral and phospholipids. A correction of the developed changes by a lipid extract of ascidia and a commercial reference preparation Omega-3 was carried out. The lipid extract of H. aurantium showed a higher efficiency in restoring the lipid composition of the blood plasma under stress impact compared to the preparation Omega-3 due to the wider range of neutral and phospholipid classes, polyunsaturated fatty acids of the n-3 and n-6 families. The tunic of ascidian can be used as a raw material for obtaining preparations with stress-protector and lipid-correcting properties. [ABSTRACT FROM AUTHOR]

Background: The association between low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C) ratio and the clinical outcomes of acute intracranial hemorrhage (ICH) remains unclear. In this study, we attempt to investigate whether low LDL-C/HDL-C ratio is associated with poor clinical outcomes in patients with ICH. Methods: The database was collected from a multicenter, prospective, observational cohort study, conducted in 13 hospitals in Beijing from January 2014 to September 2016. A total of 1,964 patients with ICH were initially screened in our database. Next, we selected patients with admission serum lipid information for retrospective analysis. Patients were categorized into four groups based on LDL-C/HDL-C ratio quartiles. The main outcomes were 30-day and 90-day poor functional outcome, which is defined as modified Rankin Scale score of 3 to 6, and 90-day all-cause death. Logistic regression was used to assess the association between LDL-C/HDL-C ratio and 30-day or 90-day poor functional outcome. Kaplan–Meier survival analysis and Cox regression were used to assess the association between LDL-C/HDL-C ratio and 90-day all-cause death. Restricted cubic splines were used to explore the nonlinear association between LDL-C/HDL-C ratio and the outcome of patients with ICH. Results: A total of 491 patients with spontaneous ICH were finally enrolled in our study. The mean age was 57.6 years old, and 72.1% (357/491) were men. After adjustment for confounders, patients in the lowest LDL-C/HDL-C quartile (< 1.74) had a significantly higher risk of 30-day and 90-day poor functional outcome compared with those in the highest quartile (> 3.16; 30-day: adjusted odds ratio 3.61, 95% confidence interval 1.68–7.72; 90-day: adjusted odds ratio 2.82, 95% confidence interval 1.33–5.95). Restricted cubic splines depicted a nonlinear association between LDL-C/HDL-C ratio and 90-day poor functional outcomes, indicating LDL-C/HDL-C ratio of 3.1–3.5 was correlated with better 90-day functional outcome. However, no significant correlation was found between low LDL-C/HDL-C ratio and 90-day all-cause death. Conclusions: Lower LDL-C/HDL-C ratio (< 1.74) is independently associated with an increased risk of poor functional outcome in patients with ICH. In the population of patients whom we studied, there is a nonlinear association between LDL-C/HDL-C ratio and 90-day poor functional outcome, and patients with an LDL-C/HDL-C ratio of 3.1 to 3.5 tend to have the lowest risk of 90-day poor functional outcome. [ABSTRACT FROM AUTHOR]

Background: Metabolic unhealth (MUH) is closely associated with cardiovascular disease (CVD). Life's Essential 8 (LE8), a recently updated cardiovascular health (CVH) assessment, has some overlapping indicators with MUH but is more comprehensive and complicated than MUH. Given the close relationship between them, it is important to compare these two measurements. Methods: This population-based cross-sectional survey included 20- to 80-year-old individuals from 7 National Health and Nutrition Examination Survey (NHANES) cycles between 2005 and 2018. Based on the parameters provided by the American Heart Association, the LE8 score (which ranges from 0 to 100) was used to classify CVH into three categories: low (0–49), moderate (50–79), and high (80–100). The MUH status was evaluated by blood glucose, blood pressure, and blood lipids. The associations were assessed by multivariable regression analysis, subgroup analysis, restricted cubic spline models, and sensitivity analysis. Results: A total of 22,582 participants were enrolled (median of age was 45 years old), among them, 11,127 were female (weighted percentage, 49%) and 16,595 were classified as MUH (weighted percentage, 73.5%). The weighted median LE8 scores of metabolic health (MH) and MUH individuals are 73.75 and 59.38, respectively. Higher LE8 scores were linked to lower risks of MUH (odds ratio [OR] for every 10 scores increase, 0.53; 95% CI 0.51–0.55), and a nonlinear dose–response relationship was seen after the adjustment of potential confounders. This negative correlation between LE8 scores, and MUH was strengthened among elderly population. Conclusions: Higher LE8 and its subscales scores were inversely and nonlinearly linked with the lower presence of MUH. MUH is consistent with LE8 scores, which can be considered as an alternative indicator when it is difficult to collect the information of health behaviors. [ABSTRACT FROM AUTHOR]

The central nervous system continuously detects circulating concentrations of lipids such as fatty acids and troglycerides. Once information has been detected, the central nervous system can in turn participate in the control of energy balance and blood sugar levels and in particular regulate the secretion and action of insulin. Neurons capable of detecting circulating lipid variations are located in the hypothalamus and in other regions such as the nucleus accumbens, the striatum or the hippocampus. An excess of lipids will have deleterious effects and may induce central lipotoxicity, in particular following local production of ceramides and the appearance of neuroinflammation which may lead to metabolic diseases such as obesity and type 2 diabetes. • Both specialized neurons and non-neuronal cells can sense circulating lipids. • lipoprotein lipase in neurons and astrocytes sense triglycerides-enriched lipoproteins. • Ceramides can induce brain lipotoxicity associated with neuroinflammation. [ABSTRACT FROM AUTHOR]

Policosanol is a blend of long-chain aliphatic alcohols (LCAAs) and is well-known for several health-beneficial activities; however, the functionality of policosanol varied substantially based on the composition of LCAAs. In this study, two distinct policosanols, Raydel® (extracted from Cuban sugarcane wax) and BOC Sciences (extracted from Chinese sugarcane wax), were dietarily supplemented (0.1% w/w) for 12 weeks in hyperlipidemic zebrafish to examine their influence on the blood lipid profile and functionality of the liver, kidney, and reproductive organs. The results demonstrated a noteworthy impact of both policosanols on preventing high-cholesterol diet (HCD, 4% w/w)-induced dyslipidemia by decreasing total cholesterol (TC) and triglyceride (TG) levels in the plasma. However, compared to BOC Sciences, the Raydel® policosanol exhibited a significantly (p < 0.05) higher efficacy in reducing HCD-induced TC and TG levels. A substantial effect was observed exclusively with the Raydel® policosanol in mitigating HCD-impaired low-density-lipoprotein cholesterol (LDL-C) and high-density-lipoprotein cholesterol (HDL-C) levels. Hepatic histology and immunohistochemistry (IHC) analysis revealed the higher efficacy of Raydel® policosanol over BOC Sciences policosanol to prevent HCD-provoked fatty liver changes, cellular senescence, oxidative stress, and interleukin (IL)-6 production. Consistently, a significantly higher effect of Raydel® over BOC Sciences policosanol was observed on the protection of kidney, testis, and ovary morphology hampered by HCD consumption. In addition, Raydel® policosanol exhibited a notably stronger effect (~2-fold, p < 0.05) on the egg-laying ability of the zebrafish compared to policosanol from BOC Sciences. Furthermore, Raydel® policosanol plays a crucial role in improving embryo viability and mitigating developmental defects caused by the intake of an HCD. Conclusively, Raydel® policosanol displayed a substantially higher efficacy over BOC Sciences policosanol to revert HCD-induced dyslipidemia, the functionality of vital organs, and the reproductive health of zebrafish. [ABSTRACT FROM AUTHOR]

Background: Preeclampsia is a pregnancy-specific clinical syndrome and can be subdivided into early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE) according to the gestational age of delivery. Patients with preeclampsia have aberrant lipid metabolism. This study aims to compare serum lipid profiles of normal pregnant women with EOPE or LOPE and screening potential biomarkers to diagnose EOPE or LOPE. Methods: Twenty normal pregnant controls (NC), 19 EOPE, and 19 LOPE were recruited in this study. Untargeted lipidomics based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to compare their serum lipid profiles. Results: The lipid metabolism profiles significantly differ among the NC, EOPE, and LOPE. Compared to the NC, there were 256 and 275 distinct lipids in the EOPE and LOPE, respectively. Furthermore, there were 42 different lipids between the LOPE and EOPE, of which eight were significantly associated with fetal birth weight and maternal urine protein. The five lipids that both differed in the EOPE and LOPE were DGTS (16:3/16:3), LPC (20:3), LPC (22:6), LPE (22:6), PC (18:5e/4:0), and a combination of them were a potential biomarker for predicting EOPE or LOPE. The receiver operating characteristic analysis revealed that the diagnostic power of the combination for distinguishing the EOPE from the NC and for distinguishing the LOPE from the NC can reach 1.000 and 0.992, respectively. The association between the lipid modules and clinical characteristics of EOPE and LOPE was investigated by the weighted gene co-expression network analysis (WGCNA). The results demonstrated that the main different metabolism pathway between the EOPE and LOPE was enriched in glycerophospholipid metabolism. Conclusions: Lipid metabolism disorders may be a potential mechanism of the pathogenesis of preeclampsia. Lipid metabolites have the potential to serve as biomarkers in patients with EOPE or LOPE. Furthermore, lipid metabolites correlate with clinical severity indicators for patients with EOPE and LOPE, including fetal birth weight and maternal urine protein levels. [ABSTRACT FROM AUTHOR]

The tumour suppressor p16/CDKN2A and the metabolic gene, methyl-thio-adenosine phosphorylase (MTAP), are frequently co-deleted in some of the most aggressive and currently untreatable cancers. Cells with MTAP deletion are vulnerable to inhibition of the metabolic enzyme, methionine-adenosyl transferase 2A (MAT2A), and the protein arginine methyl transferase (PRMT5). This synthetic lethality has paved the way for the rapid development of drugs targeting the MAT2A/PRMT5 axis. MAT2A and its liver- and pancreas-specific isoform, MAT1A, generate the universal methyl donor S-adenosylmethionine (SAM) from ATP and methionine. Given the pleiotropic role SAM plays in methylation of diverse substrates, characterising the extent of SAM depletion and downstream perturbations following MAT2A/MAT1A inhibition (MATi) is critical for safety assessment. We have assessed in vivo target engagement and the resultant systemic phenotype using multi-omic tools to characterise response to a MAT2A inhibitor (AZ'9567). We observed significant SAM depletion and extensive methionine accumulation in the plasma, liver, brain and heart of treated rats, providing the first assessment of both global SAM depletion and evidence of hepatic MAT1A target engagement. An integrative analysis of multi-omic data from liver tissue identified broad perturbations in pathways covering one-carbon metabolism, trans-sulfuration and lipid metabolism. We infer that these pathway-wide perturbations represent adaptive responses to SAM depletion and confer a risk of oxidative stress, hepatic steatosis and an associated disturbance in plasma and cellular lipid homeostasis. The alterations also explain the dramatic increase in plasma and tissue methionine, which could be used as a safety and PD biomarker going forward to the clinic. [ABSTRACT FROM AUTHOR]

Weight gain, blood lipids and/or glucose dysregulation can follow aripiprazole treatment onset. Whether aripiprazole dosage is associated with an increase in these metabolic parameters remains uncertain. The present study investigates aripiprazole dose associations with weight change, blood glucose, lipids, and blood pressure. 422 patients taking aripiprazole for a minimum of three weeks to one year were selected from PsyMetab and PsyClin cohorts. Associations between aripiprazole dose and metabolic outcomes were examined using linear mixed-effect models. Aripiprazole dose was associated with weight change when considering its interaction with treatment duration (interaction term: −0.10, p < 0.001). This interaction resulted in greater weight gain for high versus low doses at the beginning of the treatment, this result being overturned at approximately five months, with greater weight increase for low versus high doses thereafter. LDL and HDL cholesterol levels were associated with aripiprazole dose over five months independently of treatment duration, with an average of 0.06 and 0.02 mmol/l increase for each 5 mg increment, respectively (p = 0.033 and p = 0.016, respectively). Furthermore, mean dose increases were associated with greater odds (+30 % per 5 mg increase) of clinically relevant weight gain (i.e., ≥7 %) over one year (p = 0.025). Aripiprazole dose was associated with one-year weight changes when considering its interaction with treatment duration. Increasing its dose could lead to metabolic worsening over the first five months of treatment, during which minimum effective doses should be particularly preferred. [ABSTRACT FROM AUTHOR]

Objective: This study compared the ability of Liquorice roots aqueous extract (LRE) and its ingredient, isoliquiritigenin (ISL), in alleviating high-fat diet (HFD)-induced hepatic steatosis and examined if this effect involves activation of AMPK. Materials and methods: Control or HFD-fed rats were treated with the vehicle, LRE (200 mg/kg), or ISL (30 mg/kg) for 8 weeks orally. Results: ISL and LRE reduced HFD-induced hyperglycaemia, improved liver structure, lowered serum and hepatic lipids, and attenuated hepatic oxidative stress and inflammation. In the control and HFD-fed rats, ISL and LRE significantly stimulated the muscular and hepatic mRNA and protein levels of AMPK, improved oral glucose tolerance, reduced hepatic mRNA levels of SREBP1/2, and upregulated hepatic levels of PPARα and Bcl2. These effects were comparable for ISL and LRE and were prevented by co-administration of compound C, an AMPK inhibitor. Discussion and conclusion: ISL and LRE provide an effective theory to alleviate hepatic steatosis through activating AMPK. [ABSTRACT FROM AUTHOR]

Cassia fistula (C. fistula) has shown strong anti‐inflammatory, hepatoprotective, antitussive, antibacterial, and antifungal properties and is being used for healing wounds and gastrointestinal illness. This study was planned to obtain fruit extract from C. fistula using ultrasonic‐assisted extraction (UAE) technique and evaluated for phytochemical contents, anti‐hyperlipidemia, and hematological parameters. The results showed that total phenolic (TPC), total flavonoids (TFC), condensed tannin (CT), and saponins were 13.07 mg GAE/g, 5.24 mg QE/g, 4.01 mg/g, and 27.55%, respectively, in the extract. Proximate composition of the extract showed 2.48%, moisture, 1.25% fat, 2.80% ash, 4.59% fiber, 11.93% protein, and 76.95% NFE. The 2, 2‐diphenyl‐1‐picrylhydrazyl (DPPH) and ferric reducing antioxidant power assay (FRAP) activity was 63.30 μg/mL and 15.02 nmol/g, respectively. High‐fat diet (HFD)‐induced hyperlipidemic rats were orally administrated with 0.5 and 1.0 g of extract/kg body weight (bw) daily. The reduction of total cholesterol (TC: 90.83 ± 8.86 mg/dL), triglycerides (TG; 74.16 ± 9.10 mg/dL), and low‐density lipoproteins (LDL; 74.83 ± 4.66 mg/dL) and increase of high‐density lipoproteins (HDL; 41.83 ± 8.4 mg/dL) was observed. Significant changes in red blood cells (RBCs; 8.03 ± 0.67106/μL), mean corpuscular hemoglobin concentration (MCHC; 35.02 ± 1.78 g/dL), mean corpuscular hemoglobin (MCH; 18.00 ± 0.26 pg), and mean corpuscular volume (MCV; 55.36 ± 4.01 fL) at 1.0 g extract intake was observed. Extract administration also improved significantly liver enzymes, body weight, and liver morphology. Therefore, C. fistula extract can be effectively used as a therapeutic agent to improve serum biochemistry and hematological values. [ABSTRACT FROM AUTHOR]

Monascus red pigments (MRP) may have benefits against NAFLD with an unclear mechanism. This study aimed to explore the protective effect of MRP supplementation against NAFLD through regulation of gut microbiota and metabolites. The C57BL/6 mice animals were randomly allocated into the normal diet (NC), HFHS diet‐induced NAFLD model, and MRP intervention group fed with HFHS diet. Serum lipid profiles and liver function parameters were measured. Liver and colon histopathology analysis was conducted to determine the injury in the liver and colon. 16S rRNA gene sequencing was employed to analyze gut microbial composition from fecal samples. Untargeted metabonomics was performed to analyze changes in metabolites in serum and fecal samples. MRP supplementation significantly improved the HFHS‐induced alterations in body weight, lipid profiles, and liver function (p <.01). MRP supplementation decreased the abundance of Akkermansia, Candidatus saccharimonas, Dubosiella, and Oscillibacter, while increasing Lactobacillus, Lachnospiraceae NK4A136 group, and Rikenella in mice fed the HFHS diet. Furthermore, MRP supplementation improved the serum and fecal metabolic profiles induced by the HFHS diet, primarily involving the arachidonic acid metabolism, unsaturated fatty acid biosynthesis, and adipocyte lipolysis pathways. Liver function and lipid profiles were closely associated with the abundance of Lactobacillus, Streptococcus, Oscillibacter, Akkemansia, and Desulfovibrio (p <.01). These findings revealed that MRP supplementation may help restore gut microbiota composition and balance its metabolites, thereby improving NAFLD. This study presents a novel outlook on the potential benefits of MRP supplementation in ameliorating NAFLD and supports the application of MRP as a new functional food. [ABSTRACT FROM AUTHOR]

Polyphenols, natural micronutrients derived from plants, are valued for their anti‐inflammatory and antioxidant properties. The escalating global prevalence of non‐alcoholic fatty liver disease (NAFLD) underscores its status as a chronic progressive liver condition. Furthermore, the dysregulation of gut microbiota (GM) is implicated in the onset and progression of NAFLD through the actions of metabolites such as bile acids (BAs), lipopolysaccharide (LPS), choline, and short‐chain fatty acids (SCFAs). Additionally, GM may influence the integrity of the intestinal barrier. This review aims to evaluate the potential effects of polyphenols on GM and intestinal barrier function, and their subsequent impact on NAFLD. We searched through a wide range of databases, such as Web of Science, PubMed, EMBASE, and Scopus to gather information for our non‐systematic review of English literature. GM functions and composition can be regulated by polyphenols such as chlorogenic acid, curcumin, green tea catechins, naringenin, quercetin, resveratrol, and sulforaphane. Regulating GM composition improves NAFLD by alleviating inflammation, liver fat accumulation, and liver enzymes. Furthermore, it improves serum lipid profile and gut barrier integrity. All of these components affect NAFLD through the metabolites of GM, including SCFAs, choline, LPS, and BAs. Current evidence indicates that chlorogenic acid, resveratrol, quercetin, and curcumin can modulate GM, improving intestinal barrier integrity and positively impacting NAFLD. More studies are necessary to evaluate the safety and efficacy of naringenin, sulforaphane, and catechin. [ABSTRACT FROM AUTHOR]

Uncertainties still existed about the effect of high-quality protein supplementation on cardiovascular disease (CVD) risk factors, although high-quality proteins such as soy and milk proteins have proposed to be beneficial for cardiometabolic health. A systematic search in PubMed, Web of Science, Cochrane Library, Scopus, and Embase was conducted to quantify the impact of high-quality protein on CVD risk factors. 63 RCTs on 4 types of high-quality protein including soy protein, milk protein, whey, and casein were evaluated. Soy protein supplementation decreased systolic blood pressure (SBP, −1.42 [-2.68, −0.17] mmHg), total cholesterol (TC, −0.18 [-0.30, −0.07] mmol/L), and low-density lipoprotein cholesterol (LDL-C, −0.16 [-0.27, −0.05] mmol/L). Milk protein supplementation decreased SBP (−2.30 [-3.45, −1.15] mmHg) and total cholesterol (−0.27 [-0.51, −0.03] mmol/L). Whey supplementation decreased SBP (−2.20 [-3.89, −0.51] mmHg), diastolic blood pressure (DBP, −1.07 [-1.98, −0.16] mmHg), triglycerides (−0.10 [-0.17, −0.03] mmol/L), TC (−0.18 [-0.35, −0.01] mmol/L), LDL-C (−0.09 [-0.16, −0.01] mmol/L) and fasting blood insulin (FBI, −2.02 [-3.75, −0.29] pmol/L). Casein supplementation decreased SBP (−4.10 [-8.05, −0.14] mmHg). In the pooled analysis of four high-quality proteins, differential effects were seen in individuals with different health status. In hypertensive individuals, high-quality proteins decreased both SBP (−2.69 [-3.50, −1.87] mmHg) and DBP (−1.34 [-2.09, −0.60] mmHg). In overweight/obese individuals, high-quality proteins improved SBP (−1.40 [-2.22, −0.59] mmHg), DBP (−2.59 [-3.20, −1.98] mmHg), triglycerides (−0.09 [-0.15, −0.02] mmol/L), TC (−0.14 [-0.22, −0.05] mmol/L), LDL-C (−0.12 [-0.16, −0.07] mmol/L), and HDL-C levels (0.02 [0.01, 0.04] mmol/L). According to the benefits on CVD risks factors, whey ranked top for improving cardiometabolic health in hypertensive or overweight/obese individuals. Our study supports a beneficial role of high-quality protein supplementation to reduce CVD risk factors. Further studies are still warranted to investigate the effects of different high-quality proteins on CVD risks in individuals with cardiometabolic disorders. [ABSTRACT FROM AUTHOR]

Combination antiretroviral therapies (cARTs) are linked with multiple-organ system (MOS) toxicities in laboratory animals, and in humans undertaking treatment for HIV/AIDS. The ameliorative potential of low-dose quercetin following cART-associated MOS-toxicities in cardio-hepato-renal organs was evaluated in in vivo model. Oral administration of cART (Dolutegravir 50 mg, Lamivudine 300 mg and Tenofovir disoproxil fumarate 300 mg [DLT]) at 9.29 mg/kg, was challenged against low-dose quercetin 25 mg/kg body weight (bw) in Wistar rats. Group 1, the normal control (NC) received distilled water (5 mL), while groups 2 to 4 received quercetin (25 mg), DLT (9.29 mg), and DLT + quercetin (9.29 mg + 25 mg respectively), per kg bw. All administrations lasted for 14 days, and thereafter animals were humanely sacrificed after intraperitoneal anesthesia injection with 100 mg ketamine /5 mg xylazine per kg bw followed by cervical dislocation. Blood and organs were harvested for analyses using standard protocols. The serum concentrations of lipid parameters [total cholesterol, triglycerides, LDL-cholesterol, and VLDL-cholesterol], liver biomarkers (total-bilirubin, direct-bilirubin, and transaminases], and kidney biomarkers [urea and creatinine] were significantly increased (p < 0.05) while electrolytes (Na+, K+, Cl− and HCO3−) were significantly decreased (p < 0.05) in DLT group but improved in DLT + Q group. Histopathology demonstrated distorted myocytes, hepatocytes and renal tubules, fatty liver with vacuolization, dystrophied glomeruli and distorted renal interstitium in DLT group, compared with normal appearing histoarchitectural features in NC and DLT + Q groups. In conclusion, oral administration of low-dose quercetin (25 mg/kg) ameliorated cART-associated cardio-hepato-renal toxicities in rats, improving their biomarkers and histoarchitecture. [ABSTRACT FROM AUTHOR]

Antiretroviral therapy (ART) is an effective treatment for people living with HIV (PLHIVs), requiring an extended period to achieve immune reconstitution. Metabolic alterations induced by ART are crucial for predicting long‐term therapeutic responses, yet comprehensive investigation through large‐scale clinical studies is still lacking. Here, we collected plasma samples from 108 PLHIVs to the untargeted plasma metabolomics study, based on the longitudinal metabolomics design. Cross‐sectional analyzes were performed at pre‐ and post‐ART to explore the metabolic transformation induced by the therapy. Subsequently, delta values between pre‐ and post‐ART measurements were calculated to quantify metabolic alterations. Then, the optimal set of metabolic traits and clinical signatures were further identified and applied to construct random forest model for predicting the future therapeutic responses to ART. We found distinct ART‐induced metabolic transformation among PLHIVs. After confounder‐adjustments, five metabolites exhibited significant associations with future immune response: tetracosatetraenoic acid (24:4n‐6) (pre‐ART) (odds ratio [OR]: 0.978, 95% confidence interval [CI]: 0.955~0.997), 1‐(3,4‐dihydroxyphenyl)−5‐hydroxy‐3‐decanone (pre‐ART) (OR: 1.298, 95% CI: 1.061~1.727), beta‐PC‐M6 (change) (OR: 0.967, 95% CI: 0.938~0.993), d‐Galactaro‐1,4‐lactone (change) (OR: 1.032, 95% CI: 1.007~1.063), Annuionone C (change) (OR: 1.100, 95% CI: 1.030~1.190). The addition of plasma metabolites to clinical markers accurately predicted immune response to ART with an area under curve of 0.91. Notably, most disrupted metabolites were significantly correlated with blood lipids, suggesting that metabolic transformation might contribute to dyslipidemia among PLHIVs. This study highlights the distinct metabolic transformation post‐ART among PLHIVs and reveals the potential role of metabolic transformation as key determinants of ART efficacy. [ABSTRACT FROM AUTHOR]

The current study was designed to assess the impact of L-carnitine (LC) supplementation in the drinking water of growing Alexandria-line rabbits on performance and physiological parameters. Two hundred eighty-eight 35-day-old rabbits were divided into four groups of twenty-four replicates each (seventy-two rabbits/treatment). The treatment groups were a control group without LC and three groups receiving 0.5, 1, and 1.5 g/L LC in the drinking water intermittently. The results showed that the group receiving 0.5 g LC/L exhibited significant improvements in final body weight, body weight gain, feed conversion ratio, and performance index compared to the other groups. The feed intake remained unaffected except for the 1.5 g LC/L group, which had significantly decreased intake. Hematological parameters improved in all supplemented groups. Compared with those in the control group, the 0.5 g LC/L group showed significant increases in serum total protein and high-density lipoprotein, along with decreased cholesterol and low-density lipoprotein. Compared to other supplemented groups, this group also demonstrated superior carcass traits (carcass, dressing, giblets, and percentage of nonedible parts). In conclusion, intermittent supplementation of LC in the drinking water, particularly at 0.5 g/L twice a week, positively influenced the productivity, hematology, serum lipid profile, and carcass traits of Alexandria-line growing rabbits at 84 days of age. [ABSTRACT FROM AUTHOR]

Metabolic disorders, including obesity, dyslipidemia, diabetes, nonalcoholic fatty liver disease, and metabolic syndrome, are characterized by insulin resistance, abnormalities in circulating cholesterol and lipid profiles, and hypertension. The most common pathophysiologies of metabolic disorders are glucose/lipid metabolism dysregulation, insulin resistance, inflammatory response, and oxidative stress. Although several agents have been approved for the treatment of metabolic disorders, there is still a strong demand for more efficacious drugs with less side effects. Natural products have been critical sources of drug research and discovery for decades. However, the usefulness of bioactive natural products is often limited by incomplete understanding of their direct cellular targets. In this review, we highlight the current understanding of the established and emerging molecular mechanisms of metabolic disorders. We further summarize the therapeutic effects and underlying mechanisms of natural products on metabolic disorders, with highlights on their direct cellular targets, which are mainly implicated in the regulation of glucose/lipid metabolism, insulin resistance, metabolic inflammation, and oxidative stress. Finally, this review also covers the clinical studies of natural products in metabolic disorders. These progresses are expected to facilitate the application of these natural products and their derivatives in the development of novel drugs against metabolic disorders. [ABSTRACT FROM AUTHOR]

We examined whether mixtures of urinary concentrations of bisphenol A (BPA), parabens and phthalate metabolites were associated with serum lipid levels among 175 pregnant women who enrolled in the Environment and Reproductive Health (EARTH) Study (2005–2017), including triglycerides, total cholesterol, high-density lipoprotein (HDL), non-HDL, and low-density lipoprotein (LDL). We applied Bayesian Kernel Machine Regression (BKMR) and quantile g-computation while adjusting for confounders. In the BKMR models, we found no associations between chemical mixture and lipid levels, e.g., total cholesterol [mean difference (95% CRI, credible interval) = 0.02 (−0.31, 0.34)] and LDL [mean difference (95% CRI) = 0.10 (−0.22, 0.43)], when comparing concentrations at the 75th to the 25th percentile. When stratified by BMI, we found suggestive positive relationships between urinary propylparaben and total cholesterol and LDL among women with high BMI [mean difference (95% CRI) = 0.25 (−0.26, 0.75) and 0.35 (−0.25, 0.95)], but not with low BMI [mean difference (95% CRI) = 0.00 (−0.06, 0.07) and 0.00 (−0.07, 0.07)]. No association was found by quantile g-computation. This exploratory study suggests mixtures of phenol and phthalate metabolites were not associated with serum lipid levels during pregnancy, while there were some suggestive associations for certain BMI subgroups. Larger longitudinal studies with multiple assessments of both exposure and outcome are needed to corroborate these novel findings. [ABSTRACT FROM AUTHOR]

Anemia plays an important role in chronic kidney disease (CKD) progression because it worsens the quality of life and increases the risk of cardiovascular complications in CKD patients. In such cases, anemia is mainly caused by endogenous erythropoietin (EPO) and iron deficiencies. Therefore, KDIGO and ERBP guidelines for anemia treatment in CKD patients focus on recombinant EPO and iron supplementation. A recent new treatment option for anemia in CKD patients involves blocking the hypoxia-inducible factor (HIF) system with prolyl hydroxylase inhibitors (PHIs), what causes increasing endogenous EPO production and optimizing the use of iron. Clinical studies have shown that the hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) covered in this manuscript—roxadustat, vadadustat, daprodustat, and molidustat—effectively increase hemoglobin (Hb) levels in both non-dialyzed and dialyzed CKD patients. Moreover, these medicines reduce blood lipid levels and do not accelerate CKD progression. However, blockage of the HIF system by HIF-PHIs may be associated with adverse effects such as cardiovascular complications, tumorogenesis, hyperkalemia. and retinopathy. More extensive and long-term clinical trials of HIF-PHIs-based anemia treatment in CKD patients are needed, and their results will indicate whether HIF-PHIs represent an effective and safe alternative to EPO and iron supplementation for anemia treatment in CKD patients. [ABSTRACT FROM AUTHOR]

Anomalies in lipid metabolism involve multifactorial pathogenesis, among other factors, being associated with an inflammatory state and disturbances in vitamin D status. The literature has focused on the binary relationships between inflammation and dyslipidemia, vitamin D and dyslipidemia, or vitamin D and inflammation. Our study aimed to explore the link between all these three factors: 25-OH vitamin D serum levels, the presence of inflammation assessed through serum C-reactive protein (CRP), and serum lipid profile in 2747 hospitalized patients. Our results showed a positive correlation of HDL-C with 25 (OH) vitamin D and a negative correlation of HDL-C with CRP. This relationship had different patterns in the statistical network analysis. The network analysis patterns are preserved for males and females, except for the relationship between CRP and vitamin D, which is present in male cases and absent in females. The same triangular relationship between all three—CRP, vitamin D, and HDL-C was found with different strengths of partial correlation in obese and non-obese patients. This pattern was similar in patients with and without fatty liver. A shifted pattern was found in the network analysis of hypertensive patients. The CRP was negatively correlated with vitamin D and HDL-C, and vitamin D was positively correlated with HDL-C in non-hypertensive patients. Castelli's Risk indexes I and II were positively associated with CRP, suggesting that increased cardiovascular risk is proportional to an inflammatory state. The triad formed by altered serum lipid levels, inflammation, and vitamin D represents a complex relationship marked by specific dynamics between lipidic fractions such as HDL-C and C-reactive protein and vitamin D. [ABSTRACT FROM AUTHOR]

Background Endometriosis is a poorly understood disease that affects up to 196 million women worldwide and imposes high costs in terms of economic burden and quality of life of women. Traits of circulating lipids have been related to the onset and progression of endometriosis in previous observational studies but the results have remained contradictory. Methods We performed univariable and multivariable Mendelian randomization (MR) analyses using instrument variables to genetically predict the associations of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, triglycerides, and apolipoprotein (apo) A-I and B from the UK Biobank with endometriosis (consisting of 8288 cases and 68 969 controls from the FinnGen consortium). The inverse-variance weighted (IVW) method was used as the primary estimate, whereas MR-Egger and weighted median were conducted as complements to the IVW model. Results Increased levels of triglycerides were associated with higher risk of endometriosis and endometriosis of the pelvic peritoneum in the univariable MR analyses. In multivariable MR analysis including apoB, LDL cholesterol, and triglycerides in the same model, triglycerides still retained a robust effect. Decreased levels of apoA-I and HDL cholesterol were associated with increased risk of endometriosis and endometriosis of the pelvic peritoneum in univariable MR analyses. After mutual adjustment, HDL cholesterol retained a robust effect whereas the association for apoA-I was attenuated. Conclusions This is the first MR-based evidence to suggest that triglycerides and HDL cholesterol are the predominant traits that account for the aetiological relationship of lipoprotein lipids with risk of endometriosis, in particular endometriosis of the pelvic peritoneum. Further well-designed randomized controlled trials are needed to address these results. Key message What is already known on this topic Observational studies have reported associations between traits of circulating lipids and risk of endometriosis but their results have remained contradictory. What this study adds This Mendelian randomization study demonstrated that triglycerides and high-density lipoprotein (HDL) cholesterol are the predominant traits that account for the aetiological relationship of lipoprotein lipids with risk of endometriosis. How this study might affect research, practice, or policy The findings of our study imply that triglycerides and HDL cholesterol should be the focus when developing biomarkers and lipid-modifying interventions for endometriosis patients. [ABSTRACT FROM AUTHOR]

In this study, we evaluated the hepatoprotective effects of astaxanthin, a natural carotenoid, against the cholestatic liver fibrosis induced by bile duct ligation (BDL). Toward this end, male rats were subjected to BDL and treated with astaxanthin for 35 days. Afterwards, their serum and liver biochemical factors were assessed. Also, histopathological and immunohistochemical analyses were performed to determine the fibrosis and the expression levels of alpha‐smooth muscle actin (α‐SMA) and transforming growth factor beta (TGF‐ß1) in the liver tissue. Based on the results, BDL caused a significant increase in liver enzyme levels, blood lipids, and bilirubin, while decreasing the activity of superoxide dismutase(SOD), catalase (CAT), and glutathione (GSH) enzymes. Also, in the BDL rats, hepatocyte necrosis, infiltration of inflammatory lymphocytes, and hyperplasia of bile ducts were detected, along with a significant increase in α‐SMA and TGF‐ß1 expression. Astaxanthin, however, significantly prevented the BDL's detrimental effects. In all, 10 mg/kg of this drug maintained the bilirubin and cholesterol serum levels of BDL rats at normal levels. It also reduced the liver enzymes' activity and serum lipids, while increasing the SOD, CAT, and GSH activity in BDL rats. The expression of α‐SMA and TGF‐ß1 in the BDL rats treated with 10 mg/kg of astaxanthin was moderate (in 34%–66% of cells) and no considerable cholestatic fibrosis was observed in this group. However, administrating the 20 mg/kg of astaxanthin was not effective in this regard. These findings showed that astaxanthin could considerably protect the liver from cholestatic damage by improving the biochemical features and regulating the expression of related proteins. [ABSTRACT FROM AUTHOR]

Background and Objectives: Chronic hepatitis C virus (HCV) infection is intricately linked with dysregulation of lipid metabolism. In particular, cholesterol plays a crucial role in HCV replication. Direct-acting antiviral agents (DAAs) therapy has revolutionized the hepatitis C treatment landscape, achieving high rates of sustained virological response (SVR). However, viral clearance comes with some alterations in lipid-related markers. This prospective study aimed to evaluate the impact of HCV clearance on lipid homeostasis and non-invasive liver fibrosis markers in hepatitis C patients treated with DAAs. Material and Methods: Fifty-two patients with varying degrees of fibrosis treated with DAAs therapy were evaluated at baseline and 24 weeks post-SVR. Lipid profiles and non-invasive liver fibrosis markers were assessed. Results: Our findings revealed an increase in total cholesterol, triglyceride, and LDLc (low-density lipoprotein cholesterol) levels at 24 weeks post-SVR, alongside an improvement in serum liver enzymes. Although improvements in liver stiffness were observed in non-invasive tests, there was an increase in lipid-related markers post-SVR. Conclusions: This suggests a potential increased cardiovascular risk despite improvements in liver function and fibrosis, highlighting the necessity for statin therapy in some cases and extended follow-ups for these patients. These findings underscore the importance of closely monitoring lipid profiles in chronic hepatitis C patients post-SVR, as well as the potential need for statin therapy to mitigate cardiovascular risk. Additionally, extended follow-up is essential to assess long-term outcomes and ensure the optimal management of these patients. [ABSTRACT FROM AUTHOR]

Aims: Few studies investigate whether psychosocial factors (social isolation, social support, trait anger, and depressive symptoms) are associated with cardiovascular health, and none with the American Heart Association's new definition of cardiovascular health, Life's Essential 8 (LE8). Therefore, we assessed the cross-sectional associations of psychosocial factors with Life's Essential 8 and individual components of Life's Essential 8. Methods: We included 11,311 Atherosclerosis Risk in Communities cohort participants (58% females; 23% Black; mean age 57 (standard deviation: 6) years) who attended Visit 2 (1990–1992) in this secondary data analysis using cross-sectional data from the ARIC cohort study. Life's Essential 8 components included diet, physical activity, nicotine exposure, sleep quality, body mass index, blood lipids, blood glucose, and blood pressure. Life's Essential 8 was scored per the American Heart Association definition (0–100 range); higher scores indicate better cardiovascular health. Associations of categories (high, moderate, and low) of each psychosocial factor with continuous Life's Essential 8 score and individual Life's Essential 8 components were assessed using multivariable linear regressions. Results: 11% of participants had high Life's Essential 8 scores (80–100), while 67% and 22% had moderate (50–79) and low Life's Essential 8 scores (0–49) respectively. Poor scores on psychosocial factor assessments were associated with lower Life's Essential 8 scores, with the largest magnitude of association for categories of depressive symptoms (low β = Ref.; moderate β = -3.1, (95% confidence interval: -3.7, -2.5; high β = -8.2 (95% confidence interval: -8.8, -7.5)). Most psychosocial factors were associated with Life's Essential 8 scores for diet, physical activity, nicotine, and sleep, but psychosocial factors were not associated with body mass index, blood lipids, blood glucose, or blood pressure. Conclusion: Less favorable measures of psychosocial health were associated with lower Life's Essential 8 scores compared better measures of psychosocial health among middle-aged males and females. [ABSTRACT FROM AUTHOR]

Various factors have been described in the literature to explain the tendency of an individual to undergo medical screenings. This study aimed to assess the association between the level of knowledge about dyslipidaemia and the frequency of lipid testing, as well as the potential impact of predisposing, enabling, and need factors on the uptake of blood lipid screening. This study was a cross-sectional survey involving 314 participants who were Malaysian residents of Taman Selatan, Klang, aged 30 and above. The study utilized a 42-item paper-based bilingual questionnaire to evaluate the predisposing, enabling, and need factors that could potentially influence the practice of lipid testing. Out of the 314 residents approached, 271 responded to the questionnaire yielding a response rate of 86.31%. The median knowledge score was 5 out of 17. Lower monthly income (OR = 3.225, 95% CI = 0.255 to 2.141), higher number of comorbidities (OR = 2.724, 95% CI = 0.037 to 2.013), higher total knowledge score (OR = 1.334, 95% CI = 0.063 to 0.512) and respondent's belief and attitude (OR = 0.813, 95% CI = -2.033 to -0.539), were found to be significantly associated with the frequency of lipid testing. In conclusion, the knowledge level regarding dyslipidaemia was below average and associated with a lower tendency to undergo frequent lipid testing. There is a need for innovative health awareness such as active educational campaigns in various settings of the community. Further qualitative studies that explore the understanding of the publics', and antecedents of their, lipid screening behaviour are required. Appropriate communication by healthcare providers should be encouraged during patient consultations for higher impact. [ABSTRACT FROM AUTHOR]

PURPOSE: Intense androgen deprivation therapy (ADT) with androgen receptor pathway inhibitors (ARPIs) before radical prostatectomy (RP) produced favorable pathologic responses in approximately 20% of patients. The molecular reason for the low rate of response remains unclear. Lipid metabolism is known to influence androgen receptor signaling and ARPI efficacy. The aim of the study was to identify circulating lipid profiles associated with ADT/ARPI resistance in localized prostate cancer. MATERIALS AND METHODS: Two independent experimental approaches were used. Experiment 1: Post hoc analysis of the association between plasma lipidomic profiles and ADT/ARPI response was performed on patients (n = 104) from two phase II trials of neoadjuvant ADT/ARPI. Response to ADT/ARPI was defined by pathologic response. Experiment 2: Patient-derived tumor explants from RP (n = 105) were cultured in enzalutamide for 48 hours. Explant response to enzalutamide was evaluated against pre-RP plasma lipidomic profiles (n = 105) and prostate tissue lipidomic profiles (n = 36). Response was defined by Ki67 (cell proliferation marker) fold difference between enzalutamide and vehicle-treated explants. In both experiments, associations between lipid profiles and ADT/ARPI response were analyzed by latent class analysis. RESULTS: Pretreatment plasma lipid profiles classified each experimental cohort into two groups with differences in ADT/ARPI response rates. The response rates of the groups were 9.6% versus 29% in experiment 1 (chi-squared test P =.012) and 49% versus 70% in experiment 2 (chi-squared test P =.037). In both experiments, the group with a higher incidence of ADT/ARPI resistance had higher plasma levels of sphingomyelin, glycosylceramides, free fatty acids, acylcarnitines, cholesterol esters, and alkyl/alkenyl-phosphatidylcholine and lower plasma levels of triacylglycerols, diacylglycerols, and phosphoethanolamine (t-test P <.05). CONCLUSION: Pretreatment circulating lipid profiles are associated with ADT/ARPI resistance in localized cancer in both human cohorts and explant models. Plasma lipids are associated with response to neoadjuvant anti-androgen in localized prostate cancer. [ABSTRACT FROM AUTHOR]

Statins, known as hydroxymethylglutaryl coenzyme A reductase (HMG-CoA) inhibitors, are primarily used to lower blood lipids, preventing and treating cardiovascular diseases. Research indicates that statins exhibit multiple effects in the prevention and treatment of colorectal cancer. They function by inhibiting the MVA pathway, suppressing inflammation, enhancing cellular immunity, and influencing the gut microbiota, positively impacting the onset and progression of colorectal cancer. Clinical studies have additionally uncovered that statin drugs can augment the effectiveness of chemotherapy, immunotherapy, and adjuvant therapies, acting as both preventive and adjunctive measures for colorectal cancer. This article critically reviews the research progress on statins in colorectal cancer, aiming to establish a theoretical foundation for exploring innovative treatment options. [ABSTRACT FROM AUTHOR]

Objective to explore the risk assessment potential of oxLDL in patients with T2DM combined with PTB. Methods A prospective study was conducted, which included 60 cases of simple hyperlipidemia, 100 cases of PTB, 100 cases of T2DM, and 100 cases of T2DM combined with PTB. These patients visited the outpatient department of our center from June 2022 to June 2023. The PTB group, T2DM group, and T2DM combined with PTB group were further divided into subgroups based on normal blood lipids (40 cases) and hyperlipidemia (60 cases), totaling 360 cases in the case group. Additionally, a control group consisting of 60 healthy individuals was included. The age range for inclusion in the study was between 35 to70 years old. Venous blood samples were collected from each group to detect HbA1c, INS, FSG, CHOL, TG, HDL, LDL, ApoA I and Apo B. OxLDL levels were measured using the ELISA method. Differences in levels between groups were compared. Multivariate logistic regression analysis was applied to assess the association between oxLDL levels and PTB as well as T2DM combined with PTB. Results There were no statistically significant differences in BMI, blood sugar, blood lipids, and insulin resistance between the T2DM hyperlipidemia subgroup and the T2DM combined with PTB hyperlipidemia subgroup. The oxLDL level in the T2DM hypertipidemia subgroup was more than double that of the control group, while the oxLDL level in the subgroup with normal blood lipids was significantly higher than that of the control group. Moreover, both the T2DM combined with PTB hyperlipidemia subgroup and simple hyperlipidemia group exhibited significantly elevated levels of oxLDL compared to the control group: however, there were no statistically significant differences when compared to the PTB hyperlipidemia subgroup. Correlation analysis revealed a significant positive linear correlation between TG and LDL with oxLDL in both the T2DM hyperlipidemia subgroup and the T2DM combined with PTB hyperlipidemia subgroup (R = 0.352, P < 0.05) . Additionally, CHOL and LDL levels in the PTB hyperlipidemia subgroup also showed a significant positive correlation with oxLDL (R = 0.441, P < 0.05) . Multivariate logistic regression analysis indicated that having oxLDL levels more than double that of the control group was an independent risk factor for both PTB and T2DM combined with PTB (P < 0.05) . Conclusion The significantly elevated levels of oxLDL may serve as a potential risk factor for the comorbidity of T2DM and PTB. It is recommended to consider oxLDL levels exceeding twice those of the control group as a clinically meaningful pathological threshold for further assessment. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular diseases (CVDs) comprise major causes of death worldwide, leading to extensive burden on populations and societies. Alterations in normal lipid profiles, i.e., dyslipidemia, comprise important risk factors for CVDs. However, there is lack of comprehensive evidence on the genetic contribution to dyslipidemia in highly admixed populations. The identification of single nucleotide polymorphisms (SNPs) linked to blood lipid traits in the Brazilian population was based on genome-wide associations using data from the São Paulo Health Survey with Focus on Nutrition (ISA-Nutrition). Methods: A total of 667 unrelated individuals had genetic information on 330,656 SNPs available, and were genotyped with Axiom™ 2.0 Precision Medicine Research Array. Genetic associations were tested at the 10− 5 significance level for the following phenotypes: low-density lipoprotein cholesterol (LDL-c), very low-density lipoprotein cholesterol (VLDL-c), high-density lipoprotein cholesterol (HDL-c), HDL-c/LDL-c ratio, triglycerides (TGL), total cholesterol, and non-HDL-c. Results: There were 19 significantly different SNPs associated with lipid traits, the majority of which corresponding to intron variants, especially in the genes FAM81A, ZFHX3, PTPRD, and POMC. Three variants (rs1562012, rs16972039, and rs73401081) and two variants (rs8025871 and rs2161683) were associated with two and three phenotypes, respectively. Among the subtypes, non-HDL-c had the highest proportion of associated variants. Conclusions: The results of the present genome-wide association study offer new insights into the genetic structure underlying lipid traits in underrepresented populations with high ancestry admixture. The associations were robust across multiple lipid phenotypes, and some of the phenotypes were associated with two or three variants. In addition, some variants were present in genes that encode ncRNAs, raising important questions regarding their role in lipid metabolism. [ABSTRACT FROM AUTHOR]

Background: The complement system has been linked to the etiopathogenesis of rheumatoid arthritis (RA). Patients with RA exhibit a dysregulated profile of lipid molecules, which has been attributed to the inflammation present in the disease. In this study, we aimed to evaluate the association between a comprehensive assessment of the complement system and the lipid profile of patients with RA. Methods: 430 patients with RA were recruited. New-generation techniques were employed to conduct functional assays of the three pathways of the complement system. Serum levels of various complement components such as C1q, factor D, properdin, lectin, C1-inhibitor, C2, C4, C4b, C3, C3a, C5, C5a, and C9 were assessed. Furthermore, a complete pattern of lipid molecules was measured including high (HDL), low-density lipoproteins (LDL), and lipoprotein (a). Multivariable linear regression analysis was conducted to investigate the association between the complement system and lipid profile in RA patients. Results: After multivariable analysis, several noteworthy associations emerged between the complement system and lipid molecules. Notably, complement components most strongly linked to the lipid profile were C1q and properdin, representing the upstream classical and alternative pathways, along with C3 from the common cascade. These associations demonstrated significance and positivity concerning total cholesterol, LDL, atherogenic index, apolipoprotein B, and lipoprotein(a), suggesting a connection with an unfavorable lipid profile. Interestingly, complement functional assays of the three pathways and activated products such as C3a and C5a showed no correlation with the lipid pattern. Conclusion: The correlation between the complement system and lipid molecule patterns is pronounced in patients with RA. This relationship is predominantly positive and primarily associated with upstream complement components rather than activated ones. [ABSTRACT FROM AUTHOR]

Nano-sized Zn particles are recognized for its ability to elevate fish health and well-being, enhancing antimicrobial and antioxidant capacities and reinforcing the immune system. In the present study we explored the effects of Zn-NPs supplementation on augmenting the growth performance and nutritional indicators and physiological aspects of the catfish, Clarias batrachus. Zn-NPs were prepared by heating the mixture of [Zn(CH3COO)2.2H2O], ethylene glycol and polymer surfactant (PVP) at 70°C for 45  min using an oil bath heater. The resultant solution was centrifuged at 6000  rpm on a heated plate at 70°C until the precipitation of Zn-NPs was achieved. Crystal structure, growth mechanisms and shapes of Zn-NPs were characterized by the atomic force microscopy. Produced Zn-NPs was characterized by spectrophotometer and the zeta potential and mean size was recorded as −32.5  ±  1.0  mV and 14.7  ±  2.5  nm, respectively. The experiment comprised six distinct test diets, categorized by the incorporation of Zn-NPs at levels of 0, 10, 20, 30, 40, and 50  mg/kg into the feed where the initial diet was employed as a control group, devoid of any Zn-NPs supplementation. Three glass aquariums were employed for each diet. In each aquarium, 12 fish with an initial mean weight of 5.23  ±  0.06  g were stocked. The fish underwent experimental feeding for 60  days, with the feed amount set at 3% of their body weight. After the experimental period, growth performance (weight gain, length gain, average daily gain, specific growth rate, thermal growth co-efficient, condition factor and survival rate), nutritional indices (feed conversion ratio, protein efficiency ratio, annual net protein utilization), proximate composition of muscle (protein, lipid, carbohydrate, ash and moisture), hematological parameters (RBC, WBC, hemoglobin, hematocrit, MCV, MCH, MCHC, total protein, albumin and globulin), serum lipid and enzymatic parameters (total cholesterol, HDL, LDL, triglycerides, ALP, AST, ALT, amylase, lipase and protease), and bioaccumulation of Zn in different organs of fish were estimated following standard methods. Growth analysis revealed that C. batrachus fed with Zn-NPs at 40  mg/kg of feed had significantly (p  <  0.05) improved growth performance (WG  =  18.87  ±  0.91  g, SGR  =  2.52  ±  0.06% g/day, TGC  =  1.09  ±  0.05 and CF  =  1.47  ±  0.12), nutritional indices (FCR  =  1.35  ±  0.06, PER  =  2.24  ±  0.10 and ANPU  =  41.46  ±  2.56%), hematological parameters, and enzymatic activity compared to control and other groups. The optimal dietary supplementation of Zn-NPs for final weight, weight gain and specific growth rate of C. batrachus was estimated to be ranged between 30.4 and 30.5  mg/kg per diet, respectively. [ABSTRACT FROM AUTHOR]

In this study, the antidiabetic activities of Lepionurus sylvestris Blume extract (LSB) in rats was investigated. The in vitro antidiabetic properties of LSB was evaluated using α-amylase, α-glucosidase and DPP-IV inhibitory assays, while the antioxidant assay was analysed using DPPH, ABTS and FRAP assays. Type 2 diabetes was with high-fructose/streptozotocin, and the diabetic animals were treated with LSB for 5 weeks. At the end of the experiment, the effects of LSB were evaluated via insulin level, lipid profile and hepatorenal function biomarkers. The level of oxido-inflammatory parameters, histopathology and insulin immunohistochemical staining in the pancreas was evaluated. Diabetic rats manifested significant increases in the blood glucose level, food/water intake, lipid profiles, hepatorenal function biomarkers, as well as a marked decreases in the body weight and serum insulin levels. Histopathological and insulin immunohistochemical examination also revealed decreased pancreatic beta cells and insulin positive cells, respectively. These alterations were associated with significant increases in malondialdehyde, TNF-α and IL-1β, in addition to significant declines in GSH, SOD and CAT activities. LSB significantly reduced blood glucose level, glucose intolerance, serum lipids, restored altered hepatorenal and pancreatic functions in the treated diabetic rats. Further, LSB showed antioxidant and anti-inflammatory activities by reducing malondialdehyde, TNF-α, IL-1β, and increasing antioxidant enzymes activities in the pancreatic tissues. A total of 77 secondary metabolites were tentatively identified in the UPLC-Q-TOF-MS analysis of LSB. Overall, these findings provides insight into the potentials of LSB as an antidiabetic agent which may be associated to the plethora bioactive compounds in the plant. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusions Visceral adipose tissue (VAT) is highly associated with metabolic syndrome (MetS), which is rapidly increasing in young adults. However, accessible VAT measurement methods are limited, restricting the use of VAT in early detection. This cross‐sectional study sought to determine if near‐infrared reactance spectroscopy (NIRS)‐derived VAT (VATNIRS) was associated with MetS in a multi‐ethnic sample of young adults.A total of 107 male and female (F:62, M:45) participants (age: 23.0 ± 4.3y; BMI: 27.1 ± 6.6 kg/m2) completed measurements of fasting blood pressure, blood glucose (FBG), blood lipids, and anthropometric assessments including waist circumference and VATNIRS. MetS severity (MetSindex) was calculated from the aforementioned risk factors using sex and race‐specific equations.VATNIRS was higher in participants with, and at risk for, MetS compared to those with lower risks (all p < .001). VATNIRS was positively associated with MetSindex for all groups (all p < .001). VATNIRS showed positive associations with systolic (SBP), diastolic (DBP), and mean arterial pressure (MAP), LDL‐C and LDL‐C‐related biomarkers, and FBG; and negative associations with HDL‐C and HDL‐C‐to‐total cholesterol ratio (all p < .050). Associations between VATNIRS and blood pressure for females, and LDL‐C and LDL‐C‐related biomarkers for males, were nonsignificant (all p > .050). VATNIRS was positively associated with DBP in African–American participants, and SBP in White participants, resulting in positive associations with MAP for both groups (all p < .050).VATNIRS is associated with MetS and individual MetS risks factors in a multi‐ethnic sample of young adults; providing a noninvasive, cost‐effective, portable, and accessible method that may assist in the early detection of MetS and other cardiometabolic abnormalities. [ABSTRACT FROM AUTHOR]

Background: Pathologically, metabolic disorder plays a crucial role in polycystic ovarian syndrome (PCOS). However, there is no conclusive evidence lipid metabolite levels to PCOS risk. Methods: In this study, genome-wide association study (GWAS) genetic data for 122 lipid metabolites were used to assign instrumental variables (IVs). PCOS GWAS were derived from a large-scale meta-analysis of 10,074 PCOS cases and 103,164 controls. An inverse variance weighted (IVW) analysis was the primary methodology used for Mendelian randomization (MR). For sensitivity analyses, Cochran Q test, MR-Egger intercept, MR-PRESSO, leave-one-out analysis,and Steiger test were performed. Furthermore, we conducted replication analysis, meta-analysis, and metabolic pathway analysis. Lastly, reverse MR analysis was used to determine whether the onset of PCOS affected lipid metabolites. Results: This study detected the blood lipid metabolites and potential metabolic pathways that have a genetic association with PCOS onset. After IVW, sensitivity analyses, replication and meta-analysis, two pathogenic lipid metabolites of PCOS were finally identified: Hexadecanedioate (OR=1.85,95%CI=1.27-2.70, P=0.001) and Dihomo-linolenate (OR=2.45,95%CI = 1.30-4.59, P=0.005). Besides, It was found that PCOS may be mediated by unsaturated fatty acid biosynthesis and primary bile acid biosynthesis metabolic pathways. Reverse MR analysis showed the causal association between PCOS and 2-tetradecenoyl carnitine at the genetic level (OR=1.025, 95% CI=1.003-1.048, P=0.026). Conclusion: Genetic evidence suggests a causal relationship between hexadecanedioate and dihomo-linolenate and the risk of PCOS. These compounds could potentially serve as metabolic biomarkers for screening PCOS and selecting drug targets. The identification of these metabolic pathways is valuable in guiding the exploration of the pathological mechanisms of PCOS, although further studies are necessary for confirmation. [ABSTRACT FROM AUTHOR]

Background: Several studies reported that exposure to higher levels of fine particulate matter (PM2.5) was associated with deteriorated lipid profiles in children and adolescents. However, whether a sodium-rich diet could modify the associations remains unknown. We aimed to examine the associations of long-term exposure to PM2.5 with blood lipids in children and adolescents, and further examine the effect modification by dietary and urinary sodium levels based on a multi-community population in China. Methods: The 3711 study participants were from a cross-sectional study, which interviewed children and adolescents aged 6 to 17 years across Sichuan Province, China between 2015 and 2017. Blood lipid outcomes including blood total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) were assessed. Information on daily dietary sodium consumption was estimated with a semi-quantitative food frequency questionnaire (FFQ), and urinary sodium was used as an internal exposure biomarker. A linear regression model was applied to estimate the associations of prior 2-years' average exposure to ambient PM2.5 with blood lipids. The effect modification by dietary and urinary sodium was examined by stratified analyses. Results: The participants from rural areas had higher levels of daily sodium consumptions. The results of multivariable regression analysis indicated that per 10 μg/m3 incremental change in PM2.5 was associated with a 1.56% (95% confidence interval 0.90%—2.23%) and a 2.26% (1.15%—3.38%) higher blood TC and LDL-C levels, respectively. Among the study participants with higher levels of dietary sodium or urinary sodium, exposure to higher levels of PM2.5 was significantly associated with deteriorated lipid profiles. For example, each 10 μg/m3 incremental change in exposure to PM2.5 was correlated with a 2.83 (-4.65 to -0.97) lower percentage decrease in blood HDL-C levels among the participants who were from the highest quartile of urinary sodium levels. While, these associations changed to be nonsignificant in the participants who were from the lowest quartile of dietary sodium levels. Conclusion: Exposure to higher levels of PM2.5 was associated with deteriorated blood lipid levels in children and adolescents. It is noteworthy that these associations might be ameliorated through the adoption of a low-sodium dietary regimen. [ABSTRACT FROM AUTHOR]