Biochar, owing to its highly porous structure and strong adsorption capacity, has the potential to enhance gut health and nutrient utilization. Saffron (Crocus sativus L.) petal extract is rich in phenolic compounds and flavonoids and exhibits pronounced antioxidant and immunomodulatory properties. However, the potential synergistic effects of these two feed additives in poultry nutrition have not been fully elucidated. The present study evaluated the combined effects of dietary biochar and saffron petal extract on growth performance, intestinal morphology, antioxidant status, and lipid metabolism in Japanese quails (Coturnix coturnix japonica). A total of 500 quails were randomly allocated to five dietary treatments, each with five replicates of 20 birds per replicate: a control diet, probiotic-supplemented diet, biochar-supplemented diet, saffron petal extract-supplemented diet, and a combined biochar plus saffron petal extract diet. Growth performance indices, serum biochemical parameters, intestinal histomorphology, antioxidant markers, and ammonia emissions were assessed. Combined supplementation with biochar and saffron petal extract significantly improved (P < 0.05) body weight gain, FCR and cecal villus height compared with the control and probiotic-fed groups. Moreover, this group showed higher glutathione (GSH) and superoxide dismutase (SOD) compared to other treatments (P < 0.05). Additionally, combined diet decreased ammonia emissions at 24 and 48 h, suggesting improved environmental sustainability. The serum lipid profile was also favorably modulated in all additive treatments compared to the control, as evidenced by increased HDL concentrations and reduced triglyceride, LDL and total cholesterol levels. Cecal Coliforms and Salmonella populations were decreased (P < 0.05) in all additive-supplemented groups without any significant changes in total bacterial counts. In conclusion, dietary supplementation with biochar and saffron petal extract exerted synergistic effects on intestinal morphology, antioxidant defense, and lipid metabolism, ultimately resulting in enhanced growth performance and physiological health in Japanese quails.

Terminalia chebula fruit is a medicinal plant high in bioactive compounds that have potential therapeutic benefits. The current study targeted to determine the phytochemical profiles and hypolipidemic effects of aqueous and methanol-based extracts of Terminalia chebula fruits in high-fat diets that made hyperlipidemic Wistar rats. According to qualitative phytochemical examination, the aqueous extract contained phenols, flavonoids, tannins and saponins, whereas the methanol extract contained alkaloids, tannins, and flavonoids, Induction of hyperlipidemia significantly raised total serum cholesterol, triglycerides, LDL, and VLDL levels in the group with high-fat diet when compared to the normal control. Treatment with the methanol extract of Terminalia chebula (200 mg/kg) resulted in significant decreases (P<0.05) in blood total cholesterol (26.6%), triglycerides (17.3%), LDL cholesterol (43.8%), and VLDL cholesterol (17.3%) compared to hyperlipidemic control group. Similarly, the aqueous extract significantly decreased total cholesterol (15.8%), triglycerides (12.8%), LDL cholesterol (28.2%), and VLDL cholesterol (12.8%) (P<0.05). Atorvastatin treatment resulted in a significant improvement in lipid parameters and acted as a positive control. No substantial increase in HDL cholesterol levels was seen in the extract-treated groups. In conclusion, Terminalia chebula fruit extracts had considerable hypolipidemic action, with the methanol extract exceeding the aqueous extract. These effects could be attributable to the presence of polyphenols and flavonoids, which supports Terminalia chebula's potential use as a natural treatment for hyperlipidemia control.

Excessive dietary fat intake disrupts lipid metabolism and induces oxidative stress and inflammation in aquatic species, impairing growth and health. In Takifugu obscurus, a widely cultivated fish species in China, fat predominantly accumulates in the liver, making this species particularly susceptible to hepatic lipid metabolism disorders. Lycium barbarum polysaccharides (LBPs), as a biologically active macromolecule, are capable of regulating lipid metabolism. Therefore, in this study, we aimed to investigate the regulatory effects of dietary LBP supplementation on lipid metabolism, hepatic function, intestinal microbiota, and metabolomic profiles in high-fat diet (HFD)-fed T. obscurus. A control diet comprising 80 g/kg fat and five HFDs (150 g/kg fat) supplemented with 0, 0.5, 1.0, 1.5, and 2.0 g/kg LBP was administered to 630 juvenile T. obscurus individuals for 56 days. Serum biochemistry, hepatic antioxidant indices, gene expression, intestinal microbiota, and liver metabolomics were analyzed. HFD feeding significantly increased serum triglyceride (TG), total bile acid (TBA), total cholesterol (TCHO), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and hepatic malondialdehyde (MDA) levels while decreasing high-density lipoprotein cholesterol (HDL-C) and total superoxide dismutase (T-SOD) levels. Conversely, LBP supplementation significantly reversed these effects and improved the antioxidant capacity. LBP supplementation resulted in the downregulation of lipid synthesis and inflammatory gene expression and upregulation of lipid catabolism and antioxidant genes. Microbial and metabolomic analyses indicated that LBP supplementation restored gut microbial balance, enhanced diversity, and normalized bile acid and glycerophospholipid metabolism, exhibiting the most pronounced effects at a dose of 1.5 g/kg. In conclusion, LBP effectively mitigates HFD-induced lipid metabolism disorders in T. obscurus. Furthermore, based on the strong correlations observed between the gut microbiota and differential metabolites, we speculate that the gut-liver axis may play a potential role in the regulatory effects of LBP, providing valuable clues for further investigation into the underlying molecular mechanisms.

This study aimed to investigate the association of high-density lipoprotein cholesterol (HDL-C) levels with cardiovascular diseases (CVDs) and all-cause mortality and to determine differences based on the presence or absence of a history of CVDs. This retrospective cohort study included 343,321 adults aged ≥ 40 years whose survey data were recorded in the Korean National Health Insurance Service database from 2009 to 2010. HDL-C levels were divided into five groups. The association among HDL-C levels, CVDs, and all-cause mortality was examined using multivariate Cox proportional hazards regression models. During a mean follow-up period of 9.5 ± 2.0 years, CVDs, all-cause mortality, and composite outcomes occurred in 8.3%, 5.9%, and 13.2% of the study population, respectively. HDL-C levels were inversely associated with CVDs and composite outcomes, with a U-shaped association between HDL-C levels and all-cause mortality. Compared with normal HDL-C levels, very low HDL-C levels and very high HDL-C levels were associated with a higher risk of all-cause mortality. Individuals without preexisting CVDs showed similar patterns. Very low HDL-C and low HDL-C levels in individuals with preexisting CVDs were associated with a higher risk of outcomes. Our results suggest that very high HDL-C levels are associated with a decreased risk of CVDs and an increased risk of all-cause mortality. These associations varied according to preexisting CVDs status, sex, and age, challenging the notion that a higher HDL-C level is universally beneficial.

Angiopoietin-like 8 (ANGPTL8) is a calorically responsive regulator of lipoprotein lipase (LPL). It does this by forming complexes with ANGPTL3 or ANGPTL4 that either inhibit LPL in oxidative tissues or preserve LPL activity in adipose tissue, respectively. Human heterozygous (reference allele/alternate allele, R/A) carriers of rs145464906/p.Q121X and rs760351239/p.Q131X ANGPTL8 protein truncating variants (PTVs) have favorable lipid profiles and decreased cardiovascular risk. Given the purported role of ANGPTL8 in redirecting circulating lipids in response to feeding, it is not clear why these PTVs should profile as they do. We elucidated this process by investigating these ANGPTL8 PTVs along with several novel ANGPTL8 putative loss of function (pLOF) variants, including a splice donor variant rs774984872/c.459 + 1G > T that was predicted to result in an ANGPTL8 truncation (p.K165X), in a consanguineous population from the Pakistan Genomic Resource (PGR). We observed lower TG, lower total cholesterol, and increased HDL-C in heterozygous carriers of these variants, consistent with previous reports for p.Q121X and p.Q131X and confirmed decreased ANGPTL3/8 and ANGPTL4/8 complex levels in serum samples from these carriers compared to non-carriers (R/R). Biochemically, the p.Q121X, p.Q131X and c.459 + 1G > T mutations showed dramatically reduced ANGPTL3/8 complex-mediated LPL inhibition while only modestly decreasing ANGPTL4/8-mediated preservation of LPL activity. Furthermore, a cohort of 14 participants that included 8 non-carriers, 5 heterozygous carriers and a single homozygous (A/A) individual of the c.459 + 1G > T pLOF variant were recruited for kinetic studies following standard mixed meal tolerance tests. Heterozygous carriers showed significantly reduced postprandial TG excursions compared to non-carriers. Together, these results support the concept that pLOF variants in ANGPTL8 result in favorable lipid profiles by selectively reducing ANGPTL3/8-mediated LPL inhibition while largely maintaining ANGPTL4/8-mediated preservation of LPL activity.

Plasma concentration of high-density lipoprotein cholesterol (HDL) is among the most important risk factors for coronary artery disease and apolipoprotein A1 (APOA1) is an essential apolipoprotein that constitutes HDL. However, few comprehensive searches have been conducted to identify non-coding functional SNPs around the APOA1 gene. In this study, we report the identification of a functional SNP, rs12718466, which influences hepatocyte-specific APOA1 gene expression. Furthermore, we identified SOX7 as the transcription factor interacting with the rs12718466 SNP, using a novel screening method Transcription Factor Expression Library (TFEL) scan, which employs a comprehensive library of mouse transcription factors. SOX7 binding is allele-dependent, with stronger binding to the normal allele leading to increased APOA1 transcription. In vitro experiments in hepatocytes and in vivo experiments in mice confirmed that overexpressing SOX7 increased APOA1 expression, while knocking it down decreased both APOA1 gene expression and plasma HDL-C levels. Our research demonstrates that rs12718466 is a functional SNP that modulates APOA1 gene expression through its interaction with SOX7, thereby affecting plasma HDL-C concentrations.

GBS (Guillain-Barré syndrome) is an acute immune-mediated peripheral neuropathy whose pathological mechanisms remain incompletely understood. Our study aimed to explore the intrinsic link and potential mechanisms between circulating dyslipidemia and immune metabolic remodeling of monocytes in GBS. Clinical data from 163 patients diagnosed with classic GBS and 169 healthy controls were analyzed to examine the correlations between their lipid profiles and immune cell features. Leveraging our team's previously published single-cell RNA sequencing (scRNA-seq) dataset for GBS, we characterized the subpopulations, functional features, and differentiation trajectories of peripheral blood monocytes. Furthermore, through transcriptional regulatory network analysis, we identified key transcription factors governing these processes. Compared to healthy controls, GBS patients displayed a distinct dyslipidemia characterized by elevated triglycerides (TG), very low-density lipoprotein (VLDL), and residual cholesterol (RC), but decreased high-density lipoprotein (HDL) and apolipoprotein A1 (APOA1). This lipid profile coincided with higher monocyte counts in peripheral blood, suggesting a synergistic relationship. The scRNA-seq analysis results indicate that the composition of peripheral blood monocyte subsets in GBS patients undergoes fundamental remodeling. This is characterized by a significant expansion of CD14+CD163+ monocytes lipid metabolism-active monocytes and pro-inflammatory CD14+CD169+ monocytes, while the proportion of classical monocytes sharply decreases. Pseudo-time trajectory analysis revealed a differentiation pathway from classical monocytes to CD14+CD163+ monocytes via CD14+CD169+ and intermediate monocytes. This pathway was characterized by an initial increase followed by a decrease in pro-inflammatory activity, coupled with a progressive enhancement in lipid metabolism activity. Transcriptional network analysis identified CEBPB as a core transcription factor potentially associated with the phenotypic conversion of monocyte subsets, likely mediated by synergistic regulation of genes involved in lipid metabolism and cell differentiation. In summary, GBS is characterized by synergistic dyslipidemia and monocyte remodeling. The pathological signature involves lipid metabolic reprogramming in the CD14+CD163+ monocytes and pro-inflammatory phenotypes in the CD14+CD169+ monocytes. The transcription factor CEBPB is associated with this phenotypic conversion by regulating lipid metabolism and differentiation genes, revealing molecular targets for precise GBS diagnosis and therapy.

Untargeted [1]H NMR metabolomics offers a noninvasive means to identify biomarkers in breast cancer (BC) patients; however, metabolic signatures specific to Nigerian women remain poorly understood. This study aimed to identify plasma metabolomic and lipidomic biomarkers associated with BC in Nigerian patients, evaluate their diagnostic performance using machine learning (ML), and identify dysregulated metabolic pathways. This case-control study recruited 100 BC patients and 100 healthy controls from 4 Nigerian teaching hospitals. Plasma metabolites and lipids were profiled using [1]H NMR spectroscopy and the Liposcale test. Multivariate and ML analyses revealed a clear distinction between BC and controls (PLS-DA accuracy: 92.4-94.4%). Twenty-four metabolites were significantly altered (FDR < 0.05), with decreased glycine and glutamine, and increased GlycA, GlycB, glucose, and ketone bodies. Lipoprotein profiling showed reduced small HDL, LDL, and large VLDL particles, alongside with increased HDL diameter. The random forest model achieved the best classification performance (AUC = 0.985) and identified 23 key biomarkers. Pathway analysis revealed 29 enriched metabolic pathways, including glyoxylate and dicarboxylate metabolism. Overall, these findings highlight distinct metabolic alterations in Nigerian BC patients and demonstrate the potential of combining NMR-based metabolomics with ML for population-specific, noninvasive BC diagnostics.