Search Results (835)

Background: The causation of type 2 diabetes remains under debate, but evidence supports both abdominal lipid and ectopic lipid overspill into tissues including muscle as key. How these depots differentially alter cardiometabolic profile and change during body weight and fat loss is not known. Methods: Women with obesity scheduled to undergo bariatric surgery were assessed at baseline (BL, n = 28) and at 6-month follow-up (6m_FU, n = 26) after weight loss. Fasting plasma (Pla), subcutaneous thigh adipose (STA), subcutaneous abdominal adipose, (SAA), and thigh vastus lateralis muscle (VLM) samples were collected at BL through surgery and at 6m_FU using needle biopsy. An untargeted liquid chromatography mass spectrometry metabolomics platform was used. Pla and tissue-specific lipid and polar metabolite profiles were modelled as changes from BL and 6m_FU. Results: There was significant body weight (−24.5 kg) loss at 6m_FU (p < 0.05). BL vs. 6m_FU tissue metabolomics profiles showed the largest difference in lipid profiles in SAA tissue in response to surgery. Conversely, polar metabolites were more susceptible to change in STA and VLM. In Pla samples, both lipid and polar metabolite profiles showed significant differences between timepoints. Jaccard–Tanimoto coefficient t-tests identified a sub-group of gut microbiome and dietary-derived omega-3-fatty-acid-containing lipid species and core energy metabolism and adipose catabolism-associated polar metabolites that are trafficked between sample types in response to bariatric surgery. Conclusions: In this first report on channelling of lipids and polar metabolites to alternative tissues in bariatric-induced weight loss, adaptive shuttling of small molecules was identified, further promoting adipose processing and highlighting the dynamic and coordinated nature of post-surgical metabolic regulation. Full article

Plasma-activated water (PAW), enriched with reactive oxygen and nitrogen species (RONS), presents oxidative and antimicrobial characteristics with potential in cosmetic applications. This study examined the effects of two PAW formulations—nitrate-rich (PAW-N) and peroxide-rich (PAW-P)—on human hair types classified as straight (Type 1), wavy (Type 2), and coily/kinky (Type 4). The impact of PAW on hair structure and chemistry was evaluated using Fourier-transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), UV–Vis spectrophotometry, and physicochemical analyses of the liquids (pH, ORP, conductivity, and TDS). PAW-N, with high nitrate content (~500 mg/L), low pH (2.15), and elevated conductivity (6244 µS/cm), induced significant damage to porous hair types, including disulfide bond cleavage, protein oxidation, and lipid degradation, as indicated by FTIR and EDS data. SEM confirmed severe cuticle disruption. In contrast, PAW-P, containing >25 mg/L of hydrogen peroxide and exhibiting milder acidity and lower ionic strength, caused more localized and controlled oxidation with minimal morphological damage. Straight hair showed greater resistance to both treatments, while coily and wavy hair were more susceptible, particularly to PAW-N. These findings suggest that the formulation and ionic profile of PAW should be matched to hair porosity for safe oxidative treatments, supporting the use of PAW-P as a gentler alternative in hair care technologies. Full article

Background: Type 2 diabetes (T2D) is a global health epidemic with rising prevalence within Asian populations, particularly amongst individuals with high visceral adiposity and ectopic organ fat, the so-called Thin-Outside, Fat-Inside phenotype. Metabolomic and microbiome shifts may herald T2D onset, presenting potential biomarkers and mechanistic insight into metabolic dysregulation. However, multi-omics datasets across ethnicities remain limited. Methods: We performed cross-sectional multi-omics analyses on 171 adults (99 Asian Chinese, 72 European Caucasian) from the New Zealand-based TOFI_Asia cohort at 4-years follow-up. Paired plasma and faecal samples were analysed using untargeted metabolomic profiling (polar/lipid fractions) and shotgun metagenomic sequencing, respectively. Sparse multi-block partial least squares regression and discriminant analysis (DIABLO) unveiled signatures associated with ethnicity, glycaemic status, and sex. Results: Ethnicity-based DIABLO modelling achieved a balanced error rate of 0.22, correctly classifying 76.54% of test samples. Polar metabolites had the highest discriminatory power (AUC = 0.96), with trigonelline enriched in European Caucasians and carnitine in Asian Chinese. Lipid profiles highlighted ethnicity-specific signatures: Asian Chinese showed enrichment of polyunsaturated triglycerides (TG.16:0_18:2_22:6, TG.18:1_18:2_22:6) and ether-linked phospholipids, while European Caucasians exhibited higher levels of saturated species (TG.16:0_16:0_14:1, TG.15:0_15:0_17:1). The bacteria Bifidobacterium pseudocatenulatum, Erysipelatoclostridium ramosum, and Enterocloster bolteae characterised Asian Chinese participants, while Oscillibacter sp. and Clostridium innocuum characterised European Caucasians. Cross-omic correlations highlighted negative correlations of Phocaeicola vulgatus with amino acids (r = −0.84 to −0.76), while E. ramosum and C. innocuum positively correlated with long-chain triglycerides (r = 0.55–0.62). Conclusions: Ethnicity drove robust multi-omic differentiation, revealing distinctive metabolic and microbial profiles potentially underlying the differential T2D risk between Asian Chinese and European Caucasians. Full article

Background: Dyslipidemia and schistosomiasis are major public health challenges, particularly in endemic regions where their coexistence may influence host metabolism and immune responses. This study aimed to evaluate visceral adipose tissue (AT) remodeling in a murine model of acute Schistosoma mansoni infection combined with diet-induced dyslipidemia. Methodology: Female Swiss Webster mice were fed either a standard or high-fat diet (HFD) for 29 weeks and infected with S. mansoni at week 20. Nine weeks after infection, biochemical, morphometric, histopathological, and immunological analyses were performed. Results: The HFD promoted weight gain and dyslipidemia, while S. mansoni infection alone did not alter lipid profiles but partially mitigated the metabolic effects of the HFD. Morphometric analysis revealed adipocyte hypertrophy and reduced cell number in HFD-fed animals. In HFD-fed infected mice, infection partially reversed hypertrophy, suggesting a modulatory effect on AT remodeling. Histopathological examinations showed that while a HFD induced mild inflammation, infection led to intense leukocyte infiltration, hyperemia, and plasma cell degeneration. Peritoneal lavage confirmed a proinflammatory immune profile. Conclusions: These findings indicate that the interaction between a HFD and S. mansoni infection exacerbates adipose tissue inflammation and metabolic alterations, highlighting the complex interplay between parasitic infection, diet, and immune-metabolic regulation. Full article

Background: TGF-β is an immunosuppressive cytokine. Its signaling pathway plays a role in anti-inflammatory responses. Coronary artery disease (CAD) is a clinical consequence of atherosclerosis, which manifests as chronic inflammation and involves platelet mediators, including TGF-β. The aim of this study is to validate the diagnostic utility of TGF-β levels in relation to classical and molecular risk factors for CAD. Methods: The study group included 25 women and 75 men, all aged up to 55 and 50 years, respectively, who had been diagnosed with early-onset CAD. Fasting blood samples were taken to measure plasma levels of TGF-β, sCD36, PCSK9, TNF, VEGF, IL-6, and E-selectin using the ELISA method. Furthermore, a full lipid profile, apolipoproteins (Lp(a), ApoA1, and ApoB), C-reactive protein (hsCRP), and blood morphology were analyzed at the Central Hospital Laboratory. A physical examination was also performed. Results: Positive associations were observed between TGF-β concentration and TNF, platelet count, PTC, and triglyceride levels. TNF and platelet concentration were significant independent predictors of increased plasma TGF-β levels. None of the clinical parameters showed statistically significant associations with plasma TGF-β concentration. Conclusions: Our research has demonstrated that TGF-β levels, including circulating TNF, triglycerides, and platelets, are linked to specific biochemical risk factors in early-onset CAD cases. Full article

Myocardial infarction (MI) is an inflammatory disease responsible for approximately 75% of sudden cardiac deaths. In this study, we aimed to evaluate the cardio-protective influence of microencapsulated probiotic and synbiotic dietary supplements in vivo and in molecular docking studies. MI was induced in rats with the injection of isoproterenol (i.p. 67 mg/kg). Plasma lipid profiles and the levels of oxidative stress markers, inflammatory markers, and cardiac enzymes were determined. The expression levels of MMP-7 and IL-1β in the heart muscle were measured. The impact of dietary supplements on fecal bacterial counts was evaluated across all rat groups. A histopathological examination of cardiac tissue was performed. The cardio-protective potential of cyanidin 3-diglucoside 5-glucoside and arabinoxylan was studied using molecular docking. The results demonstrate that all tested dietary supplements induced an improvement in all the biochemical parameters in association with an improvement in myocardial muscle tissue. The mRNA expression levels of MMP-7 and IL-1β were significantly downregulated by all dietary supplements. All dietary supplements increased the fecal counts of probiotic strains. In the molecular docking analysis, cyanidin 3-diglucoside 5-glucoside exhibited binding affinity values of −8.8 and −10 for lactate dehydrogenase (LDH) and Paraoxonase 1 (PON1), respectively. Arabinoxylan showed similar binding affinity (−8.8) for both LDH and PON1. Conclusion: Microencapsulated probiotic and synbiotic dietary supplements demonstrated notable cardio-protective influence in vivo and in molecular docking studies. These supplements may serve as promising candidates for the prevention of myocardial infarction. Full article

Seed germination and early seedling growth are pivotal stages that define crop establishment and yield potential. Conventional agrochemicals used to improve these processes often raise environmental concerns, highlighting the need for sustainable alternatives. In this study, we demonstrated that water treated with cylindrical dielectric barrier discharge (c-DBD) plasma, enriched with nitric oxide (NO) and reactive nitrogen species (RNS), markedly enhanced onion (Allium cepa) seed germination and seedling vigor. The plasma-treated water (PTW) promoted rapid imbibition, broke dormancy, and accelerated germination rates beyond 98%. Seedlings irrigated with PTW exhibited significantly increased biomass, root and shoot length, chlorophyll content, and antioxidant enzyme activities, accompanied by reduced lipid peroxidation. Transcriptomic profiling revealed that PTW orchestrated a multifaceted regulatory network by upregulating gibberellin biosynthesis genes (GA3OX1/2), suppressing abscisic acid signaling components (ABI5), and activating phenylpropanoid metabolic pathways (PAL, 4CL) and antioxidant defense genes (RBOH1, SOD). These molecular changes coincided with elevated NO₂⁻ and NO₃⁻ levels and finely tuned hydrogen peroxide dynamics, underpinning redox signaling crucial for seed activation and stress resilience. Our findings establish plasma-generated NO-enriched water as an innovative, eco-friendly technology that leverages redox and hormone crosstalk to stimulate germination and early growth, offering promising applications in sustainable agriculture. Full article

Breast cancer (BC) is a neoplasm characterized by high heterogeneity and is influenced by intrinsic molecular subtypes and clinical stage, aspects that remain underexplored in the Colombian population. This study aimed to characterize metabolic alterations associated with subtypes and disease progression in a group of newly diagnosed, treatment-naive Colombian women using an untargeted metabolomics approach. To improve metabolite coverage, samples were analyzed using LC-QTOF-MS and GC-QTOF-MS, along with amino acid profiling. The Luminal B subtype exhibited elevated levels of long-chain acylcarnitines and higher free fatty acid concentrations than the other subtypes. It also presented elevated levels of carbohydrates and essential glycolytic intermediates, suggesting that this subtype may adopt a hybrid metabolic phenotype characterized by increased glycolytic flux as well as enhanced fatty acid catabolism. Tumor, Node, and Metastasis (TNM) staging analysis revealed progressive metabolic reprogramming of BC. In advanced stages, a sustained increase in phosphatidylcholines and a decrease in lysophosphatidylcholines were observed, reflecting lipid alterations associated with key roles in tumor progression. In early stages (I-II), plasma metabolites with high discriminatory power were identified, such as glutamic acid, ribose, and glycerol, which are associated with dysfunctions in energy and carbohydrate metabolism. These results highlight metabolomics as a promising tool for the early diagnosis, clinical follow-up, and molecular characterization of BC. Full article

Phenylketonuria (PKU) is a monogenic disorder caused by pathogenic variants in the gene encoding phenylalanine hydroxylase (PAH), an enzyme essential for phenylalanine (Phe) metabolism. It is characterized by elevated Phe levels, leading to a wide spectrum of clinical phenotypes. These phenotypes are characterized by varying Phe accumulation, dietary tolerance, and heterogeneous cognitive and neurological outcomes, but current monitoring methods, focused primarily on blood Phe levels, are limited in capturing this variability. In this study, we applied mass spectrometry-based advanced quantitative amino acid analyses, untargeted metabolomics, and lipidomics analyses. We examined the plasma metabolite and lipid profiles in a total of 73 individuals with various PKU phenotypes against healthy controls to see how the metabolome and lipidome of the patients change in different phenotypes. We investigated whether novel markers could be associated with metabolic control status. By elucidating the metabolic and lipid fingerprints of PKU’s phenotypic variability, our findings may provide novel insights that could inform the refinement of dietary and pharmacological interventions, thereby supporting the development of more personalized treatment strategies. Full article

Background: The endogenous opioid system plays a pivotal role in numerous physiological processes and is implicated in a range of diseases, including atherosclerosis, a condition contributing to nearly 50% of deaths in Western societies. Objectives: This study investigates the effects of opioid receptor blockade, using naloxone, on the plasma lipid profile and atherosclerosis progression. Methods: ApoE^−/− mice with advanced atherosclerosis were treated with naloxone for seven days, and the effects on atherosclerotic plaque development and liver steatosis were evaluated. Results: A proteomic analysis of liver samples post-treatment identified 38 proteins with altered abundance. The results revealed that naloxone treatment led to an increase in HDL cholesterol, a lipid fraction associated with protective cardiovascular effects. Furthermore, naloxone did not influence the progression of atherosclerotic plaques or the development of liver steatosis. Conclusions: In conclusion, while short-term naloxone treatment in mice with advanced atherosclerosis does not alter overall atherosclerotic plaque progression or liver steatosis, the observed elevation in HDL cholesterol and the extensive changes in liver protein abundance underscore the complex and multifaceted role of the opioid system in lipid metabolism and cardiovascular health. These findings provide a foundation for further exploration of opioid receptor antagonists as modulators of lipid profiles and potential contributors to cardiovascular therapy. Full article

Endothelial dysfunction contributes to the progression of metabolic-dysfunction-associated steatotic liver disease (MASLD). Pemafibrate has been shown to ameliorate MASLD in basic and clinical studies, but it is unclear whether it is also effective in the status of endothelial dysfunction. An MASLD animal model was induced in male wild-type (WT) and endothelial nitric oxide synthase (eNOS)-deficient (eNOSKO) mice by feeding them a high-fat/cholesterol/cholate diet, and they were administered either a vehicle or pemafibrate at 0.17 mg/kg/day for 10 weeks. Although pemafibrate treatment did not change plasma lipid profiles in either WT or eNOSKO mice, pemafibrate reduced plasma AST levels in both WT and eNOSKO mice compared to the levels in the vehicle-treated mice. Histopathological analysis of the liver showed that MASLD was improved in the pemafibrate-treated groups in both WT and eNOSKO mice. Compared to vehicle treatment, pemafibrate treatment significantly reduced the expression levels of hepatic NADPH oxidase subunit genes, M1 macrophages, inflammatory-cytokine-related genes and profibrotic genes in both WT and eNOSKO mice, along with reduction in hepatic oxidative stress assessed by dihydroethidium staining and 4-hydroxynonenal protein levels. Thus, pemafibrate ameliorated MASLD with reduction in oxidative stress and inflammation even in vascular endothelial dysfunction. Full article

Rhabdomyosarcoma (RMS), the most common pediatric soft tissue sarcoma, comprises embryonal (ERMS) and alveolar (ARMS) subtypes with distinct histopathological features, clinical outcomes, and therapeutic responses. To better characterize their molecular distinctions, we performed untargeted plasma proteomics and metabolomics profiling in children with ERMS (n = 18), ARMS (n = 17), and matched healthy controls (n = 18). Differential expression, functional enrichment (GO, KEGG, RaMP-DB), co-expression network analysis (WGCNA/WMCNA), and multi-omics integration (DIABLO, MOFA) revealed distinct molecular signatures for each subtype. ARMS displayed elevated oncogenic and stemness-associated proteins (e.g., cyclin E1, FAP, myotrophin) and metabolites involved in lipid transport, fatty acid metabolism, and polyamine biosynthesis. In contrast, ERMS was enriched in immune-related and myogenic proteins (e.g., myosin-9, SAA2, S100A11) and metabolites linked to glutamate/glycine metabolism and redox homeostasis. Pathway analyses highlighted subtype-specific activation of PI3K-Akt and Hippo signaling in ARMS and immune and coagulation pathways in ERMS. Additionally, the proteomics and metabolomics datasets showed association with clinical parameters, including disease stage, lymph node involvement, and age, demonstrating clear molecular discrimination consistent with clinical observation. Co-expression networks and integrative analyses further reinforced these distinctions, uncovering coordinated protein–metabolite modules. Our findings reveal novel, subtype-specific molecular programs in RMS and propose candidate biomarkers and pathways that may guide precision diagnostics and therapeutic targeting in pediatric sarcomas. Full article

Despite the known impacts of weaning on animal health, the underlying molecular mechanisms remain unclear, particularly how psychological and nutritional stress differentially affect gut health and immune function over time. This study hypothesized that early weaning exerts distinct short- and long-term effects on lamb stress physiology, immunity, and gut health, mediated by specific molecular pathways. Twelve pairs of full-sibling male Hu sheep lambs were assigned to control (CON) or early-weaned (EW) groups. Plasma stress/immune markers were dynamically monitored, and intestinal morphology, antioxidant capacity, apoptosis, and transcriptomic profiles were analyzed at 5 and 28 days post-weaning. Early weaning triggered transient psychological stress, elevating hypothalamic–pituitary–adrenal (HPA) axis hormones (cortisol, catecholamines) and inflammatory cytokines (TNF-α) within 1 day (p < 0.05); however, stress responses were transient and recovered by 7 days post-weaning. Sustained intestinal remodeling was observed in EW lambs, featuring reduced ileal villus height, increased crypt depth (p < 0.05), and oxidative damage (MDA levels doubled vs. CON; p < 0.01). Compensatory epithelial adaptation included increased crypt depth but paradoxically reduced villus tip apoptosis. The transcriptome analysis revealed significant changes in gene expression related to immune function, fat digestion, and metabolism. Key DEGs included APOA4, linked to lipid transport adaptation; NOS2, associated with nitric oxide-mediated immune–metabolic crosstalk; and mitochondrial gene COX1, reflecting energy metabolism dysregulation. Protein–protein interaction analysis revealed NOS2 as a hub gene interacting with IDO1 and CXCL11, connecting oxidative stress to immune cell recruitment. Early weaning exerts minimal lasting psychological stress but drives persistent gut dysfunction through transcriptome-mediated changes in metabolic and immune pathways, highlighting key genes such as APOA4, NOS2, and COX1 as potential regulators of these effects. Full article

Background: Dyslipidemia and distorted fatty acid (FA) metabolism are frequent biochemical abnormalities associated with anorexia nervosa (AN). Gut microbiota is supposed to play an important role in the etiopathogenesis of AN. Apart from the digestive function of bile acids (BAs), these compounds have multiple metabolic functions due to the activation of specific receptors. Objective/aims: The aims of the study were to investigate biochemical measures, including plasma lipids (lipoproteins, respectively), fatty acid (FA) patterns, and the profile of plasma Bas, in AN patients and healthy controls (CON). Methods: Plasma phospholipid FA and BAs profiles were analyzed in 39 women with a restrictive type of AN (AN-R; median age 17 years) and in 35 CON women (median age 20 years). Results: Compared to CON, AN had an increased concentration of HDL-C, increased content of palmitic acid, and decreased proportion of linoleic acid. Moreover, AN had a drop in the level of the sum of PUFAn-6 and increased delta 9 desaturase activity for stearic acid. In AN, we found decreased levels of plasma tauroursodeoxycholic acid (TUDCA). In AN, concentrations of 22:5n-6, 16:0, 20:3n-6 and fat mass index were predic-tors of HDL-C levels (R² = 0.43). Conclusions: Patients with AN-R had an increased concentration of HDL-C, decreased levels of total PUFA n-6, and increased activity of D9D for stearic acid. Furthermore, AN exerted decreased levels of TUDCA. Therefore, a decreased level of TUDCA could potentially serve as a marker of AN. Full article

Postprandial dysmetabolism, which refers to the impaired regulation of glucose and lipid levels after meals, is recognized as an independent risk factor for cardiovascular diseases (CVDs). Diets rich in polyphenols have demonstrated potential in improving postprandial hyperglycemia and hyperlipidemia. This study investigates the effects of olive leaf polyphenols on postprandial metabolic outcomes following a high-fat and high-carbohydrate meal. A total of 36 healthy adults participated in a three-arm randomized crossover trial. They ingested either a biscuit made from olive leaf powder (OLB), olive leaf tea (OLT), or a placebo meal (CTRL) to assess the impact of olive leaf polyphenols on postprandial glycemia, lipid levels, platelet aggregation factor (PAF), and plasma antioxidant status (TAC). Although no statistically significant differences were observed in the primary biomarkers, including glucose and lipid profiles, a delayed insulin response was noted in the interventions involving olive leaf. These findings suggest that while acute olive leaf supplementation did not significantly alter postprandial glycemia or lipidemia, it may subtly influence insulin kinetics. Further research is needed to explore the long-term effects of olive leaf polyphenols on metabolic health, especially in populations at risk for CVDs. Full article