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20 pages, 2956 KB  
Article
Effects of Dietary Strontium Supplementation on Growth Performance, Strontium Enrichment, Muscle Nutrition, and Hepatic Lipid Metabolism in Juvenile Hybrid Sturgeon (Acipenser baerii ♀ × Acipenser schrenckii ♂)
by Shilin Li, Qiang Zhao, Hang Chen, Yanhan Yang, Zhe Zhao, Jianxi Mei, Yuexin Sun, Li Peng, Hailong Ge, Fang Li and Zhijian Wang
Fishes 2026, 11(2), 71; https://doi.org/10.3390/fishes11020071 - 23 Jan 2026
Viewed by 144
Abstract
To explore a safe and effective approach for producing strontium-enriched fish, in this study, we modified the feed for juvenile hybrid sturgeon (Acipenser baerii ♀ × Acipenser schrenckii ♂) and set three different levels of strontium chloride content in their diet (0 [...] Read more.
To explore a safe and effective approach for producing strontium-enriched fish, in this study, we modified the feed for juvenile hybrid sturgeon (Acipenser baerii ♀ × Acipenser schrenckii ♂) and set three different levels of strontium chloride content in their diet (0 mg/kg (Sr0, control), 80 mg/kg (Sr80), and 160 mg/kg (Sr160)) for a period of 8 weeks, analyzing their growth performance, strontium enrichment, muscle nutrition, and hepatic physiological, biochemical, and transcriptomic characteristics. The results show that dietary strontium had no significant impact on sturgeon growth or survival rate (p > 0.05). The strontium content in tissues increased with dietary strontium levels, with the highest enrichment in bone plates (p < 0.05). However, muscle crude fat in the strontium-supplemented groups decreased significantly; the Sr160 group had higher glutamic acid, valine, docosahexaenoic acid methyl ester, lower myristic acid, palmitic acid, etc. (p < 0.05). In addition, strontium treatment alleviated hepatic lipid accumulation and mitochondrial swelling. Biochemical analyses revealed reduced plasma levels of Triglyceride (TG), Total Cholesterol (TC), Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST), as well as decreased hepatic Malondialdehyde (MDA) content, while hepatic Glutathione (GSH) levels increased (p < 0.05). Transcriptomic data further showed that strontium downregulated the expression of fasn and tfrc and upregulated the expression of cpt1a, apoa1, cyp7a1, and slc3a2 (p < 0.05). In conclusion, dietary supplementation with 80–160 mg/kg strontium enables safe strontium enrichment in hybrid sturgeon, improves muscle nutritional quality, and protects liver function by regulating the genes related to lipid metabolism and antioxidant defense, providing a scientific basis for the development of strontium-enriched fish products. Full article
(This article belongs to the Special Issue Pivotal Roles of Feed Additives for Fish)
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32 pages, 3054 KB  
Article
Identification of Cholesterol in Plaques of Atherosclerotic Using Magnetic Resonance Spectroscopy and 1D U-Net Architecture
by Angelika Myśliwiec, Dawid Leksa, Avijit Paul, Marvin Xavierselvan, Adrian Truszkiewicz, Dorota Bartusik-Aebisher and David Aebisher
Molecules 2026, 31(2), 352; https://doi.org/10.3390/molecules31020352 - 19 Jan 2026
Viewed by 135
Abstract
Cholesterol plays a fundamental role in the human body—it stabilizes cell membranes, modulates gene expression, and is a precursor to steroid hormones, vitamin D, and bile salts. Its correct level is crucial for homeostasis, while both excess and deficiency are associated with serious [...] Read more.
Cholesterol plays a fundamental role in the human body—it stabilizes cell membranes, modulates gene expression, and is a precursor to steroid hormones, vitamin D, and bile salts. Its correct level is crucial for homeostasis, while both excess and deficiency are associated with serious metabolic and health consequences. Excessive accumulation of cholesterol leads to the development of atherosclerosis, while its deficiency disrupts the transport of fat-soluble vitamins. Magnetic resonance spectroscopy (MRS) enables the detection of cholesterol esters and the differentiation between their liquid and crystalline phases, but the technical limitations of clinical MRI systems require the use of dedicated coils and sequence modifications. This study demonstrates the feasibility of using MRS to identify cholesterol-specific spectral signatures in atherosclerotic plaque through ex vivo analysis. Using a custom-designed experimental coil adapted for small-volume samples, we successfully detected characteristic cholesterol peaks from plaque material dissolved in chloroform, with spectral signatures corresponding to established NMR databases. To further enhance spectral quality, a deep-learning denoising framework based on a 1D U-Net architecture was implemented, enabling the recovery of low-intensity cholesterol peaks that would otherwise be obscured by noise. The trained U-Net was applied to experimental MRS data from atherosclerotic plaques, where it significantly outperformed traditional denoising methods (Gaussian, Savitzky–Golay, wavelet, median) across six quantitative metrics (SNR, PSNR, SSIM, RMSE, MAE, correlation), enhancing low-amplitude cholesteryl ester detection. This approach substantially improved signal clarity and the interpretability of cholesterol-related resonances, supporting more accurate downstream spectral assessment. The integration of MRS with NMR-based lipidomic analysis, which allows the identification of lipid signatures associated with plaque progression and destabilization, is becoming increasingly important. At the same time, the development of high-resolution techniques such as μOCT provides evidence for the presence of cholesterol crystals and their potential involvement in the destabilization of atherosclerotic lesions. In summary, nanotechnology-assisted MRI has the potential to become an advanced tool in the proof-of-concept of atherosclerosis, enabling not only the identification of cholesterol and its derivatives, but also the monitoring of treatment efficacy. However, further clinical studies are necessary to confirm the practical usefulness of these solutions and their prognostic value in assessing cardiovascular risk. Full article
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21 pages, 668 KB  
Article
The Effect of Short-Term and High-Intensity Functional Circuit Training on Plasma Lipidome Profiles of People Living with and Without HIV
by Marcos Yukio Yoshinaga, Flávio Gomez Faria, Adriano de Britto Chaves-Filho, Sayuri Miyamoto, Tania Cristina Pithon-Curi, Giselle Cristina Bueno, Bruno Ferrari Silva, Sidney Barnabé Peres and Solange Marta Franzoi de Moraes
Metabolites 2026, 16(1), 16; https://doi.org/10.3390/metabo16010016 - 24 Dec 2025
Viewed by 392
Abstract
Background/Objectives: Both HIV infection and antiretroviral therapy contribute to dyslipidemia and abnormal body fat distribution in people living with HIV (PLWH). Exercise training is an effective intervention to protect against these metabolic changes. However, little is known about the mechanisms underlying the impact [...] Read more.
Background/Objectives: Both HIV infection and antiretroviral therapy contribute to dyslipidemia and abnormal body fat distribution in people living with HIV (PLWH). Exercise training is an effective intervention to protect against these metabolic changes. However, little is known about the mechanisms underlying the impact of exercise training on lipid metabolism in PLWH. This study aimed to comparatively evaluate the effect of high-intensity functional circuit training on the plasma lipidome of PLWH and HIV-negative subjects (control). Methods: PLWH (n = 13) and control (n = 14) were submitted to 8 weeks of exercise training. Body composition, anthropometric, and biochemical parameters were measured. Plasma was obtained in a fasting state for lipidomic analysis. Results: Anthropometric and biochemical parameters revealed lower levels of leptin, HDL-C, body fat %, and BMI combined with elevated aspartate transaminase (AST) and Homeostasis Model Assessment of β-cell function (HOMA_beta) in PLWH when compared to control subjects that persisted from baseline to post-exercise training. Nonetheless, contrasting levels of adiponectin, fasting insulin, and phosphatidylcholine-containing lipids observed at baseline were equalized after training in PLWH. In control subjects, significant reductions in concentrations of triglycerides alongside phosphatidylinositol and glycosylated ceramides were observed post-exercise training. By contrast, PWLH displayed an increase in diglycerides, acylcarnitines, and free cholesterol levels after exercise training, together with decreased concentrations of free fatty acids, cholesteryl esters, and glycosylated ceramides. Conclusions: In addition to specific lipidome alterations in each group, particularly driven by improved insulin resistance in PLWH, this study showed concomitant modulation of several glycerophospholipids and sphingolipids, suggesting health-promoting effects of short-term exercise training. Collectively, these modulated lipid species represent interesting targets for future lipidomic-based studies evaluating not only the effects of exercise training but also the molecular mechanisms resulting in a healthier plasma lipidome profile. Full article
(This article belongs to the Special Issue The Role of Lipid Metabolism in Health and Disease)
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18 pages, 971 KB  
Article
Lipophilic Substances of the Leaves and Inflorescences of Centaurea scabiosa L.: Their Composition and Activity Against the Main Protease of SARS-CoV-2
by Tatiana P. Kukina, Ivan A. Elshin, Maria K. Marenina, Evgeniia A. Kolosova, Yulia V. Meshkova, Ol’ga I. Sal’nikova, Svetlana V. Belenkaya, Ekaterina A. Volosnikova, Mikhail V. Khvostov and Dmitry N. Shcherbakov
Molecules 2025, 30(23), 4568; https://doi.org/10.3390/molecules30234568 - 27 Nov 2025
Viewed by 616
Abstract
The composition of the lipophilic components of Centaurea scabiosa L. has been studied. The raw material was subjected to extraction with hexane and methyl tert-butyl ether (MTBE) using both exhaustive and sequential schemes for a detailed characterization. The resulting extracts were fractionated into [...] Read more.
The composition of the lipophilic components of Centaurea scabiosa L. has been studied. The raw material was subjected to extraction with hexane and methyl tert-butyl ether (MTBE) using both exhaustive and sequential schemes for a detailed characterization. The resulting extracts were fractionated into acidic and neutral components via treatment with alkali solutions. The acidic compounds were converted into methyl esters for subsequent gas chromatography–mass spectrometry (GC-MS) analysis, while the neutral unsaponifiable fractions were separated into groups of different polarities using column chromatography on silica gel. This approach enabled the identification of a complex profile of lipophilic substances. In the acidic fractions, aliphatic acids with chain lengths from C10 to C32, including unsaturated variants, were characterized. The neutral fractions revealed over compounds, encompassing n-alkanes, substantial levels of the unsaturated branched hydrocarbon squalene, and a diverse array of oxygenated terpenoids. The latter were mainly represented by highly active triterpene alcohols and ketones belonging to the ursane, oleanane, lupane, and cycloartane types. The sterol composition was dominated by β-sitosterol and accompanied by cholesterol, campesterol, stigmasterol, stigmast-7-en-3-β-ol, fucosterol, and stigmastan-3-β-ol. Bioactivity screening demonstrated that several of the obtained lipophilic extracts, particularly those of lower polarity, exhibited high inhibitory activity against the main protease of SARS-CoV-2, underscoring the potential of C. scabiosa as a valuable source of anti-coronavirus agents. Full article
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26 pages, 7389 KB  
Article
Lipid Composition and Thermotropic Properties of Meibum of Animal Models and Humans with Meibomian Gland Dysfunction
by Igor A. Butovich, Jadwiga C. Wojtowicz, Amber Wilkerson and Seher Yuksel
Int. J. Mol. Sci. 2025, 26(23), 11434; https://doi.org/10.3390/ijms262311434 - 26 Nov 2025
Viewed by 478
Abstract
Meibum—a lipid-rich secretion produced by holocrine Meibomian glands (MG)—plays a central role in maintaining ocular surface homeostasis in humans. Previously, changes in MG lipidomes induced by inactivation of critical genes of meibogenesis, such as Elovl3, Soat1, Awat2, Sdr16c5/Sdr16c6, and [...] Read more.
Meibum—a lipid-rich secretion produced by holocrine Meibomian glands (MG)—plays a central role in maintaining ocular surface homeostasis in humans. Previously, changes in MG lipidomes induced by inactivation of critical genes of meibogenesis, such as Elovl3, Soat1, Awat2, Sdr16c5/Sdr16c6, and others were shown to cause MG dysfunction (MGD) and dry eye in experimental animals. Here, we describe the impact of the changes in the lipid composition of meibum on its protective properties, specifically physiologically relevant thermotropic characteristics, using various mutant and wild-type animal models, and comparing them with healthy human subjects and patients with MGD. Meibum samples were analyzed using liquid chromatography/mass spectrometry (LC/MS) and differential scanning microcalorimetry (DSC). We found that any change in the balance between major lipid classes in meibum—wax esters, cholesteryl esters, triacylglycerols, and free cholesterol—cause detrimental changes in its thermotropic properties, loss of cohesiveness, and abnormal expressibility from MG, resulting in MGD-like phenotypes of the eyes and adnexa. We conclude that tested knockout mice can be valuable models for modeling and studying MGD. A combination of LC/MS and DSC can be a powerful diagnostic tool and may help to diagnose MGD and other pathologies, as well as determine their molecular mechanisms. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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20 pages, 8412 KB  
Article
Lipidomics-Based Analysis of the Regulatory Effects of Phytosterol Esters on Lactation Performance and Lipid Metabolism in Tarim Bactrian camels
by Penglan Dou, Yusong Shen, Weihua Zheng, Lin Zhu, Yong Chen and Fengming Li
Animals 2025, 15(19), 2827; https://doi.org/10.3390/ani15192827 - 28 Sep 2025
Viewed by 641
Abstract
Plantsterol esters (PSEs) exert beneficial effects on animal product quality, indicating their potential as a nutritional intervention strategy. This study investigated the effects of dietary PSE supplementation on lactation performance and lipid metabolism in Tarim Bactrian camels (Camelus bactrianus) to establish [...] Read more.
Plantsterol esters (PSEs) exert beneficial effects on animal product quality, indicating their potential as a nutritional intervention strategy. This study investigated the effects of dietary PSE supplementation on lactation performance and lipid metabolism in Tarim Bactrian camels (Camelus bactrianus) to establish a scientific basis for its application in their husbandry. Thirty-two mid-lactation female camels were randomly allocated to four groups (n = 8): CON (basal diet), L (200 mg/kg PSE), M (400 mg/kg PSE), and H (800 mg/kg PSE). Since lactation performance is closely linked to metabolic status, biochemical and lipidomic analyses were conducted on serum and milk samples. Analysis revealed that the H group showed significantly increased milk yield, lactose yield, and milk fat yield compared to other groups. Serum cholesterol levels decreased progressively with higher PSE supplementation, while serum urea levels rose dose-dependently. Blood Glu was lower in the L group but higher in the H group relative to CON. Lipidomic profiling identified 644 and 257 differential metabolites in milk and serum, respectively. Milk metabolites were enriched in the EGFR inhibitor resistance, MAPK, and ErbB signaling pathways; serum metabolites were linked to glycerophospholipid, arachidonic acid, and linoleic acid metabolism. These findings indicate that PSE-modulated metabolites in serum and milk significantly influence lactation performance and glucolipid metabolism in Tarim Bactrian camels, supporting further investigation into precision nutrition strategies. Full article
(This article belongs to the Section Animal Nutrition)
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11 pages, 1631 KB  
Technical Note
Sequential Injection Analysis of Cholesterol Using an Oxidation–Reduction Electrode Detector
by Takato Imanaka and Takashi Masadome
Sensors 2025, 25(18), 5863; https://doi.org/10.3390/s25185863 - 19 Sep 2025
Cited by 1 | Viewed by 782
Abstract
A new automated method for the determination of cholesterol in serum was developed by combining sequential injection analysis (SIA) with potentiometric detection using a gold oxidation–reduction potential (ORP) electrode because serum cholesterol is an important indicator of abnormal lipid metabolism, arteriosclerosis, and hypertension [...] Read more.
A new automated method for the determination of cholesterol in serum was developed by combining sequential injection analysis (SIA) with potentiometric detection using a gold oxidation–reduction potential (ORP) electrode because serum cholesterol is an important indicator of abnormal lipid metabolism, arteriosclerosis, and hypertension in clinical diagnosis. The method is based on enzymatic hydrolysis of cholesterol esters by cholesterol esterase (CE) to yield free cholesterol, followed by oxidation with cholesterol oxidase (COD) to produce hydrogen peroxide. In the presence of horseradish peroxidase (HRP) and potassium ferrocyanide (K4[Fe(CN)6]), hydrogen peroxide oxidizes ferrocyanide to ferricyanide (K3[Fe(CN)6]), and the concentration ratio of ferri-/ferrocyanide is determined potentiometrically. Experimental conditions were optimized as follows: 5.0 mM K4[Fe(CN)6], 2 min reaction time, 0.5 units/mL HRP, 0.75 units/mL COD for free cholesterol, 1.5 units/mL COD and 10.0 units/mL CE for total cholesterol, and 5.0% (w/v) Triton X-100 with 5.0% (v/v) isopropanol as solubilizing agents. Under these conditions, the calibration curve for total cholesterol exhibited a Nernstian slope of 47.6 mV/decade over the range of 1.0 × 10−5–1.0 × 10−3 M, with no significant interference from common serum constituents. This method offers low reagent consumption, high automation, and simple operation, making it promising for clinical cholesterol analysis. Full article
(This article belongs to the Special Issue Electrochemical Biosensing Devices and Their Applications)
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16 pages, 819 KB  
Article
Nitrogen Monoxide Releasing Nitric Ester Derivatives of Ibuprofen and Naproxen as COX Inhibitors, Anti-Inflammatory and Hypolipidemic Compounds
by Paraskevi Tziona, Panagiotis Theodosis-Nobelos, Dimitris Lepesiotis, Antonis Gavalas and Eleni A. Rekka
Molecules 2025, 30(18), 3744; https://doi.org/10.3390/molecules30183744 - 15 Sep 2025
Viewed by 876
Abstract
Nitric esters are among the compounds that can liberate nitrogen monoxide (NO) in the organism. Due to the vasodilatation caused by nitrogen monoxide, NO-donors have been shown to protect endothelial function, acting as vasodilators, promoting efficient oxygen supply to tissues, to lower blood [...] Read more.
Nitric esters are among the compounds that can liberate nitrogen monoxide (NO) in the organism. Due to the vasodilatation caused by nitrogen monoxide, NO-donors have been shown to protect endothelial function, acting as vasodilators, promoting efficient oxygen supply to tissues, to lower blood pressure, and to inhibit platelet aggregation. Incorporation of a NO-liberating moiety in the structure of non-steroidal anti-inflammatory drugs results in anti-inflammatory agents that are safer for the gastrointestinal system. In this research, ibuprofen and naproxen, two commonly applied non-steroidal anti-inflammatory drugs (NSAID), non-selective inhibitors of cyclooxygenases, were used to design novel anti-inflammatory agents able to release NO in the organism. Thus, the NSAIDs were amidated with beta-alanine and L-proline, which were able to incorporate the 2-nitro-oxyethyl moiety as the NO donor. The resulting compounds were anti-inflammatory agents, found to be more potent than the mother drugs, demonstrating remarkable inhibition of cyclooxygenase-2 over cyclooxygenase-1 and the ability to release NO in vitro. Furthermore, two of the most active anti-inflammatory compounds proved to be effective hypolipidemic agents, decreasing plasma total cholesterol, triglycerides, and LDL-cholesterol in hyperlipidemic rats significantly. The most effective compound in all the above tests was the ibuprofen derivative 5, which inhibited COX-2 by 95%, decreased inflammation by 73%, and reduced all lipidemic indices by more than 50%. Furthermore, docking experiments of compound 5 on the active sites of COX-1 and COX-2 showed that it interacts intensely with the binding site of COX-2, and the binding energy is equivalent to that of the relevant to celecoxib selective COX-2 inhibitor 4-[5-(4-bromophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide (SC-5580). In conclusion, the performed structural modifications resulted not only in the improvement of the anti-inflammatory activity, compared with the parent NSAID, but also acquired strong hypolipidemic activity. Thus, the combination of structural characteristics resulting in a decrease in lipidemia, with possible inhibition of atherosclerosis, due to their anti-inflammatory activity and vasodilatation ability, via the liberated NO, may constitute a useful rationale for new compounds. Full article
(This article belongs to the Special Issue Organic Synthesis of Nitrogen-Containing Molecules)
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14 pages, 1611 KB  
Article
Distinct Metabolomic and Lipoprotein Signatures in Gall Bladder Cancer Patients of Black African Ancestry
by John Devar, Nnenna Elebo, Ashna Makan, Ariel Pincus, Nicola Lahoud, Stefano Cacciatore, Geoffrey Candy, Martin Smith and Ekene Emmanuel Nweke
Cancers 2025, 17(17), 2925; https://doi.org/10.3390/cancers17172925 - 6 Sep 2025
Viewed by 1166
Abstract
Background: Gall bladder cancer (GBC) is the most common biliary tract malignancy and is often diagnosed at advanced stages, partly due to the absence of reliable biomarkers and limited understanding of its biology in African populations. This study aimed to characterize the metabolomic [...] Read more.
Background: Gall bladder cancer (GBC) is the most common biliary tract malignancy and is often diagnosed at advanced stages, partly due to the absence of reliable biomarkers and limited understanding of its biology in African populations. This study aimed to characterize the metabolomic and lipoprotein profiles of GBC patients of Black African ancestry. Methods: NMR spectroscopy was used to profile the serum samples. Group comparisons used Wilcoxon tests, correlations used Spearman’s rank test, unsupervised analysis was carried out using the KODAMA algorithm, partial least squares modeling estimated free cholesterol (FC) to cholesterol ester (CE) ratios, while multivariate logistic regression evaluated independent predictors. Results: GBC patients showed altered ethanol levels and dysregulated lipoproteins, including increased IDL-C, IDL-TG, and LDL-TG, and decreased HDL-C, HDL-P, and medium HDL-P. Total and conjugated bilirubin strongly correlated with lipoproteins. Unsupervised analysis revealed a GBC subgroup with abnormal lipoprotein profiles and elevated FC/CE ratios, suggesting cholestasis-related LpX formation. Elevated asparagine, reduced ethanol, and an inflammatory metabolic signature characterized the GBC fingerprint. Ethanol and bilirubin emerged as independent predictors of GBC. Conclusions: GBC patients exhibit distinct metabolomic and lipoprotein alterations that may underlie disease progression and serve as potential biomarkers. These findings enhance understanding of GBC pathophysiology in African populations and may inform future diagnostic strategies. Full article
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14 pages, 681 KB  
Article
Distinct Plasma LPC Signatures Differentiate COVID-19 Sepsis from Other Sepsis Aetiologies
by Vlad Pavel, Patricia Mester, Marcus Höring, Gerhard Liebisch, Stephan Schmid, Martina Müller and Christa Buechler
Biomedicines 2025, 13(9), 2110; https://doi.org/10.3390/biomedicines13092110 - 29 Aug 2025
Viewed by 1152
Abstract
Background/Objectives: Low levels of lysophosphatidylcholine (LPC) in the blood can be used as a diagnostic marker for sepsis. SARS-CoV-2 infection, a more recent cause of sepsis, shares similarities with non-SARS-CoV-2 sepsis but also exhibits distinct features. We have recently shown that plasma cholesteryl [...] Read more.
Background/Objectives: Low levels of lysophosphatidylcholine (LPC) in the blood can be used as a diagnostic marker for sepsis. SARS-CoV-2 infection, a more recent cause of sepsis, shares similarities with non-SARS-CoV-2 sepsis but also exhibits distinct features. We have recently shown that plasma cholesteryl ester levels are higher in patients with SARS-CoV-2 infection than in patients without, and this study analysed whether this may extend to differences in LPC, a bioactive constituent of lipoproteins. Methods: The plasma levels of 13 LPC species were measured by flow injection analysis tandem mass spectrometry (FIA-MS/MS) in 157 patients with systemic inflammatory response syndrome (SIRS), sepsis or septic shock. Of these patients, 24 had SARS-CoV-2 infection. Results: Patients with SIRS exhibited higher plasma levels of the minor LPC species LPC 15:0 and 22:4 compared to those with sepsis or septic shock. Five LPC species were also reduced in the plasma of 31 patients with liver cirrhosis; therefore, patients with cirrhosis or SIRS were excluded from subsequent analyses. Compared to 76 non-COVID-19 patients with sepsis or septic shock, SARS-CoV-2 infection in 21 patients was associated with significantly higher plasma levels of ten individual LPC species and total LPC concentration. In patients with sepsis/septic shock, LPC species showed negative correlations with procalcitonin and interleukin-6, and positive correlations with gamma-glutamyltransferase and cholesteryl ester levels. In contrast, no significant associations were observed between LPC levels and C-reactive protein, aminotransferases, or free cholesterol. Conclusions: Differential LPC levels, despite comparable disease severity, may serve as metabolic biomarkers to distinguish SARS-CoV-2 sepsis from other causes of sepsis and inform targeted therapeutic approaches. Full article
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13 pages, 777 KB  
Article
Seed Watermelon (Citrullus mucosospermus (Fursa))-Derived Coniferyl Alcohol as a Functional Ingredient in Remedies for Dry Skin: Evidence of Facilitated Lipogenesis in Human Sebocytes
by Shingo Fujita, Shoki Inoue, Christos C. Zouboulis, Takashi Fukuda, Toshiharu Hashizume and Tomohiro Itoh
Molecules 2025, 30(16), 3360; https://doi.org/10.3390/molecules30163360 - 13 Aug 2025
Viewed by 1400
Abstract
Sebum secreted by sebaceous glands mixes with sweat to form a protective film that aids in maintaining skin health. Reduced sebum production compromises such barrier functions, potentially leading to severe itchiness and inflammation. Therefore, incorporating moisturizers with ingredients promoting sebum secretion is desirable. [...] Read more.
Sebum secreted by sebaceous glands mixes with sweat to form a protective film that aids in maintaining skin health. Reduced sebum production compromises such barrier functions, potentially leading to severe itchiness and inflammation. Therefore, incorporating moisturizers with ingredients promoting sebum secretion is desirable. Wild watermelon possesses moisturizing and antioxidant properties, and its extracts are utilized in skin cosmetics and supplements. This study investigates whether seed watermelon (Citrullus mucosospermus (Fursa))—a species closely related to wild watermelon—influences sebum synthesis and can serve as a skin cosmetic raw ingredient. Several bioactive compounds—including coniferyl alcohol, coniferin, and p-coumaryl alcohol—were identified in the active third fraction of the fruit extract. Subsequently, SZ95 sebocytes stimulated with linoleic acid were stained using Oil Red O to detect lipogenesis facilitated by the identified bioactive compounds. Coniferyl alcohol promoted linoleic acid-stimulated lipogenesis by approximately 2.2-fold at a concentration of 300 µM. Lipidomic analyses confirmed an increase in total lipid content following coniferyl alcohol treatment, with notable increases in cholesterol ester, cardiolipin, and simple lipid content. Overall, these findings suggest that seed watermelon contains compounds that do influence sebum synthesis. Consequently, skin cosmetics containing seed watermelon fruit extracts with linoleic acid may benefit individuals with dry skin. Full article
(This article belongs to the Section Medicinal Chemistry)
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21 pages, 1005 KB  
Article
Metabolic Signature in Combination with Fecal Immunochemical Test as a Non-Invasive Tool for Advanced Colorectal Neoplasia Diagnosis
by Oihane E. Albóniga, Joaquín Cubiella, Luis Bujanda, Patricia Aspichueta, María Encarnación Blanco, Borja Lanza, Cristina Alonso and Juan Manuel Falcón-Pérez
Cancers 2025, 17(14), 2339; https://doi.org/10.3390/cancers17142339 - 15 Jul 2025
Viewed by 1029
Abstract
Background/Objectives: Colorectal cancer (CRC) is one of the most prevalent cancers worldwide. Even though the screening programs have decreased the incidence rates, the prognosis for CRC varies depending on the stage at diagnosis. Thus, early diagnosis is still a big challenge due [...] Read more.
Background/Objectives: Colorectal cancer (CRC) is one of the most prevalent cancers worldwide. Even though the screening programs have decreased the incidence rates, the prognosis for CRC varies depending on the stage at diagnosis. Thus, early diagnosis is still a big challenge due to screening methods, and subsequent diagnosis is not very sensitive. Methods: In this work, LC-MS-based metabolomics, a powerful and sensitive tool to study complex dynamic changes, was used to analyze 211 human fecal samples from control individuals (CTRL), adenoma (AA), and CRC patients. Results: Multivariate and univariate statistical analysis highlighted cholesteryl esters (CEs) and fecal haemoglobin, quantified by fecal immunochemical test (FIT), as relevant biomarkers that clearly differentiate CRC from AA and CTRL. Predictive models based on random forest and the area under the curve (AUC) of the receiver operating characteristic curve (ROC) demonstrate that CEs, together with FIT measurement, improved the CRC and CTRL classification, but not AA. This study revealed that the AA group is a transitional stage with high heterogeneity. The increased tendency observed in CEs from CTRL to CRC might be related to the imbalance of cholesterol homeostasis due to cancer cells requiring a high cholesterol level for cell development and proliferation. The free cholesterol is probably obtained from CEs, as it is the most cost/effective way to obtain the needed cholesterol. Conclusions: The accumulation of CEs is produced by two possible approaches: (1) dysfunction of cholesterol absorption in the small intestine and/or (2) transported inside exosomes from cell to cell to promote proliferation. Full article
(This article belongs to the Section Cancer Causes, Screening and Diagnosis)
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21 pages, 3693 KB  
Article
Non-Targeted Lipidomics Analysis of Characteristic Milk Using High-Resolution Mass Spectrometry (UHPLC-HRMS)
by Tingting Wei, Tianxiao Zhou, Shenping Zhang, Zhexue Quan and Yang Liu
Foods 2025, 14(12), 2068; https://doi.org/10.3390/foods14122068 - 12 Jun 2025
Cited by 3 | Viewed by 2244
Abstract
Milk lipids are fundamental to the nutritional quality, functional properties, and processing behavior of dairy products. In this study, we employed an untargeted lipidomics approach based on ultra-high-performance liquid chromatography coupled with ultra-high-performance liquid chromatography–high-resolution mass spectrometry (UHPLC-HRMS) to systematically characterize the lipid [...] Read more.
Milk lipids are fundamental to the nutritional quality, functional properties, and processing behavior of dairy products. In this study, we employed an untargeted lipidomics approach based on ultra-high-performance liquid chromatography coupled with ultra-high-performance liquid chromatography–high-resolution mass spectrometry (UHPLC-HRMS) to systematically characterize the lipid profiles of ten milk types from eight animal species, including camel, mare, donkey, goat, buffalo, yak, Jersey, and Holstein. A total of 640 lipid species were identified, spanning triglycerides (TGs), phospholipids (PLs), sphingolipids (SPs), ceramides (Cer), wax esters (WEs), and other subclasses. A statistical analysis revealed significant differences in lipid types and abundances among the milk samples. Camel milk exhibited the highest lipid diversity, with notable enrichment in phospholipids and sphingolipids, conferring superior emulsifying properties and stability. Mare milk was rich in polyunsaturated fatty acids (PUFAs), such as linoleic acid and alpha-linolenic acid, making it ideal for developing health-focused dairy products. Despite having the lowest total lipid content, donkey milk was enriched in cholesterol esters and PUFA, suitable for low-fat functional dairy products. Goat milk featured a balanced lipid composition with higher levels of medium-chain fatty acids (MCFAs), promoting digestibility. Buffalo milk was characterized by high TG and wax ester (WE) levels, offering high energy density and suitability for rich dairy products. Yak milk contained higher levels of ceramides (Cer) and saturated fatty acids, reflecting adaptations to high-altitude environments. Jersey milk and Holstein milk displayed similar lipid profiles, with stable compositions suitable for versatile dairy product development. Principal component analysis (PCA), hierarchical clustering, and volcano plot analyses further confirmed species-specific lipidomic signatures and revealed several potential lipid biomarkers, such as LPC (O-16:0) in Hongyuan yak milk, suggesting applications in geographical indication (GI) traceability. This study offers a comprehensive lipidomic landscape across diverse milk sources, providing molecular insights to guide the development of tailored, functional, and regionally branded dairy products. Full article
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17 pages, 927 KB  
Article
Multi-Targeting Valproic Acid Conjugates as Potent Agents Against Inflammation and Hyperlipidemia
by Panagiotis Theodosis-Nobelos and Eleni A. Rekka
Molecules 2025, 30(11), 2339; https://doi.org/10.3390/molecules30112339 - 27 May 2025
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Abstract
Novel derivatives of valproic acid with biologically active moieties, such as thiomorpholine, 4-aminopyridine, serine methyl ester, trolox and the cinnamic acid derivative [(E)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)acrylic acid], were synthesized at satisfactory yields. The conjugation of these moieties was based on the rationale [...] Read more.
Novel derivatives of valproic acid with biologically active moieties, such as thiomorpholine, 4-aminopyridine, serine methyl ester, trolox and the cinnamic acid derivative [(E)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)acrylic acid], were synthesized at satisfactory yields. The conjugation of these moieties was based on the rationale of design and evaluation of compounds with selected structural characteristics, aiming at derivatives with multiple targets. These compounds reduced acute inflammation considerably and, in most cases, more than several highly used, well-known, non-steroidal anti-inflammatory drugs. They also offered the inhibition of soybean lipoxygenase, and some of them (compounds 5 and 6) possessed radical scavenging and lipid peroxidation attenuating effects. Their antioxidant capacity was several times higher than that of the established antioxidant trolox. All the tested compounds decreased plasma lipid markers in tyloxapol-induced hyperlipidemia in rats. Compound 2 resulted in 71.1%, 52.8% and 79.1% decrease in total cholesterol, triglycerides and LDL-cholesterol, respectively, at 150 μmol/kg (i.p.). The effect on total and LDL cholesterol is comparable or equal to that of simvastatin, a hypocholesterolemic 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA) inhibitor, however, with additionally great triglyceride-decreasing effect compared to simvastatin. Thus, the synthesized compounds may be a valuable addition to multi-functional agents acting against various degenerative disorders that implicate inflammation and lipid derangement. Full article
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Article
Multiplatform Metabolomic Profiling of the Unilateral Ureteral Obstruction Murine Model of CKD
by Paula Cuevas-Delgado, Verónica Miguel, Santiago Lamas, Coral Barbas and Francisco J. Rupérez
Int. J. Mol. Sci. 2025, 26(10), 4933; https://doi.org/10.3390/ijms26104933 - 21 May 2025
Viewed by 1795
Abstract
In chronic kidney disease (CKD) research, animal models such as the unilateral ureteral obstruction (UUO) rodent model are crucial to understanding disease progression, particularly renal fibrosis. Despite its widespread use, the molecular mechanisms driving CKD remain incompletely understood. Given the interplay between metabolism [...] Read more.
In chronic kidney disease (CKD) research, animal models such as the unilateral ureteral obstruction (UUO) rodent model are crucial to understanding disease progression, particularly renal fibrosis. Despite its widespread use, the molecular mechanisms driving CKD remain incompletely understood. Given the interplay between metabolism and fibrosis, a comprehensive metabolomic analysis of UUO renal tissue is necessary. This study involved untargeted multiplatform analysis using liquid chromatography (LC), gas chromatography (GC), and capillary electrophoresis (CE) coupled with mass spectrometry (MS) to examine murine kidney tissue from the UUO model. The results highlight metabolic changes associated with tubulointerstitial fibrosis, which affect pathways such as the tricarboxylic acid (TCA) cycle, the urea cycle, and lipid metabolism. In particular, fibrosis impacts the lipidomic profile, with decreases in most lipid classes and increases in specific glycerophospholipids, hexosylceramides, and cholesterol esters. These findings demonstrate the value of a multiplatform approach in elucidating metabolic alterations in CKD, providing information on the underlying molecular mechanisms and paving the way for further research. Full article
(This article belongs to the Topic Animal Models of Human Disease 3.0)
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