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23 pages, 7539 KB  
Article
Effect and Mechanism of Qihua Tongtiao Formula (QHTTF) on Improving Glucose and Lipid Metabolism Disorders in ZDF Rats by Integrating Network Pharmacology, Metabolomics, and Biological Validation
by Yuhua Jiang, Hong Yu, Yajing Pan, Binghan Zhang, Yeteng Jing, Jingjing Lei, Ning Li and Jinsheng Yang
Pharmaceuticals 2025, 18(9), 1347; https://doi.org/10.3390/ph18091347 (registering DOI) - 8 Sep 2025
Abstract
Background: The dysregulation of both glucose and lipid metabolism is the main clinical features of type 2 diabetes. Qihua Tongtiao Formula (QHTTF) is our team’s current clinical empirical formula, and the related patent has been granted. It is composed of Astragalus membranaceus, [...] Read more.
Background: The dysregulation of both glucose and lipid metabolism is the main clinical features of type 2 diabetes. Qihua Tongtiao Formula (QHTTF) is our team’s current clinical empirical formula, and the related patent has been granted. It is composed of Astragalus membranaceus, Atractylodes macrocephala koidz, Aurantii Fructus Immaturus, Radix Bupleuri, Ligusticum chuanxiong hort, Angelicae sinensis radix, Raphanus sativus, and Polyporus umbellatus. It can alleviate tissue pathological damage in type 2 diabetic rats by improving glycolipid metabolism disorders. Nevertheless, the specific mechanisms of QHTTF in the treatment of type 2 diabetes remain unclear. Purpose: This research aims to explore the fundamental effect and underlying mechanism of the QHTTF formula in ZDF rats via network pharmacology, biological validation, and metabolomics technology. Methods: The chemical compounds of QHTTF were initially identified via UHPLC-MS/MS analysis. Meanwhile, drug targets, genes, related diseases, and differential metabolites of QHTTF in the treatment of T2DM were obtained through network pharmacology, molecular docking, and metabolomics. Then, we conducted animal experiments to further explore the therapeutic molecular mechanism of QHTTF in ZDF rats. Results: A total of 39 main chemical components were recognized through LC-MS/MS technology, and 22 remained after the second screening. Network pharmacology and molecular docking results revealed that 59 intersection targets were involved in the treatment of glycolipid metabolic disorders, and the PPARα, PPARγ, and TNF proteins were identified as crucial targets through PPI network analysis. Additionally, serum metabolomics analysis of ZDF rats showed that QHTTF could regulate linoleic acid metabolism, fructose and mannose metabolism, galactose metabolism, fatty acid biosynthesis, and other related signaling pathways. The results of biological experiments proved that QHTTF effectively lowered blood glucose and lipid levels, alleviated hepatic and pancreatic pathological damage, increased the expression of IRS-1 and GLUT4 in the pancreas, and improved insulin resistance, while inhibiting the inflammatory response and oxidative stress, as well as enhancing the expression of liver PPARα, PPARγ, and AMPK proteins in ZDF rats. Conclusions: In summary, QHTTF exerted a significant effect in improving glycolipid metabolism disorders of ZDF rats, which might show therapeutic effects by relieving insulin resistance, mitigating inflammation and oxidative damage, regulating related glucose, fatty acid, and amino acid metabolism, and increasing the expression of PPARα, PPARγ, and AMPK proteins by combining network analysis, metabolomics, and biological research. Full article
(This article belongs to the Special Issue Emerging Therapies for Diabetes and Obesity)
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30 pages, 2882 KB  
Article
Fatty Acids in Lumbricidae as Biomarkers of In Situ Metals Exposure
by Aleksandra Garbacz, Danuta Kowalczyk-Pecka and Weronika Kursa
Sustainability 2025, 17(17), 8076; https://doi.org/10.3390/su17178076 (registering DOI) - 8 Sep 2025
Abstract
Hard coal mining activity generates post-mining waste (waste rock). Waste rock is deposited in the environment in large quantities for reclamation of agricultural land. In this study, waste rock was treated as a potential source of metal pollutants. The research material (waste rock, [...] Read more.
Hard coal mining activity generates post-mining waste (waste rock). Waste rock is deposited in the environment in large quantities for reclamation of agricultural land. In this study, waste rock was treated as a potential source of metal pollutants. The research material (waste rock, soil, plant roots, and Lumbricidae earthworms) was obtained from sites that had been reclaimed using waste rock as well as sites without waste rock. From each site, 30 individuals (n = 30) were collected, divided into five groups, 6 individuals each. Within the group, individuals were analyzed collectively. The study tested whether selected metals (Cr, Ni, Cd, Ba, Pb, Zn, and Cu) are present in waste rock and whether they can be transferred to the soil, plant root systems, and representatives of Lumbricidae, which are important bioindicators and a source of biomarkers. Particular attention was focused on the assessment of the effects of metals deposited in situ on fatty acids in representatives of Lumbricidae and on selecting a set of fatty acids that can be used as biomarkers of physiological effects, including oxidative stress. A panel of biomarker fatty acids was used, which included a panel of 17 biomarker fatty acids from 35 fatty acids analyzed. To confirm or disprove the usefulness of the biomarker fatty acid panel in earthworms, superoxide dismutase (SOD), catalase (CAT), and thiobarbituric acid reactive substances (TBARS) were determined. The study enabled an effective comparison of reference locations with locations potentially burdened with anthropogenic sediment. The results indicate that selected metals present in the waste rock are transferred to the soil, plant root systems, and soil organisms such as Lumbricidae. Selected metals affected the lipid metabolism of Lumbricidae as stressors, leading to changes in the composition and oxidation of fatty acids. The effect on the physiological state of Lumbricidae depended on the duration of the deposit and the type of use (field, meadow, wasteland) of the land with the waste rock deposit. In earthworms obtained from sites with waste rock deposits, higher contents of biomarker saturated fatty acids and biomarker monounsaturated fatty acids and lower contents of biomarker polyunsaturated fatty acids were found compared to earthworms obtained from sites without waste rock deposits. Only Pb (lead) showed a statistically significant correlation with all analyzed parameters in earthworms obtained from sites with waste rock deposits. The results have significant practical implications for environmental protection management. The proposed set of biomarker fatty acids in Lumbricidae can be used to assess the impact of pollutants and environmental monitoring. Full article
(This article belongs to the Section Hazards and Sustainability)
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15 pages, 2866 KB  
Article
Phenolic-Rich Indian Almond (Terminalia catappa Linn) Leaf Extract Ameliorates Lipid Metabolism and Inflammation in High-Fat Diet (HFD)-Induced Obese Mice
by Opeyemi O. Deji-Oloruntoba, Ji Eun Kim, Hee Jin Song, Ayun Seol, Dae Youn Hwang and Miran Jang
Metabolites 2025, 15(9), 594; https://doi.org/10.3390/metabo15090594 - 8 Sep 2025
Abstract
Background: Obesity is a global health issue closely associated with dysregulated lipid metabolism and chronic inflammation. Effective strategies targeting both lipogenesis and inflammation are essential for managing obesity and its related metabolic disorders. Methods: This study evaluated the effects of Terminalia catappa Linn. [...] Read more.
Background: Obesity is a global health issue closely associated with dysregulated lipid metabolism and chronic inflammation. Effective strategies targeting both lipogenesis and inflammation are essential for managing obesity and its related metabolic disorders. Methods: This study evaluated the effects of Terminalia catappa Linn. leaf extract (TCE) on lipogenic and lipolytic pathways in high-fat diet (HFD)-induced obese mice. UPLC-QTOF-MS analysis was conducted to identify and quantify the major phenolic compounds in TCE. Mice were administered low and high doses of TCE, and various metabolic parameters, including lipid profiles, liver function markers, adipokine levels, and gene/protein expressions related to lipid metabolism and inflammation, were assessed. Results: UPLC-QTOF-MS analysis identified four major phenolic compounds in TCE—gallic acid, orientin, vitexin, and ellagic acid—with respective contents of 112.5, 163.3, 184.7, and 295.7 mg/g extract. TCE administration significantly reduced liver and adipose tissue weights, along with hepatic and adipose lipid accumulation. Both low and high doses of TCE markedly lowered serum lipid levels. Liver function was improved, as indicated by reduced levels of AST, ALT, and ALP, while BUN levels remained unchanged. On the molecular level, TCE downregulated adipogenic and lipogenic genes (PPARγ, PPARα, C/EBPα, aP2) and upregulated metabolic regulators, including leptin, adiponectin, p-HSL/HSL, and p-perilipin/perilipin, without affecting ATGL expression. TCE also suppressed pro-inflammatory cytokines such as IL-6, IL-1β, TNF-α, and TGFβ-1. Conclusions: These findings highlight the therapeutic potential of TCE in managing obesity by inhibiting lipogenesis, enhancing lipolysis, and reducing inflammation. Full article
(This article belongs to the Section Pharmacology and Drug Metabolism)
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22 pages, 1043 KB  
Article
Strategies for Reducing Fat in Mayonnaise and Their Effects on Physicochemical Properties
by Cecilia Abirached, María Noel Acuña, Tatiana Carreras and Ignacio Vieitez
Foods 2025, 14(17), 3133; https://doi.org/10.3390/foods14173133 - 8 Sep 2025
Abstract
Mayonnaise is a widely consumed food emulsion. Traditional mayonnaise contains approximately 70–80% lipids, making it a high-fat, calorie-dense food. This study aimed to develop a reduced-fat mayonnaise with physicochemical properties comparable to commercial low-fat formulations but with a lower oil content (<30%). Three [...] Read more.
Mayonnaise is a widely consumed food emulsion. Traditional mayonnaise contains approximately 70–80% lipids, making it a high-fat, calorie-dense food. This study aimed to develop a reduced-fat mayonnaise with physicochemical properties comparable to commercial low-fat formulations but with a lower oil content (<30%). Three formulations were prepared using canola oil and high-oleic sunflower oil at different concentrations (10%, 15%, and 30%), with and without the addition of synthetic antioxidants (BHA and BHT). Guar gum was used to control the viscosity of the continuous phase, adjusting its concentration between 0.75% and 1.55%. The formulations were compared with a commercial low-fat sample (MH) in terms of flow and rheological properties, color, phase separation stability, particle size, microscopy, and oxidative stability. The formulations exhibited flow behavior and Konini’s viscosity similar to MH. The 15% oil formulation (MHO-15%) had a particle size comparable to MH. Both MH and the experimental formulations exhibited a weak gel structure. To achieve the characteristic yellow color, β-carotene should be added to MHO-15%. Formulations containing canola oil and those without antioxidants showed higher susceptibility to oxidation, leading to the selection of high-oleic oil with added antioxidants. Based on these findings, a potential reduced-fat mayonnaise-type sauce could be formulated by decreasing lipid content from 30% to 15%. Full article
(This article belongs to the Special Issue Healthy Lipids for Food Processing)
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24 pages, 5051 KB  
Article
Carbon Dots from Dried German Chamomile Flower and Its Residual Biomass: Characteristics, Bioactivities, Cytotoxicity and Its Preservative Effect on the Refrigerated Precooked Baby Clam (Paphia undulata)
by Birinchi Bora, Suriya Palamae, Bin Zhang, Tao Yin, Jun Tae Kim, Jong-Whan Rhim and Soottawat Benjakul
Foods 2025, 14(17), 3130; https://doi.org/10.3390/foods14173130 - 7 Sep 2025
Abstract
The growing demand for natural and sustainable food preservatives has drawn interest in carbon dots (CDs) derived from plant sources. This study aimed to synthesize CDs from dried German chamomile flowers (DF) and residual biomass (RB) obtained after essential oil extraction using a [...] Read more.
The growing demand for natural and sustainable food preservatives has drawn interest in carbon dots (CDs) derived from plant sources. This study aimed to synthesize CDs from dried German chamomile flowers (DF) and residual biomass (RB) obtained after essential oil extraction using a hydrothermal process. Their characteristics, bioactivities and cytotoxicity were examined. Both DF-CDs and RB-CDs were spherical (7–10 nm), exhibited strong UV blocking properties and tunable fluorescence and were rich in polyphenolic functional groups, especially the –OH group. DF-CDs generally showed higher antioxidant capacity than RB-CDs as assayed by DPPH, ABTS radical scavenging activities, FRAP and metal chelation activity. Both CDs showed antibacterial effects toward pathogenic bacterial strains (Escherichia coli and Listeria monocytogenes) and spoilage bacteria (Shewanella putrefaciens and Pseudomonas aeruginosa) in a dose-dependent manner. Cytotoxicity was assessed in BJ human fibroblasts, and both CDs exhibited high biocompatibility (>88% viability at 1000 µg/mL). When both CDs at 300 and 600 ppm were applied in a precooked baby clam edible portion (PBC-EP) stored at 4 °C, microbial growth, TVB and TMA contents were lower than those of the control. The total viable count was still under the limit (5.8 log CFU/mL) for the sample treated with CDs at 600 ppm up to 9 days, while the control was kept for only 3 days. Furthermore, the lipid oxidation level (PV and TBARS value) of PBC-EP decreased with CD treatment, especially at higher concentrations (600 ppm). Therefore, chamomile-derived CDs could serve as a promising alternative for perishable seafood preservation. Full article
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24 pages, 9489 KB  
Article
Moringa (Moringa oleifera) Leaf Attenuates the High-Cholesterol Diet-Induced Adverse Events in Zebrafish: A 12-Week Dietary Intervention Resulted in an Anti-Obese Effect and Blood Lipid-Lowering Properties
by Kyung-Hyun Cho, Ashutosh Bahuguna, Yunki Lee, Ji-Eun Kim, Sang Hyuk Lee and Krismala Djayanti
Pharmaceuticals 2025, 18(9), 1336; https://doi.org/10.3390/ph18091336 - 5 Sep 2025
Viewed by 118
Abstract
Objective: The study investigates the dietary effects of Moringa oleifera leaf powder on obesity, blood biochemical parameters, and organ health in hyperlipidemic zebrafish (Danio rerio). Methodology: Adult hyperlipidemic zebrafish (n = 56/group) were fed for 12 weeks either with a [...] Read more.
Objective: The study investigates the dietary effects of Moringa oleifera leaf powder on obesity, blood biochemical parameters, and organ health in hyperlipidemic zebrafish (Danio rerio). Methodology: Adult hyperlipidemic zebrafish (n = 56/group) were fed for 12 weeks either with a high-cholesterol diet (HCD, 4% w/w) or HCD supplemented with 0.5% (w/w) M. oleifera leaf powder (0.5% MO) or HCD with 1.0% (w/w) M. oleifera leaf powder (1.0% MO). At different time points (0 to 12 weeks), the survivability and body weight (BW) of zebrafish were measured, while various biochemical and histological evaluations were performed after 12 weeks of feeding the respective diets. Additionally, an in silico approach was used to assess the binding interactions of MO phytoconstituents with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Results: Following 12-week supplementation, higher zebrafish survivability was observed in the MO-supplemented groups compared to the survivability of the HCD group. Relative to the initial BW, only 4% BW enhancement was observed post 12 weeks of dietary intake of 1.0% MO, in contrast to 27% BW gain in the HCD group. MO supplementation at both (0.5% and 1.0%) effectively mitigates the HCD-induced dyslipidemia and significantly minimizes the atherogenic coefficient and atherogenic index. Similarly, MO reduces elevated blood glucose levels, the ALT/AST ratio, and augments ferric ion reduction (FRA) and paraoxonase (PON) activity in a dose-dependent manner. Likewise, MO (particularly at 1.0%) effectively restrained HCD-induced steatosis, hepatic interleukin (IL)-6 production, and protected the kidneys, testes, and ovaries from oxidative stress and cellular senescence. The in silico findings underscore that the six phytoconstituents (chlorogenic acid, isoquercetin, kaempferol 3-O-rutinoside, astragalin, apigetrin, and myricetin) of MO exhibited a strong interaction with HMG-CoA reductase active and binding site residues via hydrogen and hydrophobic interactions. Conclusions: The findings demonstrated an antioxidant, anti-inflammatory, and hypoglycemic effect of MO, guiding the events to prevent HCD-induced metabolic stress and safeguard vital organs. Full article
(This article belongs to the Special Issue Drug Candidates for the Treatment of Obesity, 2nd Edition)
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22 pages, 1802 KB  
Article
Proteolytic Bacillus sp. Isolation and Identification from Tannery Alkaline Baths
by Manuela Lageiro, Fernanda Simões, Nuno Alvarenga and Alberto Reis
Molecules 2025, 30(17), 3632; https://doi.org/10.3390/molecules30173632 - 5 Sep 2025
Viewed by 304
Abstract
The application of microbial alkaline proteases holds significant potential for eco-sustainable industrial processes by reducing chemical usage and lowering the costs of effluent treatment. In the search for novel proteases with industrial relevance, several microbial strains were isolated from alkaline baths of the [...] Read more.
The application of microbial alkaline proteases holds significant potential for eco-sustainable industrial processes by reducing chemical usage and lowering the costs of effluent treatment. In the search for novel proteases with industrial relevance, several microbial strains were isolated from alkaline baths of the Portuguese tannery agroindustry. The most promising protease-producing strains were selected for identification and further study. Two isolates demonstrated the highest proteolytic activity, reaching 0.51 ± 0.01 U mL−1 and 0.70 ± 0.01 U mL−1 after 7.5 h of submerged cultivation in nutrient broth. Based on API biochemical tests, molecular biology techniques, and GC-FAME analysis of membrane lipids, the isolates were identified as Bacillus subtilis and incorporated into INIAV’s collection of industrial microbial cultures as B. subtilis CCMI 1253 (BMR2) and B. subtilis CCMI 1254 (BMR1). The most promising protease producer, B. subtilis CCMI 1253 (BMR2), exhibited a maximum specific growth rate of 0.88 ± 0.10 h−1. The proteases produced exhibited good extracellular proteolytic activity, with adaptability to industrial conditions, indicating their suitability for agroindustry applications such as leather making, detergent formulations and the treatment of effluents and protein residues. The results support the potential of microbial proteases as valuable tools in the bioeconomy and green chemistry. Full article
(This article belongs to the Special Issue Bioactive Molecules from Natural Sources and Their Functions)
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18 pages, 1700 KB  
Article
Valorization of Grape Pomace Through Integration in Chocolate: A Functional Strategy to Enhance Antioxidants and Fiber Content
by Daniela Freitas, Ana Rita F. Coelho, João Dias, Miguel Floro, Ana Coelho Marques, Carlos Ribeiro, Manuela Simões and Olga Amaral
Sci 2025, 7(3), 125; https://doi.org/10.3390/sci7030125 - 5 Sep 2025
Viewed by 142
Abstract
Grape pomace (i.e., the residual skins, seeds, and pulp left after vinification) retains up to 70% of the fruit’s original phenolic compounds and is also rich in dietary fiber. As such, because this by-product is generated in large quantities worldwide and its disposal [...] Read more.
Grape pomace (i.e., the residual skins, seeds, and pulp left after vinification) retains up to 70% of the fruit’s original phenolic compounds and is also rich in dietary fiber. As such, because this by-product is generated in large quantities worldwide and its disposal is both technologically problematic and costly, reusing it as a food ingredient could simultaneously mitigate environmental burdens, lower winery waste-management expenses, and enhance the nutritional profile of fortified foods. In this context, this study investigated the nutritional enrichment of dark chocolate by incorporating flour produced from red (cv. Syrah) and white (cv. Arinto) grape pomace at three levels (5, 10, and 15% w/w). Formulated chocolates and controls were manufactured under industrial tempering conditions and subsequently analyzed for protein, lipids, sugars, dietary fiber, total phenolic content, antioxidant capacity (DPPH and ORAC), color, texture, and consumer perception (hedonic test). All fortified samples showed higher fiber and antioxidant activity than the control, with “White_15” showing higher fiber content (43.1%) and “Red_5” for ORAC (69,483 µmol TE/100 g) and DPPH (6587 µmol TE/100 g). Dietary fiber showed an increase in content with the increase in grape pomace incorporation, regardless of the type (red or white). Texture softening was observed in all fortified chocolates independently of the incorporation level or type (red or white). Principal Component Analysis (PCA) and hierarchical clustering confirmed clear separation between control and fortified chocolates based on the parameters analyzed. Sensory evaluation with untrained panelists revealed good overall acceptability across all formulations. These findings demonstrate that grape pomace flour can be effectively valorized as a functional ingredient in dark chocolates, supporting circular economy practices in the wine and confectionery sectors while delivering products with enhanced health-promoting attributes (nutritional and antioxidant). Full article
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16 pages, 1299 KB  
Article
Role of Lipids in Water Permeation of Different Curl Pattern Hair Types
by Luisa Coderch, Laura Sabatier, Isabelle Pasini, Cristina Alonso, Meritxell Martí and Nawel Baghdadli
Cosmetics 2025, 12(5), 193; https://doi.org/10.3390/cosmetics12050193 - 4 Sep 2025
Viewed by 230
Abstract
Background: Dark-base hair fibers with Curl Pattern (CP) types 2 and 3 from Asian and European populations, respectively, are very similar, although each presents different behaviors regarding water diffusion and cosmetic treatments, including in relation to dyeing. This study aims to identify the [...] Read more.
Background: Dark-base hair fibers with Curl Pattern (CP) types 2 and 3 from Asian and European populations, respectively, are very similar, although each presents different behaviors regarding water diffusion and cosmetic treatments, including in relation to dyeing. This study aims to identify the key drivers of water diffusion in hair, particularly the role of lipids in the diffusion processes. Methods: Virgin, externally delipidized, and internally delipidized CP2 and CP3 hair strands were subjected to Dynamic Vapor Sorption (DVS) and ATR-FTIR investigations. In addition, external and internal lipid extracts were quantified and analyzed via thin-layer chromatography–flame ionization detection (TLC/FID). Results: The results obtained indicate that CP2 hairs present lower water regain at all humidity steps and a different diffusion behavior depending on the humidity. Lower diffusion was obtained at low humidity and higher diffusion at high humidity. TLC/FID analyses indicate that CP2 fibers present a significantly higher amount of external lipids (1.4% vs. 0.4%) and internal lipids (3.2% vs. 2.6%) as compared with the CP3 fibers. Conclusions: The higher amount of internal lipids is mainly due to the greater amount of polar lipids (ceramides). Lipid extraction tends to modify the water content, leading to a more hydrated and less permeable lipid-depleted fiber. The similar water properties of the two types of lipid fiber support the fundamental role of lipids, even when present in small quantities, in the differentiation of hair types. This study highlights a potential link between the lipid composition of CP3 and CP2 hair fibers and their differences in behaviors regarding water diffusion, which could also explain varying responses to cosmetic treatments. Full article
(This article belongs to the Special Issue Feature Papers in Cosmetics in 2025)
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26 pages, 3958 KB  
Article
Nebulized Bacterioruberin/Astaxanthin-Loaded Nanovesicles: Antitumoral Activity and Beyond
by Victoria Rebeca Dana González Epelboim, Diego G. Lamas, Cristián Huck-Iriart, Ezequiel Nicolas Caputo, Maria Julia Altube, Horacio Emanuel Jerez, Yamila Roxana Simioni, Kajal Ghosal, Maria Jose Morilla, Leticia Herminia Higa and Eder Lilia Romero
Int. J. Mol. Sci. 2025, 26(17), 8607; https://doi.org/10.3390/ijms26178607 - 4 Sep 2025
Viewed by 299
Abstract
The membranes of halophilic archaea are a source of novel biomaterials, mainly of isoprenoid nature, with therapeutic properties practically unraveled. Here, we explored the antitumoral activity of neutral archaeolipids (NAs, such as bacterioruberin, astaxanthin, and dihydrosqualene) present in the total archaeolipids (TAs) (a [...] Read more.
The membranes of halophilic archaea are a source of novel biomaterials, mainly of isoprenoid nature, with therapeutic properties practically unraveled. Here, we explored the antitumoral activity of neutral archaeolipids (NAs, such as bacterioruberin, astaxanthin, and dihydrosqualene) present in the total archaeolipids (TAs) (a fraction from the first step of lipid extraction by the modified Blight and Dyer technique) extracted from halophilic archaea Halorubrum tebenquichense, and formulated as TA-nanoarchaeosomes (TA: polar archaeolipids (PAs): Tween 80, 5:5:4 w:w:w, TA-nanoARC). The structure of 300.3 ± 84.2 nm TA-nanoARC of 0.59 ± 0.12 polydispersity index and −20 ± 3.7 mV ζ potential as determined by SAXS modelling, revealed that NA reduced the hydrophobic core and enlarged its hydrophilic section in comparison to TA-lacking bilayers (nanoARC), while preserving the width (~50 Å) and unilamellarity. Stable to storage and nebulization, TA-nanoARC was cytotoxic on A549 cells after 48 h, with an IC50 expressed as [bacterioruberin] of 0.15 μg/mL (~0.20 µM), comparable to or lower than the IC50 of docetaxel or cisplatin. Such cytotoxicity was exerted at a concentration harmless to macrophages (mTHP-1 cells). Besides, the conditioned medium from TA-nanoARC nebulized on A549 cells reduced the expression of the CD204/SRA-1, an M2 phenotype marker, and induced pro-inflammatory activity, comparable to or to a greater extent than that induced by lipopolysaccharide, including IL-6 and TNF-α, in mTHP-1 as a model of tumor-associated macrophages. The endocytosis of TA-nanoARC by A549 cells induced Lysotracker red fluorescence to fade and blur. This suggested the internalization of the highly viscous and ordered TA-nanoARC rich in NAs and subsequent lysosomal dysfunction (and not its antioxidant activity), as responsible for the selective damage on A549 cells. These are the first results showing that nebulized TA-nanoARC, lethal to A549 cells and modulating mTHP-1 cell phenotype, may act as antitumorals in the absence of cytotoxic drugs. Full article
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17 pages, 2626 KB  
Article
Multivariate Assessment of Thyroid, Lipid, and Inflammatory Profiles by HBV Status and Viral Load: Age- and Sex-Specific Findings
by Hyeokjun Yun, Jong Wan Kim and Jae Kyung Kim
Viruses 2025, 17(9), 1208; https://doi.org/10.3390/v17091208 - 3 Sep 2025
Viewed by 432
Abstract
Chronic hepatitis B virus (HBV) infection may influence extrahepatic systems, including endocrine and lipid regulation. In this cross-sectional study, 186 adults were stratified by HBV DNA status and viral load to examine thyroid function, systemic inflammation, and lipid metabolism, with further analyses by [...] Read more.
Chronic hepatitis B virus (HBV) infection may influence extrahepatic systems, including endocrine and lipid regulation. In this cross-sectional study, 186 adults were stratified by HBV DNA status and viral load to examine thyroid function, systemic inflammation, and lipid metabolism, with further analyses by age and sex. Thyroid-stimulating hormone (TSH, a pituitary regulator of thyroid function) levels were significantly lower in HBsAg-positive individuals compared with controls; however, this association was attenuated after stratification by viral load, indicating that the relationship is not unequivocally independent of HBV DNA levels, as free thyroxine (FT4, the circulating thyroid hormone reflecting gland activity) levels remained stable. Lipid profiles displayed demographic-specific patterns: males with high viral load exhibited lower HDL cholesterol, whereas younger HBV-positive individuals showed higher LDL cholesterol. CRP levels were unaffected by HBV status or viral load, aligning with the absence of systemic inflammation in early or inactive disease stages. Age was a major determinant across biomarkers, with complex interactions involving sex and viral load. These findings indicate subtle but clinically relevant extrahepatic effects of HBV infection and underscore the need for personalized monitoring and longitudinal studies to clarify metabolic and cardiovascular implications. These subgroup trends should be interpreted with caution given the absence of BMI, liver enzyme, fibrosis, medication, and comorbidity data in this retrospective cohort. Full article
(This article belongs to the Special Issue Viral Hepatitis and Liver Diseases)
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20 pages, 9688 KB  
Article
Hypolipidemic Effects of Alpinia japonica Extracts: Modulation of PPAR Signaling, Gut Microbiota, and Intestinal Barrier Function in Hyperlipidemic Rats
by Liqing Zhou, Cong Fang, Hongwei Li, Yifan Lin, Huiqing Que, Hongxu Liu, Lihong Ma and Wenjin Lin
Pharmaceuticals 2025, 18(9), 1320; https://doi.org/10.3390/ph18091320 - 3 Sep 2025
Viewed by 316
Abstract
Objectives: Alpinia japonica (A. japonica) is traditionally used for digestive disorders, but its hypolipidemic mechanisms remain unclear. This study investigated the lipid-lowering effects of its fruit (SJGS), rhizome (SJGJ), and leaf (SJY) extracts, exploring their bioactive constituents and organ-specific mechanisms. [...] Read more.
Objectives: Alpinia japonica (A. japonica) is traditionally used for digestive disorders, but its hypolipidemic mechanisms remain unclear. This study investigated the lipid-lowering effects of its fruit (SJGS), rhizome (SJGJ), and leaf (SJY) extracts, exploring their bioactive constituents and organ-specific mechanisms. Methods: Sprague Dawley rats (n = 8/group) fed a high-fat diet received SJGS, SJGJ, or SJY (200 mg/kg/day) for 4 weeks. Serum lipids (TC, TG), liver enzymes (AST, ALT), and intestinal barrier markers (DAO) were measured. Gut microbiota (16S rDNA sequencing), hepatic histopathology, and ileal tight junction proteins were analyzed. Transcriptomics and qPCR assessed ileal gene expression. LC-MS identified chemical constituents, while network pharmacology predicted compound-target interactions. Results: All extracts significantly reduced serum TC (↓ 27–33%), TG (↓ 29–38%), AST/ALT (↓ 22–30%), and DAO (↓ 35–42%) versus controls (p < 0.05). They improved hepatic steatosis, enhanced intestinal barrier function, and modulated gut microbiota (↑ α-diversity, ↓ Firmicutes/Bacteroidetes ratio). Transcriptomics revealed PPAR signaling as the core pathway: SJGS/SJGJ downregulated fatty acid oxidation genes (ACSL1, ACOX1, ACADM), while SJY upregulated APOA1 (2.3-fold). LC-MS identified 33–48 compounds/part, with seven shared constituents. Network analysis prioritized three flavonoids (pinocembrin, luteolin, galangin) targeting TNF, AKT1, and PPAR pathways. Conclusions: The findings suggest A. japonica extracts ameliorate hyperlipidemia through distinct mechanisms—SJGS/SJGJ may inhibit fatty acid oxidation, while SJY potentially enhances APOA1-mediated clearance. Shared flavonoids likely contribute to these effects via PPAR signaling, supporting its traditional use. This study provides a scientific basis for the sustainable utilization of A. japonica resources. Full article
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11 pages, 245 KB  
Article
The Impact of Ketogenic Capacity on Lipid Profile in Individuals with Prediabetes or Newly Diagnosed Type 2 Diabetes
by Jaehyun Bae, Minyoung Lee, Yong-ho Lee, Sang-Guk Lee and Byung-Wan Lee
Int. J. Mol. Sci. 2025, 26(17), 8566; https://doi.org/10.3390/ijms26178566 - 3 Sep 2025
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Abstract
In individuals with non-adipogenic traits and enhanced ketogenic capacity, plasma triglyceride (TG) levels are typically low, while low-density lipoprotein cholesterol (LDL-C) levels often exceed the normal range, complicating cardiovascular risk assessment. We analyzed lipid profiles to better characterize cardiovascular risk in this population. [...] Read more.
In individuals with non-adipogenic traits and enhanced ketogenic capacity, plasma triglyceride (TG) levels are typically low, while low-density lipoprotein cholesterol (LDL-C) levels often exceed the normal range, complicating cardiovascular risk assessment. We analyzed lipid profiles to better characterize cardiovascular risk in this population. Drug-naïve patients newly diagnosed with prediabetes or type 2 diabetes (T2D) were divided into two groups based on serum β-hydroxybutyrate levels: enhanced versus non-enhanced ketogenesis. Among those with enhanced ketogenesis, 27 individuals with high LDL-C (≥100 mg/dL) and low TG (<150 mg/dL) were selected. For comparison, 27 individuals with high TG (>150 mg/dL) from the non-enhanced group were included. The enhanced ketogenesis group demonstrated more favorable lipid characteristics, including a significantly larger average LDL particle size (26.8 ± 0.3 nm vs. 25.9 ± 0.6 nm, p < 0.001), a lower proportion of small dense LDL particles, and reduced oxidized LDL to LDL-C ratio. Importantly, enhanced ketogenesis remained an independent predictor of larger LDL particle size after adjusting for potential confounders including TG. Despite the potential of selection bias intentionally induced by the predefined inclusion criteria, our findings suggest that patients with T2D or prediabetes who exhibit enhanced ketogenesis, even in the presence of elevated LDL-C levels, may have a more favorable atherogenic profile and are not necessarily at increased cardiovascular risk. Full article
(This article belongs to the Special Issue New Insights into the Treatment of Metabolic Syndrome and Diabetes)
18 pages, 271 KB  
Article
Bariatric Patient Profiles After RYGB and SG Surgery: A 24-Month Observation of Metabolic Changes and Qualitative Malnutrition
by Aleksandra Pankowska, Dariusz Kotlęga, Karina Ryterska, Izabela Gutowska, Maciej Ziętek and Małgorzata Szczuko
Nutrients 2025, 17(17), 2857; https://doi.org/10.3390/nu17172857 - 3 Sep 2025
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Abstract
Background/Objectives: Introduction: Bariatric surgery, including laparoscopic sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), is an effective treatment for severe obesity and its metabolic complications. This study aimed to assess and compare the clinical outcomes of both procedures over a 24-month follow-up. Few [...] Read more.
Background/Objectives: Introduction: Bariatric surgery, including laparoscopic sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), is an effective treatment for severe obesity and its metabolic complications. This study aimed to assess and compare the clinical outcomes of both procedures over a 24-month follow-up. Few studies have compared 24-month SG and RYGB results in terms of metabolic and nutritional profiles in the Polish cohort. Materials and Methods: A retrospective analysis was conducted on 54 patients (27 SG, 27 RYGB) treated between 2018 and 2022. Anthropometric (body weight, BMI), biochemical (lipid profile, glucose, HbA1c, and liver enzymes), and nutritional (iron, ferritin, and vitamin B12) parameters were measured at 1, 6, 12, and 24 months postoperatively. Results: Both surgical techniques led to a significant reduction in body weight and BMI during the first postoperative year. After 24 months, weight stabilization was observed in the RYGB group, while statistically significant weight regain occurred in the SG group (p < 0.0001). HDL levels significantly increased and triglyceride levels decreased in both groups (p < 0.0001), with no significant changes in LDL levels. AST, ALT, decreased dramatically at the first measurement in both methods, while a greater decrease in glycemia was recorded with the SG method (at the same time). A significant reduction in ferritin and vitamin B12 levels was observed in both groups but was more pronounced after RYGB. Iron levels increased until 12 months, followed by a decline by month 24. Conclusions: Both RYGB and SG are effective for weight loss and metabolic improvement. RYGB demonstrates greater long-term weight stability but carries a higher risk of nutritional deficiencies. SG should be the first method to consider due to its lower risk, invasiveness, and lower risk of nutritional deficiencies. Full article
(This article belongs to the Special Issue Nutrition and Supplementation in Lipid Disorders)
20 pages, 3413 KB  
Article
Dysregulated Oxidative Stress Pathways in Schizophrenia: Integrating Single-Cell Transcriptomic and Human Biomarker Evidence
by Mohammad Mohabbulla Mohib, Mohammad Borhan Uddin, Md Majedur Rahman, Munichandra Babu Tirumalasetty, Md. Mamun Al-Amin, Shakila Jahan Shimu, Md. Faruk Alam, Shahida Arbee, Afsana R. Munmun, Asif Akhtar and Mohammad Sarif Mohiuddin
Psychiatry Int. 2025, 6(3), 104; https://doi.org/10.3390/psychiatryint6030104 - 3 Sep 2025
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Abstract
Background: Schizophrenia is a complex neuropsychiatric disorder whose pathophysiology may involve oxidative stress-induced neuronal damage and inflammation. We conducted a cross-species study to elucidate oxidative stress dysregulation in schizophrenia. Methods: We measured peripheral oxidative stress biomarkers (malondialdehyde [MDA], nitric oxide [NO], reduced glutathione [...] Read more.
Background: Schizophrenia is a complex neuropsychiatric disorder whose pathophysiology may involve oxidative stress-induced neuronal damage and inflammation. We conducted a cross-species study to elucidate oxidative stress dysregulation in schizophrenia. Methods: We measured peripheral oxidative stress biomarkers (malondialdehyde [MDA], nitric oxide [NO], reduced glutathione [GSH], superoxide dismutase [SOD], catalase [CAT], advanced protein oxidation products [APOP]), and C-reactive protein (CRP) in antipsychotic-naïve schizophrenia patients and matched controls. We also assayed liver enzymes (ALP, ALT, AST) as indicators of systemic metabolic stress. In parallel, we re-analyzed published single-cell RNA-sequencing data from a Setd1a^+/–^ mouse model of schizophrenia, focusing on prefrontal cortex (PFC) cell types and oxidative stress-related gene expression. Results: Patients with schizophrenia showed markedly elevated MDA and NO (indicators of lipid and nitrosative stress) and significantly reduced antioxidant defenses (GSH, SOD, CAT) versus controls (p < 0.01 for all comparisons). Notably, urban patients exhibited higher oxidative stress biomarker levels than rural patients, implicating environmental contributions. Liver function tests revealed increased ALT, AST, and ALP in schizophrenia, suggesting hepatic/metabolic dysregulation. Single-cell analysis confirmed dysregulated redox pathways in the schizophrenia model; PFC neurons from Setd1a^+/–^ mice displayed significantly lower expression of key antioxidant genes (e.g., Gpx4, Nfe2l2) compared to wild-type, indicating impaired glutathione metabolism. Conclusions: Our integrative data identify convergent oxidative stress imbalances in schizophrenia across species. These findings advance a mechanistic understanding of schizophrenia as a disorder of redox dysregulation and inflammation. They also have translational implications as augmenting antioxidant defenses (for example, with N-acetylcysteine or vitamins C/E) could mitigate oxidative injury and neuroinflammation in schizophrenia, representing a promising adjunct to antipsychotic therapy. Full article
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