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22 pages, 775 KiB  
Review
Bioactive Compounds, Technological Advances, and Sustainable Applications of Avocado (Persea americana Mill.): A Critical Review
by Amanda Priscila Silva Nascimento, Maria Elita Martins Duarte, Ana Paula Trindade Rocha and Ana Novo Barros
Foods 2025, 14(15), 2746; https://doi.org/10.3390/foods14152746 (registering DOI) - 6 Aug 2025
Abstract
Avocado (Persea americana), originally from Mesoamerica, has emerged as a focus of intense scientific and industrial interest due to its unique combination of nutritional richness, bioactive potential, and technological versatility. Its pulp, widely consumed across the globe, is notably abundant in [...] Read more.
Avocado (Persea americana), originally from Mesoamerica, has emerged as a focus of intense scientific and industrial interest due to its unique combination of nutritional richness, bioactive potential, and technological versatility. Its pulp, widely consumed across the globe, is notably abundant in monounsaturated fatty acids, especially oleic acid, which can comprise over two-thirds of its lipid content. In addition, it provides significant levels of dietary fiber, fat-soluble vitamins such as A, D, E and K, carotenoids, tocopherols, and phytosterols like β-sitosterol. These constituents are consistently associated with antioxidant, anti-inflammatory, glycemic regulatory, and cardioprotective effects, supported by a growing body of experimental and clinical evidence. This review offers a comprehensive and critical synthesis of the chemical composition and functional properties of avocado, with particular emphasis on its lipid profile, phenolic compounds, and phytosterols. It also explores recent advances in environmentally sustainable extraction techniques, including ultrasound-assisted and microwave-assisted processes, as well as the application of natural deep eutectic solvents. These technologies have demonstrated improved efficiency in recovering bioactives while aligning with the principles of green chemistry. The use of avocado-derived ingredients in nanostructured delivery systems and their incorporation into functional foods, cosmetics, and health-promoting formulations is discussed in detail. Additionally, the potential of native cultivars and the application of precision nutrition strategies are identified as promising avenues for future innovation. Taken together, the findings underscore the avocado’s relevance as a high-value matrix for sustainable development. Future research should focus on optimizing extraction protocols, clarifying pharmacokinetic behavior, and ensuring long-term safety in diverse applications. Full article
(This article belongs to the Special Issue Feature Review on Nutraceuticals, Functional Foods, and Novel Foods)
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18 pages, 5256 KiB  
Article
Impact of Alginate Oligosaccharides on Ovarian Performance and the Gut Microbial Community in Mice with D-Galactose-Induced Premature Ovarian Insufficiency
by Yan Zhang, Hongda Pan, Dao Xiang, Hexuan Qu and Shuang Liang
Antioxidants 2025, 14(8), 962; https://doi.org/10.3390/antiox14080962 (registering DOI) - 5 Aug 2025
Abstract
Premature ovarian insufficiency (POI) is an important factor in female infertility and is often associated with oxidative stress. Alginate oligosaccharides (AOSs), derived from the degradation of alginate, have been demonstrated to have protective effects against various oxidative stress-related diseases. However, the impact of [...] Read more.
Premature ovarian insufficiency (POI) is an important factor in female infertility and is often associated with oxidative stress. Alginate oligosaccharides (AOSs), derived from the degradation of alginate, have been demonstrated to have protective effects against various oxidative stress-related diseases. However, the impact of AOSs on POI has not been previously explored. The current study explored the effects of AOSs on ovarian dysfunction in a mouse model of POI induced by D-galactose (D-gal). Female C57BL/6 mice were randomly divided into five groups: the control (CON), POI model (D-gal), and low-, medium-, and high-dose AOS groups (AOS-L, 100 mg/kg/day; AOS-M, 150 mg/kg/day; AOS-H, 200 mg/kg/day). For 42 consecutive days, mice in the D-gal, AOS-L, AOS-M, and AOS-H groups received daily intraperitoneal injections of D-gal (200 mg/kg/day), whereas those in the CON group received equivalent volumes of sterile saline. Following D-gal injection, AOSs were administered via gavage at the specified doses; mice in the CON and D-gal groups received sterile saline instead. AOS treatment markedly improved estrous cycle irregularities, normalized serum hormone levels, reduced granulosa cell apoptosis, and increased follicle counts in POI mice. Moreover, AOSs significantly reduced ovarian oxidative stress and senescence in POI mice, as indicated by lower levels of malondialdehyde (MDA), higher activities of catalase (CAT) and superoxide dismutase (SOD), and decreased protein expression of 4-hydroxynonenal (4-HNE), nitrotyrosine (NTY), 8-hydroxydeoxyguanosine (8-OHdG), and p16 in ovarian tissue. Analysis of the gut microbiota through 16S rRNA gene sequencing and short-chain fatty acid (SCFA) analysis revealed significant differences in gut microbiota composition and SCFA levels (acetic acid and total SCFAs) between control and D-gal-induced POI mice. These differences were largely alleviated by AOS treatment. AOSs changed the gut microbiota by increasing the abundance of Ligilactobacillus and decreasing the abundance of Clostridiales, Clostridiaceae, Marinifilaceae, and Clostridium_T. Additionally, AOSs mitigated the decline in acetic acid and total SCFA levels observed in POI mice. Notably, the total SCFA level was significantly correlated with the abundance of Ligilactobacillus, Marinifilaceae, and Clostridium_T. In conclusion, AOS intervention effectively mitigates ovarian oxidative stress, restores gut microbiota homeostasis, and regulates the microbiota–SCFA axis, collectively improving D-gal-induced POI. Therefore, AOSs represent a promising therapeutic strategy for POI management. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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27 pages, 2559 KiB  
Review
Virgin Coconut Oil and Its Lauric Acid, Between Anticancer Activity and Modulation of Chemotherapy Toxicity: A Review
by Debalina Bose, Adetayo Olorunlana, Rania Abdel-Latif, Ademola C. Famurewa and Eman M. Othman
J. Xenobiot. 2025, 15(4), 126; https://doi.org/10.3390/jox15040126 - 5 Aug 2025
Abstract
Virgin coconut oil (VCO) has emerged as a functional food oil with considerable health benefits and wide applications in the food, pharmaceutical, and cosmetic industries due to its resident bioactive compounds, including lauric acid (LA). LA is the most abundant saturated medium-chain fatty [...] Read more.
Virgin coconut oil (VCO) has emerged as a functional food oil with considerable health benefits and wide applications in the food, pharmaceutical, and cosmetic industries due to its resident bioactive compounds, including lauric acid (LA). LA is the most abundant saturated medium-chain fatty acid in VCO and has been associated with several pharmacological activities. The literatures show the pharmacological effects of VCO and LA on chronic pathologies, infectious diseases, and metabolic disorders. A robust body of evidence shows that LA and other phenolic compounds are responsible for the VCO protection against toxicities and pharmacological efficacies. This review elucidates the anticancer mechanisms of VCO/LA and their modulation of the chemotherapy-induced side effect toxicity. VCO, LA, and their nanomaterial/encapsulated derivatives promote ROS generation, antiproliferation, apoptosis, cell cycle arrest, the inhibition of metastasis, and the modulation of cancer-related signaling pathways for cancer cell death in vivo and in vitro. VCO mitigates oxidative inflammation and apoptosis to block the underlying mechanisms of the side effect toxicity of chemotherapy. However, the possible beneficial effect of LA on the toxicity of chemotherapy is currently unknown. The available evidence emphasizes the anticancer effect and mechanism of VCO and LA, and the VCO potential to combat adverse side effects of chemotherapy. Thus, VCO and LA are potential adjuvant therapeutic agents in the management of various cancers. Nevertheless, future studies should be targeted at elucidating cancer-related molecular mechanisms to bridge the gap in knowledge. Full article
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18 pages, 674 KiB  
Article
Oil Extraction Systems Influence the Techno-Functional and Nutritional Properties of Pistachio Processing By-Products
by Rito J. Mendoza-Pérez, Elena Álvarez-Olmedo, Ainhoa Vicente, Felicidad Ronda and Pedro A. Caballero
Foods 2025, 14(15), 2722; https://doi.org/10.3390/foods14152722 - 4 Aug 2025
Viewed by 42
Abstract
Low-commercial-value natural pistachios (broken, closed, or immature) can be revalorised through oil extraction, obtaining a high-quality oil and partially defatted flour as by-product. This study evaluated the techno-functional and nutritional properties of the flours obtained by hydraulic press (HP) and single-screw press (SSP) [...] Read more.
Low-commercial-value natural pistachios (broken, closed, or immature) can be revalorised through oil extraction, obtaining a high-quality oil and partially defatted flour as by-product. This study evaluated the techno-functional and nutritional properties of the flours obtained by hydraulic press (HP) and single-screw press (SSP) systems, combined with pretreatment at 25 °C and 60 °C. The extraction method significantly influenced flour’s characteristics, underscoring the need to tailor processing conditions to the specific technological requirements of each food application. HP-derived flours presented lighter colour, greater tocopherol content, and higher water absorption capacity (up to 2.75 g/g), suggesting preservation of hydrophilic proteins. SSP-derived flours showed higher concentration of protein (44 g/100 g), fibre (12 g/100 g), and minerals, and improved emulsifying properties, enhancing their suitability for emulsified products. Pretreatment at 25 °C enhanced functional properties such as swelling power (~7.0 g/g) and water absorption index (~5.7 g/g). The SSP system achieved the highest oil extraction yield, with no significant effect of pretreatment temperature. The oils extracted showed high levels of unsaturated fatty acids, particularly oleic acid (~48% of ω-9), highlighting their nutritional and industrial value. The findings support the valorisation of pistachio oil extraction by-products as functional food ingredients, offering a promising strategy for reducing food waste and promoting circular economy approaches in the agri-food sector. Full article
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22 pages, 1641 KiB  
Article
Site-Specific Trafficking of Lipid and Polar Metabolites in Adipose and Muscle Tissue Reveals the Impact of Bariatric Surgery-Induced Weight Loss: A 6-Month Follow-Up Study
by Aidan Joblin-Mills, Zhanxuan E. Wu, Garth J. S. Cooper, Ivana R. Sequeira-Bisson, Jennifer L. Miles-Chan, Anne-Thea McGill, Sally D. Poppitt and Karl Fraser
Metabolites 2025, 15(8), 525; https://doi.org/10.3390/metabo15080525 - 2 Aug 2025
Viewed by 233
Abstract
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 [...] Read more.
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
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24 pages, 1244 KiB  
Article
HPLC-ESI-HRMS/MS-Based Metabolite Profiling and Bioactivity Assessment of Catharanthus roseus
by Soniya Joshi, Chen Huo, Rabin Budhathoki, Anita Gurung, Salyan Bhattarai, Khaga Raj Sharma, Ki Hyun Kim and Niranjan Parajuli
Plants 2025, 14(15), 2395; https://doi.org/10.3390/plants14152395 - 2 Aug 2025
Viewed by 834
Abstract
A comprehensive metabolic profiling of Catharanthus roseus (L.) G. Don was performed using tandem mass spectrometry, along with an evaluation of the biological activities of its various solvent extracts. Among these, the methanolic leaf extract exhibited mild radical scavenging activity, low to moderate [...] Read more.
A comprehensive metabolic profiling of Catharanthus roseus (L.) G. Don was performed using tandem mass spectrometry, along with an evaluation of the biological activities of its various solvent extracts. Among these, the methanolic leaf extract exhibited mild radical scavenging activity, low to moderate antimicrobial activity, and limited cytotoxicity in both the brine shrimp lethality assay and MTT assay against HeLa and A549 cell lines. High-performance liquid chromatography–electrospray ionization–high-resolution tandem mass spectrometry (HPLC-ESI-HRMS/MS) analysis led to the annotation of 34 metabolites, primarily alkaloids. These included 23 indole alkaloids, two fatty acids, two pentacyclic triterpenoids, one amino acid, four porphyrin derivatives, one glyceride, and one chlorin derivative. Notably, two metabolites—2,3-dihydroxypropyl 9,12,15-octadecatrienoate and (10S)-hydroxypheophorbide A—were identified for the first time in C. roseus. Furthermore, Global Natural Products Social Molecular Networking (GNPS) analysis revealed 18 additional metabolites, including epoxypheophorbide A, 11,12-dehydroursolic acid lactone, and 20-isocatharanthine. These findings highlight the diverse secondary metabolite profile of C. roseus and support its potential as a source of bioactive compounds for therapeutic development. Full article
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15 pages, 4969 KiB  
Article
Duplicated Genes on Homologous Chromosomes Decipher the Dominant Epistasis of the Fiberless Mutant in Cotton
by Yu Le, Xingchen Xiong, Zhiyong Xu, Meilin Chen, Yuanxue Li, Chao Fu, Chunyuan You and Zhongxu Lin
Biology 2025, 14(8), 983; https://doi.org/10.3390/biology14080983 (registering DOI) - 2 Aug 2025
Viewed by 100
Abstract
Cotton fiber initiation determines the fiber yield, yet the genetic basis underlying lint and fuzz initiation has still not been fully uncovered. Here, map-based cloning was carried out to identify the fiberless mutant genes derived from a cross between Gossypium hirsutum acc. WT [...] Read more.
Cotton fiber initiation determines the fiber yield, yet the genetic basis underlying lint and fuzz initiation has still not been fully uncovered. Here, map-based cloning was carried out to identify the fiberless mutant genes derived from a cross between Gossypium hirsutum acc. WT and a natural fiberless mutant, fblSHZ. The 12:3:1 segregation ratio in F2 populations (including 1848 and 3100 individuals that were developed in 2016 and 2018, respectively) revealed dominant epistasis, with the fuzz gene exerting dominance over the lint gene. Genetic linkage analysis revealed that GhMYB25like_A12 controls fuzz fiber initiation, while both GhMYB25like_A12 and GhMYB25like_D12 regulate lint fiber development. Sequencing analyses showed that the fblSHZ mutant exhibited a K104M mutation in the R2R3 domain of GhMYB25like_A12 and a transposable element insertion in GhMYB25like_D12, leading to fiberless seeds. Knockout of GhMYB25like_A12 produced fuzzless seeds, knockout of GhMYB25like_D12 led to no obvious change in seeds, and knockout of both (GhMYB25like_A12&D12) resulted in fiberless seeds. The 12:3:1 ratio reappeared in the F2 population developed from the GhMYB25like_A12&D12 mutated plants as female and Jin668 as the male, which further confirmed the genetic interaction observed in fblSHZ. RNA-seq analysis revealed that GhMYB25like regulates cotton fiber initiation through multiple pathways, especially fatty acid metabolism. This study elucidates the key genes and their genetic interaction mechanisms governing cotton fiber initiation, providing a theoretical foundation for genetic improvement of cotton fiber traits. Full article
(This article belongs to the Special Issue Cotton: Genomics, Biotechnology and Molecular Breeding)
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15 pages, 1258 KiB  
Article
Synthesis and Evaluation of Sunflower-Oil-Based Esters as Biolubricant Base Oils Using Ca/TEA Alkoxide Catalyst
by Dimosthenis Filon, George Anastopoulos and Dimitrios Karonis
Lubricants 2025, 13(8), 345; https://doi.org/10.3390/lubricants13080345 - 2 Aug 2025
Viewed by 178
Abstract
This study evaluates the production of base oils for biolubricants using fatty acid methyl esters (FAMEs) derived from sunflower oil as the raw material. The production process involved the synthesis of oleochemical esters through a single-step alkaline transesterification reaction with a high-molecular-weight polyol, [...] Read more.
This study evaluates the production of base oils for biolubricants using fatty acid methyl esters (FAMEs) derived from sunflower oil as the raw material. The production process involved the synthesis of oleochemical esters through a single-step alkaline transesterification reaction with a high-molecular-weight polyol, such as trimethylolpropane (TMP). To assess the effectiveness of the developed catalytic system in conducting the transesterification reactions and its impact on the properties of the final product, two types of alkaline catalysts were used. Specifically, the reactions were carried out using either Ca/TEA alkoxide or sodium methoxide as catalysts in various configurations and concentrations to determine the optimal catalyst concentration and reaction conditions. Sodium methoxide served as the commercial benchmark catalyst, while the Ca/TEA alkoxide was prepared in the laboratory. The optimal concentration of Ca/TEA was determined to be 3.0% wt. in the presence of iso-octane and 3.5% wt. under vacuum, while the corresponding concentrations of CH3ONa for both cases were determined to be 2.0% wt. The synthesized biolubricant esters exhibit remarkable performance characteristics, such as high kinematic viscosities and low pour points—ranging from 33–48 cSt at 40 °C, 7.68–10.03 cSt at 100 °C, to −14 to −7 °C, respectively—which are comparable to or improved over those of mineral oils such as SN-150 or SN-500, with the Ca/TEA alkoxide-catalyzed systems showing superior oxidation stability and reduced byproduct formation. Full article
(This article belongs to the Special Issue Tribological Properties of Biolubricants)
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30 pages, 1428 KiB  
Review
The Oral–Gut Microbiota Axis Across the Lifespan: New Insights on a Forgotten Interaction
by Domenico Azzolino, Margherita Carnevale-Schianca, Luigi Santacroce, Marica Colella, Alessia Felicetti, Leonardo Terranova, Roberto Carlos Castrejón-Pérez, Franklin Garcia-Godoy, Tiziano Lucchi and Pier Carmine Passarelli
Nutrients 2025, 17(15), 2538; https://doi.org/10.3390/nu17152538 - 1 Aug 2025
Viewed by 178
Abstract
The oral–gut microbiota axis is a relatively new field of research. Although most studies have focused separately on the oral and gut microbiota, emerging evidence has highlighted that the two microbiota are interconnected and may influence each other through various mechanisms shaping systemic [...] Read more.
The oral–gut microbiota axis is a relatively new field of research. Although most studies have focused separately on the oral and gut microbiota, emerging evidence has highlighted that the two microbiota are interconnected and may influence each other through various mechanisms shaping systemic health. The aim of this review is therefore to provide an overview of the interactions between oral and gut microbiota, and the influence of diet and related metabolites on this axis. Pathogenic oral bacteria, such as Porphyromonas gingivalis and Fusobacterium nucleatum, can migrate to the gut through the enteral route, particularly in individuals with weakened gastrointestinal defenses or conditions like gastroesophageal reflux disease, contributing to disorders like inflammatory bowel disease and colorectal cancer. Bile acids, altered by gut microbes, also play a significant role in modulating these microbiota interactions and inflammatory responses. Oral bacteria can also spread via the bloodstream, promoting systemic inflammation and worsening some conditions like cardiovascular disease. Translocation of microorganisms can also take place from the gut to the oral cavity through fecal–oral transmission, especially within poor sanitary conditions. Some metabolites including short-chain fatty acids, trimethylamine N-oxide, indole and its derivatives, bile acids, and lipopolysaccharides produced by both oral and gut microbes seem to play central roles in mediating oral–gut interactions. The complex interplay between oral and gut microbiota underscores their crucial role in maintaining systemic health and highlights the potential consequences of dysbiosis at both the oral and gastrointestinal level. Some dietary patterns and nutritional compounds including probiotics and prebiotics seem to exert beneficial effects both on oral and gut microbiota eubiosis. A better understanding of these microbial interactions could therefore pave the way for the prevention and management of systemic conditions, improving overall health outcomes. Full article
(This article belongs to the Special Issue Exploring the Lifespan Dynamics of Oral–Gut Microbiota Interactions)
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20 pages, 2782 KiB  
Article
Urban Forest Fragmentation Reshapes Soil Microbiome–Carbon Dynamics
by Melinda Haydee Kovacs, Nguyen Khoi Nghia and Emoke Dalma Kovacs
Diversity 2025, 17(8), 545; https://doi.org/10.3390/d17080545 - 1 Aug 2025
Viewed by 169
Abstract
Urban expansion fragments once-contiguous forest patches, generating pronounced edge gradients that modulate soil physicochemical properties and biodiversity. We quantified how fragmentation reshaped the soil microbiome continuum and its implications for soil carbon storage in a temperate urban mixed deciduous forest. A total of [...] Read more.
Urban expansion fragments once-contiguous forest patches, generating pronounced edge gradients that modulate soil physicochemical properties and biodiversity. We quantified how fragmentation reshaped the soil microbiome continuum and its implications for soil carbon storage in a temperate urban mixed deciduous forest. A total of 18 plots were considered in this study, with six plots for each fragment type. Intact interior forest (F), internal forest path fragment (IF), and external forest path fragment (EF) soils were sampled at 0–15, 15–30, and 30–45 cm depths and profiled through phospholipid-derived fatty acid (PLFA) chemotyping and amino sugar proxies for living microbiome and microbial-derived necromass assessment, respectively. Carbon fractionation was performed through the chemical oxidation method. Diversity indices (Shannon–Wiener, Pielou evenness, Margalef richness, and Simpson dominance) were calculated based on the determined fatty acids derived from the phospholipid fraction. The microbial biomass ranged from 85.1 to 214.6 nmol g−1 dry soil, with the surface layers of F exhibiting the highest values (p < 0.01). Shannon diversity declined systematically from F > IF > EF. The microbial necromass varied from 11.3 to 23.2 g⋅kg−1. Fragmentation intensified the stratification of carbon pools, with organic carbon decreasing by approximately 14% from F to EF. Our results show that EFs possess a declining microbiome continuum that weakens their carbon sequestration capacity in urban forests. Full article
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35 pages, 6006 KiB  
Review
Enhancing Mitochondrial Maturation in iPSC-DerivedCardiomyocytes: Strategies for Metabolic Optimization
by Dhienda C. Shahannaz, Tadahisa Sugiura and Brandon E. Ferrell
BioChem 2025, 5(3), 23; https://doi.org/10.3390/biochem5030023 - 31 Jul 2025
Viewed by 241
Abstract
Background: Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) hold transformative potential for cardiovascular regenerative medicine, yet their clinical application is hindered by suboptimal mitochondrial maturation and metabolic inefficiencies. This systematic review evaluates targeted strategies for optimizing mitochondrial function, integrating metabolic preconditioning, substrate selection, and [...] Read more.
Background: Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) hold transformative potential for cardiovascular regenerative medicine, yet their clinical application is hindered by suboptimal mitochondrial maturation and metabolic inefficiencies. This systematic review evaluates targeted strategies for optimizing mitochondrial function, integrating metabolic preconditioning, substrate selection, and pathway modulation to enhance energy production and cellular resilience. Additionally, we examine the role of extracellular matrix stiffness and mechanical stimulation in mitochondrial adaptation, given their influence on metabolism and maturation. Methods: A comprehensive analysis of recent advancements in iPSC-CM maturation was conducted, focusing on metabolic interventions that enhance mitochondrial structure and function. Studies employing metabolic preconditioning, lipid and amino acid supplementation, and modulation of key signaling pathways, including PGC-1α, AMPK, and mTOR, were reviewed. Computational modeling approaches predicting optimal metabolic shifts were assessed, alongside insights into reactive oxygen species (ROS) signaling, calcium handling, and the impact of electrical pacing on energy metabolism. Results: Evidence indicates that metabolic preconditioning with fatty acids and oxidative phosphorylation enhancers improves mitochondrial architecture, cristae density, and ATP production. Substrate manipulation fosters a shift toward adult-like metabolism, while pathway modulation refines mitochondrial biogenesis. Computational models enhance precision, predicting interventions that best align iPSC-CM metabolism with native cardiomyocytes. The synergy between metabolic and biomechanical cues offers new avenues for accelerating maturation, bridging the gap between in vitro models and functional cardiac tissues. Conclusions: Strategic metabolic optimization is essential for overcoming mitochondrial immaturity in iPSC-CMs. By integrating biochemical engineering, predictive modeling, and biomechanical conditioning, a robust framework emerges for advancing iPSC-CM applications in regenerative therapy and disease modeling. These findings pave the way for more physiologically relevant cell models, addressing key translational challenges in cardiovascular medicine. Full article
(This article belongs to the Special Issue Feature Papers in BioChem, 2nd Edition)
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20 pages, 13309 KiB  
Article
Biomarker-Driven Optimization of Saponin Therapy in MASLD: From Mouse Models to Human Liver Organoids
by Hye Young Kim, Ju Hee Oh, Hyun Sung Kim and Dae Won Jun
Antioxidants 2025, 14(8), 943; https://doi.org/10.3390/antiox14080943 (registering DOI) - 31 Jul 2025
Viewed by 273
Abstract
(1) Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by liver damage similar to alcoholic fatty liver disease, including triglyceride infiltration of hepatocytes, regardless of alcohol consumption. It leads to progressive liver damage, such as loss of liver function, cirrhosis, and liver [...] Read more.
(1) Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by liver damage similar to alcoholic fatty liver disease, including triglyceride infiltration of hepatocytes, regardless of alcohol consumption. It leads to progressive liver damage, such as loss of liver function, cirrhosis, and liver cancer, and the response rate of drugs under clinical research is less than 50%. There is an urgent need for biomarkers to evaluate the efficacy of these drugs. (2) Methods: MASLD was induced in mice using a High-Fat diet (HF), Western diet (WD), and Methionine/Choline-Deficient diet (MCD) for 20 weeks (4 weeks for MCD). Liver tissue biopsies were performed, and the treatment effects of saponin and non-saponin feeds were evaluated. Fat accumulation and hepatic inflammation were measured, and mRNA sequencing analysis was conducted. The therapeutic effects were validated using patient-derived liver organoids. (3) Results: The NAFLD Activity Score (NAS) significantly increased in all MASLD models compared with controls. Saponin treatment decreased NAS in the HF and WD groups but not in the MCD group. RNA sequencing and PCA analysis showed that the HF saponin response samples were similar to normal controls. DAVID analysis revealed significant changes in lipid, triglyceride, and fatty acid metabolic processes. qRT-PCR confirmed decreased fibrosis markers in the HF saponin response group, and GSEA analysis showed reduced HAMP1 gene expression. (4) Conclusions: Among the diets, red ginseng was most effective in the HF diet, with significant effects in the saponin-treated group. The therapeutic efficacy was better when HAMP1 expression was increased. Therefore, we propose HAMP1 as a potential exploratory biomarker to assess the saponin response in a preclinical setting. In addition, the reduction of inflammation and hepatic iron accumulation suggests that saponins may exert antioxidant effects through modulation of oxidative stress. Full article
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14 pages, 1862 KiB  
Review
Update of Natural Compounds in Transthyretin Amyloidosis, Years 2020–2025
by Carlo Marotta, Lidia Ciccone and Susanna Nencetti
Crystals 2025, 15(8), 696; https://doi.org/10.3390/cryst15080696 - 30 Jul 2025
Viewed by 155
Abstract
Transthyretin amyloidosis (ATTR) is a disease caused by the deposition of transthyretin-derived fibrils in the body. Despite extensive research conducted over the years, there are currently only four drugs available in clinical use to treat this condition, two of which are repurposed drugs [...] Read more.
Transthyretin amyloidosis (ATTR) is a disease caused by the deposition of transthyretin-derived fibrils in the body. Despite extensive research conducted over the years, there are currently only four drugs available in clinical use to treat this condition, two of which are repurposed drugs used off-label. However, these treatments present several limitations; therefore, there is an urgent need for new therapeutic options. In this context, dietary supplements containing natural compounds capable of stabilizing the transthyretin (TTR) protein could represent a promising approach to contrast the disease progression, potentially supporting the therapeutic effects of the aforementioned drugs. In light of this, the present review highlights and analyzes the natural compounds that have most recently been reported in the literature as TTR stabilizers. In particular, the studies elucidating the potential of these compounds in the treatment of ATTR, along with the available crystallographic data explaining their binding mode to TTR, are reported. Overall, although the use of natural compounds as supplements shows promise in managing ATTR, further research is still needed to explore its feasibility and confirm its effectiveness. Hopefully, this work will help shed light on these issues and serve as a useful starting point for the development of new strategies to treat this disease. Full article
(This article belongs to the Collection Feature Papers in Biomolecular Crystals)
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18 pages, 875 KiB  
Review
Monounsaturated Fatty Acids in Cardiovascular Disease: Intake, Individual Types, and Content in Adipose Tissue as a Biomarker of Endogenous Exposure
by Jonas Pedersen, Berit Storgaard Hedegaard, Erik Berg Schmidt, Christina C. Dahm, Kirsten B. Holven, Kjetil Retterstøl, Philip C. Calder and Christian Bork
Nutrients 2025, 17(15), 2509; https://doi.org/10.3390/nu17152509 - 30 Jul 2025
Viewed by 268
Abstract
Unhealthy dietary patterns are a major modifiable risk factor for atherosclerotic cardiovascular disease (ASCVD). International guidelines recommend reducing saturated fatty acid intake while increasing polyunsaturated and monounsaturated fatty acids (MUFAs) to mitigate cardiovascular risk. However, evidence regarding MUFAs and risk of ASCVD remains [...] Read more.
Unhealthy dietary patterns are a major modifiable risk factor for atherosclerotic cardiovascular disease (ASCVD). International guidelines recommend reducing saturated fatty acid intake while increasing polyunsaturated and monounsaturated fatty acids (MUFAs) to mitigate cardiovascular risk. However, evidence regarding MUFAs and risk of ASCVD remains conflicting, with recent studies raising concern about a potential higher risk associated with MUFA intake. The aim of this narrative review is to provide an overview of current knowledge and gaps in the literature regarding MUFAs and the risk of ASCVD with a focus on intake, individual types, and content in adipose tissue as a biomarker of endogenous exposure. Main findings reveal that most studies have inappropriately combined all MUFAs together, despite individual MUFA types having different biological effects and showing varying correlations between dietary intake and adipose tissue content. Adipose tissue composition may serve as a biomarker of long-term MUFA exposure, reflecting cumulative intake over one to two years while minimizing biases inherent in dietary assessments. However, tissue levels reflect both dietary intake and endogenous synthesis, complicating interpretation. Importantly, the source of MUFAs appears critical, with plant-derived MUFAs potentially offering advantages over animal-derived sources. In conclusion, we suggest that future research should focus on individual MUFA types rather than treating them as a homogeneous group, investigate their specific dietary sources and associations with ASCVD risk, and use adipose tissue biomarkers to improve exposure assessment and clarify causal relationships while considering overall dietary patterns. Full article
(This article belongs to the Special Issue Diet, Nutrition and Cardiovascular Health—2nd Edition)
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41 pages, 2975 KiB  
Review
Algal Metabolites as Novel Therapeutics Against Methicillin-Resistant Staphylococcus aureus (MRSA): A Review
by Ibraheem Borie M. Ibraheem, Reem Mohammed Alharbi, Neveen Abdel-Raouf, Nouf Mohammad Al-Enazi, Khawla Ibrahim Alsamhary and Hager Mohammed Ali
Pharmaceutics 2025, 17(8), 989; https://doi.org/10.3390/pharmaceutics17080989 (registering DOI) - 30 Jul 2025
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Abstract
Methicillin-resistant Staphylococcus aureus (MRSA), a multidrug-resistant pathogen, poses a significant threat to global healthcare. This review evaluates the potential of marine algal metabolites as novel antibacterial agents against MRSA. We explore the clinical importance of S. aureus, the emergence of MRSA as [...] Read more.
Methicillin-resistant Staphylococcus aureus (MRSA), a multidrug-resistant pathogen, poses a significant threat to global healthcare. This review evaluates the potential of marine algal metabolites as novel antibacterial agents against MRSA. We explore the clinical importance of S. aureus, the emergence of MRSA as a “superbug”, and its resistance mechanisms, including target modification, drug inactivation, efflux pumps, biofilm formation, and quorum sensing. The limitations of conventional antibiotics (e.g., β-lactams, vancomycin, macrolides) are discussed, alongside the promise of algal-derived compounds such as fatty acids, pigments, polysaccharides, terpenoids, and phenolic compounds. These metabolites exhibit potent anti-MRSA activity by disrupting cell division (via FtsZ inhibition), destabilizing membranes, and inhibiting protein synthesis and metabolic pathways, effectively countering multiple resistance mechanisms. Leveraging advances in algal biotechnology, this review highlights the untapped potential of marine algae to drive innovative, sustainable therapeutic strategies against antibiotic resistance. Full article
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