Fucoidan ameliorates lipid accumulation, oxidative stress, and NF-κB-mediated inflammation by regulating the PI3K/AKT/Nrf2 signaling pathway in a free fatty acid-induced NAFLD spheroid model

Lipids in Health and Disease, Journal Year: 2025, Volume and Issue: 24(1)

Published: Feb. 17, 2025

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic worldwide. Previous studies have reported that fucoidan can relieve obesity and hepatic steatosis in vivo, although molecular mechanism remains unclear. This study aimed to explore effect potential of NAFLD using free acid (FFA)-induced spheroid model. The spheroids were constructed by fusing HepG2 LX-2 cells. Spheroids cells stimulated with FFAs fucoidan, then intracellular lipid contents oxidative stress levels (ROS/MDA/GSH/GR/GPx/NQO1/GCLC/HO-1) detected. Furthermore, regulation PI3K/AKT/Nrf2 pathway expression inflammatory factors (TNF-α IL-6) measured. Fucoidan markedly reduced FFA-induced accumulation Notably, relieved reducing ROS MDA, elevating GSH, GR, GPx. activating signaling inhibiting ROS-induced P65 NF-κB activation responses via Nrf2 activation. Our results demonstrated ameliorated accumulation, stress, NF-κB-mediated inflammation through model NAFLD. These provided new evidence for clinical use treatment its action.

Language: Английский

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Transforming Toxicity Assessment through Microphysiology, Bioprinting, and Computational Modeling

Advances in Clinical Toxicology, Journal Year: 2024, Volume and Issue: 9(1), P. 1 - 14

Published: Jan. 1, 2024

Background: Traditional toxicity testing emphasizes animal models with growing concerns regarding predictive capacity, throughput and ethics. Rapid innovation surrounding human cell platforms, bioengineered tissues, omics techniques computational tools offers more modern alternatives aligned expanding knowledge of chemical biological pathways. These disruptive approaches promise immense potential to transform next-generation safety assessment drug development pipelines. Purpose: This review provides clinical researchers an updated, comprehensive perspective across evolving areas focus in new methods analysis latest advances translational context. Main Body: We survey progress two- three-dimensional cultures recapitulating tissue/organ complexity impossible conventional assays. Complementing this, modeling integrates structure-activity relationships, physicochemical properties physiological interactions predict pharmacokinetics silico. Expanding model organisms add further dimensionality demographic relevance. High-throughput imaging technologies unravel mechanisms illuminate biomarkers undetectable by standard measures. Specialized show high addressing toxicodynamic intricacies within disease contexts like diabetes NAFLD. Evaluating traditional medicines phytochemicals likewise represents area growth well-suited for contemporary platforms. Future outlook weighs remarkable advantages reducing demands, enabling precision toxicology links medicine overhauling core risk frameworks. Conclusion: intends catalyze discourse on strategic optimization priorities roadmaps towards fully unlocking the yet still emerging public health these poising transformation sciences centered human-focused models.

Language: Английский

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An Assist for Arthritis Studies: A 3D Cell Culture of Human Fibroblast‐Like Synoviocytes by Encapsulation in a Chitosan‐Based Hydrogel

Advanced Therapeutics, Journal Year: 2024, Volume and Issue: 7(12)

Published: Aug. 2, 2024

Abstract Osteoarthritis (OA) and Rheumatoid arthritis (RA) are the most common in which synovium is involved, but cellular molecular basis of these pathologies still need better elucidation. Fibroblast‐like synoviocytes (FLS), one elements synovium, play a key role RA, an autoimmune disease characterized by joint inflammation systemic symptoms that afflicts 1% worldwide population. Despite articular damage starts from then proceeds involving cartilage till bone erosion, several 3D vitro models reported for while only few studies focused on synovial component. Here, hydrogel formulation suitable culturing human fibroblast‐like evaluated its suitability with non‐RA RA patients derived‐cells developed. Among different formulations, chitosan (Cs)‐based hydrogel, constituted 70% Cs 30% Matrigel, showed best results terms stability as well cell growth morphology: FLS able to grow within forming complex network. Thanks low cost, high market availability chitosan, this system represents good alternative use sole Matrigel encapsulating synoviocytes.

Language: Английский

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Drosera rotundifolia L. as E. coli biofilm inhibitor: insights into the mechanism of action using proteomics/metabolomics and toxicity studies

Biofilm, Journal Year: 2025, Volume and Issue: 9, P. 100268 - 100268

Published: March 1, 2025

The successful sustainable cultivation of the well-known medicinal plant sundew on rewetted peatlands not only leads to preservation natural populations, but also provides a basis for pharmaceutical use plant. bioactive compounds sundew, flavonoids and naphthoquinones, show biofilm-inhibiting properties against multidrug-resistant, ESBL-producing E. coli strains open up new therapeutic possibilities. This study investigates molecular mechanisms these in biofilm inhibition through proteomic analyses. Specific fractions as well individual substances like 7-methyljuglone 2″-O-galloylhyperoside, are analyzed. Results that naphthoquinones appear act via central regulatory proteins such OmpR alter stress response while likely affect formation by creating an iron-poor environment iron complexation additionally influence polyamine balance, reducing intracellular spermidine levels. Further investigations including assays analysis polyamines confirmed data. Safety evaluations cytotoxicity tests 3D cell cultures Galleria mellonella vivo model confirm safety extracts used. These findings highlight promising candidate phytopharmaceuticals.

Language: Английский

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Transforming Drug Discovery with Miniaturized Predictive Tissue Models

Micromachines, Journal Year: 2025, Volume and Issue: 16(3), P. 299 - 299

Published: March 3, 2025

Drug development is a lengthy and expensive process that involves screening thousands of potential candidates in vitro, followed by pre-clinical efficacy, pharmacokinetic, pharmacodynamic studies relevant animal models, before evaluating the safety efficacy drug clinical trials [...]

Language: Английский

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Multi-scale additive manufacturing of 3D porous networks integrated with hydrogel for sustained in vitro tissue growth

Acta Biomaterialia, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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Advanced liver-on-chip model mimicking hepatic lobule with continuous microvascular network via high-definition laser patterning

Materials Today Bio, Journal Year: 2025, Volume and Issue: 32, P. 101643 - 101643

Published: March 7, 2025

There is a great demand for development of advanced in vitro liver models to predict the efficacy and safety drug candidates accurately preclinical development. Despite efforts develop biomimetic models, it remains challenging precisely mimic functional unit (i.e., hepatic lobule) with continuous microvascular network. Recent progress laser patterning has allowed us create arbitrary structures high resolution. Here, we propose an liver-on-chip model mimicking lobule network, ranging from microvessels central vein liver, utilizing femtosecond patterning. Firstly, optimize power pattern microchannels microvessel by using within collagen-based hydrogel containing cells. Secondly, construct luminal comparing different microchannel sizes diameter. Finally, assemble millimeter-scale lobule-like structure multiple layers networks liver-on-chip. Furthermore, our exhibits major functions drug-induced hepatotoxicity, as evidenced albumin urea productions toxic response acetaminophen, respectively. Our approach provides valuable strategies physiological pathological pharmaceutical toxicological studies.

Language: Английский

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Advancing Precision Surgery: The Role of 3D Printing in Liver Surgery

3D Printing and Additive Manufacturing, Journal Year: 2025, Volume and Issue: unknown

Published: March 7, 2025

Language: Английский

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Advances in humanoid organoid-based research on inter-organ communications during cardiac organogenesis and cardiovascular diseases

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 28, 2025

The intimate correlation between cardiovascular diseases and other organ pathologies, such as metabolic kidney diseases, underscores the intricate interactions among these organs. Understanding inter-organ communications is crucial for developing more precise drugs effective treatments systemic diseases. While animal models have traditionally been pivotal in studying interactions, human-induced pluripotent stem cells (hiPSCs) offer distinct advantages when constructing vitro models. Beyond conventional two-dimensional co-culture model, hiPSC-derived humanoid organoids emerged a substantial advancement, capable of replicating essential structural functional attributes internal organs vitro. This breakthrough has spurred development multilineage organoids, assembloids, organoids-on-a-chip technologies, which allow enhanced physiological relevance. These technologies shown great potential mimicking coordinated organogenesis, exploring disease pathogenesis, facilitating drug discovery. As central system, heart serves focal point an extensively studied network interactions. review focuses on advancements challenges organs, presenting comprehensive exploration this cutting-edge approach research.

Language: Английский

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Functional Synovium‐Based 3D Models in the Context of Human Disease and Inflammation

Advanced NanoBiomed Research, Journal Year: 2025, Volume and Issue: unknown

Published: April 26, 2025

The synovium plays a crucial role in joint function and is primary site of pathology inflammatory diseases, such as rheumatoid arthritis (RA). Immune‐mediated diseases (IMIDs), including RA, are becoming increasingly prevalent worldwide. However, the development effective treatments remains hindered by limitations preclinical modeling techniques. Traditional methods, 2D vitro monolayer cultures animal models, often fail to replicate complexity human tissues. To address these challenges, tissue engineering (TE) biofabrication strategies have emerged promising alternatives. These approaches enable creation 3D models that better mimic physiological conditions. Techniques like bioprinting allow researchers cellular interactions extracellular matrix, improving accuracy disease models. application therapy development, drug screening, personalized medicine has grown significantly. platforms offer valuable insights into IMID pathophysiology simulating relevant microenvironments. This review examines current used research explores future directions TE biofabrication. Additionally, impact inflammation on tissues discuss clinical potential disregarded aspects coexistent highlighted.

Language: Английский

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