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Search Results (557)

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Keywords = Caenorhabditis elegans model

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17 pages, 3779 KB  
Article
Cycloastragenol Improves Fatty Acid Metabolism Through NHR-49/FAT-7 Suppression and Potent AAK-2 Activation in Caenorhabditis elegans Obesity Model
by Liliya V. Mihaylova, Martina S. Savova, Monika N. Todorova, Valeria Tonova, Biser K. Binev and Milen I. Georgiev
Int. J. Mol. Sci. 2026, 27(2), 772; https://doi.org/10.3390/ijms27020772 - 13 Jan 2026
Abstract
Obesity is among the top contributing factors for non-communicable chronic disease development and has attained menacing global proportions, affecting approximately one of eight adults. Phytochemicals that support energy metabolism and prevent obesity development have been the subject of intense research endeavors over the [...] Read more.
Obesity is among the top contributing factors for non-communicable chronic disease development and has attained menacing global proportions, affecting approximately one of eight adults. Phytochemicals that support energy metabolism and prevent obesity development have been the subject of intense research endeavors over the past several decades. Cycloastragenol is a natural triterpenoid compound and aglycon of astragaloside IV, known for activating telomerase and mitigating cellular aging. Here, we aim to characterize the effect of cycloastragenol on lipid metabolism in a glucose-induced obesity model in Caenorhabditis elegans. We assessed the changes in the body length, width, and area in C. elegans maintained under elevated glucose through automated WormLab system. Lipid accumulation in the presence of either cycloastragenol (100 μM) or orlistat (12 μM), used as a positive anti-obesity control drug, was quantified through Nile Red fluorescent staining. Furthermore, we evaluated the changes in key energy metabolism molecular players in GFP-reporter transgenic strains. Our results revealed that cycloastragenol treatment decreased mean body area and reduced lipid accumulation in the C. elegans glucose-induced model. The mechanistic data indicated that cycloastragenol suppresses the nuclear hormone receptor family member NHR-49 and the delta(9)-fatty-acid desaturase 7 (FAT-7) enzyme, and activates the 5′-AMP-activated protein kinase catalytic subunit alpha-2 (AAK-2) and the protein skinhead 1 (SKN-1) signaling. Collectively, our findings highlight that cycloastragenol reprograms lipid metabolism by down-regulating the insulin-like receptor (daf-2)/phosphatidylinositol 3-kinase (age-1)/NHR-49 signaling while simultaneously enhancing the activity of the AAK-2/NAD-dependent protein deacetylase (SIR-2.1) pathway. The anti-obesogenic potential of cycloastragenol rationalizes further validation in the context of metabolic diseases and obesity management. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Obesity and Metabolic Diseases)
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23 pages, 1525 KB  
Review
A Review of the Literature on the Endocrine Disruptor Activity Testing of Bisphenols in Caenorhabditis elegans
by Patrícia Hockicková, Alžbeta Kaiglová, Marie Korabečná and Soňa Kucharíková
J. Xenobiot. 2026, 16(1), 7; https://doi.org/10.3390/jox16010007 - 4 Jan 2026
Viewed by 381
Abstract
Endocrine disruptors, including bisphenol A, S, AF, and F, have been demonstrated to exhibit endocrine-disrupting activity. This phenomenon has been associated with a variety of health problems, including (but not limited to) neurological and reproductive disorders. Given the potential hazards, it is essential [...] Read more.
Endocrine disruptors, including bisphenol A, S, AF, and F, have been demonstrated to exhibit endocrine-disrupting activity. This phenomenon has been associated with a variety of health problems, including (but not limited to) neurological and reproductive disorders. Given the potential hazards, it is essential to have effective tools to assess their toxicity. The nematode Caenorhabditis elegans has become a widely used model organism for studying bisphenols because of its genetic simplicity and the conservation of its fundamental biological processes. This review article summarizes current knowledge of bisphenol toxicity and the use of the model organism C. elegans as a high-throughput system for investigating the toxicological profiles of BPA and its emerging alternatives. Furthermore, we highlight the specific methodologies for assessing the toxic effects of bisphenols in C. elegans. While highlighting its advantages, we critically discuss its limitations, including the absence of specific metabolic organs, which constrain direct extrapolation to mammalian systems. Based on available evidence, we conclude that C. elegans serves as an essential bridge between in vitro assays and mammalian models, offering a powerful platform for the early hazard identification and mechanistic screening of bisphenol analogues. Full article
(This article belongs to the Section Emerging Chemicals)
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15 pages, 3294 KB  
Article
The Influence of Nematocidal Plants on the Effectiveness of Pleurotus ostreatus Mycelium Against Caenorhabditis elegans and Heterodera schachtii
by Ewa Moliszewska, Małgorzata Nabrdalik, Robert Nelke and Mirosław Nowakowski
Agriculture 2026, 16(1), 72; https://doi.org/10.3390/agriculture16010072 - 29 Dec 2025
Viewed by 211
Abstract
The vegetative mycelium of Pleurotus ostreatus (oyster mushroom) exhibits the ability to reduce nematode populations. This property may be utilized in integrated management programs targeting harmful nematodes such as Heterodera schachtii, a major pest of sugar beet crops. In addition to sugar [...] Read more.
The vegetative mycelium of Pleurotus ostreatus (oyster mushroom) exhibits the ability to reduce nematode populations. This property may be utilized in integrated management programs targeting harmful nematodes such as Heterodera schachtii, a major pest of sugar beet crops. In addition to sugar beet, many other plant species serve as hosts for this nematode; susceptible plants promote H. schachtii development and population growth. Current control strategies rely on integrated plant protection methods, including the use of tolerant cultivars, fallowing, and trap crops such as oilseed radish and white mustard. This study aimed to determine whether sugar beet cv. Janetka or nematocidal plants—oilseed radish cv. Romesa and white mustard cv. Bardena—affect the nematocidal activity of P. ostreatus mycelium when applied together. Specifically, the influence of root or seed secretions from these plants on the activity of ten P. ostreatus mycelial strains was assessed using the model nematode Caenorhabditis elegans and the target pest H. schachtii. Experiments were conducted under laboratory conditions on water agar media colonized by P. ostreatus mycelium. Seeds or root exudates of the tested plants were applied to the mycelial surface. Following incubation, nematode mobility (C. elegans) and cyst entwining by the mycelium (H. schachtii) were evaluated, along with the ability of the mycelium to produce toxocysts. The results indicate that trap plants did not significantly alter the nematocidal activity of the mycelium. However, certain mycelial strains were slightly stimulated by seed diffusates or root exudates. Oilseed radish moderately influenced the nematocidal activity of four mycelial strains against C. elegans, whereas in the case of H. schachtii, similar effects were observed with white mustard. The mycelial elimination of H. schachtii occurred through cyst entwining, which was generally more effective in the presence of plant exudates. Overall, the findings demonstrate that incorporating trap crops such as oilseed radish cv. Romesa or white mustard cv. Bardena, as green manure in crop rotation systems, does not interfere with the nematocidal activity of P. ostreatus mycelium and simultaneously may enrich the soil with nutrients. The study further confirms that P. ostreatus maintains its ability to effectively entwine and eliminate H. schachtii cysts even in the presence of sugar beet, supporting its potential role as a biological control agent. To our knowledge, this is the first experiment that integrates the activities of trap plants and sugar beet with the nematocidal effects of P. ostreatus mycelium. Full article
(This article belongs to the Section Crop Protection, Diseases, Pests and Weeds)
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24 pages, 3461 KB  
Article
Zearalenone Biotransformation by Tibetan Plateau-Derived Yeast Hannaella zeae: Biological Pattern Elucidation, Metabolite Safety, and Environmental Tolerance
by Chenxiaoye Yang, Jiali Hu, Disha Jiang, Geng Ni, Changling Wu, Qiang Chu, Sergei A. Eremin, Liliya I. Mukhametova, Xiaofang Guo, Ji De, Xingquan Liu and Hao Hu
Toxins 2026, 18(1), 2; https://doi.org/10.3390/toxins18010002 - 19 Dec 2025
Viewed by 306
Abstract
Zearalenone (ZEN) poses serious risks to human and animal health. Compared with physical and chemical methods, microbial transformation offers a safer and more sustainable strategy for ZEN detoxification. The yeast Hannaella zeae, isolated from the Qinghai–Tibet Plateau, showed the highest ZEN removal [...] Read more.
Zearalenone (ZEN) poses serious risks to human and animal health. Compared with physical and chemical methods, microbial transformation offers a safer and more sustainable strategy for ZEN detoxification. The yeast Hannaella zeae, isolated from the Qinghai–Tibet Plateau, showed the highest ZEN removal efficiency among 11 strains, achieving an 85.87% transformation rate within 36 h. Optimal conditions for ZEN transformation were determined by varying culture time, temperature, and pH. The products were putatively identified as zearalenone-14-β-D-glucopyranoside (C24H32O10) and zearalenone-16-β-D-glucopyranoside (C24H32O10) by UHPLC-Q-Orbitrap-HRMS. The safety of the mixed culture medium extract was further evaluated using a Caenorhabditis elegans model, showing significantly lower toxicity than untreated ZEN. H. zeae maintained high transformation efficiency under low temperature (57.48%) and acidic stress (47.10%), supported by active antioxidant enzymes (SOD, CAT, APX, GPx) and stress metabolites (trehalose, proline). Overall, this study identifies H. zeae as a promising, stress-tolerant biocontrol agent and elucidates its glycosylation-based detoxification mechanism, providing a foundation for future application in real food and feed systems. Full article
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26 pages, 12786 KB  
Article
Neuroprotective Effects of Mushroom Biomass Digestive Fractions and Gut Microbiota Metabolites in Microglial and Caenorhabditis elegans Models of Neurodegeneration
by Helena Araújo-Rodrigues, Lidia Garzón-García, Ana Sofia Salsinha, João Bettencourt Relvas, Freni K. Tavaria, Celestino Santos-Buelga, Ana M. González-Paramás and Manuela E. Pintado
Nutrients 2025, 17(24), 3867; https://doi.org/10.3390/nu17243867 - 11 Dec 2025
Viewed by 528
Abstract
Background: The accumulation of β-amyloid plaques, neurofibrillary tangles, and neuroinflammation are key hallmarks of Alzheimer’s disease (AD). Reactive oxygen species (ROS) act as major triggers and amplifiers of neuroinflammatory responses, contributing to immune dysregulation and neuronal damage. Despite extensive research, no effective therapy [...] Read more.
Background: The accumulation of β-amyloid plaques, neurofibrillary tangles, and neuroinflammation are key hallmarks of Alzheimer’s disease (AD). Reactive oxygen species (ROS) act as major triggers and amplifiers of neuroinflammatory responses, contributing to immune dysregulation and neuronal damage. Despite extensive research, no effective therapy halts or reverses AD progression, emphasizing the need for alternative preventive strategies, including the use of natural compounds. Objectives: This study evaluated the neuroprotective effects of simulated digestive fractions (permeate fraction) of mushroom biomass (MB)—Trametes versicolor (TV), Hericium erinaceus (HE), and Pleurotus ostreatus (PO)—and key gut microbiota-derived metabolites, such as short-chain fatty acids (SCFAs) and γ-aminobutyric acid (GABA) on ROS production in human microglial cells (HMC3) and in transgenic Caenorhabditis elegans models exhibiting hyperphosphorylated Tau and β-amyloid-induced toxicity. Methods: Cell viability and ROS production were assessed in HMC3 cells treated with mushroom fractions and metabolites. Chemotaxis and paralysis assays were performed in transgenic C. elegans strains expressing hyperphosphorylated Tau or β-amyloid proteins. Results: Mushroom digestive fractions and SCFAs significantly decreased ROS levels in HMC3 cells. Moreover, mushroom digestive fractions, butyric acid, and GABA improved behavioral outcomes in C. elegans, enhancing chemotaxis and delaying paralysis. These effects were dose-dependent and varied among mushroom species and metabolites. Conclusions: Mushroom-derived digestive fractions and microbiota-related metabolites exhibit neuroprotective activity by modulating oxidative stress and mitigating neurodegeneration-associated behaviors. Diets enriched with such MBs may support preventive strategies for neurodegenerative diseases. Further research is required to elucidate the molecular mechanisms underlying these protective effects and their translational potential for human neurodegenerative diseases. Full article
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22 pages, 14862 KB  
Article
Apiin Promotes Healthy Aging in C. elegans Through Nutritional Activation of DAF-16/FOXO, Enhancing Fatty Acid Catabolism and Oxidative Stress Resistance
by Yimin Qian, Xuebin Ding, Xinping Guo, Nan Bian, Ying Chen, Shaoyu Han, Wu Song, Lin Wei and Shuang Jiang
Int. J. Mol. Sci. 2025, 26(24), 11888; https://doi.org/10.3390/ijms262411888 - 10 Dec 2025
Viewed by 414
Abstract
Apiin, a natural flavonoid sourced from parsley, demonstrates antioxidant properties; however, its specific anti-aging effects have yet to be investigated in Caenorhabditis elegans (C. elegans). This research utilized C. elegans models to examine the anti-aging effects of apiin and the underlying [...] Read more.
Apiin, a natural flavonoid sourced from parsley, demonstrates antioxidant properties; however, its specific anti-aging effects have yet to be investigated in Caenorhabditis elegans (C. elegans). This research utilized C. elegans models to examine the anti-aging effects of apiin and the underlying mechanisms. The findings indicated that 100 μg/mL apiin extended the mean lifespan of C. elegans by 26.70%. Furthermore, apiin improved age-related characteristics in C. elegans, such as reducing intestine lipofuscin accumulation and increasing head thrashes and body bends. Additionally, apiin significantly improved stress resistance under thermal, ultraviolet, and oxidative stress conditions. Transcriptomic analysis revealed that apiin induced the differential expression of genes related to fatty acid metabolism, lipid catabolism, and oxidoreductase activity in C. elegans. Metabolomic data further corroborated the modulation of fatty acid metabolic processes by apiin. Biochemical assays, including lipid staining, triglyceride quantification, and measurements of antioxidant enzyme activity, demonstrated a decrease in lipid content and an enhancement in antioxidant capacity in C. elegans treated with apiin. Moreover, apiin promoted the nuclear translocation of DAF-16 and upregulated key longevity-associated genes, including sod-3, hsp-12.6, mtl-1, and ech-9. These results indicate that apiin mitigates aging in C. elegans through mechanisms involving the activation of DAF-16 and the regulation of lipid metabolism and oxidative stress responses. Our findings underscore the potential of apiin as a natural therapeutic agent for aging and associated metabolic disorders. Full article
(This article belongs to the Section Bioactives and Nutraceuticals)
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20 pages, 3005 KB  
Article
Biological Activities of Stachys rupestris, Development of S. rupestris Extract-Loaded Alginate Films as Wound Dressing
by Erkan Rayaman, Turgut Taşkın, Elif Çalışkan Salihi, Shalaleh Hasan Niari Niar, Duygu Taşkın, Ceyda Ekentok Atıcı, Ömer Kılıç, Pervin Rayaman, Pelin Özçelik and Hatice Kübra Elçioğlu
Pharmaceuticals 2025, 18(12), 1868; https://doi.org/10.3390/ph18121868 - 8 Dec 2025
Viewed by 487
Abstract
Background/Objectives: Regardless of the underlying cause, wound infections are among the most common complications associated with wound formation. The increasing prevalence of antibiotic resistance poses significant challenges in wound management. Due to their favorable therapeutic properties, alginate films have recently emerged as [...] Read more.
Background/Objectives: Regardless of the underlying cause, wound infections are among the most common complications associated with wound formation. The increasing prevalence of antibiotic resistance poses significant challenges in wound management. Due to their favorable therapeutic properties, alginate films have recently emerged as promising biomaterials for wound treatment. Methods: The petroleum ether, chloroform, and methanol extracts of the endemic plant Stachys rupestris were prepared using the maceration technique. The antimicrobial activity of the extracts and the extract-loaded alginate film was evaluated by agar well diffusion and microdilution assays, while their antibiofilm activity was assessed by crystal violet staining in microplates. The anti-infective potential was investigated using the Caenorhabditis elegans infection model, the phytochemical composition was analyzed by HPLC-DAD, and cytotoxicity was determined by the MTT assay. The alginate film was prepared by the solvent casting method and characterized using FTIR spectroscopy and light microscopy. Results: All extracts demonstrated antimicrobial activity, with the methanol extract exhibiting the most potent antimicrobial and antibiofilm effects. Quinic acid was identified as the major constituent. Both the methanol extract and the film displayed no cytotoxic effects and showed significant antimicrobial and antibiofilm activities. Conclusions: The S. rupestris methanol extract-loaded film exhibited strong antimicrobial and antibiofilm properties, indicating its potential as a valuable therapeutic agent in supporting wound healing. Full article
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16 pages, 308 KB  
Review
Molecular and Functional Insights into Thyrostimulin and Its Subunits-GPA2/GPB5
by Nasreen Nakad and Fuad Fares
Int. J. Mol. Sci. 2025, 26(23), 11523; https://doi.org/10.3390/ijms262311523 - 27 Nov 2025
Viewed by 394
Abstract
Thyrostimulin is a heterodimeric glycoprotein hormone composed of two subunits, GPA2 and GPB5, first identified in 2002. It is considered an ancestral member of the glycoprotein hormone family and is highly conserved across species, including vertebrates and invertebrates. Unlike classical pituitary glycoprotein hormones [...] Read more.
Thyrostimulin is a heterodimeric glycoprotein hormone composed of two subunits, GPA2 and GPB5, first identified in 2002. It is considered an ancestral member of the glycoprotein hormone family and is highly conserved across species, including vertebrates and invertebrates. Unlike classical pituitary glycoprotein hormones such as TSH, LH, and FSH, thyrostimulin appears to function predominantly through paracrine and autocrine mechanisms, with its expression reported in diverse tissues such as the pituitary, ovary, skin, and brain. In humans, thyrostimulin has been implicated in ovarian cancer cell proliferation, stem cell quiescence in the pituitary, and metabolic regulation. However, its role in metabolism remains unclear, with studies showing both beneficial and adverse effects such as weight loss in some models and elevated levels in polycystic ovary syndrome and metabolic syndrome patients. In Caenorhabditis elegans, orthologs of GPA2 and GPB5 have been shown to influence growth and intestinal function via a neuroendocrine pathway involving thyrotropin hormone-like peptides. These findings suggest that thyrostimulin has conserved multifunctional roles in development, metabolism, and endocrine signaling. The aim of this review is to summarize the structure–function relationships and the currently known roles of thyrostimulin and its subunits, GPA2/GPB5, particularly in the reproductive system, metabolic syndrome, skeletal development, and obesity. Full article
19 pages, 2943 KB  
Article
Ginseng Oligopeptides Promote Longevity and Enhance Stress Resistance in Caenorhabditis elegans via the DAF-16/FOXO Pathway
by Qian Du, Yiping Zhang, Xiaoyu Guo, Meng Cai, Yong Li and Meihong Xu
Antioxidants 2025, 14(12), 1390; https://doi.org/10.3390/antiox14121390 - 21 Nov 2025
Viewed by 1087
Abstract
Background: Ginseng oligopeptides (GOPs), small bioactive peptides with potent antioxidant capacity and high bioavailability, have shown promise in promoting healthy aging; however, their underlying molecular mechanisms remain largely unexplored. Methods: Using the model organism Caenorhabditis elegans (C. elegans), we comprehensively evaluated [...] Read more.
Background: Ginseng oligopeptides (GOPs), small bioactive peptides with potent antioxidant capacity and high bioavailability, have shown promise in promoting healthy aging; however, their underlying molecular mechanisms remain largely unexplored. Methods: Using the model organism Caenorhabditis elegans (C. elegans), we comprehensively evaluated the anti-aging effects of GOPs on lifespan, locomotion, oxidative stress, and gene expression. Integrated phenotypic assays and transcriptomic analyses were conducted to elucidate GOP-mediated molecular mechanisms. The transgenic strain TJ356 (DAF-16::GFP) and the loss-of-function mutant CF1038 [daf-16(mu86)] were employed to functionally validate the role of the DAF-16/FOXO pathway. Results: GOP supplementation significantly extended median lifespan by approximately 11.5% and improved age-related locomotion decline in C. elegans. Transcriptomic profiling identified 1928 differentially expressed genes (DEGs) enriched in metabolic, antioxidant defense, and longevity-regulating pathways. GOPs upregulated key antioxidant and stress-response genes (gst-4, sod-5, mtl-1) and longevity-related regulators (daf-16, lin-31, Y51B9A.9, and daf-12), while downregulating ins-7, an insulin-like peptide. Moreover, GOPs enhanced cytochrome P450–related detoxification and vitamin-dependent (retinol, ascorbate, and riboflavin) metabolic pathways, establishing a multidimensional antioxidant defense network. Phenotypic validation confirmed that GOPs markedly reduced reactive oxygen species (ROS) levels and lipofuscin accumulation (p < 0.001). Notably, GOPs promoted DAF-16 nuclear translocation in TJ356 worms, whereas the lifespan-extending effects were abolished in CF1038 mutants, highlighting the essential role of DAF-16/FOXO in mediating GOP effects. Conclusions: GOPs delay aging in C. elegans by activating the DAF-16/FOXO signaling cascade and reinforcing antioxidant networks, thereby maintaining redox and metabolic homeostasis. These findings provide novel mechanistic evidence supporting GOPs as promising dietary antioxidants for promoting healthy aging through modulation of conserved redox and longevity pathways. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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18 pages, 1485 KB  
Article
Probiotic Modulation in Aging: Strain-Specific Geroprotective Effects in Caenorhabditis elegans
by Barbara Sciandrone, Diletta Francesca Squarzanti, Patrizia Malfa and Maria Elena Regonesi
Int. J. Mol. Sci. 2025, 26(22), 11205; https://doi.org/10.3390/ijms262211205 - 20 Nov 2025
Viewed by 895
Abstract
Elderly individuals are more vulnerable to disease due to their increased frailty. Emerging evidence highlights the potential of probiotics as geroprotective agents by maintaining gut health and modulating key physiological processes involved in aging, such as inflammation, cognitive functions, and metabolism. Here, we [...] Read more.
Elderly individuals are more vulnerable to disease due to their increased frailty. Emerging evidence highlights the potential of probiotics as geroprotective agents by maintaining gut health and modulating key physiological processes involved in aging, such as inflammation, cognitive functions, and metabolism. Here, we investigated the geroprotective potential of four probiotic strains (Lacticaseibacillus paracasei LPC1114, Limosilactobacillus reuteri PBS072, Bifidobacterium breve BB077, and Bifidobacterium animalis subsp. lactis BL050) using Caenorhabditis elegans as an aging model. Mid-life healthspan parameters were assessed, including lifespan, motility, ROS levels, lipofuscin accumulation, and cognitive capabilities. The probiotics exhibited strain-specific effects. L. reuteri PBS072 and B. lactis BL050 significantly increased locomotion by 20% and decreased ROS levels by 70% and 30% respectively, suggesting enhanced oxidative stress response and neuromuscular maintenance. B. breve BB077, L. paracasei LPC1114, and L. reuteri PBS072 enhanced associative learning performance, whereas B. lactis BL050 improved chemotactic response. Notably, only L. paracasei LPC1114 and L. reuteri PBS072 extended the maximum lifespan by 4 and 5 days, respectively, an effect mediated by the longevity-related genes skn1, sir2.1, and daf16. Our findings highlight the multifaceted, strain-specific geroprotective properties of probiotics and support their potential as microbiome-based interventions to promote healthy aging. Full article
(This article belongs to the Special Issue Molecular Studies in Aging, 2nd Edition)
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19 pages, 7639 KB  
Article
Ethyl Acetate Extract of Cynanchi Auriculati Radix Inhibits LPS-Induced M1 Polarization of RAW264.7 Macrophages and Prolongs the Lifespan of Caenorhabditis elegans by Regulating NF-κB and PMK-1/SKN-1 Signaling Pathways
by Jiawei Fan, Ya Su, Yi Xing, Kun Hu, Jie Ren and Jia Yang
Curr. Issues Mol. Biol. 2025, 47(11), 934; https://doi.org/10.3390/cimb47110934 - 10 Nov 2025
Viewed by 616
Abstract
Extracts of Cynanchi Auriculati Radix (RCA), derived from the roots of Cynanchum auriculatum Royle ex Wight. (CA), have been documented to possess anti-inflammatory and antioxidant properties. However, the molecular mechanisms of their anti-aging action remain unclear. The present study aimed to explore the [...] Read more.
Extracts of Cynanchi Auriculati Radix (RCA), derived from the roots of Cynanchum auriculatum Royle ex Wight. (CA), have been documented to possess anti-inflammatory and antioxidant properties. However, the molecular mechanisms of their anti-aging action remain unclear. The present study aimed to explore the potential anti-aging components and mechanisms of RCA. LC-MS/MS and network pharmacology were used to identify components and targets. In vitro, LPS-induced RAW264.7 macrophages were used to assess anti-inflammatory effects. In vivo, Caenorhabditis elegans models were employed to evaluate lifespan and stress resistance. Five bioactive components were identified. The ethyl acetate extract of RCA (RCAEA) inhibited LPS-induced M1 macrophage polarization by suppressing the expression of NO, PGE2, IL-1β, iNOS, COX-2, TNF-α, and IL-6 via the NF-κB pathway. In C. elegans, RCAEA extended lifespan and enhanced oxidative and heat stress resistance, without affecting reproduction. These benefits were mediated by the PMK-1/SKN-1 pathway, as confirmed using mutant strains. RCAEA is a promising anti-aging and anti-inflammatory agent, acting through NF-κB and PMK-1/SKN-1 signaling pathways. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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23 pages, 707 KB  
Review
Beyond Rodents: Alternative Animal Models in Colorectal Cancer Research
by Wei Xiong, Solène Favier, Ting Wu, Frédérique Ponce, Charles Dumontet, Marie Alexandra Albaret, Frédéric Hollande, Jean-Jacques Diaz and Hichem C. Mertani
Int. J. Mol. Sci. 2025, 26(22), 10874; https://doi.org/10.3390/ijms262210874 - 9 Nov 2025
Viewed by 907
Abstract
Colorectal cancer (CRC) is the third most common cancer worldwide, imposing a significant burden on public health. Despite the use of various therapeutic strategies, the prognosis for patients with metastatic and drug-resistant CRC remains poor, which underscores the need for further investigations into [...] Read more.
Colorectal cancer (CRC) is the third most common cancer worldwide, imposing a significant burden on public health. Despite the use of various therapeutic strategies, the prognosis for patients with metastatic and drug-resistant CRC remains poor, which underscores the need for further investigations into cancer mechanisms to develop more effective treatments. Rodents, particularly mice, are the most frequently used animal models for CRC research. However, as the demand for more precise simulations and higher ethical standards in animal experimentation grows, the applicability of rodent models may face increasing limitations. This review highlights a variety of non-rodent animals, including model organisms such as zebrafish (Danio rerio), fruit flies (Drosophila melanogaster), and Caenorhabditis elegans (C. elegans), as well as the chorioallantoic membrane (CAM) model and mammals such as rabbits (Oryctolagus cuniculus), dogs (Canis lupus familiaris), and pigs (Sus scrofa domesticus), which have been utilized in CRC research. Each of these alternatives offers specific advantages in certain areas of cancer research. Their use has enabled new insights into the mechanisms of carcinogenesis, metastasis, and drug resistance in CRC, as well as the development of novel therapies. Full article
(This article belongs to the Special Issue Cancer Models: Development and Applications)
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18 pages, 3250 KB  
Article
Safety and Potential Neuromodulatory Effects of Multi-Wall Carbon Nanotubes in Vertebrate and Invertebrate Animal Models In Vivo
by Valentina Latina, Marzia Soligo, Tatiana Da Ros, Emily Schifano, Marco Guarnieri, Arianna Montanari, Giuseppina Amadoro and Silvana Fiorito
Int. J. Mol. Sci. 2025, 26(22), 10844; https://doi.org/10.3390/ijms262210844 - 8 Nov 2025
Viewed by 535
Abstract
Multi-Wall Carbon Nanotubes (MWCNTs) are under investigation for their use in biomedical applications, especially in neurological diseases, due to their electrochemical properties. Nevertheless, conflicting results have cast doubt on their safety. To advance their translational potential, we evaluated the cytotoxicity of two MWCNT [...] Read more.
Multi-Wall Carbon Nanotubes (MWCNTs) are under investigation for their use in biomedical applications, especially in neurological diseases, due to their electrochemical properties. Nevertheless, conflicting results have cast doubt on their safety. To advance their translational potential, we evaluated the cytotoxicity of two MWCNT samples in vivo in both vertebrate and invertebrate animal models. Pristine MWCNTs were, in part, used as prepared (MWCNTs), and, in part, annealed at 2400 °C (a-MWCNTs). The two samples differ in their electrochemical properties: MWCNTs are not electro-conductive, while a-MWCNTs are electro-conductive and negatively charged on their surface. We evaluated the effects of both intranasally delivered MWCNTs on several key markers of cell viability in the olfactory bulbs and hippocampus from healthy adult Wistar rats, as well as their impact on lifespan, genotoxicity, oxidative stress, and aging-related functional markers in the nematode Caenorhabditis elegans. Neither of the two MWCNT samples was cytotoxic towards neuronal cells in the hippocampus. In olfactory bulbs, only electro-conductive a-MWCNTs interacted with two positively charged mitochondrial proteins: Translocase of Outer Mitochondrial Membrane 20 (TOM20) and Cytochrome C (CytC). In C. elegans, neither type of MWCNT affected lifespan or brood size, and cytosolic ROS levels remained unchanged. Notably, treated worms exhibited a significantly delayed aging phenotype. Metallic MWCNTs are biocompatible in living organisms and possess the potential to modulate neural cells functioning in vivo. Full article
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34 pages, 3699 KB  
Article
Tea-Residue-Derived Klebsiella pneumoniae CGMCC 31459: Genomic Insights and Antioxidant Activity of Its Exopolysaccharides
by Yuanyuan Wang, Shengbo Shi, Mingchun Lin, Gangrui Zhang, Longyu Fang, Jinghua Li, Rui Geng, Yuanxue Zheng and Lujiang Hao
Biomolecules 2025, 15(11), 1569; https://doi.org/10.3390/biom15111569 - 7 Nov 2025
Viewed by 658
Abstract
Exopolysaccharides (EPSs) are important extracellular metabolites secreted by microorganisms. Klebsiella pneumoniae is an opportunistic pathogen widely distributed in the environment, host mucosal and intestinal surfaces, and EPS from Klebsiella pneumoniae are of significant interest. Conventional studies have mainly focused on hypervirulent strains, whereas [...] Read more.
Exopolysaccharides (EPSs) are important extracellular metabolites secreted by microorganisms. Klebsiella pneumoniae is an opportunistic pathogen widely distributed in the environment, host mucosal and intestinal surfaces, and EPS from Klebsiella pneumoniae are of significant interest. Conventional studies have mainly focused on hypervirulent strains, whereas comprehensive investigations of non-hypervirulent strains and their EPS functionalities remain limited. This study employed ST678-type Klebsiella pneumoniae CGMCC 31459 as the model to investigate genomic characteristics, EPS structural features, and biological activities. Its genome comprises one chromosome and four plasmids, functionally enriched in carbohydrate metabolism genes, including abundant glycoside hydrolases and glycosyltransferases essential for EPS biosynthesis. Virulence and antimicrobial resistance assessments confirmed the absence of typical hypervirulence loci, indicating genetic stability with low pathogenic and resistance potential. EPS-KP is a weakly acidic, branched heteropolysaccharide composed of glucose, galactose, mannose, and glucuronic acid. EPS-KP exhibited significant antioxidant and anti-aging activities, with a 77.47% (5 mg/mL) superoxide anion scavenging rate and a 30.9% (200 μg/mL) lifespan extension in Caenorhabditis elegans, accompanied by enhanced SOD/CAT enzyme activity and reduced lipofuscin accumulation. This integrated genomic and biochemical analysis provides new insights into the safe, non-hypervirulent Klebsiella pneumoniae strain and its functional EPS, highlighting its potential for biotechnological applications. Full article
(This article belongs to the Section Biomacromolecules: Proteins, Nucleic Acids and Carbohydrates)
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Article
The Controllability of Caenorhabditis elegans Neural Network from Larva to Adult
by Jian Liu, Peng Zhao, Gang Wang, Tao Fang and Ye Yuan
Biomimetics 2025, 10(11), 744; https://doi.org/10.3390/biomimetics10110744 - 5 Nov 2025
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Abstract
Biological neural networks undergo dynamic structural and functional changes during development, yet how their controllability evolves across different life stages remains largely unexplored. Here, we investigate the neural network of Caenorhabditis elegans (C. elegans), a fully mapped model organism, to examine [...] Read more.
Biological neural networks undergo dynamic structural and functional changes during development, yet how their controllability evolves across different life stages remains largely unexplored. Here, we investigate the neural network of Caenorhabditis elegans (C. elegans), a fully mapped model organism, to examine changes in network controllability from larval stages to adulthood. Using structural controllability and target control frameworks, we show that while global neural controllability progressively increases with developmental complexity, muscle-target controllability declines after early larval stages, indicating a functional shift in control priorities. Furthermore, a comparative analysis between hermaphroditic and male adults reveals that overall controllability remains similar despite substantial differences in neural architecture, with hermaphrodites exhibiting slightly higher efficiency. These findings highlight fundamental principles of how neural circuits reorganize during maturation and suggest that controllability analysis can provide valuable insights into neural function, sex-specific behaviors, and potential applications in modeling developmental and degenerative disorders. Full article
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