{"title":"Rosmarinic Acid Attenuates <i>Salmonella enteritidis</i>-Induced Inflammation via Regulating TLR9/NF-κB Signaling Pathway and Intestinal Microbiota.","authors":"Dandan Yi, Menghui Wang, Xia Liu, Lanqian Qin, Yu Liu, Linyi Zhao, Ying Peng, Zhengmin Liang, Jiakang He","doi":"10.3390/antiox13101265","DOIUrl":"10.3390/antiox13101265","url":null,"abstract":"<p><p><i>Salmonella enteritidis</i> (<i>SE</i>) infection disrupts the homeostasis of the intestinal microbiota, causing an intestinal inflammatory response and posing a great threat to human and animal health. The unreasonable use of antibiotics has led to an increase in the prevalence of drug-resistant <i>SE</i>, increasing the difficulty of controlling <i>SE</i>. Therefore, new drug strategies and research are urgently needed to control <i>SE</i>. Rosmarinic acid (RA) is a natural phenolic acid with various pharmacological activities, including antioxidant, anti-inflammatory and antibacterial properties. However, the protective effects and mechanism of RA on intestinal inflammation and the gut microbial disorders caused by <i>SE</i> have not been fully elucidated. In this study, RAW264.7 cells, MCECs and BALB/c mice were challenged with <i>SE</i> to assess the protective effects and mechanisms of RA. The results showed that RA enhanced the phagocytic ability of RAW264.7 cells, reduced the invasion and adhesion ability of <i>SE</i> in MCECs, and inhibited <i>SE</i>-induced inflammation in cells. Moreover, RA inhibited the activation of the NF-κB signaling pathway by upregulating TLR9 expression. Importantly, we found that RA provided protection against <i>SE</i> and increased the diversity and abundance of the intestinal microbiota in mice. Compared with infection control, RA significantly increased the abundance of <i>Firmicutes</i> and <i>Acidibacteria</i> and decreased the abundance of <i>Proteobacteria</i>, <i>Epsilonbacteraeota</i> and <i>Bacteroidota</i>. However, RA failed to alleviate <i>SE</i>-induced inflammation and lost its regulatory effects on the TLR9/NF-κB signaling pathway after destroying the gut microbiota with broad-spectrum antibiotics. These results indicated that RA attenuated <i>SE</i>-induced inflammation by regulating the TLR9/NF-κB signaling pathway and maintaining the homeostasis of the gut microbiota. Our study provides a new strategy for preventing <i>SE</i>-induced intestinal inflammation.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"13 10","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Microplastic-Enhanced Cadmium Toxicity: A Growing Threat to the Sea Grape, <i>Caulerpa lentillifera</i>.","authors":"Weilong Zhou, Haolong Zheng, Yingyin Wu, Junyi Lin, Xiaofei Ma, Yixuan Xing, Huilong Ou, Hebert Ely Vasquez, Xing Zheng, Feng Yu, Zhifeng Gu","doi":"10.3390/antiox13101268","DOIUrl":"10.3390/antiox13101268","url":null,"abstract":"<p><p>The escalating impact of human activities has led to the accumulation of microplastics (MPs) and heavy metals in marine environments, posing serious threats to marine ecosystems. As essential components of oceanic ecosystems, large seaweeds such as <i>Caulerpa lentillifera</i> play a crucial role in maintaining ecological balance. This study investigated the effects of MPs and cadmium (Cd) on the growth, physiology, biochemistry, and Cd accumulation in <i>C. lentillifera</i> while elucidating the underlying molecular regulatory mechanisms. The results demonstrated that exposure to MPs alone significantly promoted the growth. In contrast, exposure to Cd either alone or in combination with MPs significantly suppressed growth by reducing stem and stolon length, bud count, weight gain, and specific growth rates. Combined exposure to MPs and Cd exhibited the most pronounced inhibitory effect on growth. MPs had negligible impact while Cd exposure either alone or combined with MPs impaired antioxidant defenses and exacerbated oxidative damage; with combined exposure being the most detrimental. Analysis of Cd content revealed that MPs significantly increased Cd accumulation in algae intensifying its toxic effects. Gene expression analysis revealed that Cd exposure down-regulated key genes involved in photosynthesis, impairing both photosynthetic efficiency and energy conversion. The combined exposure of MPs and Cd further exacerbated these effects. In contrast, MPs alone activated the ribosome pathway, supporting ribosomal stability and protein synthesis. Additionally, both Cd exposure alone or in combination with MPs significantly reduced chlorophyll B and soluble sugar content, negatively impacting photosynthesis and nutrient accumulation. In summary, low concentrations of MPs promoted <i>C. lentillifera</i> growth, but the presence of Cd hindered it by disrupting photosynthesis and antioxidant mechanisms. Furthermore, the coexistence of MPs intensified the toxic effects of Cd. These findings enhance our understanding of how both MPs and Cd impact large seaweed ecosystems and provide crucial insights for assessing their ecological risks.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"13 10","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Radical Scavenging Capacity and In Vitro Cytoprotective Effects of Great Salt Lake-Derived Processed Mineral Water.","authors":"Takayuki Mokudai, Seiko Nakagawa, Hiroyasu Kanetaka, Kazuo Oda, Hiroya Abe, Yoshimi Niwano","doi":"10.3390/antiox13101266","DOIUrl":"10.3390/antiox13101266","url":null,"abstract":"<p><p>The Great Salt Lake, located in Utah, USA, is a saltwater lake with no outlet and is surrounded by vast mountains and salt deserts. We aimed to use Great Salt Lake-derived processed mineral water (hereafter termed as GSL-MW) for maintaining oral health. Therefore, we examined its radical scavenging activity as an antioxidant and its cytoprotective effect on human gingival fibroblasts (hGFs). The scavenging activity against O<sub>2</sub><sup>•-</sup> radicals was determined by an electron spin resonance (ESR)-spin trapping technique using two kinds of O<sub>2</sub><sup>•-</sup> generation systems; however, we could not reach any concrete conclusion because of the interference caused by GSL-MW in both systems. Detection of ·OH radicals using the ESR-spin trapping technique and kinetic analyses using double-reciprocal plots (corresponding to Lineweaver-Burk plots that are used to represent enzyme kinetics) revealed that GSL-MW has the ability to scavenge ·OH radicals. GSL-MW also showed a weak 2,2-diphenyl-1-picrylhydrazyl (DPPH; a stable radical)-scavenging activity. Regarding the cytoprotective effects, subconfluent hGFs pretreated with 10× and 100× dilutions of GSL-MW for 3 min and then exposed to harsh environmental conditions, such as pure water or 100 μM H<sub>2</sub>O<sub>2</sub> for 3 min, showed enhanced cell viability rate. Moreover, 10× and 100× dilutions of GSL-MW reduced oxidative damage in confluent hGFs exposed to 12.5 and 25 mM H<sub>2</sub>O<sub>2</sub>. Our findings show that GSL-MW has antioxidant potential and cytoprotective effects on hGFs, suggesting that GSL-MW can be used to maintain oral health.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"13 10","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AntioxidantsPub Date : 2024-10-17DOI: 10.3390/antiox13101260
Roberto Carnevale, Cristina Nocella, Raffaella Marocco, Paola Zuccalà, Anna Carraro, Vittorio Picchio, Alessandra Oliva, Roberto Cangemi, Maria Claudia Miele, Massimiliano De Angelis, Francesca Cancelli, Giovanni Enrico Casciaro, Luca Cristiano, Pasquale Pignatelli, Giacomo Frati, Mario Venditti, Francesco Pugliese, Claudio Maria Mastroianni, Francesco Violi, Lorenzo Ridola, Cosmo Del Borgo, Silvia Palmerio, Emiliano Valenzi, Rita Carnevale, Domenico Alvaro, Miriam Lichtner, Vincenzo Cardinale
{"title":"Association Between NOX2-Mediated Oxidative Stress, Low-Grade Endotoxemia, Hypoalbuminemia, and Clotting Activation in COVID-19.","authors":"Roberto Carnevale, Cristina Nocella, Raffaella Marocco, Paola Zuccalà, Anna Carraro, Vittorio Picchio, Alessandra Oliva, Roberto Cangemi, Maria Claudia Miele, Massimiliano De Angelis, Francesca Cancelli, Giovanni Enrico Casciaro, Luca Cristiano, Pasquale Pignatelli, Giacomo Frati, Mario Venditti, Francesco Pugliese, Claudio Maria Mastroianni, Francesco Violi, Lorenzo Ridola, Cosmo Del Borgo, Silvia Palmerio, Emiliano Valenzi, Rita Carnevale, Domenico Alvaro, Miriam Lichtner, Vincenzo Cardinale","doi":"10.3390/antiox13101260","DOIUrl":"10.3390/antiox13101260","url":null,"abstract":"<p><p>Low-grade endotoxemia by lipopolysaccharide (LPS) has been detected in COVID-19 and could favor thrombosis via eliciting a pro-inflammatory and pro-coagulant state. The aim of this study was to analyze the mechanism accounting for low-grade endotoxemia and its relationship with oxidative stress and clotting activation thrombosis in COVID-19. We measured serum levels of sNOX2-dp, zonulin, LPS, D-dimer, and albumin in 175 patients with COVID-19, classified as having or not acute respiratory distress syndrome (ARDS), and 50 healthy subjects. Baseline levels of sNOX2-dp, LPS, zonulin, D-dimer, albumin, and hs-CRP were significantly higher in COVID-19 compared to controls. In COVID-19 patients with ARDS, sNOX2-dp, LPS, zonulin, D-dimer, and hs-CRP were significantly higher compared to COVID-19 patients without ARDS. Conversely, concentration of albumin was lower in patients with ARDS compared with those without ARDS and inversely associated with LPS. In the COVID-19 cohort, the number of patients with ARDS progressively increased according to sNOX2-dp and LPS quartiles; a significant correlation between LPS and sNOX2-dp and LPS and D-dimer was detected in COVID-19. In a multivariable logistic regression model, LPS/albumin levels and D-dimer predicted thrombotic events. In COVID-19 patients, LPS is significantly associated with a hypercoagulation state and disease severity. In vitro, LPS can increase endothelial oxidative stress and coagulation biomarkers that were reduced by the treatment with albumin. In conclusion, impaired gut barrier permeability, increased NOX2 activation, and low serum albumin may account for low-grade endotoxemia and may be implicated in thrombotic events in COVID-19.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"13 10","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AntioxidantsPub Date : 2024-10-17DOI: 10.3390/antiox13101252
Seunghwan Choi, Soo-Ho Choi, Tonking Bastola, Keun-Young Kim, Sungsik Park, Robert N Weinreb, Yury I Miller, Won-Kyu Ju
{"title":"AIBP Protects Müller Glial Cells Against Oxidative Stress-Induced Mitochondrial Dysfunction and Reduces Retinal Neuroinflammation.","authors":"Seunghwan Choi, Soo-Ho Choi, Tonking Bastola, Keun-Young Kim, Sungsik Park, Robert N Weinreb, Yury I Miller, Won-Kyu Ju","doi":"10.3390/antiox13101252","DOIUrl":"10.3390/antiox13101252","url":null,"abstract":"<p><p>Glaucoma, an optic neuropathy with the loss of retinal ganglion cells (RGCs), is a leading cause of irreversible vision loss. Oxidative stress and mitochondrial dysfunction have a significant role in triggering glia-driven neuroinflammation and subsequent glaucomatous RGC degeneration in the context of glaucoma. It has previously been shown that apolipoprotein A-I binding protein (APOA1BP or AIBP) has an anti-inflammatory function. Moreover, <i>Apoa1bp<sup>-/-</sup></i> mice are characterized by retinal neuroinflammation and RGC loss. In this study, we found that AIBP deficiency exacerbated the oxidative stress-induced disruption of mitochondrial dynamics and function in the retina, leading to a further decline in visual function. Mechanistically, AIBP deficiency-induced oxidative stress triggered a reduction in glycogen synthase kinase 3β and dynamin-related protein 1 phosphorylation, optic atrophy type 1 and mitofusin 1 and 2 expression, and oxidative phosphorylation, as well as the activation of mitogen-activated protein kinase (MAPK) in Müller glia dysfunction, leading to cell death and inflammatory responses. In vivo, the administration of recombinant AIBP (rAIBP) effectively protected the structural and functional integrity of retinal mitochondria under oxidative stress conditions and prevented vision loss. In vitro, incubation with rAIBP safeguarded the structural integrity and bioenergetic performance of mitochondria and concurrently suppressed MAPK activation, apoptotic cell death, and inflammatory response in Müller glia. These findings support the possibility that AIBP promotes RGC survival and restores visual function in glaucomatous mice by ameliorating glia-driven mitochondrial dysfunction and neuroinflammation.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"13 10","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AntioxidantsPub Date : 2024-10-17DOI: 10.3390/antiox13101253
Hammad Qamar, Rong He, Yuanfei Li, Min Song, Dun Deng, Yiyan Cui, Miao Yu, Xianyong Ma
{"title":"Metabolome and Metagenome Integration Unveiled Synthesis Pathways of Novel Antioxidant Peptides in Fermented Lignocellulosic Biomass of Palm Kernel Meal.","authors":"Hammad Qamar, Rong He, Yuanfei Li, Min Song, Dun Deng, Yiyan Cui, Miao Yu, Xianyong Ma","doi":"10.3390/antiox13101253","DOIUrl":"10.3390/antiox13101253","url":null,"abstract":"<p><p>Approximately one-third of the entire world's food resources are deemed to be wasted. Palm kernel meal (PKM), a product that is extensively generated by the palm oil industry, exhibits a unique nutrient-rich composition. However, its recycling is seldom prioritized due to numerous factors. To evaluate the impact of enzymatic pretreatment and <i>Lactobacillus plantarum</i> and <i>Lactobacillus reuteri</i> fermentation upon the antioxidant activity of PKM, we implemented integrated metagenomics and metabolomics approaches. The substantially enhanced (<i>p</i> < 0.05) property of free radicals scavenging, as well as total flavonoids and polyphenols, demonstrated that the biotreated PKM exhibited superior antioxidant capacity. Non-targeted metabolomics disclosed that the <i>Lactobacillus</i> fermentation resulted in substantial (<i>p</i> < 0.05) biosynthesis of 25 unique antioxidant biopeptides, along with the increased (<i>p</i> < 0.05) enrichment ratio of the isoflavonoids and secondary metabolites biosynthesis pathways. The 16sRNA sequencing and correlation analysis revealed that <i>Limosilactobacillus reuteri</i>, <i>Pediococcus acidilactici</i>, <i>Lacticaseibacillus paracasei</i>, <i>Pediococcus pentosaceus</i>, <i>Lactiplantibacillus plantarum</i>, <i>Limosilactobacillus fermentum</i>, and polysaccharide lyases had significantly dominated (<i>p</i> < 0.05) proportions in PMEL, and these bacterial species were strongly (<i>p</i> < 0.05) positively interrelated with antioxidants peptides. Fermented PKM improves nutritional value by enhancing beneficial probiotics, enzymes, and antioxidants and minimizing anti-nutritional factors, rendering it an invaluable feed ingredient and gut health promoter for animals, multifunctional food elements, or as an ingredient in sustainable plant-based diets for human utilization, and functioning as a culture substrate in the food sector.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"13 10","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Recovery of Selenium-Enriched Polysaccharides from <i>Cardamine violifolia</i> Residues: Comparison on Structure and Antioxidant Activity by Different Extraction Methods.","authors":"Yong Liang, Jiali Yu, Lulu Wu, Xin Cong, Haiyuan Liu, Xu Chen, Shuyi Li, Zhenzhou Zhu","doi":"10.3390/antiox13101251","DOIUrl":"10.3390/antiox13101251","url":null,"abstract":"<p><p>The residues from selenium-enriched <i>Cardamine violifolia</i> after the extraction of protein were still rich in polysaccharides. Thus, the recovery of selenium polysaccharides (SePSs) was compared using hot water extraction and ultrasonic-assisted extraction techniques. The yield, extraction rate, purity, specific energy consumption, and content of total and organic selenium from different SePS extracts were determined. The results indicated that at conditions of 250 W (ultrasonic power), 30 °C, and a liquid-to-material ratio of 30:1 extracted for 60 min, the yield of SePSs was 3.97 ± 0.07%, the extraction rate was 22.76 ± 0.40%, and the purity was 65.56 ± 0.35%, while the total and organic selenium content was 749.16 ± 6.91 mg/kg and 628.37 ± 5.93 mg/kg, respectively. Compared to traditional hot water extraction, ultrasonic-assisted extraction significantly improves efficiency, reduces energy use, and boosts both total and organic selenium content in the extract. Measurements of particle size, molecular weight, and monosaccharide composition, along with infrared and ultraviolet spectroscopy, revealed that ultrasonic-assisted extraction breaks down long-chain structures, decreases particle size, and changes monosaccharide composition in SePSs, leading to lower molecular weight and reduced dispersity. The unique structure of SePSs, which integrates selenium with polysaccharide groups, results in markedly improved antioxidant activity and reducing power, even at low concentrations, due to the synergistic effects of selenium and polysaccharides. This study establishes a basis for using SePSs in functional foods.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"13 10","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AntioxidantsPub Date : 2024-10-17DOI: 10.3390/antiox13101257
Federica De Cecco, Sara Franceschelli, Valeria Panella, Maria Anna Maggi, Silvia Bisti, Arturo Bravo Nuevo, Damiano D'Ardes, Francesco Cipollone, Lorenza Speranza
{"title":"Biological Response of Treatment with Saffron Petal Extract on Cytokine-Induced Oxidative Stress and Inflammation in the Caco-2/Human Leukemia Monocytic Co-Culture Model.","authors":"Federica De Cecco, Sara Franceschelli, Valeria Panella, Maria Anna Maggi, Silvia Bisti, Arturo Bravo Nuevo, Damiano D'Ardes, Francesco Cipollone, Lorenza Speranza","doi":"10.3390/antiox13101257","DOIUrl":"10.3390/antiox13101257","url":null,"abstract":"<p><p>The pathogenesis of Inflammatory Bowel Disease (IBD) involves complex mechanisms, including immune dysregulation, gut microbiota imbalances, oxidative stress, and defects in the gastrointestinal mucosal barrier. Current treatments for IBD often have significant limitations and adverse side effects, prompting a search for alternative therapeutic strategies. Natural products with anti-inflammatory and antioxidant properties have demonstrated potential for IBD management. There is increasing interest in exploring food industry waste as a source of bioactive molecules with healthcare applications. In this study, a co-culture system of Caco-2 cells and PMA-differentiated THP-1 macrophages was used to simulate the human intestinal microenvironment. Inflammation was induced using TNF-α and IFN-γ, followed by treatment with Saffron Petal Extract (SPE). The results demonstrated that SPE significantly attenuated oxidative stress and inflammation by downregulating the expression of pro-inflammatory mediators such as iNOS, COX-2, IL-1β, and IL-6 via modulation of the NF-κB pathway. Given that NF-κB is a key regulator of macrophage-driven inflammation, our findings support further investigation of SPE as a potential complementary therapeutic agent for IBD treatment.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"13 10","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"α-Terpineol Induces Shelterin Components TRF1 and TRF2 to Mitigate Senescence and Telomere Integrity Loss via A Telomerase-Independent Pathway.","authors":"Marianna Kapetanou, Sophia Athanasopoulou, Andreas Goutas, Dimitra Makatsori, Varvara Trachana, Efstathios Gonos","doi":"10.3390/antiox13101258","DOIUrl":"10.3390/antiox13101258","url":null,"abstract":"<p><p>Cellular senescence is a hallmark of aging characterized by irreversible growth arrest and functional decline. Progressive telomeric DNA shortening in dividing somatic cells, programmed during development, leads to critically short telomeres that trigger replicative senescence and thereby contribute to aging. Therefore, protecting telomeres from DNA damage is essential in order to avoid entry into senescence and organismal aging. In several organisms, including mammals, telomeres are protected by a protein complex named shelterin that prevents DNA damage at the chromosome ends through the specific function of its subunits. Here, we reveal that the nuclear protein levels of shelterin components TRF1 and TRF2 decline in fibroblasts reaching senescence. Notably, we identify α-terpineol as an activator that effectively enhances TRF1 and TRF2 levels in a telomerase-independent manner, counteracting the senescence-associated decline in these crucial proteins. Moreover, α-terpineol ameliorates the cells' response to oxidative DNA damage, particularly at the telomeric regions, thus preserving telomere length and delaying senescence. More importantly, our findings reveal the significance of the PI3K/AKT pathway in the regulation of shelterin components responsible for preserving telomere integrity. In conclusion, this study deepens our understanding of the molecular pathways involved in senescence-associated telomere dysfunction and highlights the potential of shelterin components to serve as targets of therapeutic interventions, aimed at promoting healthy aging and combating age-related diseases.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"13 10","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AntioxidantsPub Date : 2024-10-17DOI: 10.3390/antiox13101250
Chak-Kwong Cheng, Lianwei Ye, Yuanyuan Zuo, Yaling Wang, Li Wang, Fuyong Li, Sheng Chen, Yu Huang
{"title":"Aged Gut Microbiome Induces Metabolic Impairment and Hallmarks of Vascular and Intestinal Aging in Young Mice.","authors":"Chak-Kwong Cheng, Lianwei Ye, Yuanyuan Zuo, Yaling Wang, Li Wang, Fuyong Li, Sheng Chen, Yu Huang","doi":"10.3390/antiox13101250","DOIUrl":"10.3390/antiox13101250","url":null,"abstract":"<p><p>Aging, an independent risk factor for cardiometabolic diseases, refers to a progressive deterioration in physiological function, characterized by 12 established hallmarks. Vascular aging is driven by endothelial dysfunction, telomere dysfunction, oxidative stress, and vascular inflammation. This study investigated whether aged gut microbiome promotes vascular aging and metabolic impairment. Fecal microbiome transfer (FMT) was conducted from aged (>75 weeks old) to young C57BL/6 mice (8 weeks old) for 6 weeks. Wire myography was used to evaluate endothelial function in aortas and mesenteric arteries. ROS levels were measured by dihydroethidium (DHE) staining and lucigenin-enhanced chemiluminescence. Vascular and intestinal telomere function, in terms of relative telomere length, telomerase reverse transcriptase expression and telomerase activity, were measured. Systemic inflammation, endotoxemia and intestinal integrity of mice were assessed. Gut microbiome profiles were studied by 16S rRNA sequencing. Some middle-aged mice (40-42 weeks old) were subjected to chronic metformin treatment and exercise training for 4 weeks to evaluate their anti-aging benefits. Six-week FMT impaired glucose homeostasis and caused vascular dysfunction in aortas and mesenteric arteries in young mice. FMT triggered vascular inflammation and oxidative stress, along with declined telomerase activity and shorter telomere length in aortas. Additionally, FMT impaired intestinal integrity, and triggered AMPK inactivation and telomere dysfunction in intestines, potentially attributed to the altered gut microbial profiles. Metformin treatment and moderate exercise improved integrity, AMPK activation and telomere function in mouse intestines. Our data highlight aged microbiome as a mechanism that accelerates intestinal and vascular aging, suggesting the gut-vascular connection as a potential intervention target against cardiovascular aging and complications.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"13 10","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}