Archives of biochemistry and biophysics最新文献

{"title":"Blueberry-derived exosome like nanovesicles carry RNA cargo into HIEC-6 cells and down-regulate LPS-induced inflammatory gene expression: A proof-of-concept study","authors":"Sharon Natasha Cox ,&nbsp;Vito Porcelli ,&nbsp;Simona Romano ,&nbsp;Luigi Palmieri ,&nbsp;Deborah Fratantonio","doi":"10.1016/j.abb.2024.110266","DOIUrl":"10.1016/j.abb.2024.110266","url":null,"abstract":"<div><div>Exosome-like nanovesicles (ELNs) of food origin have received great attention in the last decade, due to the hypothesis that they contain bioactive molecules. ELNs purified from edible species have been shown to be protective and are able to regulate intestinal homeostasis. Despite ELNs being potential rising stars in modern healthy diets and biomedical applications, further research is needed to address underlying knowledge gaps, especially related to the specific molecular mechanism through which they exert their action. Here, we investigate the cellular uptake of blueberry-derived ELNs (B-ELNs) using a human stabilized intestinal cell line (HIEC-6) and assess the ability of B-ELNs to modulate the expression of inflammatory genes in response to lipopolysaccharide (LPS). Our findings show that B-ELNs are internalized by HIEC-6 cells and transport labeled RNA cargo into them. Pretreatment with B-ELNs reduces LPS-induced ROS generation and cell viability loss, while modulating the expression of 28 inflammatory genes compared to control. Pathway analysis demonstrates their ability to suppress inflammatory responses triggered by LPS. In conclusion, our data indicate that B-ELNs are up taken by HIEC-6 cells and can modulate inflammatory responses after LPS stimulation, suggesting a therapeutic potential. This study demonstrates the role of B-ELNs in regulating crucial biological processes, like anti-inflammatory responses, which could support intestinal health.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"764 ","pages":"Article 110266"},"PeriodicalIF":3.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of high-calorie diet-induced obesity on molecular structures of lipids and proteins - A multi-organ study using FTIR spectroscopy","authors":"Kaja Piana ,&nbsp;Agata Ziomber-Lisiak ,&nbsp;Blazej Ruszczycki ,&nbsp;Andrzej Bugajski ,&nbsp;Magdalena Szczerbowska-Boruchowska","doi":"10.1016/j.abb.2025.110325","DOIUrl":"10.1016/j.abb.2025.110325","url":null,"abstract":"<div><div>In the presented study, we evaluated changes in the molecular structures of lipids and proteins in organs/tissues at the early stage of obesity induced by a high-calorie diet (HCD), using animal models. We examined several different molecular parameters and the organs most affected by obesity. Fourier transform infrared (FTIR) spectroscopy combined with Principal Component Analysis (PCA) and Receiver Operating Characteristic (ROC) analysis were used to evaluate molecular changes in tissues taken from HCD-induced obese Wistar rats and their lean counterparts. We observed that at the early stage of obesity, changes occurred mainly in lipid structures, primarily affecting white epididymal adipose tissue (WAT) and the liver (Lr). No changes in protein molecular structures were observed in any of the examined organs. PCA showed distinctly different organ/tissue compositions, in terms of molecular parameters, for both groups. In turn, ROC analysis indicated that fatty acid chain length (FACL), lipid unsaturation (L_Unsat), and carbonyl/lipid ratio (Carb/L) for WAT, and FACL and lipid/protein ratio (L/P) for Lr, were the molecular parameters, whose levels differentiated the most between both groups. We demonstrated that studies using FTIR spectroscopy combined with advanced data mining methods could deepen the current knowledge about obesity and the biochemical changes occurring in the organs affected by this disease. Thus, they can help in the future with better and faster diagnosis and prevention of obesity and its complications.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"765 ","pages":"Article 110325"},"PeriodicalIF":3.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neural-symbolic hybrid model for myosin complex in cardiac ventriculum decodes structural bases for inheritable heart disease from its genetic encoding","authors":"Thomas P. Burghardt","doi":"10.1016/j.abb.2025.110323","DOIUrl":"10.1016/j.abb.2025.110323","url":null,"abstract":"<div><h3>Background</h3><div>Human ventriculum myosin (βmys) powers contraction sometimes in complex with myosin binding protein C (MYBPC3). The latter regulates βmys activity and impacts cardiac function. Single residue variants (SRVs) change protein sequence in βmys or MYBPC3 causing inheritable heart diseases by affecting the βmys/MYBPC3 complex. Muscle genetics encode instructions for contraction informing native protein construction, functional integration, and inheritable disease impairment. A digital model decodes these instructions and evolves by processing new information content from diverse data modalities using a human partner-driven virtuous cycle optimization.</div></div><div><h3>Methods</h3><div>A general neural-network contraction model characterizes SRV impacts on human health. It rationalizes phenotype and pathogenicity assignment given the SRVs characteristics and, in this sense, decodes βmys/MYBPC3 complex genetics and implicitly captures ventricular muscle functionality. When an SRV modified domain locates to an inter-protein contact in βmys/MYBPC3 it affects complex coordination. Domains involved, one in βmys and the other in MYBPC3, form coordinated domains (co-domains). Bilateral co-domains imply potential for their SRV modification probabilities to respond jointly to a common perturbation revealing location. Human genetic diversity from the serial founder effect is the common systemic perturbation coupling co-domains subsequently mapped by a method called 2-dimensional correlation genetics (2D-CG).</div></div><div><h3>Results</h3><div>Interpreting general neural-network contraction model output involves 2D-CG co-domain mapping providing structural insights with natural language expression. It aligns machine-learned intelligence from the neural network model with human provided structural insight from the 2D-CG map, and other data from the literature, to form a neural-symbolic hybrid model integrating genetic and protein-interaction data into a nascent digital twin. The process forms a template for combining new information content from diverse data modalities into an evolving digital model. This nascent digital twin interprets SRV implications for disease mechanism discovery.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"765 ","pages":"Article 110323"},"PeriodicalIF":3.8,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Suppression of TLR4/NF-κB signaling by kaurenoic acid in a mice model of monosodium urate crystals-induced acute gout","authors":"Maryam Jamil ,&nbsp;Sana Zafar ,&nbsp;Tehmina Bibi ,&nbsp;Parveen Akhtar Buttar ,&nbsp;Bushra Shal ,&nbsp;Kifayatullah Shah ,&nbsp;Fakhar ud Din ,&nbsp;Eun Kyoung Seo ,&nbsp;Salman Khan","doi":"10.1016/j.abb.2025.110317","DOIUrl":"10.1016/j.abb.2025.110317","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Aim&lt;/h3&gt;&lt;div&gt;The aim of the current study was to investigate the potential therapeutic effect of kaurenoic acid (KA) against Monosodium Urate Crystals (MSU)-induced acute gout by downregulation of NF-κB signaling pathway, mitigating inflammation and oxidative stress. KA potentially targeted NF-κB pathway activation and provided comprehensive insights through multiple approaches. This was accomplished by advanced analytical techniques. This methodology highlighted the efficacy of KA in acute gout attacks offering new approach for gout management.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;In-vivo model of acute gout was established in BALB/c mice. Anti-inflammatory and urate-lowering potential was determined through pain behavioral evaluation, biochemical analysis, histological and immunohistochemical assays, radiological assessments, Fourier Transform Infrared (FTIR) analysis, and computational analysis.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The paw edema, joint thickness, and the frequency and duration of acute gout flare-ups were all significantly (p &lt; 0.001) decreased by the administration of KA. A considerable reversal of inflammation and deterioration was observed in the KA-treated groups in X-ray examination. The FTIR spectroscopy indicated the changes in the molecular makeup of tissues, and modifications of biomolecules including proteins, lipids, and carbohydrates. Histopathological changes showed marked (p &lt; 0.001) improvements in cellular structure of the paw, and inflammatory cell infiltration in the treatment groups. Trichrome staining revealed suppressed collagen deposition, inflammation, and tissue repair in the paw. In paw tissues, the KA therapy up-regulated IκB-α expression while down-regulating toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) expression. On the other hand, KA therapy greatly increased antioxidants and decreased oxidative stress indicators significantly (p &lt; 0.001). According to Evans's blue permeability analysis, results showed that the treatment groups' vascular permeability was intensely reduced in comparison to the diseased group. Molecular docking studies indicated that KA appeared to have a high tendency to bind to protein targets. KA was associated with the drop in the cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;In conclusion, this study highlighted the potential therapeutic effect of KA in alleviating MSU-induced gout by suppressing the NF-κB signaling pathway. The anti-inflammatory and antioxidant activity was demonstrated by behavioral studies and advanced biochemical evaluations including blood analysis and oxido-nitrosative stress markers. Histopathological analysis, including H&amp;E staining, immunohistochemistry, and Masson Trichrome staining, revealed tissue preservation, while FTIR and X-ray revealed structural improvements. M","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"765 ","pages":"Article 110317"},"PeriodicalIF":3.8,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ornithine decarboxylase and its role in cancer","authors":"Jessica Georgina Filisola-Villaseñor ,&nbsp;Beatriz Irene Arroyo-Sánchez ,&nbsp;Luis Janiel Navarro-González ,&nbsp;Edgar Morales-Ríos ,&nbsp;Viridiana Olin-Sandoval","doi":"10.1016/j.abb.2025.110321","DOIUrl":"10.1016/j.abb.2025.110321","url":null,"abstract":"<div><div>Cancer is among the leading causes of death worldwide. The effectiveness of conventional chemotherapy has some drawbacks, therefore, there is an urgency to develop novel strategies to fight this disease. Ornithine decarboxylase (ODC) is the most finely tuned enzyme of the polyamine (PA) biosynthesis pathway as it is regulated at different levels: transcriptional, translational, post-translational, and by feedback inhibition. In cancer, this enzyme is overexpressed due to its regulation by the protooncogene c-Myc, thus it has been proposed as a drug target against this disease. This review describes information regarding the biochemistry and regulation of the ODC at different levels and its role in cancer. Moreover, we discuss the molecules aiming on the inhibition of the ODC activity that have been tested as therapeutic options. ODC remains as a therapeutic opportunity that needs to be more explored.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"765 ","pages":"Article 110321"},"PeriodicalIF":3.8,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143050999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biochemical, structural, and cellular characterization of S-but-3-yn-2-ylglycine as a mechanism-based covalent inactivator of the flavoenzyme proline dehydrogenase","authors":"Kaylen R. Meeks ,&nbsp;Juan Ji ,&nbsp;Gary K. Scott ,&nbsp;Ashley C. Campbell ,&nbsp;Jay C. Nix ,&nbsp;Ada Tadeo ,&nbsp;Lisa M. Ellerby ,&nbsp;Christopher C. Benz ,&nbsp;John J. Tanner","doi":"10.1016/j.abb.2025.110319","DOIUrl":"10.1016/j.abb.2025.110319","url":null,"abstract":"<div><div>The mitochondrial flavoenzymes proline dehydrogenase (PRODH) and hydroxyproline dehydrogenase (PRODH2) catalyze the first steps of proline and hydroxyproline catabolism, respectively. The enzymes are targets for chemical probe development because of their roles in cancer cell metabolism (PRODH) and primary hyperoxaluria (PRODH2). Mechanism-based inactivators of PRODH target the FAD by covalently modifying the N5 atom, with N-propargylglycine (NPPG) being the current best-in-class of this type of probe. Here we investigated a close analog of NPPG, but-3-yn-2-ylglycine (B32G), distinguished by having a methyl group adjacent to the ethynyl group of the propargyl warhead. UV–visible spectroscopy shows that a bacterial PRODH catalyzes the oxidation of the S-enantiomer of B32G, a necessary first step in mechanism-based inactivation. In contrast, the enzyme does not react with the R-enantiomer. Enzyme activity assays show that S–B32G inhibits bacterial PRODH in a time-dependent manner consistent with covalent inactivation; however, the inactivation efficiency is ∼600-times lower than NPPG. We generated the crystal structure of PRODH inactivated by S–B32G at 1.68 Å resolution and found that inactivation induces a covalent link between the FAD N5 and the ε-nitrogen of an active site lysine, confirming that S–B32G follows the same mechanism as NPPG. Despite its lower inactivation efficiency at the purified bacterial enzyme, S–B32G exhibited comparable activity to NPPG against PRODH and PRODH2 in human cells and mouse livers. Molecular modeling is used to rationalize the stereospecificity of B32G.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"765 ","pages":"Article 110319"},"PeriodicalIF":3.8,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kinetic and structural investigation of the 4-allyl syringol oxidase from Streptomyces cavernae","authors":"Daniel Eggerichs ,&nbsp;Heiner G. Weddeling ,&nbsp;Laura Alvigini ,&nbsp;Tobias Rapsch ,&nbsp;Nils Weindorf ,&nbsp;Andrea Mattevi ,&nbsp;Dirk Tischler","doi":"10.1016/j.abb.2025.110320","DOIUrl":"10.1016/j.abb.2025.110320","url":null,"abstract":"<div><div>4-Phenol oxidases are proposed to be involved in the utilization of lignin-derived aromatic compounds. While enzymes with selectivity towards 4-hydroxyphenyl and guaiacyl motifs are well described, we identified the first syringyl-specific oxidase from <em>Streptomyces cavernae</em> (<em>Sc</em>4ASO) only very recently. Here, in-depth studies were conducted to unravel the molecular origins of the outstanding selectivity of <em>Sc</em>4ASO. Kinetic experiments revealed high activities on dimethoxylated substrates (up to 2.9 ± 0.1 s⁻¹), but also strong cooperativity between both protein subunits, as well as substrate inhibition in dependency of <em>ortho</em> methoxylation and chain length of the <em>para</em> substituent. Rapid mixing kinetics in combination with the determination of the crystal structure in complex with three substrates allowed to connect the kinetic behavior with never-observed positioning of the conserved residue Y471. Ultimately, the catalytic potential of <em>Sc</em>4ASO was investigated in a 100 mL scale cascade reaction to produce the natural product syringaresinol.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"765 ","pages":"Article 110320"},"PeriodicalIF":3.8,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diffuse large B-cell lymphoma cell-derived exosomal NSUN2 stabilizes PDL1 to promote tumor immune escape and M2 macrophage polarization in a YBX1-dependent manner","authors":"Huayu Ling ,&nbsp;Yuling Li ,&nbsp;Panjun Wang ,&nbsp;Zhengxiang Zhang ,&nbsp;Zhong Yang","doi":"10.1016/j.abb.2025.110322","DOIUrl":"10.1016/j.abb.2025.110322","url":null,"abstract":"<div><h3>Background</h3><div>Diffuse large B-cell lymphoma (DLBCL) is a prevalent and aggressive form of non-Hodgkin's lymphoma with a complex etiology. NOP2/Sun domain 2 (NSUN2) is an RNA methyltransferase that has been linked to the regulation of gene expression in various cancers. However, the function of NSUN2 in DLBCL, specifically its contribution to exosome-driven tumor progression, remains to be thoroughly elucidated.</div></div><div><h3>Methods</h3><div>Quantitative real-time polymerase chain reaction was used to analyze the expression of NSUN2 and programmed death ligand 1 variant (PDL1). Western blotting assay was performed to detect the protein levels of NSUN2, PDL1 and Y-box binding protein 1 (YBX1). Cell proliferation was analyzed by cell counting kit-8 and 5-Ethynyl-2′-deoxyuridine assays. Cell apoptosis and CD206-positive cells were quantified by flow cytometry. The levels of tumor necrosis factor-alpha and interferon-γ in cell supernatant were analyzed by enzyme-linked immunosorbent assays. m6A RNA immunoprecipitation and RNA pull-down assays were performed to determine the association between NSUN2 and PDL1. An RNA immunoprecipitation assay was used to analyze the association of YBX1 and PDL1. <em>In vitro</em> findings were validated in a mouse model.</div></div><div><h3>Results</h3><div>NSUN2 was overexpressed in DLBCL tissues and cells. DLBCL cell-derived exosomes facilitated the transfer of NSUN2 to DLBCL cells, which in turn promoted tumor cell proliferation, M2 macrophage polarization, and immune escape and inhibited cell apoptosis. In addition, NSUN2 stabilized PDL1 mRNA through an m5C-dependent mechanism and a YBX1-dependent pathway. Moreover, the suppression of PDL1 significantly mitigated the effects induced by NSUN2 within DLBCL cell-derived exosomes on cellular proliferation, apoptosis, M2 macrophage polarization, and immune evasion. Further, DLBCL cell-derived exosomal NSUN2 promoted tumor growth by regulating PDL1.</div></div><div><h3>Conclusion</h3><div>NSUN2 in DLBCL cell-derived exosomes stabilized PDL1 in a YBX1-dependent manner and thus promoted tumor immune escape and M2 macrophage polarization. These findings highlight the potential of targeting the NSUN2-PDL1 axis as a novel therapeutic strategy for DLBCL.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"766 ","pages":"Article 110322"},"PeriodicalIF":3.8,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sivelestat sodium protects against renal ischemia/reperfusion injury by reduction of NETs formation","authors":"Yanqi Liu ,&nbsp;Yu Xin ,&nbsp;Mengyao Yuan ,&nbsp;Yuhan Liu ,&nbsp;Yuchen Song ,&nbsp;Lifeng Shen ,&nbsp;Yu Xiao ,&nbsp;Xinran Wang ,&nbsp;Dawei Wang ,&nbsp;Linqiong Liu ,&nbsp;Yuxi Liu ,&nbsp;Yinghao Luo ,&nbsp;Pengfei Huang ,&nbsp;Qianqian Zhang ,&nbsp;Weiting Zhang ,&nbsp;Hongxu Li ,&nbsp;Yuxin Zhou ,&nbsp;Xibo Wang ,&nbsp;Kaijiang Yu ,&nbsp;Changsong Wang","doi":"10.1016/j.abb.2025.110318","DOIUrl":"10.1016/j.abb.2025.110318","url":null,"abstract":"<div><h3>Background</h3><div>Ischemia-reperfusion injury (IRI) often results in renal impairment. While the presence of neutrophil extracellular traps (NETs) is consistently observed, their specific impact on IRI is not yet defined. Sivelestat sodium, an inhibitor of neutrophil elastase which is crucial for NET formation, may offer a therapeutic approach to renal IRI, warranting further research.</div></div><div><h3>Methods</h3><div>A mouse model was established for early-stage renal IRI, confirmed by injury markers and histological assessments. The involvement of NETs in renal I/R was demonstrated using immunofluorescence and Western blot. Renal function and pathology were further evaluated through a comprehensive set of methods, including Periodic Acid-Schiff staining (PAS) and Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling (TUNEL) staining, enzyme-linked immunosorbent assay (ELISA), Real time Glomerular Filtration Rate (RT-GFR) monitoring, Polymerase Chain Reaction (PCR), biochemical analysis, and additional Western blot and immunofluorescence assays.</div></div><div><h3>Results</h3><div>We firstly quantified NET expression in renal IRI mice, noting a peak at 24 h. Subsequently, sivelestat sodium treatment was administered, resulting in decreased MPO, CitH3, and attenuated tubular damage. Moreover, it resulted in a decrease in serum levels of creatinine, blood urea nitrogen (BUN), as well as neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1). Additionally, it lowered the abundance of renal tissue inflammatory markers interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and mitigated the levels of oxidative stress indicators malondialdehyde (MDA) and 4 Hydroxynonenal (4HNE), accompanied by a decline in renal cell apoptosis and an enhancement of GFR in renal I/R mice.</div></div><div><h3>Conclusion</h3><div>Sivelestat sodium ameliorates renal IRI by downregulating neutrophil NETs, reducing inflammation, oxidative stress, and apoptosis, thereby enhancing renal function.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"765 ","pages":"Article 110318"},"PeriodicalIF":3.8,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astaxanthin-loaded polylactic acid-glycolic acid nanoparticles alleviates atherosclerosis by suppressing macrophage ferroptosis via the NRF2/SLC7A11/GPX4 pathway","authors":"Mengying Jin ,&nbsp;Xiao Chen ,&nbsp;Lanzhuoying Zheng ,&nbsp;Yuanyuan Peng ,&nbsp;Mingying Lin ,&nbsp;Ke Liang ,&nbsp;Xinran Liu ,&nbsp;Zihan Xu ,&nbsp;Yiming Yang ,&nbsp;Baozhu Wei ,&nbsp;Jing Wan","doi":"10.1016/j.abb.2025.110316","DOIUrl":"10.1016/j.abb.2025.110316","url":null,"abstract":"<div><h3>Background</h3><div>Astaxanthin (ASX), a fat-soluble carotenoid mainly sourced from Haematococcus pluvialis, shows promise for clinical applications in chronic inflammatory diseases. This study investigates whether ASX can mitigate atherosclerosis (AS) by modulating macrophage ferroptosis and provides astaxanthin-loaded polylactic acid-glycolic acid nanoparticles (ASX-PLGA NPs) as comparison.</div></div><div><h3>Method</h3><div>ApoE−/− mice were fed a high-fat diet with ASX or statin intervention. Plaque area, lipid aggregation, collagen content, and ferroptosis-related indicators were assessed. Moreover, ASX-PLGA NPs were synthesized and characterized and were used to pretreat macrophages induced with oxidized low-density lipoprotein (ox-LDL). Indicators linked to ferroptosis and oxidative stress were detected. Finally, the expression of nuclear factor erythroid -related factor 2 (NRF2) was evaluated.</div></div><div><h3>Results</h3><div>ASX intervention significantly delayed the progression of AS plaques, characterized by reductions in plaque area and increased collagen fibers. The observed improvements in AS were consistent with statins. ASX-PLGA NPs demonstrate good safety and stability and have better therapeutic effects than ASX alone. Indicators linked to ferroptosis and oxidative stress were significantly improved in groups containing ASX in vivo and vitro. Additionally, ASX facilitated the nuclear translocation of NRF2, which could be attenuated with ML385, a specific inhibitor of NRF<strong>2.</strong></div></div><div><h3>Conclusion</h3><div>ASX-PLGA NPs have better therapeutic effects than ASX alone. The regulation of NRF2/SLC7A11/GPX4 represents a novel mechanism by which ASX can counteract ferroptosis and impede AS progression.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"765 ","pages":"Article 110316"},"PeriodicalIF":3.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}