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LncRNA SNHG15 facilitates the advancement of preeclampsia via the miR-451a/ATF2 axis. LncRNA SNHG15通过miR-451a/ATF2轴促进先兆子痫的进展。
IF 3 3区 生物学
Archives of biochemistry and biophysics Pub Date : 2025-07-31 DOI: 10.1016/j.abb.2025.110570
Min Wu, Jing Li, Xiaoqian Fu, Xiujing Lu, Lu Xiao, Yachang Zeng
{"title":"LncRNA SNHG15 facilitates the advancement of preeclampsia via the miR-451a/ATF2 axis.","authors":"Min Wu, Jing Li, Xiaoqian Fu, Xiujing Lu, Lu Xiao, Yachang Zeng","doi":"10.1016/j.abb.2025.110570","DOIUrl":"https://doi.org/10.1016/j.abb.2025.110570","url":null,"abstract":"<p><p>Preeclampsia (PE) is a pregnancy complication that poses a major risk to both the maternal and the fetal's safety. By studying the role and mechanism of LncRNA SNHG15 in preeclampsia pathogenesis, this study aimed to better understand the pathophysiology and prevention of PE. Placental samples and hypoxic trophoblast cell line--HTR8/SVneo were analyzed using qPCR to determine the differential expression of LncRNA SNHG15. Nuclear-cytoplasmic fractionation assays confirmed that LncRNA SNHG15 is predominantly localized in the cytoplasm of HTR8/SVneo cells, where it modulates cellular functions including proliferation, migration, and invasion. Using a dual luciferase reporter assay and rescue experiment, functions of miRNA-451a and LncRNA SNHG15 in HTR8/SVneo cells were examined. ATF2 expression levels in the hypoxic cell model and after LncRNA SNHG15 and miR-451a interference were confirmed by qPCR and Western blot. Evidence from this study indicates that LncRNA SNHG15 may be involved in the onset of preeclampsia, suggesting its viability as a novel treatment target.</p>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":" ","pages":"110570"},"PeriodicalIF":3.0,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768319","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}
引用次数: 0
Correlation between methyltransferase METTL7B and atherosclerosis 甲基转移酶METTL7B与动脉粥样硬化的相关性
IF 3 3区 生物学
Archives of biochemistry and biophysics Pub Date : 2025-07-31 DOI: 10.1016/j.abb.2025.110560
Jian Xiong , Xiaoyun Peng , Liming Ma , Fangcheng Zhu , Yan Ding , Zhixiao Wang
{"title":"Correlation between methyltransferase METTL7B and atherosclerosis","authors":"Jian Xiong ,&nbsp;Xiaoyun Peng ,&nbsp;Liming Ma ,&nbsp;Fangcheng Zhu ,&nbsp;Yan Ding ,&nbsp;Zhixiao Wang","doi":"10.1016/j.abb.2025.110560","DOIUrl":"10.1016/j.abb.2025.110560","url":null,"abstract":"<div><div>Atherosclerosis (AS) is a serious threat to human health. Although glucose balance, lipid metabolism, inflammation and hypertension are closely related to AS, whether methyltransferase-like (METTL) family members are involved in the occurrence and development of AS remains elusive.</div><div>Differentially expressed genes of METTLs in AS and normal blood vessels in GSE43292 and GSE100927 databases were analyzed. Random forest screening was used to screen marker genes, and the intersection genes in the two databases were selected. GSE28829/GSE41571 and clinical tissue samples were used for verification. The databases were further used to analyze marker genes’ tissue and cellular localization and their correlation with lipid metabolism and efferocytosis.</div><div>7 and 17 differentially expressed METTL genes were obtained from GSE43292 and GSE100927 databases, respectively. METTL7B and METTL5 were verified as the intersection marker genes. Compared with the control group, the expression of METTL7B was significantly increased in advanced AS, AS ruptured plaque and clinical heavy-load plaque tissues. ROC curve analysis showed that the AUC of METTL7B in GSE28829 and GSE41571 was greater than 0.9. In addition, it was found that METTL7B was significantly correlated with lipid metabolism-related genes and promoted the formation of lipid droplets. METTL7B was positively correlated with atherosclerosis and macrophage-mediated efferocytosis. RNA-seq and targeted lipidomics results also confirmed that METTL7B is closely related to lipid metabolism and atherosclerosis. And further analysis also indicated that METTL7B could regulate 104 kinds of lipids, such as Lipid-n-0041, Lipid-n-0056, Lipid-n-0057, Lipid-n-0098, Lipid-n-0099 and Lipid-n-0169, mediated by AKR1C1, CETP and RORA. This study reveals a new mechanism for the occurrence and development of AS, thereby providing a potential target for the treatment of AS.</div><div>In conclusion, METTL7B can be used as a predictor and therapeutic target for AS.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"772 ","pages":"Article 110560"},"PeriodicalIF":3.0,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144757355","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}
引用次数: 0
Dexmedetomidine attenuates oxaliplatin-induced neuropathic pain by modulating the TLR4/NF-κB pathway to reduce spinal inflammation and oxidative stress 右美托咪定通过调节TLR4/NF-κB通路减轻奥沙利铂诱导的神经性疼痛,减轻脊髓炎症和氧化应激。
IF 3 3区 生物学
Archives of biochemistry and biophysics Pub Date : 2025-07-29 DOI: 10.1016/j.abb.2025.110572
Yuchao Lin, Kexin Chen, Lei Zhao, Ming Zhao, Yuanyuan Liu, Yu Li
{"title":"Dexmedetomidine attenuates oxaliplatin-induced neuropathic pain by modulating the TLR4/NF-κB pathway to reduce spinal inflammation and oxidative stress","authors":"Yuchao Lin,&nbsp;Kexin Chen,&nbsp;Lei Zhao,&nbsp;Ming Zhao,&nbsp;Yuanyuan Liu,&nbsp;Yu Li","doi":"10.1016/j.abb.2025.110572","DOIUrl":"10.1016/j.abb.2025.110572","url":null,"abstract":"<div><h3>Purpose</h3><div>This study aimed to investigate the effects of Dexmedetomidine (Dex) on oxaliplatin-induced neuropathic pain and its underlying mechanisms.</div></div><div><h3>Methods</h3><div>A murine model of oxaliplatin-induced neuropathic pain was established using intraperitoneal injections of oxaliplatin. Dex was administered at different doses, and behavioral tests were performed to assess pain. Spinal cord tissues were analyzed for inflammatory cytokines, oxidative stress markers, and key signaling molecules related to the toll-like receptor 4 (TLR4)/nuclear factor kappa B using quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, and immunohistochemistry. In addition, in vitro experiments were conducted using TNF-α-stimulated C6 glial cells to further assess the anti-inflammatory effects of Dex.</div></div><div><h3>Results</h3><div>Dex significantly alleviated oxaliplatin-induced neuropathic pain, as shown by an increase in paw withdrawal thresholds and a marked reduction in spontaneous flinching. Molecular analyses further demonstrated that Dex treatment reduced interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) expression, as well as malondialdehyde (MDA) and cyclooxygenase-2 (COX2) in the spinal cord. Concurrently, there was a notable enhancement in the activity of Manganese superoxide dismutase (Mn-SOD) and glutathione (GSH), suggesting improved antioxidative defense. Additionally, Dex reduced spinal inflammation and oxidative stress by downregulating TLR4 expression and inhibiting NF-κB activation. Consistent with these findings, Dex also suppressed NF-κB phosphorylation and cytokine expression in TNF-α-treated C6 cells in vitro.</div></div><div><h3>Conclusions</h3><div>Dex significantly reduced oxaliplatin-induced neuropathic pain by downregulating TLR4 expression and inhibiting NF-κB activation.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"772 ","pages":"Article 110572"},"PeriodicalIF":3.0,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759000","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}
引用次数: 0
Molecular insights into CYP19A1 mutations and their role in estrogen production CYP19A1突变及其在雌激素产生中的作用
IF 3 3区 生物学
Archives of biochemistry and biophysics Pub Date : 2025-07-29 DOI: 10.1016/j.abb.2025.110573
Yoo-bin Lee, Changmin Kim, Jiyeon Hong, Donghak Kim
{"title":"Molecular insights into CYP19A1 mutations and their role in estrogen production","authors":"Yoo-bin Lee,&nbsp;Changmin Kim,&nbsp;Jiyeon Hong,&nbsp;Donghak Kim","doi":"10.1016/j.abb.2025.110573","DOIUrl":"10.1016/j.abb.2025.110573","url":null,"abstract":"<div><div>Human cytochrome P450 enzyme CYP19A1, commonly referred to as aromatase, plays a critical role in estrogen biosynthesis by catalyzing the conversion of C19 androgens into aromatic C18 estrogens. Alterations in aromatase activity have been implicated in the development and progression of estrogen-dependent diseases. Genetic mutations, including nonsynonymous single nucleotide polymorphisms (SNPs), can markedly impact the catalytic function of CYP19A1. In this study, we investigated the functional implications of six CYP19A1 variants (R192H, R192Q, T201M, R264C, P308F, and M364T). These variants were generated via site-directed mutagenesis, expressed in <em>Escherichia coli</em>, and purified. The T201M, R264C, and P308F variants exhibited measurable expression levels ranging from 90 to 150nmol P450 per liter culture, whereas no detectable P450 holoenzyme was observed for the R192H, R192Q, and M364T variants. Spectral binding assays revealed typical type I spectral shifts upon androgen binding for all purified variants with tight affinity. Catalytic activities of testosterone and androstenedione aromatization were assessed by UPLC–mass spectrometry, and steady-state kinetic analyses demonstrated that T201M and R264C retained catalytic efficiencies comparable to wild-type, with efficiency ratios of 1.1–0.9 for androstenedione and 0.6–0.8 for testosterone, respectively, relative to the wild-type. In contrast, P308F showed marked reductions in catalytic efficiencies (0.2 and 0.1), driven by decreases in both <em>k</em><sub>cat</sub> and <em>K</em><sub>m</sub> values. Structural analysis indicates that the proline residue at position 308, situated within the I-helix, is likely critical for stabilizing a catalytically active conformation of the enzyme-substrate complex. These results provide valuable insights into the functional role of CYP19A1 in estrogen biosynthesis and could inform the design of innovative therapies for estrogen-related diseases.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"772 ","pages":"Article 110573"},"PeriodicalIF":3.0,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144723950","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}
引用次数: 0
Catalytic and Structural Comparisons of Fatty Acid Dioxygenases Related to Cyclooxygenases and Peroxidases. 与环加氧酶和过氧化物酶相关的脂肪酸双加氧酶的催化和结构比较。
IF 3 3区 生物学
Archives of biochemistry and biophysics Pub Date : 2025-07-28 DOI: 10.1016/j.abb.2025.110574
Ernst H Oliw
{"title":"Catalytic and Structural Comparisons of Fatty Acid Dioxygenases Related to Cyclooxygenases and Peroxidases.","authors":"Ernst H Oliw","doi":"10.1016/j.abb.2025.110574","DOIUrl":"https://doi.org/10.1016/j.abb.2025.110574","url":null,"abstract":"<p><p>Linoleic acid (LA) 8-, 9-, and 10-dioxygenases (DOX) of microorganisms are hemoproteins, structurally related to cyclooxygenases (COX) and, occasionally, to cytochrome C peroxidase (Ccp). These DOX are often fused to cytochromes P450 for biosynthesis of diols, epoxy alcohols, and allene oxides. AlphaFold2 (AF2) predicted the tertiary structures of COX with less than 0.45 Å deviation and central α-helices of selected DOX with very high confidence. The homology with COX was compared by superposition of the tertiary structure of COX and the COX:LA complex with the substrate recognition sites. The C<sub>α</sub> protein fold, central α-helices of COX, and catalytic Tyr residue were conserved. The substrate cavities of COX and DOX differed notably between the catalytic Tyr and the separate orifices at the protein surface. COX and 9-DOX bound fatty acids in carboxylate-out configuration, but 8- and 10-DOX in the opposite orientation. 10S-DOX of the cyanobacterium Nostoc punctiforme preserved the α-helices of COX along with amino acid residues of the active sites of COX and DOX. The 10S-DOX of Pseudomonas aeruginosa belongs to the Ccp family and the AF2 model revealed unique structural features. The AF2 models have complemented the oxygenation process with mechanistic and evolutionary information in a pioneering manner.</p>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":" ","pages":"110574"},"PeriodicalIF":3.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752114","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}
引用次数: 0
Motifs in the histone H3 and H4 and chromatin modifying factors are crucial to regulate the multifactorial zinc response pathway in Saccharomyces cerevisiae 组蛋白H3和H4中的基序以及染色质修饰因子对酿酒酵母多因子锌反应通路的调控至关重要
IF 3.8 3区 生物学
Archives of biochemistry and biophysics Pub Date : 2025-07-26 DOI: 10.1016/j.abb.2025.110571
Rajshree Pal , Smriti Anand , Santoshi Acharjee , Vandana Anjana , Prateeksha Thakur , Ashis Biswas , Raghuvir Singh Tomar
{"title":"Motifs in the histone H3 and H4 and chromatin modifying factors are crucial to regulate the multifactorial zinc response pathway in Saccharomyces cerevisiae","authors":"Rajshree Pal ,&nbsp;Smriti Anand ,&nbsp;Santoshi Acharjee ,&nbsp;Vandana Anjana ,&nbsp;Prateeksha Thakur ,&nbsp;Ashis Biswas ,&nbsp;Raghuvir Singh Tomar","doi":"10.1016/j.abb.2025.110571","DOIUrl":"10.1016/j.abb.2025.110571","url":null,"abstract":"<div><div>Zinc is a trace element that plays a crucial role in regulating various biological processes. To identify the factors involved in maintaining zinc homeostasis, we analysed the growth of histone mutants and gene deletions of chromatin-modifying factors. Growth assays revealed that specific regions and amino acid residues of histones H3 and H4, along with several chromatin-modifying factors, are essential for survival under zinc stress. Cells lacking certain motifs within H3 and H4 or in absence of chromatin modifiers exhibited hypersensitivity to zinc. ICP-MS analysis and fluorescence microscopy using a zinc-specific probe showed that zinc sensitive histone mutants accumulate higher zinc levels. The fluorescence microscopic analysis suggests that zinc sensitive mutants of chromatin modifying factors also contain more intracellular zinc. qRT-PCR analysis revealed that zinc-sensitive mutants exhibit upregulation of <em>ZRT1</em>, a high-affinity zinc transporter. Chromatin immunoprecipitation (ChIP) experiments further demonstrated constitutive recruitment of TBP at the <em>ZRT1</em> promoter in zinc sensitive histone mutants in zinc untreated condition. Supplementation with amino acids, glutathione, and iron alleviated the zinc sensitivity, indicating a potential interplay between zinc toxicity and metabolic or redox imbalance. Notably, iron supplementation suppressed zinc-induced growth defects, implying disrupted iron homeostasis in the mutants. In summary, our findings provide evidence that specific regions of the H3 and H4 histones and chromatin-modifying factors are critical for regulating the cellular response to zinc. The mutations in histones and chromatin modifiers probably exhibit altered chromatin structure, leading to disruption in zinc metabolism.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"772 ","pages":"Article 110571"},"PeriodicalIF":3.8,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144714349","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}
引用次数: 0
β-Galactosidase inhibition explored by biochemical methods and in silico studies for plant polyphenols. 植物多酚类物质对β-半乳糖苷酶抑制作用的生物化学方法和硅片研究。
IF 3 3区 生物学
Archives of biochemistry and biophysics Pub Date : 2025-07-25 DOI: 10.1016/j.abb.2025.110568
Ahmed Zayed, Karima Sayah, Kalicharan Sharma, Rasha Ali Radwan, Shahira M Ezzat
{"title":"β-Galactosidase inhibition explored by biochemical methods and in silico studies for plant polyphenols.","authors":"Ahmed Zayed, Karima Sayah, Kalicharan Sharma, Rasha Ali Radwan, Shahira M Ezzat","doi":"10.1016/j.abb.2025.110568","DOIUrl":"https://doi.org/10.1016/j.abb.2025.110568","url":null,"abstract":"<p><p>β-Galactosidase is a lysosomal enzyme whose deficiency is associated with genetic disorders such as GM1 gangliosidosis, prompting the search for novel enzyme modulators with therapeutic potential. The current study evaluated the inhibitory potential of selected natural polyphenols against β-galactosidase using a combined approach of biochemical assays and computational modeling. Sixteen plant-derived compounds were initially screened through molecular docking against Aspergillus oryzae β-galactosidase. Among these, hesperidin, rutin, and chlorogenic acid exhibited the most favorable interactions and were subsequently assessed through in vitro enzyme inhibition assays and MM/GBSA binding energy calculations. These compounds showed potential inhibitory effects and stable binding within the enzyme's active site. Although classical pharmacological chaperone activity was not directly demonstrated, the observed modulation of enzyme function suggests potential for further development of these polyphenols as structurally distinct glycosidase inhibitors. The findings provide a basis for future investigations aimed at natural product-based strategies to manage lysosomal storage disorders such as GM1 gangliosidosis.</p>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":" ","pages":"110568"},"PeriodicalIF":3.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726937","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}
引用次数: 0
Interaction of two key biological targets —trypsin and DNA— with phenolic Phytochemicals: Insights from molecular docking and radical scavenging potential 两个关键的生物靶点-胰蛋白酶和DNA-与酚类植物化学物质的相互作用:来自分子对接和自由基清除潜力的见解。
IF 3 3区 生物学
Archives of biochemistry and biophysics Pub Date : 2025-07-25 DOI: 10.1016/j.abb.2025.110567
Duygu İnci Özbağcı
{"title":"Interaction of two key biological targets —trypsin and DNA— with phenolic Phytochemicals: Insights from molecular docking and radical scavenging potential","authors":"Duygu İnci Özbağcı","doi":"10.1016/j.abb.2025.110567","DOIUrl":"10.1016/j.abb.2025.110567","url":null,"abstract":"<div><div>Phenolic acids represent a diverse class of phytochemicals that are abundantly present in fruits, vegetables, and other plant-based sources. The wide-ranging biological properties of these compounds have stimulated considerable interest within the scientific community. Syringic and isovanillic acid, the aromatic natural phytochemicals, are found in fruits and vegetables and exhibit a range of biological activities, including antioxidant and enzyme-modulating effects. In this study, we investigated their binding interactions with biologically significant macromolecules: calf thymus DNA (CT-DNA) and trypsin. The effects of both the phenolic acids on the structure and activity of these macromolecules were analyzed using fluorescence spectroscopy, including quenching type, binding constants, binding sites, thermodynamic parameters, synchronous fluorescence, fluorescence resonance energy transfer (FRET) analysis, two-dimensional (2D), and three-dimensional (3D) fluorescence analysis, effect of metal ions), Fourier transform infrared spectroscopy (FTIR) and molecular docking techniques. The results show that both phenolic acids could bind to CT-DNA via a minor groove mode. The fluorescence experiments indicated that both the phenolic acids bind and cause quenching of trypsin fluorescence. Molecular docking simulations were carried out to examine the interaction profiles of both the phenolic acids with CT-DNA and trypsin. Results revealed that both phenolic acids bind to the DNA minor groove via hydrogen bonding and π–π interactions, with syringic acid showing slightly higher affinity. In the case of trypsin, the isovanillic acid exhibited a stronger binding energy and formed a more compact interaction pattern within the enzyme's active site. These findings support the potential of both the phenolic acids to form stable, non-covalent complexes with biologically relevant macromolecules and contribute to their observed antioxidant and enzymatic effects. The radical scavenging activity of both phenolic acids was measured via the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) method and reported in terms of their IC<sub>50</sub> value. Based on the results, it can be inferred that the radical scavenging potential of both phenolic acids is significantly affected by the number and position of their substituents.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"772 ","pages":"Article 110567"},"PeriodicalIF":3.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726935","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}
引用次数: 0
Sacsin deletion decreases cell viscoelasticity and motility in a glial cell model of autosomal recessive spastic ataxia of Charlevoix Saguenay 在常染色体隐性痉挛性共济失调的胶质细胞模型中,Sacsin缺失降低了细胞的粘弹性和运动性
IF 3 3区 生物学
Archives of biochemistry and biophysics Pub Date : 2025-07-25 DOI: 10.1016/j.abb.2025.110569
Fernanda Murtinheira , João Belo , Ana Sofia Boasinha , Tiago T. Robalo , Vukosava M. Torres , Francisco R. Pinto , Constança Pimenta , Patricia Nascimento , Mario S. Rodrigues , Federico Herrera
{"title":"Sacsin deletion decreases cell viscoelasticity and motility in a glial cell model of autosomal recessive spastic ataxia of Charlevoix Saguenay","authors":"Fernanda Murtinheira ,&nbsp;João Belo ,&nbsp;Ana Sofia Boasinha ,&nbsp;Tiago T. Robalo ,&nbsp;Vukosava M. Torres ,&nbsp;Francisco R. Pinto ,&nbsp;Constança Pimenta ,&nbsp;Patricia Nascimento ,&nbsp;Mario S. Rodrigues ,&nbsp;Federico Herrera","doi":"10.1016/j.abb.2025.110569","DOIUrl":"10.1016/j.abb.2025.110569","url":null,"abstract":"<div><div>Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a movement disorder caused by loss-of-function mutations in the sacsin gene. The most common hallmark of this disease is the disruption of intermediate filament networks in cells as diverse as neurons, kidney cells, fibroblasts, astroglia and microglia. Intermediate filaments are the main filaments responsible for the mechanical and viscoelastic properties of cells and tissues, but these have never been investigated in the context of ARSACS. Here, we analyzed the consequences of sacsin loss on the mechanical functions of astroglial-like C6 cells. The phenotype of C6<sup>Sacs−/−</sup> cells was analyzed by immunocytochemistry, electron microscopy, mass spectrometry, atomic force microscopy and motility/proliferation assays. C6<sup>Sacs−/−</sup> cells presented an abnormal cytoskeletal and organelle distribution, global proteome alterations linked to cell motility and mechanics, a significant decrease in cell elasticity in the cytoplasm, and a striking reduction in cell motility. These mechanical alterations in glial-like cells could be especially relevant for neuroinflammation and glial scar formation upon CNS injury. Our results support a possible role for alterations in glial functions in ARSACS and provide new tools for understanding the glial-specific mechanisms involved in this movement disorder.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"772 ","pages":"Article 110569"},"PeriodicalIF":3.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144723951","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}
引用次数: 0
Research progress on the hallmarks of radiation-induced intestinal injury: Mechanisms, biomarkers and therapeutic targets 辐射诱发肠道损伤特征的研究进展:机制、生物标志物和治疗靶点。
IF 3 3区 生物学
Archives of biochemistry and biophysics Pub Date : 2025-07-25 DOI: 10.1016/j.abb.2025.110562
Zixin Hu , Jingzhi Zhang , Haiming Li , Xiaomin Wang , Ganlin Zhang , Huijuan Cui , Jiayun Nian
{"title":"Research progress on the hallmarks of radiation-induced intestinal injury: Mechanisms, biomarkers and therapeutic targets","authors":"Zixin Hu ,&nbsp;Jingzhi Zhang ,&nbsp;Haiming Li ,&nbsp;Xiaomin Wang ,&nbsp;Ganlin Zhang ,&nbsp;Huijuan Cui ,&nbsp;Jiayun Nian","doi":"10.1016/j.abb.2025.110562","DOIUrl":"10.1016/j.abb.2025.110562","url":null,"abstract":"<div><div>Radiation-induced intestinal injury (RIII) is a major factor limiting the dose in abdominal and pelvic radiotherapy. This review summarizes our current understanding of RIII, focusing on its mechanisms, biomarkers, and potential treatment targets. Radiation directly induces DNA damage in intestinal epithelial cells and contributes to excessive reactive oxygen species (ROS), which together lead to increased apoptosis and decreased regeneration of intestinal stem cells (ISCs). An impaired antioxidant system also contributes to excessive ROS levels. Damage to ISCs results in decreased mucus production and compromised tight junctions, causing damage to the intestinal barrier. Epithelial cells impairment triggers ongoing inflammation, which promotes fibrogenesis and angiogenesis, processes involved in excessive wound healing during this damage. Endothelial cells experience DNA damage and ROS injury similar to that of epithelial cells. Intestinal vascular dysfunction, including increased permeability, ischemia, and angiogenesis, is involved throughout all stages of RIII. Additionally, dysbiosis of intestinal flora is characterized by reduced diversity, an overgrowth of conditional pathogens, and a decrease in probiotics. Current treatments for RIII include anti-inflammatory drugs, antibiotics, mucosal protective agents, and probiotics. Other therapies, such as anti-ferroptosis agents and targeted drugs, are still in preclinical studies. Traditional Chinese medicine, including decoctions, single herbs, or extracts, shows potential in treating RIII. The pathophysiology of RIII involves multiple dynamic steps, each with both harmful and protective aspects. Future research should delve deeper into these dual aspects of radiation-induced damage and its associated complications.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"772 ","pages":"Article 110562"},"PeriodicalIF":3.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726936","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}
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