Biochimica et biophysica acta. General subjects最新文献

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Utility of Brownian dynamics simulations in chemistry and biology: A comprehensive review 布朗动力学模拟在化学和生物学中的应用综述。
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2025-02-01 DOI: 10.1016/j.bbagen.2024.130740
Karim M. ElSawy
{"title":"Utility of Brownian dynamics simulations in chemistry and biology: A comprehensive review","authors":"Karim M. ElSawy","doi":"10.1016/j.bbagen.2024.130740","DOIUrl":"10.1016/j.bbagen.2024.130740","url":null,"abstract":"<div><div>Brownian dynamics (BD) simulations, a powerful computer simulation tool that has gained significant attraction in investigating the intricate dynamics of chemical and biological systems. By meticulously modeling the diffusive motion of molecules and their intricate interactions, BD simulations offer invaluable insights into a diverse array of phenomena, including reaction kinetics, molecular transport, and biomolecular association. This comprehensive review delves into the utility of BD simulations within the realms of chemistry and biology. We meticulously explore the theoretical underpinnings of the technique, critically analyze its strengths and limitations, and showcase its diverse applications across various scientific domains. By providing a comprehensive analysis of the existing literature, we aim to illuminate the potential of BD simulations to significantly advance our understanding of complex chemical and biological systems, ultimately contributing to the development of innovative therapeutic solutions serving a broad range of biomedical applications.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 2","pages":"Article 130740"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852301","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
Evaluating lactate metabolism for prognostic assessment and therapy response prediction in gastric cancer with emphasis on the oncogenic role of SLC5A12 评估乳酸代谢在胃癌预后评估和治疗反应预测中的作用,重点关注SLC5A12的致癌作用。
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2025-02-01 DOI: 10.1016/j.bbagen.2024.130739
Chenyi Lin , Jianjian Ye , Chao Xu , Ying Zheng , Yining Xu , Yuluo Chen , Liangjie Chi , Jia Lin , Feng Li , Yao Lin , Qingshui Wang
{"title":"Evaluating lactate metabolism for prognostic assessment and therapy response prediction in gastric cancer with emphasis on the oncogenic role of SLC5A12","authors":"Chenyi Lin ,&nbsp;Jianjian Ye ,&nbsp;Chao Xu ,&nbsp;Ying Zheng ,&nbsp;Yining Xu ,&nbsp;Yuluo Chen ,&nbsp;Liangjie Chi ,&nbsp;Jia Lin ,&nbsp;Feng Li ,&nbsp;Yao Lin ,&nbsp;Qingshui Wang","doi":"10.1016/j.bbagen.2024.130739","DOIUrl":"10.1016/j.bbagen.2024.130739","url":null,"abstract":"<div><h3>Background</h3><div>Gastric cancer remains a common malignancy with poor prognosis. While lactate metabolism is recognized as a significant factor in tumor progression, its potential as a predictive tool for treatment response remains unexplored. This study introduces a novel Lactate-Related Gene Signature (LRGS) designed to predict both survival outcomes and therapy responses in gastric cancer patients.</div></div><div><h3>Methods</h3><div>We comprehensively analyzed 335 lactate-related genes from 11 metabolic pathways using MSigDB, identifying 278 differentially expressed genes between gastric cancer and normal tissues. Employing the LASSO Cox regression model, we developed an innovative LRGS formula based on the expression of 16 key lactate-related genes. The impact of Solute Carrier Family 5 Member 12 (SLC5A12), a gene of particular interest, on gastric cancer cell functions was evaluated using in vitro assays and an in vivo zebrafish model.</div></div><div><h3>Results</h3><div>Our newly established LRGS demonstrated robust capability in stratifying gastric cancer patients by survival risk. Notably, the LRGS-low subtype showed significantly improved overall and disease-free survival rates compared to the LRGS-high subtype. A key finding was LRGS's ability to predict patient responses to both adjuvant chemotherapy and immunotherapy. Random forest analysis identified SLC5A12 as the most significant gene differentiating gastric cancer from normal tissues. Functional experiments confirmed SLC5A12's role in promoting gastric cancer cell proliferation, invasion, and migration both in vitro and in vivo.</div></div><div><h3>Conclusion</h3><div>The LRGS is a dependable and efficient prognostic tool for assessing the survival outcomes in individuals with gastric cancer, as well as a predictor of patient response to adjuvant chemotherapy and immunotherapy.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 2","pages":"Article 130739"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821708","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}
引用次数: 0
Fucosyltransferase 4 upregulates P-gp expression for chemoresistance via NF-κB signaling pathway focusyltransferase 4通过NF-κB信号通路上调P-gp的表达,参与化学耐药。
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2025-02-01 DOI: 10.1016/j.bbagen.2024.130753
Zixuan Cai , Tomoya Isaji , Caixia Liang , Tomohiko Fukuda , Dongmei Zhang , Jianguo Gu
{"title":"Fucosyltransferase 4 upregulates P-gp expression for chemoresistance via NF-κB signaling pathway","authors":"Zixuan Cai ,&nbsp;Tomoya Isaji ,&nbsp;Caixia Liang ,&nbsp;Tomohiko Fukuda ,&nbsp;Dongmei Zhang ,&nbsp;Jianguo Gu","doi":"10.1016/j.bbagen.2024.130753","DOIUrl":"10.1016/j.bbagen.2024.130753","url":null,"abstract":"<div><h3>Background</h3><div>Multidrug resistance (MDR) poses a significant obstacle to developing chemotherapeutic treatments. In previous studies using a traditional model of adriamycin resistance (ADR) with K562 cells, we demonstrated that <em>N</em>-acetylglucosaminyltransferase III (GnT-III) expression negatively regulates chemoresistance. Additionally, we observed that fucosylation levels were increased in the ADR cells.</div></div><div><h3>Method</h3><div>Fucosylation levels were determined using lectin blot, western blot, and flow cytometry. Gene expression levels were analyzed via qPCR. We generated a <em>FUT4</em> knockout (KO) ADR cell line using CRISPR/Cas9 technology. Cytotoxicity and drug efflux assays were conducted to evaluate chemotherapy tolerance.</div></div><div><h3>Results</h3><div>The expression levels of FUT4 and its products, the Le<sup>X</sup> antigens, were significantly upregulated in the ADR cells compared to the parental K562 cells. The <em>FUT4</em> KO reduced the elevated levels of P-glycoprotein (P-gp) found in ADR cells and exhibited increased sensitivity to chemotherapeutic drugs. Furthermore, restoring <em>FUT4</em> expression in the KO cells effectively reversed P-gp expression, drug efflux, and chemoresistance. Given the critical role of the NF-κB pathway in P-gp expression, we investigated NF-κB signaling and found that the phosphorylation levels of p65 were significantly increased in the ADR cells but were downregulated in the <em>FUT4</em> KO cells. Furthermore, the restoration of <em>FUT4</em> rescued the phosphorylation levels of p65.</div></div><div><h3>Conclusions</h3><div>FUT4 specifically upregulates P-gp expression related to chemoresistance through the NF-κB signaling pathway.</div></div><div><h3>General significance</h3><div>This study highlights the importance of FUT4 in chemoresistance and suggests it may serve as a promising target for combating MDR.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 2","pages":"Article 130753"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891769","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
High dose of ascorbic acid induces selective cell growth inhibition and cell death in human gastric signet-ring cell carcinoma-derived NUGC-4 cells 高剂量抗坏血酸诱导人胃印戒细胞癌源性NUGC-4细胞选择性生长抑制和细胞死亡。
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2025-02-01 DOI: 10.1016/j.bbagen.2024.130738
Yasukazu Saitoh , Kaori Takeda , Koichi Okawachi , Yusuke Tanimura
{"title":"High dose of ascorbic acid induces selective cell growth inhibition and cell death in human gastric signet-ring cell carcinoma-derived NUGC-4 cells","authors":"Yasukazu Saitoh ,&nbsp;Kaori Takeda ,&nbsp;Koichi Okawachi ,&nbsp;Yusuke Tanimura","doi":"10.1016/j.bbagen.2024.130738","DOIUrl":"10.1016/j.bbagen.2024.130738","url":null,"abstract":"<div><div>Anticancer effects of high-dose vitamin C (VC) have been evaluated on many cancer cell lines, and its efficacy in clinical trials and in combination with anticancer drugs or radiation have been reported; however, its effect on gastric cancer and its mechanisms remain unclear. In the present study, the cell growth inhibitory/lethal effects of high-dose ascorbic acid (AsA), a reduced form of VC was examined on three gastric cancer cell lines. Of these, signet ring cell carcinoma NUGC-4 cells were the most sensitive, but the effects were small and limited in normal cells. Second, high-dose AsA was effective in NUGC-4 cells, whereas dehydroascorbic acid, an oxidized form of VC, was less effective. Third, high-dose AsA showed stronger cell growth inhibitory/lethal effects on floating cells than on adherent cells, and was effective even under hypoxic microenvironment conditions. A single 1-h treatment of high-dose AsA strongly inhibited cell growth, causing apoptosis-like cell death over 72 h after treatment, triggered by hydrogen peroxide generation, actin abnormality, DNA synthesis suppression, DNA damage induction, and ATP level decrease. The effects of high-dose AsA were inhibited either by adding or chelating iron ions, but was not affected via inhibiting AsA transport. Inhibition of glutathione synthesis enhanced the anticancer effects of high-dose AsA. These results indicate that a single high-dose of AsA induces cancer cell-selective, sustained cell growth inhibition and cell death, and these effects may be regulated by iron ion and/or intracellular oxidative stress levels in human gastric signet-ring cell carcinoma-derived NUGC-4 cells.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 2","pages":"Article 130738"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827298","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
Beyond protein folding: The pleiotropic functions of PPIases in cellular processes and microbial virulence 超越蛋白质折叠:PPIases在细胞过程和微生物毒力中的多效性功能。
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2025-02-01 DOI: 10.1016/j.bbagen.2024.130754
Roopshali Rakshit , Aayush Bahl , Arunima Arunima , Saurabh Pandey , Deeksha Tripathi
{"title":"Beyond protein folding: The pleiotropic functions of PPIases in cellular processes and microbial virulence","authors":"Roopshali Rakshit ,&nbsp;Aayush Bahl ,&nbsp;Arunima Arunima ,&nbsp;Saurabh Pandey ,&nbsp;Deeksha Tripathi","doi":"10.1016/j.bbagen.2024.130754","DOIUrl":"10.1016/j.bbagen.2024.130754","url":null,"abstract":"<div><div>Peptidyl prolyl cis/trans isomerases (PPIases), a ubiquitously distributed superfamily of enzymes, associated with signal transduction, trafficking, assembly, biofilm formation, stress tolerance, cell cycle regulation, gene expression and tissue regeneration, is a key regulator of metabolic disorders and microbial virulence. This review assumes an integrative approach, to provide a holistic overview of the structural and functional diversity of PPIases, examining their conformational dynamics, cellular distribution, and physiological significance. We explore their intricate involvement in cellular processes and virulence modulation in both eukaryotic and prokaryotic systems. Additionally, we evaluate the potential of these molecular chaperones as drug targets and vaccine candidates, emphasizing their relevance in therapeutic development. By synthesizing recent findings and providing a broader perspective on these proteins, this review aims to enhance our understanding of their multifaceted roles in biology and their potential applications in medicine.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 2","pages":"Article 130754"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891751","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
From non-coding to coding: The importance of long non-coding RNA translation in de novo gene birth 从非编码到编码:长链非编码RNA翻译在新生基因出生中的重要性。
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2025-02-01 DOI: 10.1016/j.bbagen.2024.130747
Taichi Shiraishi, Akinobu Matsumoto
{"title":"From non-coding to coding: The importance of long non-coding RNA translation in de novo gene birth","authors":"Taichi Shiraishi,&nbsp;Akinobu Matsumoto","doi":"10.1016/j.bbagen.2024.130747","DOIUrl":"10.1016/j.bbagen.2024.130747","url":null,"abstract":"<div><div>Recent emerging evidence demonstrates that some long non-coding RNAs (lncRNAs) can indeed be translated into functional polypeptides. These discoveries are pivotal for understanding de novo gene birth, the process by which new genes evolve from previously non-genic regions. In this review, we first introduce key methods, such as Ribo-seq and translation initiation site detection by translation complex analysis, for identifying coding sequences within lncRNAs and highlight examples of functional polypeptides derived from lncRNAs across species. These polypeptides play essential roles in maintaining cellular homeostasis and contribute to pathological processes, including cancer. However, because not all lncRNA-derived polypeptides appear to be functional, these lncRNAs may act as gene reservoirs. We also discuss how lncRNAs change their intracellular localization, how lncRNA-derived polypeptides evade immune surveillance, and how they gradually evolve into typical coding RNAs, providing evidence for the evolutionary model of de novo gene birth.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 2","pages":"Article 130747"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871064","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
Structural investigation of erdafitinib, an anticancer drug, with ctDNA: A spectroscopic and computational study 抗癌药物埃达非替尼与ctDNA的结构研究:光谱和计算研究。
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2025-02-01 DOI: 10.1016/j.bbagen.2024.130751
Mohd Amir , Mohd Aamir Qureshi , Javed Musarrat , Saleem Javed
{"title":"Structural investigation of erdafitinib, an anticancer drug, with ctDNA: A spectroscopic and computational study","authors":"Mohd Amir ,&nbsp;Mohd Aamir Qureshi ,&nbsp;Javed Musarrat ,&nbsp;Saleem Javed","doi":"10.1016/j.bbagen.2024.130751","DOIUrl":"10.1016/j.bbagen.2024.130751","url":null,"abstract":"<div><div>The interaction of drugs with DNA is crucial for understanding their mechanism of action, particularly in the context of gene expression regulation. Erdafitinib (EDB), a pan-FGFR (fibroblast growth factor receptor) inhibitor approved by the FDA, is a potent anticancer agent used primarily in the treatment of urothelial carcinoma. In this study, the binding interaction between EDB and calf thymus DNA (ctDNA) was assessed using molecular docking, UV-absorption spectroscopy, fluorescence spectroscopy, and circular dichroism (CD) spectroscopy. The absorption spectra indicated a hypochromic effect when EDB was combined with ctDNA. The binding constant (K<sub>a</sub>) of EDB-ctDNA complex was calculated as 7.84 × 10<sup>3</sup> M<sup>−1</sup>, corresponds to a free energy change (ΔG) value of approximately −5.06 kcal/mol, indicating a moderate binding affinity. Fluorometric analysis revealed a static binding mechanism in the ground state, with a bimolecular enhancement constant (K<sub>B</sub>) of 7.56 × 10<sup>11</sup> M<sup>−1</sup>. Displacement experiments demonstrated that EDB preferentially binds to the minor groove of ctDNA, with a Ksv value of 5.14 × 10<sup>4</sup> M<sup>−1</sup>. Further, KI quenching and CD spectroscopy confirmed the minor groove binding mode, which was associated with a decrease in the T<sub>m</sub> from 68.28 °C to 65.84 °C, reflecting a destabilizing effect on DNA helix. Molecular docking supported these findings, showing that EDB exhibits a strong affinity for the minor groove of ctDNA and hydrogen bonding and Vander Waal interactions are the major forces involved in the binding. These results suggest that EDB primarily binds to the minor groove of ctDNA, which may play a role in its anticancer activity.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 2","pages":"Article 130751"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891771","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
Unraveling the intricate tapestry of bamboo transcription factors in abiotic stress signaling and resilience with special reference to moso bamboo family 揭示竹子转录因子在非生物胁迫信号和恢复中的复杂织锦,特别涉及毛竹家族。
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2025-02-01 DOI: 10.1016/j.bbagen.2024.130755
Anita Kumari , Sudhir K. Sopory , Rohit Joshi
{"title":"Unraveling the intricate tapestry of bamboo transcription factors in abiotic stress signaling and resilience with special reference to moso bamboo family","authors":"Anita Kumari ,&nbsp;Sudhir K. Sopory ,&nbsp;Rohit Joshi","doi":"10.1016/j.bbagen.2024.130755","DOIUrl":"10.1016/j.bbagen.2024.130755","url":null,"abstract":"<div><div>The abiotic stress tolerance mechanism in plants is regulated by multiple physiological, biochemical, and molecular processes; hence, omics approaches to underpin these mechanisms are essential. It is clear that transcription factors (TFs) are one of the fundamental molecular switches that play a crucial role in modulating, regulating, and orchestrating plants in response to various climatic vagaries. Several reports are available now, focusing on understanding the roles of TFs, including those in Poaceae family in regulating different biological processes and stress responses. However, research on bamboo TFs' regulatory role in providing abiotic stress tolerance is limited. Hence the present review offers innovative insights into unraveling the molecular regulation of known family of TFs in different species of bamboo which have been identified as regulators of transcript abundance in numerous genes responsive to various abiotic stresses. Additionally, this review highlights recent discoveries concerning bamboo TFs, encompassing their classification, promoter analysis and functional dynamics in response to different abiotic stresses. Attempt has also been made to delve into the molecular interplay and cross-talk among these TFs during abiotic stresses, thus proposing potential strategies for enhancing the intricate regulatory networks involved in the adaptive responses of bamboo species.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 2","pages":"Article 130755"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142908760","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
Computational analysis of the alpha−2 domain of apolipoprotein B − 100, a potential triggering factor in LDL aggregation 载脂蛋白B α -2结构域 - 100的计算分析,这是LDL聚集的潜在触发因子。
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2025-02-01 DOI: 10.1016/j.bbagen.2024.130742
Joanne Jennifer E. Tan , Marvin M. Bilog , Adam A. Profit , Francisco M. Heralde III , Ruel Z.B. Desamero
{"title":"Computational analysis of the alpha−2 domain of apolipoprotein B − 100, a potential triggering factor in LDL aggregation","authors":"Joanne Jennifer E. Tan ,&nbsp;Marvin M. Bilog ,&nbsp;Adam A. Profit ,&nbsp;Francisco M. Heralde III ,&nbsp;Ruel Z.B. Desamero","doi":"10.1016/j.bbagen.2024.130742","DOIUrl":"10.1016/j.bbagen.2024.130742","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Atherosclerosis, the major underlying cause of cardiovascular disease, is believed to arise from the accumulation of low-density lipoprotein (LDL) in the arterial subendothelial space, ultimately leading to plaque formation. It is proposed that the accumulation of LDL is linked to its intrinsic aggregation propensity. Although the native LDL is not prone to aggregation, LDL(−), an electronegative LDL characterized in the plasma, has been shown to prime LDL aggregation in a domino-like behavior similar to amyloidogenic proteins. LDL(−) has also been observed to have a misfolded apolipoprotein B-100 (apo B-100), a huge protein consisting of 4563 amino acid residues. As misfolding of proteins is commonly associated with amyloid formation, apo B-100 is therefore being considered as the possible triggering factor in LDL aggregation. Previous computational studies have implicated the α2 domain to be the aggregation-prone region of apo B-100. In this study, the amyloidogenic properties of the α2 domain of apo B-100 were interrogated using both &lt;em&gt;in silico&lt;/em&gt; and &lt;em&gt;in vitro&lt;/em&gt; techniques.&lt;/div&gt;&lt;div&gt;Since the crystal structure of the 570-amino acid α2 domain of apo B-100 is yet to be solved, we used several secondary structure prediction tools to model putative helical regions that make up the α2 domain. The stability of each of the 17 helices thus identified was further probed using molecular dynamics (MD), with the least stable of the helices considered as potentially amyloidogenic. In a 100 ns simulation window, helices &lt;strong&gt;&lt;em&gt;k&lt;/em&gt;&lt;/strong&gt; (YFEKLVGFIDDAVK), &lt;strong&gt;&lt;em&gt;m&lt;/em&gt;&lt;/strong&gt; (YHQFVDETNDKIREVTQRLNGEIQA), and &lt;strong&gt;&lt;em&gt;p&lt;/em&gt;&lt;/strong&gt; (QQELQRYLSLVGQVYS) were the least stable and appeared to transition to β-structures, the hallmark of amyloidogenesis. When the simulation was extended to longer times, only helices &lt;strong&gt;&lt;em&gt;k&lt;/em&gt;&lt;/strong&gt; and &lt;strong&gt;&lt;em&gt;p&lt;/em&gt;&lt;/strong&gt; formed stable β-sheets that persisted. Analysis of the data indicates that the final β-sheet conformation was stabilized by the π-π stacking interactions between the aromatic rings of Tyr-1 and Phe-8 for helix &lt;strong&gt;&lt;em&gt;k&lt;/em&gt;&lt;/strong&gt; and likely π-π stacking contacts between Arg-6 guanidino group and Tyr-15 ring for helix &lt;strong&gt;&lt;em&gt;p&lt;/em&gt;&lt;/strong&gt;.&lt;/div&gt;&lt;div&gt;Based on the &lt;em&gt;in silico&lt;/em&gt; work, we proceeded to synthesize and spectroscopically characterize helices &lt;strong&gt;&lt;em&gt;k&lt;/em&gt;&lt;/strong&gt;, &lt;strong&gt;&lt;em&gt;m&lt;/em&gt;&lt;/strong&gt;&lt;sub&gt;&lt;strong&gt;&lt;em&gt;17&lt;/em&gt;&lt;/strong&gt;&lt;/sub&gt;&lt;sub&gt;&lt;strong&gt;&lt;em&gt;–&lt;/em&gt;&lt;/strong&gt;&lt;/sub&gt;&lt;sub&gt;&lt;strong&gt;&lt;em&gt;25&lt;/em&gt;&lt;/strong&gt;&lt;/sub&gt; (QRLNGEIQA), and &lt;strong&gt;&lt;em&gt;p&lt;/em&gt;&lt;/strong&gt;. As expected, &lt;strong&gt;&lt;em&gt;k&lt;/em&gt;&lt;/strong&gt; and &lt;strong&gt;&lt;em&gt;p&lt;/em&gt;&lt;/strong&gt; formed detectable amyloids, with the latter appearing to be substantially more amyloidogenic based on kinetic aggregation assays. Amyloid fibrils formed by &lt;strong&gt;&lt;em&gt;p&lt;/em&gt;&lt;/strong&gt; were confirmed using circular dichroism spectroscopy and transmission electron microscopy. Data obtained could be ex","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 2","pages":"Article 130742"},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833772","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
Synthesis of spherical and rods-like titanium oxide nanoparticles (TiO2 NPs) and evaluation of their cytotoxicity towards colon cells in vitro 球形和棒状氧化钛纳米颗粒(TiO2 NPs)的合成及其体外对结肠细胞的细胞毒性评价
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2025-02-01 DOI: 10.1016/j.bbagen.2024.130743
Bartosz Klebowski , Karolina Kosinska , Agnieszka Bukowska , Piotr M. Zieliński , Magdalena Parlinska-Wojtan , Joanna Depciuch
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