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The Connection Between Lipid Metabolism in the Heart and Liver of Wuzhishan Pigs. 五指山猪心脏和肝脏脂质代谢的关系。
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-07-16 DOI: 10.3390/biom15071024
Yuwei Ren, Feng Wang, Ruiping Sun, Xinli Zheng, Yanning Lin, Zhe Chao
{"title":"The Connection Between Lipid Metabolism in the Heart and Liver of Wuzhishan Pigs.","authors":"Yuwei Ren, Feng Wang, Ruiping Sun, Xinli Zheng, Yanning Lin, Zhe Chao","doi":"10.3390/biom15071024","DOIUrl":"10.3390/biom15071024","url":null,"abstract":"<p><p>Lipid metabolism is critical for the physiological activities of signal transduction, metabolic regulation, and energy provision, and Wuzhishan (WZS) pigs are a promising animal model for studying human diseases. However, lipid metabolites in the heart and liver of WZS pigs are indistinct. In this study, we detected gene expression, blood biochemical parameters, and metabolic profiles of hearts and livers of WZS and Large White (LW) pigs, and analyzed correlations between metabolites. The results showed that the fatty acid metabolic process was present in both the heart and liver, and was more dominant in the liver. Although the expression of lipid absorption-related genes of <i>CYP7A1</i> increased in the liver, <i>CEBPB</i> levels increased in both the liver and heart; the fatty acid beta-oxidation genes <i>RXRA</i> and <i>ACSS2</i> also showed increased expression. The quantity of metabolites related to lipid synthesis decreased in the liver, heart, and blood for WZS pigs compared to that of LW pigs, indicating a balance of lipid synthesis and breakdown for WZS pigs. Moreover, the lipid metabolites in the liver and heart exhibited strong correlations with each other and showed similar correlations to blood biochemical parameters, respectively. This study declared the balance of lipid metabolism in both the heart and liver, and identified their connections for WZS pigs.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144727711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Three-Dimensional Models of Implantation Using Human Stem Cells: Scientific Insights and Broader Considerations. 使用人类干细胞植入的三维模型:科学见解和更广泛的考虑。
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-07-16 DOI: 10.3390/biom15071023
Megan Munsie, Jock K Findlay
{"title":"Three-Dimensional Models of Implantation Using Human Stem Cells: Scientific Insights and Broader Considerations.","authors":"Megan Munsie, Jock K Findlay","doi":"10.3390/biom15071023","DOIUrl":"10.3390/biom15071023","url":null,"abstract":"<p><p>The ability to model the earliest stages of human embryonic development in vitro using pluripotent stem cells offers researchers new ways to understand and interrogate the intricacies of implantation. It also raises important ethical and regulatory considerations, both those common to research involving human embryos, as well as those unique to stem cell-based embryo and endometrial models. This review examines the underpinning scientific discoveries that have led to the development of this rapidly expanding area of research, and how three-dimensional embryo models could be employed in advancing assisted reproductive technologies and understanding implantation failure. Importantly, we also discuss the ethical and legal implications and explore various governance models that have been proposed to foster responsibility and innovation in this area of research. Given the heightened interest in the scientific community on this topic, we finish on the question of how and when to involve the public in the development of this technology and its regulation.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144727732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Transcription-Coupled Nucleotide Excision Repair: A Faster Solution or the Only Option? 转录偶联核苷酸切除修复:更快的解决方案还是唯一的选择?
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-07-16 DOI: 10.3390/biom15071026
Andriy Khobta, Leen Sarmini
{"title":"Transcription-Coupled Nucleotide Excision Repair: A Faster Solution or the Only Option?","authors":"Andriy Khobta, Leen Sarmini","doi":"10.3390/biom15071026","DOIUrl":"10.3390/biom15071026","url":null,"abstract":"<p><p>A branch of the nucleotide excision repair (NER) pathway, transcription-coupled repair (TCR or TC-NER) specifically operates on the template DNA strand of actively transcribed genes. Initiated by stalling of elongating RNA polymerase complexes at damaged sites, TC-NER has historically been viewed as \"accelerated repair\", arguably necessary for the maintenance of vital transcription function. Conversely, the conventional \"global genome\" (GG-NER) mechanism, operating throughout the genome, is usually regarded as a much slower process, even though it has long been found that differences in repair kinetics between transcribed DNA and the rest of the genome are not manifested for all structural types of DNA damage. Considering that damage detection is the rate-limiting step of overall repair reactions in most cases and that the mechanisms of the initial recognition of modified DNA structure are fundamentally different between TC-NER and GG-NER, it is suggestive to attribute the observed kinetic differences to different damage spectra recognized by the two pathways. This review summarizes current knowledge on the differential requirements of TC-NER and GG-NER towards specific damage types, based on their structural rather than spatial characteristics, and highlights some common features of DNA modifications repaired preferentially or exclusively by TC-NER, while evading other repair mechanisms.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144727734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Role of Oral Bacteria in Mediating Gemcitabine Resistance in Pancreatic Cancer. 口腔细菌介导胰腺癌患者吉西他滨耐药的作用。
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-07-15 DOI: 10.3390/biom15071018
Geng Xu, Yaling Jiang, Chen Sun, Bernd W Brandt, Kamran Nazmi, Luca Morelli, Giulia Lencioni, Elisa Giovannetti, Dongmei Deng
{"title":"Role of Oral Bacteria in Mediating Gemcitabine Resistance in Pancreatic Cancer.","authors":"Geng Xu, Yaling Jiang, Chen Sun, Bernd W Brandt, Kamran Nazmi, Luca Morelli, Giulia Lencioni, Elisa Giovannetti, Dongmei Deng","doi":"10.3390/biom15071018","DOIUrl":"10.3390/biom15071018","url":null,"abstract":"<p><p>Oral microbiota have been implicated in pancreatic ductal adenocarcinoma (PDAC) and may contribute to chemotherapy resistance. While previous studies attributed bacteria-induced resistance to indirect host modulation, recent findings suggest a direct mechanism. <i>Escherichia coli</i> expressing long-form cytidine deaminase (CDD<sub>L</sub>) can degrade gemcitabine, a chemotherapeutic agent, into a non-toxic form, leading to resistance. In contrast, bacteria carrying short form (CDD<sub>S</sub>) or lacking CDD did not induce resistance. This study investigates whether oral bacteria can cause gemcitabine resistance in PDAC cells through CDD-mediated degradation. Oral microbes associated with PDAC were selected based on CDD isoforms: <i>Aggregatibacter actinomycetemcomitans</i> carrying CDD<sub>L</sub>, <i>Enterococcus faecalis</i>, <i>Streptococcus mutans</i>, <i>Porphyromonas gingivalis</i>, all carrying CDD<sub>S</sub>, and <i>Fusobacterium nucleatum</i> lacking CDD. The selected microbes, along with wild-type and CDD-deficient <i>E. coli</i>, were co-incubated with gemcitabine to assess its degradation and PDAC cell proliferation. <i>A. actinomycetemcomitans</i> fully degraded gemcitabine and induced resistance. Surprisingly, CDD<sub>S</sub>-expressing oral bacteria partially degraded gemcitabine in a strain-dependent manner. Expressing either CDD<sub>L</sub> or CDD<sub>S</sub> in CDD-deficient <i>E. coli</i> resulted in equivalent gemcitabine degradation and resistance, indicating that CDD function is independent of isoform length. These findings highlight the role of oral bacteria in gemcitabine resistance and the need for strategies to mitigate microbial-driven resistance in PDAC treatment.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144727692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Quantitative Alterations in Short-Chain Fatty Acids in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis. 短链脂肪酸在炎症性肠病中的定量改变:一项系统综述和荟萃分析。
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-07-15 DOI: 10.3390/biom15071017
Laura Chulenbayeva, Zharkyn Jarmukhanov, Karlygash Kaliyekova, Samat Kozhakhmetov, Almagul Kushugulova
{"title":"Quantitative Alterations in Short-Chain Fatty Acids in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.","authors":"Laura Chulenbayeva, Zharkyn Jarmukhanov, Karlygash Kaliyekova, Samat Kozhakhmetov, Almagul Kushugulova","doi":"10.3390/biom15071017","DOIUrl":"10.3390/biom15071017","url":null,"abstract":"<p><strong>Background: </strong>Reduced short-chain fatty acids (SCFAs) in inflammatory bowel disease (IBD) impair the gut barrier and immune function, promoting inflammation and highlighting microbiome-targeted therapies' therapeutic potential. The purpose of this meta-analysis was to study the changes in SCFAs in IBD and their potential role in the occurrence and development of IBD.</p><p><strong>Methods: </strong>The analysis employed a random-effects model to assess the standardized mean difference (SMD) with a 95% confidence interval. A literature search was conducted in databases from 2014 to 20 July 2024 to identify studies investigating SCFAs in IBD.</p><p><strong>Results: </strong>Subgroup analyses revealed a significant reduction in fecal SCFA levels-specifically butyrate, acetate, and propionate-in all IBD subgroups compared to healthy controls. Active IBD showed a greater decrease in butyrate (<i>p</i> = 0.004), and UC showed a notable reduction in propionate (<i>p</i> = 0.03). When comparing UC and CD, differences were observed mainly in propionate (SMD = -0.76, <i>p</i> = 0.00001). Dietary interventions in IBD patients led to increased SCFA levels, with butyrate showing the most improvement (SMD = 1.03), suggesting the potential therapeutic value of dietary modulation.</p><p><strong>Conclusions: </strong>In conclusion, this meta-analysis demonstrates a significant reduction in fecal SCFA levels in patients with IBD, particularly during active phases of the disease and most markedly in CD.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144727685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Targeting Sodium Transport Reveals CHP1 Downregulation as a Novel Molecular Feature of Malignant Progression in Clear Cell Renal Cell Carcinoma: Insights from Integrated Multi-Omics Analyses. 靶向钠转运揭示CHP1下调是透明细胞肾细胞癌恶性进展的新分子特征:来自综合多组学分析的见解
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-07-15 DOI: 10.3390/biom15071019
Yun Wu, Ri-Ting Zhu, Jia-Ru Chen, Xiao-Min Liu, Guo-Liang Huang, Jin-Cheng Zeng, Hong-Bing Yu, Xin Liu, Cui-Fang Han
{"title":"Targeting Sodium Transport Reveals CHP1 Downregulation as a Novel Molecular Feature of Malignant Progression in Clear Cell Renal Cell Carcinoma: Insights from Integrated Multi-Omics Analyses.","authors":"Yun Wu, Ri-Ting Zhu, Jia-Ru Chen, Xiao-Min Liu, Guo-Liang Huang, Jin-Cheng Zeng, Hong-Bing Yu, Xin Liu, Cui-Fang Han","doi":"10.3390/biom15071019","DOIUrl":"10.3390/biom15071019","url":null,"abstract":"<p><p>Clear cell renal cell carcinoma (ccRCC), the most common RCC subtype, displays significant intratumoral heterogeneity driven by metabolic reprogramming, which complicates our understanding of disease progression and limits treatment efficacy. This study aimed to construct a comprehensive cellular and transcriptional landscape of ccRCC, with emphasis on gene expression dynamics during malignant progression. An integrated analysis of 90 scRNA-seq samples comprising 534,227 cells revealed a progressive downregulation of sodium ion transport-related genes, particularly CHP1 (calcineurin B homologous protein isoform 1), which is predominantly expressed in epithelial cells. Reduced CHP1 expression was confirmed at both mRNA and protein levels using bulk RNA-seq, CPTAC proteomics, immunohistochemistry, and ccRCC cell lines. Survival analysis showed that high CHP1 expression correlated with improved prognosis. Functional analyses, including pseudotime trajectory, Mfuzz clustering, and cell-cell communication modeling, indicated that CHP1<sup>+</sup> epithelial cells engage in immune interaction via PPIA-BSG signaling. Transcriptomic profiling and molecular docking suggested that CHP1 modulates amino acid transport through SLC38A1. ZNF460 was identified as a potential transcription factor of CHP1. Virtual screening identified arbutin and imatinib mesylate as candidate CHP1-targeting compounds. These findings establish CHP1 downregulation as a novel molecular feature of ccRCC progression and support its utility as a prognostic biomarker.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144727709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Generation of Novel Monoclonal Antibodies Recognizing Rabbit CD34 Antigen. 识别兔CD34抗原的新型单克隆抗体的产生。
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-07-15 DOI: 10.3390/biom15071021
Jaromír Vašíček, Miroslav Bauer, Eva Kontseková, Andrej Baláži, Andrea Svoradová, Linda Dujíčková, Eva Tvrdá, Jakub Vozaf, Peter Supuka, Peter Chrenek
{"title":"Generation of Novel Monoclonal Antibodies Recognizing Rabbit CD34 Antigen.","authors":"Jaromír Vašíček, Miroslav Bauer, Eva Kontseková, Andrej Baláži, Andrea Svoradová, Linda Dujíčková, Eva Tvrdá, Jakub Vozaf, Peter Supuka, Peter Chrenek","doi":"10.3390/biom15071021","DOIUrl":"10.3390/biom15071021","url":null,"abstract":"<p><p>The rabbit is a widely used experimental model for human translational research and stem cell therapy. Many studies have focused on rabbit mesenchymal stem cells from different biological sources for their possible application in regenerative medicine. However, a minimal number of studies have been published aimed at rabbit hematopoietic stem/progenitor cells, mainly due to the lack of specific anti-rabbit CD34 antibodies. In general, CD34 antigen is commonly used to identify and isolate hematopoietic stem/progenitor cells in humans and other animal species. The aim of this study was to develop novel monoclonal antibodies highly specific to rabbit CD34 antigen. We used hybridoma technology, two synthetic peptides derived from predicted rabbit CD34 protein, and a recombinant rabbit CD34 protein as immunogens to produce monoclonal antibodies (mAbs) specific to rabbit CD34. The produced antibodies were screened for their binding activity and specificity using ELISA, flow cytometry, and Western blot analysis. Finally, four mAbs (58/47/26, 58/47/34, 182/7/80, and 575/36/8) were selected for the final purification process. The purified mAbs recognized up to 2-3% of total rabbit bone marrow cells, while about 2% of those cells exhibited CD45 expression, which are likely rabbit primitive hematopoietic stem cells and their hematopoietic progenitors, respectively. The newly generated and purified mAbs specifically recognize CD34 antigen in rabbit bone marrow or peripheral blood and can be therefore used for further immunological applications, to study rabbit hematopoiesis or to establish a new animal model for hematopoietic stem cell transplantation studies.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144727651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
A Scoping Review of Sarcoglycan Expression in Non-Muscle Organs: Beyond Muscles. 非肌肉器官中肌糖聚糖表达的综述:肌肉以外。
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-07-15 DOI: 10.3390/biom15071020
Fabiana Nicita, Josè Freni, Antonio Centofanti, Angelo Favaloro, Davide Labellarte, Giuseppina Cutroneo, Michele Runci Anastasi, Giovanna Vermiglio
{"title":"A Scoping Review of Sarcoglycan Expression in Non-Muscle Organs: Beyond Muscles.","authors":"Fabiana Nicita, Josè Freni, Antonio Centofanti, Angelo Favaloro, Davide Labellarte, Giuseppina Cutroneo, Michele Runci Anastasi, Giovanna Vermiglio","doi":"10.3390/biom15071020","DOIUrl":"10.3390/biom15071020","url":null,"abstract":"<p><p>This scoping review explores the expression patterns and molecular features of sarcoglycans (SGs) in non-muscle organs, challenging the long-standing assumption that their function is confined to skeletal and cardiac muscle. By analyzing evidence from both animal models and human studies, the review highlights the widespread presence of SG subunits in organs, including the nervous system, glands, adipose tissue, oral mucosa, retina, and other structures, with distinct regional and cell-type-specific patterns. Studies on the central nervous system demonstrate a widespread \"spot-like\" distribution of SG subunits in neurons and glial cells, implicating their involvement in synaptic organization and neurotransmission. Similarly, SGs maintain cellular integrity and homeostasis in glands and adipose tissue. At the same time, the altered expression of SGs is associated with pathological conditions in the gingival epithelium of the oral mucosa. These findings underscore the multifaceted roles of SGs beyond muscle, suggesting that they may contribute to cellular signaling, membrane stability, and neurovascular coupling. However, significant gaps remain regarding SG post-translational modifications and functional implications in non-muscle organs. Future research integrating molecular, cellular, and functional approaches in animal models and human tissues is essential to fully elucidate these roles and explore their potential as therapeutic targets in various diseases.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144727591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
The Immune Regulatory Functions of CD226 and Its Implications in Immune-Mediated Diseases. CD226的免疫调节功能及其在免疫介导疾病中的意义
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-07-14 DOI: 10.3390/biom15071007
Keyan Liu, Yuanzhen Liu, Huabao Xiong, Zhaochen Ning
{"title":"The Immune Regulatory Functions of CD226 and Its Implications in Immune-Mediated Diseases.","authors":"Keyan Liu, Yuanzhen Liu, Huabao Xiong, Zhaochen Ning","doi":"10.3390/biom15071007","DOIUrl":"10.3390/biom15071007","url":null,"abstract":"<p><p>CD226, a member of the immunoglobulin superfamily, serves as a critical regulator in various immunological processes. CD226 is expressed across immune and non-immune cells, with predominant expression being observed in natural killer (NK) cells and T cells. By engaging ligands CD155 and CD112, it orchestrates diverse signaling pathways that modulate T cell differentiation and effector functions while enhancing NK cell activation and cytotoxicity. Genetic polymorphisms and the dysregulated expression of CD226 are closely associated with susceptibility to autoimmune diseases, infectious diseases, allergic diseases, and cancer progression. Growing evidence highlight CD226's emerging promise as a therapeutic target for immune-mediated diseases. The present work aims to review the current understanding of CD226's role in immune responses and to comprehensively outline its multifaceted involvement in different immunological diseases, providing insights for future research to advance our mechanistic understanding of its roles in disease pathogenesis.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144727715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 and Cytotoxicity Evaluation of Denitroaristolochic Acids: Structural Insights and Mechanistic Implications in Nephrotoxicity. 反硝化马兜铃酸的合成和细胞毒性评价:肾毒性的结构见解和机制意义。
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-07-14 DOI: 10.3390/biom15071014
Jianfei Gao, Mengtong Zhao, Jianhua Su, Yi Gao, Xiaofeng Zhang, Yongzhao Ding, Xiaoping Liu, Yang Luan, Chun Hu
{"title":"Synthesis and Cytotoxicity Evaluation of Denitroaristolochic Acids: Structural Insights and Mechanistic Implications in Nephrotoxicity.","authors":"Jianfei Gao, Mengtong Zhao, Jianhua Su, Yi Gao, Xiaofeng Zhang, Yongzhao Ding, Xiaoping Liu, Yang Luan, Chun Hu","doi":"10.3390/biom15071014","DOIUrl":"10.3390/biom15071014","url":null,"abstract":"<p><p>The efficient synthetic routes and evaluates cytotoxic profiles of denitroaristolochic acids II-V (DAA-II-V) were demonstrated in this study. Based on retrosynthetic analysis, a modular synthetic strategy was developed through Suzuki-Miyaura coupling, Wittig reaction, and bismuth triflate-catalyzed intramolecular Friedel-Crafts cyclization to efficiently construct the phenanthrene core. Process optimization significantly improved yields: aryl bromide intermediate A reached 50.8% yield via bromination refinement, while arylboronic ester intermediate B overcame selectivity limitations. Combining Darzens condensation with Wittig reaction enhanced throughput, achieving 88.4% yield in the key cyclization. Structures were confirmed by NMR and mass spectra. CCK-8 cytotoxicity assays in human renal proximal tubular epithelial cells revealed distinct toxicological profiles: DAA-III and DAA-IV exhibited IC<sub>50</sub> values of 371 μM and 515 μM, respectively, significantly higher than the nitro-containing prototype AA-I (270 μM), indicating that the absence of nitro group attenuates but does not eliminate toxicity, potentially via altered metabolic activation. DAA-II and DAA-V showed no detectable cytotoxicity within assay limits, suggesting reduced toxicological impact. Structure-activity analysis exhibited that the nitro group is not essential for cytotoxicity, with methoxy substituents exerting limited influence on potency. This challenges the conventional DNA adduct-dependent toxicity paradigm, implying alternative mechanisms like oxidative stress or mitochondrial dysfunction may mediate damage in denitro derivatives. These systematic findings provide new perspectives for AA analog research and a foundation for the rational use and safety assessment of <i>Aristolochiaceae</i> plants.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144727705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
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