Cell Biochemistry and Biophysics最新文献

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Molecular Mechanisms and Therapeutic Targeting of the Macrophage Metabolic-Epigenetic Interaction Network in Chronic Obstructive Pulmonary Disease 慢性阻塞性肺疾病巨噬细胞代谢-表观遗传相互作用网络的分子机制和治疗靶向
IF 3 4区 生物学
Cell Biochemistry and Biophysics Pub Date : 2026-08-13 DOI: 10.1007/s12013-026-02124-x
Qi Liu, Weiying Liu
{"title":"Molecular Mechanisms and Therapeutic Targeting of the Macrophage Metabolic-Epigenetic Interaction Network in Chronic Obstructive Pulmonary Disease","authors":"Qi Liu,&nbsp;Weiying Liu","doi":"10.1007/s12013-026-02124-x","DOIUrl":"10.1007/s12013-026-02124-x","url":null,"abstract":"<div><p>Pulmonary macrophages serve as one of the primary mediators of the complex and persistent inflammation in chronic obstructive pulmonary disease (COPD). While driven by multiple mechanisms—including oxidative stress pathways, macrophage heterogeneity, microbiome interactions, and the dynamics of acute exacerbations—the intrinsic drivers promoting continuous inflammatory amplification remain incompletely defined. Recent findings point to a bidirectional relationship between cellular metabolism and epigenetic regulation as a driver of this abnormal activation. This review outlines the biochemical components of this crosstalk, linking shifts in glucose, lipid, and glutamine metabolism to chromatin remodeling events. We detail four major molecular axes: α-ketoglutarate-dependent DNA methylation, NAD⁺/SIRT1-mediated deacetylation, the acetyl-CoA-fueled histone acetylation feedback loop, and the regulatory influence of non-coding RNAs (ncRNAs). Together, these pathways create a self-sustaining cycle where altered metabolic fluxes reshape the epigenetic landscape, which subsequently reinforces the initial metabolic abnormalities. This loop helps establish a stable “functional memory” in macrophages, accelerating alveolar damage. Finally, we discuss current gaps, including the need for spatial mapping and multi-omics integration, and evaluate how emerging targeted therapies—such as dual-inhibitors, PROTACs, and RNA-based treatments—could disrupt this pathogenic loop to provide novel preclinical strategies for COPD management.</p></div>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":"84 3","pages":"3231 - 3244"},"PeriodicalIF":3.0,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148721258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Insects as a New Source of Biomolecules and their Application in Agroindustry, Cosmetics and Pharmacology 昆虫作为生物分子的新来源及其在农用工业、化妆品和药理学中的应用。
IF 3 4区 生物学
Cell Biochemistry and Biophysics Pub Date : 2026-08-12 DOI: 10.1007/s12013-026-02123-y
Mariam El Joubari, Manar Ibrahimi
{"title":"Insects as a New Source of Biomolecules and their Application in Agroindustry, Cosmetics and Pharmacology","authors":"Mariam El Joubari,&nbsp;Manar Ibrahimi","doi":"10.1007/s12013-026-02123-y","DOIUrl":"10.1007/s12013-026-02123-y","url":null,"abstract":"<div><p>This article highlights recent developments and the latest progress made in the use of insects as a new source of biomolecules in various fields like agro-industry, cosmetics and pharmacology. Indeed, numerous insect species such as the honeybee (<i>Apis mellifera</i>), the mealybug (<i>Coccus cacti</i>), the silkworm (<i>Bombyx mori</i>), the mealworm (<i>Tenebrio molitor</i>) and others constitute a rich source of bioactive molecules (enzymes, hormones, peptides, proteins, fatty acids, polysaccharides…) that can be used to develop innovative and effective products with various activities: antioxidant, antimicrobial, anticancer, anti-inflammatory, etc. The advantages and challenges associated with the use of insects as a source of biomolecules are also discussed. The article concludes by stressing the importance of further research into biomolecules of insect origin and their potential applications in a wide range of industries.</p></div>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":"84 3","pages":"3205 - 3229"},"PeriodicalIF":3.0,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Ferroptosis–Inflammation Crosstalk: Mechanistic Insights and Emerging Drug Targets 氧化铁-炎症串扰:机制见解和新兴药物靶点。
IF 3 4区 生物学
Cell Biochemistry and Biophysics Pub Date : 2026-08-12 DOI: 10.1007/s12013-026-02131-y
Sanjivani Gupta, Sayali Mukherjee
{"title":"Ferroptosis–Inflammation Crosstalk: Mechanistic Insights and Emerging Drug Targets","authors":"Sanjivani Gupta,&nbsp;Sayali Mukherjee","doi":"10.1007/s12013-026-02131-y","DOIUrl":"10.1007/s12013-026-02131-y","url":null,"abstract":"<div><p>Ferroptosis, a non-apoptotic form of regulated cell death characterized by iron accumulation and lipid peroxidation, has recently established its crucial role in inflammation and immune - related diseases. The current review aims at offering a comprehensive synthesis of the Interaction between ferroptosis and inflammation that governs the ferroptosis-inflammation axis, in which the inflammation environment and cell death process operates that can influence each other through difficult molecular pathways. In this context, this article discusses how inflammatory signalling pathways works, in terms of the inflammation environment, as exemplified by the pathway of the IFN-γ JAK/STAT1 axis, that regulates the ferroptotic pathway by inhibiting system Xc<sup>-</sup> activity and reducing GPX4 function, and how ferroptotic cell death releases, in terms of how the spatiotemporal activation of oxidized lipid mediators and Damage–Associated Molecular Patterns (DAMPs) catalyses a process of NLRP3 inflammasome activation and myeloid cell polarization, by complying with a series of crucial metabolic checkpoints, including the ACSL-mediated lipid metabolism. Finally, we discuss the therapeutic strategies with particular emphasis on the opportunities afforded by next-generation Radical Trapping Antioxidants (RTAs) and iron-focused chelating agents. This overview understands the crosstalk of ferroptosis and inflammation as a keystone of immunometabolism which may provide new therapeutic opportunities of tackling intractable cancers, neurodegenerative disorders, and ischemic diseases.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":"84 3","pages":"3273 - 3289"},"PeriodicalIF":3.0,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 Viral Fossils to β-Cell Futures: A Retro-Exposome Framework for Type 1 Diabetes 从病毒化石到β细胞未来:1型糖尿病的逆转录暴露框架。
IF 3 4区 生物学
Cell Biochemistry and Biophysics Pub Date : 2026-08-11 DOI: 10.1007/s12013-026-02115-y
Rajesh Prasad Jayaswal, Deen Dayal, Anuj Kumar Rana
{"title":"From Viral Fossils to β-Cell Futures: A Retro-Exposome Framework for Type 1 Diabetes","authors":"Rajesh Prasad Jayaswal,&nbsp;Deen Dayal,&nbsp;Anuj Kumar Rana","doi":"10.1007/s12013-026-02115-y","DOIUrl":"10.1007/s12013-026-02115-y","url":null,"abstract":"<div><p>Type 1 diabetes affects over 8.4 million individuals worldwide, with approximately 0.5 million new cases annually, and continues to impose substantial morbidity and mortality, particularly in settings where delayed diagnosis is common. Diabetic ketoacidosis occurs at presentation in 20–80% of newly diagnosed children, underscoring persistent gaps in early detection and prevention. Recent evidence linking antibody signatures against human endogenous retroviruses and <i>Mycobacterium avium</i> subspecies <i>paratuberculosis</i> provides a mechanistically provocative perspective on disease pathogenesis. Building on this work, we propose a “retro-exposome-to-β-cell” framework in which microbial exposure and retroelement activation converge to amplify interferon signaling, antigen presentation, and β-cell vulnerability. We highlight the need for cross-population validation, functional studies in β-cell and immune systems, and longitudinal evaluation to determine the causal and predictive relevance of these signatures. Integrating microbial immunology with retroelement biology may offer a pathway toward earlier detection and more equitable prevention strategies in type 1 diabetes.</p></div>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":"84 3","pages":"3043 - 3044"},"PeriodicalIF":3.0,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148704838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 Isoprene Units to Polyprenols and Dolichols: 70 Years of Polyisoprenoid Biosynthesis Research 从异戊二烯单元到聚戊烯醇和聚醇:聚异戊二烯类生物合成研究70年。
IF 3 4区 生物学
Cell Biochemistry and Biophysics Pub Date : 2026-06-26 DOI: 10.1007/s12013-026-02112-1
Zuzanna Bechler, Liliana Surmacz
{"title":"From Isoprene Units to Polyprenols and Dolichols: 70 Years of Polyisoprenoid Biosynthesis Research","authors":"Zuzanna Bechler,&nbsp;Liliana Surmacz","doi":"10.1007/s12013-026-02112-1","DOIUrl":"10.1007/s12013-026-02112-1","url":null,"abstract":"<div><p>Polyisoprenoids (polyprenols and dolichols) are a class of linear hydrophobic polymers present across all domains of life, serving essential functions for cellular viability and survival. Research on polyisoprenoids has progressed steadily since their discovery in the 1950s; however, these advances continue to highlight gaps in our understanding. This review provides a comprehensive overview of their biosynthesis, which occurs in three sequential stages: the formation of five-carbon precursors via the mevalonate (MVA) and methylerythritol phosphate (MEP) pathways, the elongation of the prenyl chain by prenyltransferases (PTs), and the final conversion into specific alcohol forms. Recent discoveries have substantially revised the classical understanding of dolichol biosynthesis, indicating a paradigm shift in the field. Furthermore, we discuss the essential biological roles of polyisoprenoids as lipid carriers for protein glycosylation, modulators of membrane fluidity, and key mediators in physiological defense systems against environmental stress, as well as their relevance to human disease and diagnostic applications. Finally, this article addresses critical knowledge gaps, focusing on the largely unexplored molecular mechanisms that regulate prenyltransferase activity and the yet-to-be-defined roles of these compounds in long-term stress adaptation.</p></div>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":"84 3","pages":"3163 - 3188"},"PeriodicalIF":3.0,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12013-026-02112-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148337386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Computational Identification of Paederia foetida Linn. Phytochemicals as Potential Inhibitors of Staphylococcus aureus Peptide Deformylase 小檗的计算鉴别。植物化学物质作为金黄色葡萄球菌肽去甲酰基酶的潜在抑制剂。
IF 3 4区 生物学
Cell Biochemistry and Biophysics Pub Date : 2026-06-10 DOI: 10.1007/s12013-026-02092-2
Sikha Borah, Jinu Devi Rajkumari, Saurov Mahanta, Nabajyoti Goswami
{"title":"Computational Identification of Paederia foetida Linn. Phytochemicals as Potential Inhibitors of Staphylococcus aureus Peptide Deformylase","authors":"Sikha Borah,&nbsp;Jinu Devi Rajkumari,&nbsp;Saurov Mahanta,&nbsp;Nabajyoti Goswami","doi":"10.1007/s12013-026-02092-2","DOIUrl":"10.1007/s12013-026-02092-2","url":null,"abstract":"<div><p><i>Staphylococcus aureus</i> is a common cause of foodborne gastroenteritis and poses a growing public health concern due to its heat-stable enterotoxins and increasing antimicrobial resistance. In this study, an integrated in silico strategy was employed to investigate phytochemicals from <i>Paederia foetida</i> Linn. as potential inhibitors of <i>S. aureus</i> peptide deformylase (PDF), an essential bacterial enzyme absent in humans. LC-MS profiling of the hexane leaf extract tentatively annotated 139 phytochemicals, of which 110 structurally suitable compounds were selected for molecular docking. From these, the top 12 compounds possessing functional groups capable of forming stabilizing interactions within the catalytic pocket of PDF were shortlisted for further evaluation. Among them, the four best-performing compounds were 12-Epi-Scalaradial (− 8.7 ± 0.10 kcal/mol), Obliquine (− 8.6 ± 0.10 kcal/mol), Anisotine (− 8.5 ± 0.10 kcal/mol), and Deoxytubulosine (− 8.4 ± 0.10 kcal/mol), all of which demonstrated stronger predicted binding affinities than the native ligand MDB (− 8.2 ± 0.10 kcal/mol).</p><p>To further assess the stability and binding behavior of these complexes, six independent 100 ns molecular dynamics simulations were performed. 12-Epi-Scalaradial exhibited a rigid and persistent binding pose stabilized by interactions with Gly110 and Leu112, suggesting a conformational restriction mechanism. In comparison, Obliquine and Deoxytubulosine maintained stable yet flexible interactions with key active-site residues. MM-PBSA analysis identified Deoxytubulosine (− 66 kJ/mol) and Obliquine (− 61 kJ/mol) as the most energetically favorable binders, whereas 12-Epi-Scalaradial appeared to contribute primarily to stabilization of the conformational dynamics of PDF. SwissADME predictions indicated favorable drug-likeness and gastrointestinal absorption for the prioritized compounds, although their limited aqueous solubility may require further formulation optimization. Overall, Deoxytubulosine and Obliquine emerged as promising natural candidates for further investigation as potential inhibitors of <i>S. aureus</i> PDF, which require experimental validation.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":"84 3","pages":"3845 - 3872"},"PeriodicalIF":3.0,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148215736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Vinca Extract Infused Silk Fibroin Hydrogel for Treatment of Artificially Induced Diabetic Foot Ulcer in Murine Model 长春花提取物灌注丝素凝胶治疗人工诱导的小鼠糖尿病足溃疡模型。
IF 3 4区 生物学
Cell Biochemistry and Biophysics Pub Date : 2026-06-10 DOI: 10.1007/s12013-026-02089-x
Ayesha Afzal, Hafiz Muhammad Tahir, Aamir Ali, Ayesha Muzamil, Navera Afzal, Sania Faiz, Farwa Shafeeq, Sidra Arshad, Rida Mahnoor
{"title":"Vinca Extract Infused Silk Fibroin Hydrogel for Treatment of Artificially Induced Diabetic Foot Ulcer in Murine Model","authors":"Ayesha Afzal,&nbsp;Hafiz Muhammad Tahir,&nbsp;Aamir Ali,&nbsp;Ayesha Muzamil,&nbsp;Navera Afzal,&nbsp;Sania Faiz,&nbsp;Farwa Shafeeq,&nbsp;Sidra Arshad,&nbsp;Rida Mahnoor","doi":"10.1007/s12013-026-02089-x","DOIUrl":"10.1007/s12013-026-02089-x","url":null,"abstract":"<div><p>Diabetic foot ulcers are challenging to manage and require intensive treatment as they heal slowly and greatly affect quality of life due to reduced mobility, infection and sepsis. The aim of current study was to develop novel hybrid hydrogels of silk fibroin containing 0.5%, 1.0% and 1.5% of <i>Catharanthus roseus</i> extract. Prepared hydrogels were characterized and GC-MS analysis of <i>C. roseus</i> extract was done to assess the component composition. Swiss albino mice were injected with alloxan to develop diabetic models and foot ulcer was induced. Hydrogels were administered every other day and wound healing potential was observed. GC-MS analysis revealed various antidiabetic and antibacterial constituents in <i>C. roseus</i>, while FT-IR results of hydrogels indicated intramolecular interactions between CMC, sodium alginate, fibroin and <i>C. roseus</i> extracts. The hydrogels showed more than 100% swelling ratio along with uniform surface morphology depicted by SEM analysis. Wound healing was notably faster (more than 80%) in mice treated with formulated hydrogels as compared to negative control group which showed just a 42% reduction in ulcer size by day 14. Similarly, in the treatment groups, IL-10 and TIMPs were significantly increased, whereas pro-inflammatory cytokines and matrix metalloproteinases were decreased. Histological analysis showed clear distinctions between diabetic and non-diabetic pancreas supported by HbA1c and C-peptide levels. Hydrogels treated groups exhibited enhanced angiogenesis, collagen fiber restoration and granulation tissue formation, indicating wound healing. In conclusion, this research shows that 1.5% <i>C. roseus</i> extract infused with silk Fibroin hydrogel has proved an efficient healing and rapid wound contraction of the diabetic foot ulcer in mice on day 14.</p></div>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":"84 3","pages":"3797 - 3815"},"PeriodicalIF":3.0,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148215891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 Synthesis and Biological Activity of Series of New Polyfunctional Pyrroles with the Potential to Modulate Neuronal Viability 一系列具有调节神经元活力潜力的新型多功能吡咯的合成及其生物活性。
IF 3 4区 生物学
Cell Biochemistry and Biophysics Pub Date : 2026-06-10 DOI: 10.1007/s12013-026-02090-4
Joumaa Merza, Mouhamed Alsaqati, Corinne Wills, Paul G. Waddell, Mark Ashton
{"title":"The Synthesis and Biological Activity of Series of New Polyfunctional Pyrroles with the Potential to Modulate Neuronal Viability","authors":"Joumaa Merza,&nbsp;Mouhamed Alsaqati,&nbsp;Corinne Wills,&nbsp;Paul G. Waddell,&nbsp;Mark Ashton","doi":"10.1007/s12013-026-02090-4","DOIUrl":"10.1007/s12013-026-02090-4","url":null,"abstract":"<div><p>The polyfunctional pyrrole 3,5-dichloro-1<i>H</i>-pyrrole-2,4-dicarbaldehyde (<b>2</b>) was reacted with malononitrile and Meldrum’s acid in a regioselective manner to yield derivatives (<b>4</b>, <b>5</b>, <b>6</b>, <b>8</b>, <b>9</b>, and <b>10</b>). Compound <b>8</b> was isolated and its structure was characterised by crystallography and 1 and 2D-<sup>1</sup>H, <sup>13</sup>C-NMR spectroscopy. The biological effects of these derivatives were evaluated on differentiated SH-SY5Y human neuroblastoma cells, under control conditions and following Aβ exposure as an in vitro model of Alzheimer’s disease. MTT assays were performed to assess neuronal viability, and Annexin V staining was used to quantify apoptosis. Compounds <b>2</b> and <b>8</b> significantly increased cell viability in control differentiated neurons, suggesting a neurotrophic or protective effect. However, in Aβ-treated cells, all tested compounds, namely <b>5</b>, <b>6</b>, <b>8</b> and <b>2</b>, reduced viability, indicating a possible interaction between our derivatives and Aβ-induced neurotoxicity. These findings reveal that certain polyfunctional pyrrole derivatives can differentially modulate neuronal survival depending on the cellular environment. This suggests that the neuronal cell death induced by Aβ in Alzheimer’s patients can be enhanced in the presence of those compounds. Since pyrrole scaffolds are present both in biologically essential molecules and in various environmental compounds, this dual action suggests their potential relevance in understanding the mechanisms of neurodegeneration and highlights the need for further mechanistic and translational studies to explore their impact on neurodegenerative disorders, including Alzheimer’s.</p></div>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":"84 3","pages":"3817 - 3829"},"PeriodicalIF":3.0,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12013-026-02090-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148215776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Allosteric Interactions of Flavonoids with ACE2 and Potential Implications for COVID-19: Computational Insights, Metabolic and Mitochondrial Effects of Rutin in A549 Cells 黄酮类化合物与ACE2的变构相互作用及其对COVID-19的潜在影响:计算见解、芦丁在A549细胞中的代谢和线粒体作用。
IF 3 4区 生物学
Cell Biochemistry and Biophysics Pub Date : 2026-06-08 DOI: 10.1007/s12013-026-02093-1
Fave Y. Tata, Mthokozisi B. Nxumalo, Vincent A. Obakachi, Hezekiel M. Kumalo, René B. Khan
{"title":"Allosteric Interactions of Flavonoids with ACE2 and Potential Implications for COVID-19: Computational Insights, Metabolic and Mitochondrial Effects of Rutin in A549 Cells","authors":"Fave Y. Tata,&nbsp;Mthokozisi B. Nxumalo,&nbsp;Vincent A. Obakachi,&nbsp;Hezekiel M. Kumalo,&nbsp;René B. Khan","doi":"10.1007/s12013-026-02093-1","DOIUrl":"10.1007/s12013-026-02093-1","url":null,"abstract":"<div><p>There has been a compelling need to identify new therapeutic targets and agents owing to the increasing complexity of disease mechanisms. Angiotensin-converting enzyme 2 (ACE2), the primary host receptor for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2, plays a crucial role in the pathophysiology of COVID-19, making ACE2 a potential biological target. Identification of small molecules that can interact with ACE2 may offer insights into a host-targeted approach relevant to viral entry and ACE2-associated cellular pathways. The study evaluated allosteric interactions of selected flavonoids with ACE2, the cytotoxicity and metabolic effects of the promising candidate in A549 cells through computational and in vitro methods. Molecular docking identified flavonoid binding to ACE2, followed by a 120 ns molecular dynamics (MD) simulation to characterize the stability and dynamic behaviour of ACE2-flavonoid complexes. MM/GBSA binding free energy calculations and per residue energy decomposition were performed to identify key interactions stabilizing ligand binding. The in silico analyses showed ARG255, PRO328, GLU357, GLU384, GLU388, and ARG500 as the key allosteric residues contributing to ACE2-flavonoid complex stability. Rutin exhibited the most favourable binding affinity, followed by isoquercetin. Based on computational findings, rutin was selected for evaluation in A549 cells to assess cytotoxicity, metabolic and mitochondrial effects using MTT assay, ATP quantification, mitochondrial membrane potential (MMP), CYP3A4 activity and LDH release for membrane integrity. In vitro analyses showed that rutin is non-cytotoxic up to 500µM, enhances ATP production without adversely affecting MMP and membrane integrity. These findings indicate that rutin formed stable interactions with ACE2, with the potential to influence cellular energy metabolism without inducing cytotoxicity and therapeutic benefits in conditions linked to mitochondrial dysfunction and metabolic stress. While direct ACE2 enzymatic modulation was not confirmed experimentally, these findings provide a mechanistic basis for further studies on ACE2-flavonoid interactions and their potential biological implications in ACE2-associated diseases.</p></div>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":"84 3","pages":"3873 - 3898"},"PeriodicalIF":3.0,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12013-026-02093-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148196860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Electrochemical Investigation of Cu(II) Complexation with a Novel Pyridine-Based Schiff Base Ligand: Cyclic Voltammetry, Molecular Docking, and Antioxidant Evaluation 新型吡啶基席夫碱配体与Cu(II)络合的电化学研究:循环伏安法、分子对接和抗氧化评价。
IF 3 4区 生物学
Cell Biochemistry and Biophysics Pub Date : 2026-06-08 DOI: 10.1007/s12013-026-02091-3
Elsayed M. AbouElleef, Rania A. H. Saad, M. A. Diab, A. Z. El-Sonbati, Esam A. Gomaa, M. I. Abou-Dobara, Sh. M. Morgan
{"title":"Electrochemical Investigation of Cu(II) Complexation with a Novel Pyridine-Based Schiff Base Ligand: Cyclic Voltammetry, Molecular Docking, and Antioxidant Evaluation","authors":"Elsayed M. AbouElleef,&nbsp;Rania A. H. Saad,&nbsp;M. A. Diab,&nbsp;A. Z. El-Sonbati,&nbsp;Esam A. Gomaa,&nbsp;M. I. Abou-Dobara,&nbsp;Sh. M. Morgan","doi":"10.1007/s12013-026-02091-3","DOIUrl":"10.1007/s12013-026-02091-3","url":null,"abstract":"<div><p>This study investigates the electrochemical interaction between CuCl<sub>2</sub> and a pyridine-based Schiff base ligand in aqueous KCl using cyclic voltammetry at 302.15 K. Significant shifts in peak potentials and currents confirmed stable Cu(II)–ligand complex formation. Kinetic and thermodynamic parameters revealed diffusion-controlled processes and favorable complexation with negative Gibbs free energy values. Molecular docking studies were conducted on the free ligand against the SARS-CoV-2 protein (7JWY), showing moderate binding affinity through hydrogen bonding interactions. The ligand also exhibited antioxidant activity with an IC50 value of 0.154 mg mL− 1.</p></div>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":"84 3","pages":"3831 - 3844"},"PeriodicalIF":3.0,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148196868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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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