BiomoleculesPub Date : 2025-07-25DOI: 10.3390/biom15081075
Cenyi Luo, Juan Xue, Qingyi Huang, Yuxiang Deng, Zhixin Zhao, Jiafeng Li, Xiaoyan Gao, Zhengqiu Li
{"title":"3D-Printed Poly (l-lactic acid) Scaffolds for Bone Repair with Oriented Hierarchical Microcellular Foam Structure and Biocompatibility.","authors":"Cenyi Luo, Juan Xue, Qingyi Huang, Yuxiang Deng, Zhixin Zhao, Jiafeng Li, Xiaoyan Gao, Zhengqiu Li","doi":"10.3390/biom15081075","DOIUrl":"https://doi.org/10.3390/biom15081075","url":null,"abstract":"<p><p>This study proposes a continuous preparation strategy for poly (l-lactic acid) (PLLA) scaffolds with oriented hierarchical microporous structures for bone repair. A PLLA-oriented multi-stage microporous bone repair scaffold (hereafter referred to as the oriented multi-stage microporous scaffold) was designed using a novel extrusion foaming technology that integrates fused deposition modeling (FDM) 3D printing with supercritical carbon dioxide (SC-CO<sub>2</sub>) microcellular foaming technology. The influence of the 3D-printed structure on the microcellular morphology of the oriented multi-stage microporous scaffold was investigated and optimized. The combination of FDM and SC-CO<sub>2</sub> foaming technology enables a continuous extrusion foaming process for preparing oriented multi-stage microporous scaffolds. The mechanical strength of the scaffold reached 15.27 MPa, meeting the requirements for bone repair in a low-load environment. Notably, the formation of open pores on the surface of the oriented multi-stage microporous scaffold positively affected cell proliferation, differentiation, and activity, as well as the expression of anti-inflammatory and pro-inflammatory factors. In vitro cell experiments (such as CCK-8) showed that the cell proliferation rate in the oriented multi-stage microporous scaffold reached 100-300% after many days of cultivation. This work provides a strategy for the design and manufacture of PLLA scaffolds with hierarchical microcellular structures and biocompatibility for bone repair.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 8","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12383668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomoleculesPub Date : 2025-07-25DOI: 10.3390/biom15081079
Xuantai Wu, Kui Wang, Gang Hu, Lukasz Kurgan
{"title":"Empirical Assessment of Sequence-Based Predictions of Intrinsically Disordered Regions Involved in Phase Separation.","authors":"Xuantai Wu, Kui Wang, Gang Hu, Lukasz Kurgan","doi":"10.3390/biom15081079","DOIUrl":"https://doi.org/10.3390/biom15081079","url":null,"abstract":"<p><p>Phase separation processes facilitate the formation of membrane-less organelles and involve interactions within structured domains and intrinsically disordered regions (IDRs) in protein sequences. The literature suggests that the involvement of proteins in phase separation can be predicted from their sequences, leading to the development of over 30 computational predictors. We focused on intrinsic disorder due to its fundamental role in related diseases, and because recent analysis has shown that phase separation can be accurately predicted for structured proteins. We evaluated eight representative amino acid-level predictors of phase separation, capable of identifying phase-separating IDRs, using a well-annotated, low-similarity test dataset under two complementary evaluation scenarios. Several methods generate accurate predictions in the easier scenario that includes both structured and disordered sequences. However, we demonstrate that modern disorder predictors perform equally well in this scenario by effectively differentiating phase-separating IDRs from structured regions. In the second, more challenging scenario-considering only predictions in disordered regions-disorder predictors underperform, and most phase separation predictors produce only modestly accurate results. Moreover, some predictors are broadly biased to classify disordered residues as phase-separating, which results in low predictive performance in this scenario. Finally, we recommend PSPHunter as the most accurate tool for identifying phase-separating IDRs in both scenarios.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 8","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12383833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomoleculesPub Date : 2025-07-24DOI: 10.3390/biom15081074
Francesca La Rosa, Simone Agostini, Elisabetta Bolognesi, Ivana Marventano, Roberta Mancuso, Franca Rosa Guerini, Ambra Hernis, Lorenzo Agostino Citterio, Federica Piancone, Pietro Davide Trimarchi, Jorge Navarro, Federica Rossetto, Arianna Amenta, Pierfausto Seneci, Silvia Sesana, Francesca Re, Mario Clerici, Marina Saresella
{"title":"Engineered Glibenclamide-Loaded Nanovectors Hamper Inflammasome Activation in an Ex Vivo Alzheimer's Disease Model-A Novel Potential Therapy for Neuroinflammation: A Pilot Study.","authors":"Francesca La Rosa, Simone Agostini, Elisabetta Bolognesi, Ivana Marventano, Roberta Mancuso, Franca Rosa Guerini, Ambra Hernis, Lorenzo Agostino Citterio, Federica Piancone, Pietro Davide Trimarchi, Jorge Navarro, Federica Rossetto, Arianna Amenta, Pierfausto Seneci, Silvia Sesana, Francesca Re, Mario Clerici, Marina Saresella","doi":"10.3390/biom15081074","DOIUrl":"https://doi.org/10.3390/biom15081074","url":null,"abstract":"<p><strong>Background: </strong>Inflammasomes regulate the activation of caspases resulting in inflammation; inflammasome activation is dysregulated in Alzheimer's disease (AD) and plays a role in the pathogenesis of this condition. Glibenclamide, an anti-inflammatory drug, could be an interesting way to down-modulate neuroinflammation.</p><p><strong>Methods: </strong>In this pilot study we verified with ex vivo experiments whether a glibenclamide-loaded nanovector (GNV) could reduce the NLRP3-inflammasome cascade in cells of AD patients. Monocytes isolated from healthy controls (HC) and AD patients were cultured in medium, alone or stimulated with LPS + nigericin in presence/absence of GNV. ASC-speck positive cells and inflammasome-related genes, proteins, and miRNAs expressions were measured. The polymorphisms of <i>ApoE</i> (Apolipoprotein E), specifically rs7412 and rs429358, as well as those of <i>NLRP3</i>, namely rs35829419, rs10733113, and rs4925663, were also investigated.</p><p><strong>Results: </strong>Results showed that ASC-speck+ cells and Caspase-1, IL-1β, and IL-18 production was significantly reduced (<i>p</i> < 0.005 in all cases) by GNV in LPS + nigericin-stimulated cells of both AD and HC. Notably, the <i>NLRP3</i> rs10733113 AG genotype was associated with excessive inflammasome-related gene and protein expression. GNV significantly down-regulates inflammasome activation in primary monocytes, at least at protein levels, and its efficacy seems to partially depend on the presence of the <i>NLRP3</i> rs10733113 genotype.</p><p><strong>Conclusions: </strong>All together, these results showed that GNV is able to dampen inflammation and NLRP-3 inflammasome activation in an ex vivo monocyte model, suggesting a possible role for GNV in controlling AD-associated neuroinflammation.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 8","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12383602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Yin Yang 1 (YY1) as a Central Node in Drug Resistance Pathways: Potential for Combination Strategies in Cancer Therapy.","authors":"Zhiyan Li, Xiang Jia, Ian Timothy Sembiring Meliala, Yanjun Li, Vivi Kasim","doi":"10.3390/biom15081069","DOIUrl":"https://doi.org/10.3390/biom15081069","url":null,"abstract":"<p><p>Tumor drug resistance, a major cause of treatment failure, involves complex multi-gene networks, remodeling of signaling pathways, and interactions with the tumor microenvironment. Yin Yang 1 (YY1) is a critical oncogene overexpressed in many tumors and mediates multiple tumor-related processes, such as cell proliferation, metabolic reprogramming, immune evasion, and drug resistance. Notably, YY1 drives resistance through multiple mechanisms, such as upregulation of drug efflux, maintenance of cancer stemness, enhancement of DNA repair capacity, modulation of the tumor microenvironment, and epithelial-mesenchymal transition, thereby positioning it as a pivotal regulator of drug resistance. This review examines the pivotal role of YY1 in resistance, elucidating its molecular mechanisms and clinical relevance. We demonstrate that YY1 inhibition could effectively reverse drug resistance and restore therapeutic sensitivity across various treatment modalities. Importantly, we highlight the promising potential of YY1-targeted strategies, particularly combined with anti-tumor agents, to overcome resistance barriers. Furthermore, we discuss critical translational considerations for advancing these combinatorial approaches into clinical practice.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 8","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12383853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"S-Nitrosylation in Cardiovascular Disorders: The State of the Art.","authors":"Caiyun Mao, Jieyou Zhao, Nana Cheng, Zihang Xu, Haoming Ma, Yunjia Song, Xutao Sun","doi":"10.3390/biom15081073","DOIUrl":"https://doi.org/10.3390/biom15081073","url":null,"abstract":"<p><p>Protein S-nitrosylation is a selective post-translational modification in which a nitrosyl group is covalently attached to the reactive thiol group of cysteine, forming S-nitrosothiol. This modification plays a pivotal role in modulating physiological and pathological cardiovascular processes by altering protein conformation, activity, stability, and other post-translational modifications. It is instrumental in regulating vascular and myocardial systolic and diastolic functions, vascular endothelial cell and cardiomyocyte apoptosis, and cardiac action potential and repolarization. Aberrant S-nitrosylation levels are implicated in the pathogenesis of various cardiovascular diseases, including systemic hypertension, pulmonary arterial hypertension, atherosclerosis, heart failure, myocardial infarction, arrhythmia, and diabetic cardiomyopathy. Insufficient S-nitrosylation leads to impaired vasodilation and increased vascular resistance, while excessive S-nitrosylation contributes to cardiac hypertrophy and myocardial fibrosis, thereby accelerating ventricular remodeling. This paper reviews the S-nitrosylated proteins in the above-mentioned diseases and their impact on these conditions through various signaling pathways, with the aim of providing a theoretical foundation for the development of novel therapeutic strategies or drugs targeting S-nitrosylated proteins.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 8","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12383306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomoleculesPub Date : 2025-07-24DOI: 10.3390/biom15081071
Muhammad Rafiq, Umaira Bugti, Muhammad Hayat, Wasim Sajjad, Imran Ali Sani, Nazeer Ahmed, Noor Hassan, Yanyan Wang, Yingqian Kang
{"title":"Optimization and Characterization of Bioactive Metabolites from Cave-Derived <i>Rhodococcus jialingiae</i> C1.","authors":"Muhammad Rafiq, Umaira Bugti, Muhammad Hayat, Wasim Sajjad, Imran Ali Sani, Nazeer Ahmed, Noor Hassan, Yanyan Wang, Yingqian Kang","doi":"10.3390/biom15081071","DOIUrl":"https://doi.org/10.3390/biom15081071","url":null,"abstract":"<p><p>Extremophilic microorganisms offer an untapped potential for producing unique bioactive metabolites with therapeutic applications. In the current study, bacterial isolates were obtained from samples collected from Chamalang cave located in Kohlu District, Balochistan, Pakistan. The cave-derived isolate C1 (<i>Rhodococcus jialingiae</i>) exhibits prominent antibacterial activity against multidrug-resistant pathogens (MDR), including <i>Escherichia coli</i>, <i>Staphylococcus aureus</i>, and <i>Micrococcus luteus</i>. It also demonstrates substantial antioxidant activity, with 71% and 58.39% DPPH radical scavenging. Optimization of physicochemical conditions, such as media, pH, temperature, and nitrogen and carbon sources and concentrations substantially enhanced both biomass and metabolite yields. Optimal conditions comprise specialized media, a pH of 7, a temperature of 30 °C, peptone (1.0 g/L) as the nitrogen source, and glucose (0.5 g/L) as the carbon source. HPLC and QTOF-MS analyses uncovered numerous metabolites, including a phenolic compound, 2-[(E)-3-hydroxy-3-(4-methoxyphenyl) prop-2-enoyl]-4-methoxyphenolate, Streptolactam C, Puromycin, and a putative aromatic polyketide highlighting the C1 isolate chemical. Remarkably, one compound (C<sub>14</sub>H<sub>36</sub>N<sub>7</sub>) demonstrated a special molecular profile, signifying structural novelty and warranting further characterization by techniques such as <sup>1</sup>H and <sup>13</sup>C NMR. These findings highlight the biotechnological capacity of the C1 isolate as a source of novel antimicrobials and antioxidants, linking environmental adaptation to metabolic potential and supporting natural product discovery pipelines against antibiotic resistance.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 8","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12383431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomoleculesPub Date : 2025-07-23DOI: 10.3390/biom15081064
Carmen Ciavarella, Francesco Vasuri, Alessio Degiovanni, Lena Christ, Raffaella Mauro, Mauro Gargiulo, Gianandrea Pasquinelli
{"title":"A Distinct miRNA Profile in Intimal Hyperplasia of Failed Arteriovenous Fistulas Reveals Key Pathogenic Pathways.","authors":"Carmen Ciavarella, Francesco Vasuri, Alessio Degiovanni, Lena Christ, Raffaella Mauro, Mauro Gargiulo, Gianandrea Pasquinelli","doi":"10.3390/biom15081064","DOIUrl":"https://doi.org/10.3390/biom15081064","url":null,"abstract":"<p><p>Intimal hyperplasia (IH) compromises the patency of arteriovenous fistula (AVF) vascular access in patients with end-stage kidney disease. Uncontrolled cell proliferation and migration, driven by inflammation, shear stress and surgery, are well-known triggers in IH. Recently, microRNAs (miRNAs) have emerged as regulators of core mechanisms in cardiovascular diseases and as potential markers of IH. This study was aimed at identifying a specific miRNA panel in failed AVFs and clarifying the miRNA involvement in IH. miRNA profiling performed in tissues from patients with IH (AVFs) and normal veins (NVs) highlighted a subset of four miRNAs significantly deregulated (hsa-miR-155-5p, hsa-miR-449a-5p, hsa-miR-29c-3p, hsa-miR-194-5p) between the two groups. These miRNAs were analyzed in tissue-derived cells (NVCs and AVFCs), human aortic smooth muscle cells (HAOSMCs) and human umbilical vein endothelial cells (HUVECs). The panel of hsa-miR-449a-5p, hsa-miR-155-5p, hsa-miR-29c-3p and hsa-miR-194-5p was up-regulated in AVFCs, HAOSMCs and HUVEC under inflammatory stimuli. Notably, overexpression of hsa-miR-449a-5p exacerbated the proliferative, migratory and inflammatory features of AVFCs. In vitro pharmacological modulation of these miRNAs with pioglitazone, particularly the down-regulation of hsa-miR-155-5p and hsa-miR-29c-3p, suggested their involvement in IH pathogenesis and a potential translational application. Overall, these findings provide new insights into the pathogenesis of AVF failure, reinforcing the miRNA contribution to IH detection and prevention.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 8","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12383664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomoleculesPub Date : 2025-07-23DOI: 10.3390/biom15081065
Bogdan-Sorin Tudurachi, Larisa Anghel, Andreea Tudurachi, Răzvan-Liviu Zanfirescu, Silviu-Gabriel Bîrgoan, Radu Andy Sascău, Cristian Stătescu
{"title":"Myocardial Infarction in Young Adults: A Case Series and Comprehensive Review of Molecular and Clinical Mechanisms.","authors":"Bogdan-Sorin Tudurachi, Larisa Anghel, Andreea Tudurachi, Răzvan-Liviu Zanfirescu, Silviu-Gabriel Bîrgoan, Radu Andy Sascău, Cristian Stătescu","doi":"10.3390/biom15081065","DOIUrl":"https://doi.org/10.3390/biom15081065","url":null,"abstract":"<p><p>Acute myocardial infarction (AMI) in young adults, though less common than in older populations, is an emerging clinical concern with increasing incidence and diverse etiologies. Unlike classic atherosclerotic presentations, a significant proportion of AMI cases in individuals under 45 years are due to nonatherothrombotic mechanisms such as coronary vasospasm, spontaneous coronary artery dissection (SCAD), vasculitis, hypercoagulable states, and drug-induced coronary injury. This manuscript aims to explore the multifactorial nature of AMI in young adults through a focused review of current evidence and a series of illustrative clinical cases. We present and analyze four distinct cases of young patients with AMI, each demonstrating different pathophysiological mechanisms and risk profiles-including premature atherosclerosis, substance use, human immunodeficiency virus (HIV)-related coronary disease, and SCAD. Despite the heterogeneity of underlying causes, early diagnosis, individualized management, and aggressive secondary prevention were key to favorable outcomes. Advanced imaging, lipid profiling, and risk factor modification played a central role in guiding therapy. AMI in young adults requires heightened clinical suspicion and a comprehensive, multidisciplinary approach. Early intervention and recognition of nontraditional risk factors are essential to improving outcomes and preventing recurrent events in this vulnerable population.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 8","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12383299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomoleculesPub Date : 2025-07-22DOI: 10.3390/biom15081057
Irmgard Classen-Linke, Volker U Buck, Anna K Sternberg, Matthias Kohlen, Liubov Izmaylova, Rudolf E Leube
{"title":"Changes in Epithelial Cell Polarity and Adhesion Guide Human Endometrial Receptivity: How In Vitro Systems Help to Untangle Mechanistic Details.","authors":"Irmgard Classen-Linke, Volker U Buck, Anna K Sternberg, Matthias Kohlen, Liubov Izmaylova, Rudolf E Leube","doi":"10.3390/biom15081057","DOIUrl":"https://doi.org/10.3390/biom15081057","url":null,"abstract":"<p><p>Tissue remodeling of human endometrium occurs during the menstrual cycle to prepare for embryo adhesion and invasion. The ovarian steroid hormones 17β-estradiol and progesterone control the menstrual cycle to achieve the receptive state during the \"window of implantation\" (WOI). Here, we focus on the human endometrial epithelium and its changes in polarity, adhesion, cytoskeletal organization and the underlying extracellular matrix enabling embryo implantation. The adhesion and invasion of the trophoblast via the apical plasma membrane of epithelial cells is a unique cell biological process, which is coupled to partial epithelial-mesenchymal transition (EMT). Given the fundamental species differences during implantation, we restrict the review mainly to the human situation and focus on cell culture systems to study the interaction between human trophoblast and endometrial cells. We summarize current knowledge based on the relatively scarce in vivo data and the steadily growing in vitro observations using various cell culture systems.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 8","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12383966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomoleculesPub Date : 2025-07-22DOI: 10.3390/biom15081063
Robert S Eisenberg
{"title":"Current Flow in Nerves and Mitochondria: An Electro-Osmotic Approach.","authors":"Robert S Eisenberg","doi":"10.3390/biom15081063","DOIUrl":"https://doi.org/10.3390/biom15081063","url":null,"abstract":"<p><p>The electrodynamics of current provide much of our technology, from telegraphs to the wired infrastructure powering the circuits of our electronic technology. Current flow is analyzed by its own rules that involve the Maxwell Ampere law and magnetism. Electrostatics does not involve magnetism, and so current flow and electrodynamics cannot be derived from electrostatics. Practical considerations also prevent current flow from being analyzed one charge at a time. There are too many charges, and far too many interactions to allow computation. Current flow is essential in biology. Currents are carried by electrons in mitochondria in an electron transport chain. Currents are carried by ions in nerve and muscle cells. Currents everywhere follow the rules of current flow: Kirchhoff's current law and its generalizations. The importance of electron and proton flows in generating ATP was discovered long ago but they were not analyzed as electrical currents. The flow of protons and transport of electrons form circuits that must be analyzed by Kirchhoff's law. A chemiosmotic theory that ignores the laws of current flow is incorrect physics. Circuit analysis is easily applied to short systems like mitochondria that have just one internal electrical potential in the form of the Hodgkin Huxley Katz (HHK) equation. The HHK equation combined with classical descriptions of chemical reactions forms a computable model of cytochrome c oxidase, part of the electron transport chain. The proton motive force is included as just one of the components of the total electrochemical potential. Circuit analysis includes its role just as it includes the role of any other ionic current. Current laws are now needed to analyze the flow of electrons and protons, as they generate ATP in mitochondria and chloroplasts. Chemiosmotic theory must be replaced by an electro-osmotic theory of ATP production that conforms to the Maxwell Ampere equation of electrodynamics while including proton movement and the proton motive force.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 8","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12383336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}