Pub Date : 2026-02-05DOI: 10.1016/j.pbiomolbio.2026.02.003
Lang Yang, Zou Yan, Yanhui Liu, Yuyu Feng
RNA-small molecule interactions are fundamental to cellular regulation and have emerged as highly attractive therapeutic targets. Despite their potential, discovering RNA-binding small molecules remains challenging due to RNA's intrinsic structural flexibility, transient and context-dependent binding pockets, and the limited availability of high-resolution complex structures. Computational prediction approaches have evolved from early statistical models relying on handcrafted descriptors to advanced machine and deep learning frameworks that integrate sequence, structural, energetic, and topological information. More recently, large language models have enabled the capture of long-range sequence dependencies and contextual patterns, complementing structure-based encoders for multimodal modeling of RNA- ligand interactions. In this review, we summarize the principles and current state of computational strategies for RNA-ligand binding site prediction, highlighting methodological evolution, multimodal feature integration, and persisting challenges, and we discuss emerging directions toward accurate, generalizable, and interpretable predictions to accelerate rational RNA-targeted drug discovery.
{"title":"Computational Advances in RNA-Small Molecule Binding Site Prediction.","authors":"Lang Yang, Zou Yan, Yanhui Liu, Yuyu Feng","doi":"10.1016/j.pbiomolbio.2026.02.003","DOIUrl":"https://doi.org/10.1016/j.pbiomolbio.2026.02.003","url":null,"abstract":"<p><p>RNA-small molecule interactions are fundamental to cellular regulation and have emerged as highly attractive therapeutic targets. Despite their potential, discovering RNA-binding small molecules remains challenging due to RNA's intrinsic structural flexibility, transient and context-dependent binding pockets, and the limited availability of high-resolution complex structures. Computational prediction approaches have evolved from early statistical models relying on handcrafted descriptors to advanced machine and deep learning frameworks that integrate sequence, structural, energetic, and topological information. More recently, large language models have enabled the capture of long-range sequence dependencies and contextual patterns, complementing structure-based encoders for multimodal modeling of RNA- ligand interactions. In this review, we summarize the principles and current state of computational strategies for RNA-ligand binding site prediction, highlighting methodological evolution, multimodal feature integration, and persisting challenges, and we discuss emerging directions toward accurate, generalizable, and interpretable predictions to accelerate rational RNA-targeted drug discovery.</p>","PeriodicalId":54554,"journal":{"name":"Progress in Biophysics & Molecular Biology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146138075","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}
Pub Date : 2026-02-05DOI: 10.1016/j.pbiomolbio.2026.02.001
Taslima Musa Zerin, Brian W Booth
About 10-15% of all instances of breast cancer are triple-negative breast cancer (TNBC). TNBCs are not responsive to hormonal or anti-HER2 therapies because they lack estrogen and progesterone receptors and have low HER2 levels. TNBC is a highly aggressive subtype of breast cancer and has a prognosis often worse than that of other subtypes. Usually, chemotherapy and surgery are combined since this is a very efficient way to remove tumors. Chemotherapy medications that effectively remove cancer cells may adversely affect healthy cells and have severe repercussions, which can impair patients' psychological well-being and quality of life (QOL). To minimize adverse effects, improve patient quality of life, and maintain therapeutic efficacy, a more targeted therapy approach for TNBC should be explored. Magnetic hyperthermia (MHT) is a passive-targeting, minimally invasive treatment for TNBC that minimizes the requirement for other severe, well-established therapies having both short- and long-term toxicities for patients. MHT involves heating magnetic nanoparticles (MNPs) in an alternating magnetic field (AMF) to heat local tissues/cells without killing normal epithelial cells, as they are more temperature-resistant than tumor cells. Additionally, MNPs can bind chemotherapeutics, nucleic acids, synthetic antibodies, or radionuclide compounds, a strategy considered for drug delivery. This review summarizes the implications and current treatment options for TNBC, highlighting the use of MNPs for MHT as a potential treatment strategy.
{"title":"Magnetic hyperthermia's potential in triple-negative breast cancer treatment.","authors":"Taslima Musa Zerin, Brian W Booth","doi":"10.1016/j.pbiomolbio.2026.02.001","DOIUrl":"10.1016/j.pbiomolbio.2026.02.001","url":null,"abstract":"<p><p>About 10-15% of all instances of breast cancer are triple-negative breast cancer (TNBC). TNBCs are not responsive to hormonal or anti-HER2 therapies because they lack estrogen and progesterone receptors and have low HER2 levels. TNBC is a highly aggressive subtype of breast cancer and has a prognosis often worse than that of other subtypes. Usually, chemotherapy and surgery are combined since this is a very efficient way to remove tumors. Chemotherapy medications that effectively remove cancer cells may adversely affect healthy cells and have severe repercussions, which can impair patients' psychological well-being and quality of life (QOL). To minimize adverse effects, improve patient quality of life, and maintain therapeutic efficacy, a more targeted therapy approach for TNBC should be explored. Magnetic hyperthermia (MHT) is a passive-targeting, minimally invasive treatment for TNBC that minimizes the requirement for other severe, well-established therapies having both short- and long-term toxicities for patients. MHT involves heating magnetic nanoparticles (MNPs) in an alternating magnetic field (AMF) to heat local tissues/cells without killing normal epithelial cells, as they are more temperature-resistant than tumor cells. Additionally, MNPs can bind chemotherapeutics, nucleic acids, synthetic antibodies, or radionuclide compounds, a strategy considered for drug delivery. This review summarizes the implications and current treatment options for TNBC, highlighting the use of MNPs for MHT as a potential treatment strategy.</p>","PeriodicalId":54554,"journal":{"name":"Progress in Biophysics & Molecular Biology","volume":" ","pages":"255-266"},"PeriodicalIF":4.5,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146133573","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}
Pub Date : 2026-02-03DOI: 10.1016/j.pbiomolbio.2026.02.002
Fernando Pesantez Torres, Michael Detweiler, Charles R Keese
Shear stress, a stress that acts co-planar with the cross-section of a system, profoundly influences cellular behavior and function. Understanding how cells respond to shear stress is critical for advancing research in vascular biology, tissue engineering, and cancer metastasis. On the other hand, Electric Cell-Substrate Impedance Sensing (ECIS) is a powerful tool for real-time, label-free monitoring of cellular behavior. This review examines the application of combining ECIS and flow systems to study, in real-time, the effects of shear stress on cell monolayers, such as the impact on barrier function. It highlights its advantages, the various experimental setups, and key experimental findings.
{"title":"Electric Cell-Substrate Impedance Sensing (ECIS) for the analysis of shear stress effects on cell monolayers.","authors":"Fernando Pesantez Torres, Michael Detweiler, Charles R Keese","doi":"10.1016/j.pbiomolbio.2026.02.002","DOIUrl":"10.1016/j.pbiomolbio.2026.02.002","url":null,"abstract":"<p><p>Shear stress, a stress that acts co-planar with the cross-section of a system, profoundly influences cellular behavior and function. Understanding how cells respond to shear stress is critical for advancing research in vascular biology, tissue engineering, and cancer metastasis. On the other hand, Electric Cell-Substrate Impedance Sensing (ECIS) is a powerful tool for real-time, label-free monitoring of cellular behavior. This review examines the application of combining ECIS and flow systems to study, in real-time, the effects of shear stress on cell monolayers, such as the impact on barrier function. It highlights its advantages, the various experimental setups, and key experimental findings.</p>","PeriodicalId":54554,"journal":{"name":"Progress in Biophysics & Molecular Biology","volume":" ","pages":"246-254"},"PeriodicalIF":4.5,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146127501","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}
Various rare earth magnets have been successfully applied in clinical orthodontics; however, their interactions with the oral environment remain only partially understood. Various controversies remain regarding magnetic fields (MFs) in cell biophysics owing to the heterogeneity of field parameters (including intensity, exposure time, and waveform) and experimental conditions, with little consensus on the topic. This article aimed to comprehensively review recent findings on biomagnetism in oral tissues, the mechanisms of action of exogenous MFs, the behavior of MF-stimulated cell membranes, the biocompatibility of magnetic materials, and their effects on oral microflora. Additionally, novel concepts regarding orthodontic movement, such as biomagnetism, diamagnetic anisotropy of biological tissues, and bone semiconduction, are discussed. The interplay of these phenomena with external MFs and bone piezoelectricity may provide novel insights into the electromagnetic phenomena involved in orthodontic movements. To date, research on MFs and oral microbiota has yielded inconclusive results. Hence, improving magnetic materials, clarifying the magnetic properties of tissues and their interactions, and considering the use of magnetic materials as complementary therapy in orthodontic movement is crucial for achieving a new level of clinical excellence.
{"title":"Biomagnetism of oral tissues and external magnetic field interactions with cell membranes, oral microflora, and orthodontic magnetic therapies: A review","authors":"Sisenando Itabaiana Sobrinho , Luiz Claudio Meira-Belo , Nelcy Della Santina Mohallem","doi":"10.1016/j.pbiomolbio.2026.01.003","DOIUrl":"10.1016/j.pbiomolbio.2026.01.003","url":null,"abstract":"<div><div>Various rare earth magnets have been successfully applied in clinical orthodontics; however, their interactions with the oral environment remain only partially understood. Various controversies remain regarding magnetic fields (MFs) in cell biophysics owing to the heterogeneity of field parameters (including intensity, exposure time, and waveform) and experimental conditions, with little consensus on the topic. This article aimed to comprehensively review recent findings on biomagnetism in oral tissues, the mechanisms of action of exogenous MFs, the behavior of MF-stimulated cell membranes, the biocompatibility of magnetic materials, and their effects on oral microflora. Additionally, novel concepts regarding orthodontic movement, such as biomagnetism, diamagnetic anisotropy of biological tissues, and bone semiconduction, are discussed. The interplay of these phenomena with external MFs and bone piezoelectricity may provide novel insights into the electromagnetic phenomena involved in orthodontic movements. To date, research on MFs and oral microbiota has yielded inconclusive results. Hence, improving magnetic materials, clarifying the magnetic properties of tissues and their interactions, and considering the use of magnetic materials as complementary therapy in orthodontic movement is crucial for achieving a new level of clinical excellence.</div></div>","PeriodicalId":54554,"journal":{"name":"Progress in Biophysics & Molecular Biology","volume":"199 ","pages":"Pages 209-221"},"PeriodicalIF":4.5,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146047300","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}
Pub Date : 2026-01-23DOI: 10.1016/j.pbiomolbio.2026.01.002
Christopher Eugenio Williem , Viranitasya Stephanie Himawan , Maykel T.E. Manawan , Sun Theo Constan Lotebulo Ndruru , Dicky Annas , Jia Hong Pan , Mega Safithri , I Made Artika , Robertus Wahyu N. Nugroho
Cryogenic electron tomography (cryo-ET) enables in situ structural analysis of macromolecular assemblies within their native cellular environments, spanning more than four orders of magnitude in spatial scale, from micrometre-level cellular context accessed through correlative imaging to near–sub-nanometre resolution achieved through subtomogram averaging (STA). This review summarises recent advances in mapping cellular architecture, encompassing membrane-bound organelles, cytoskeletal networks, adhesion complexes, and discrete cellular subsystems such as cilia and the nuclear pore complex (NPC). We discuss the principal challenges associated with cellular cryo-ET, including specimen thickness and electron transparency limitations, structural heterogeneity, the transient nature of many assemblies, restricted targeting precision, unreliable molecular identification, preparation-induced artefacts, and labelling constraints. Recent strategies developed to address these challenges are reviewed, with particular emphasis on innovations in sample preparation and their integration with cryo-focused ion beam milling (cryo-FIB), cryo-correlative light and electron microscopy (cryo-CLEM), STA, and complementary volume-imaging approaches such as cryo-scanning transmission electron tomography (cryo-STET) and cryo-soft X-ray tomography (cryo-SXT). We further highlight emerging density-based modelling strategies that enable molecular interpretation when sufficient resolution is achieved, as well as two-dimensional (2D) template-matching approaches. Collectively, these developments position cryo-ET as a central framework for interrogating cellular ultrastructure in its native context.
{"title":"Recent advances in targeting regions of interest for In situ cryo-electron tomography of cellular architecture","authors":"Christopher Eugenio Williem , Viranitasya Stephanie Himawan , Maykel T.E. Manawan , Sun Theo Constan Lotebulo Ndruru , Dicky Annas , Jia Hong Pan , Mega Safithri , I Made Artika , Robertus Wahyu N. Nugroho","doi":"10.1016/j.pbiomolbio.2026.01.002","DOIUrl":"10.1016/j.pbiomolbio.2026.01.002","url":null,"abstract":"<div><div>Cryogenic electron tomography (cryo-ET) enables <em>in situ</em> structural analysis of macromolecular assemblies within their native cellular environments, spanning more than four orders of magnitude in spatial scale, from micrometre-level cellular context accessed through correlative imaging to near–sub-nanometre resolution achieved through subtomogram averaging (STA). This review summarises recent advances in mapping cellular architecture, encompassing membrane-bound organelles, cytoskeletal networks, adhesion complexes, and discrete cellular subsystems such as cilia and the nuclear pore complex (NPC). We discuss the principal challenges associated with cellular cryo-ET, including specimen thickness and electron transparency limitations, structural heterogeneity, the transient nature of many assemblies, restricted targeting precision, unreliable molecular identification, preparation-induced artefacts, and labelling constraints. Recent strategies developed to address these challenges are reviewed, with particular emphasis on innovations in sample preparation and their integration with cryo-focused ion beam milling (cryo-FIB), cryo-correlative light and electron microscopy (cryo-CLEM), STA, and complementary volume-imaging approaches such as cryo-scanning transmission electron tomography (cryo-STET) and cryo-soft X-ray tomography (cryo-SXT). We further highlight emerging density-based modelling strategies that enable molecular interpretation when sufficient resolution is achieved, as well as two-dimensional (2D) template-matching approaches. Collectively, these developments position cryo-ET as a central framework for interrogating cellular ultrastructure in its native context.</div></div>","PeriodicalId":54554,"journal":{"name":"Progress in Biophysics & Molecular Biology","volume":"199 ","pages":"Pages 222-245"},"PeriodicalIF":4.5,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146047319","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}
Pub Date : 2026-01-20DOI: 10.1016/j.pbiomolbio.2026.01.005
Kevser Kübra Kırboğa , Ecir Uğur Küçüksille
Energy models play a crucial role in the advancement of computational de novo protein engineering, enabling the design of novel proteins with tailored functionalities. Proteins serve as the foundation of biochemical processes, making their precise engineering essential for applications in biotechnology, medicine, and synthetic biology. Unlike traditional approaches that focus on modifying existing proteins, de novo engineering introduces entirely new constructs, a paradigm shift driven by energy-based strategies that guide protein folding, stability, and functionality through comprehensive simulations of energy landscapes. Computational techniques such as molecular dynamics (MD), thermodynamic integration, and Monte Carlo sampling are fundamental in evaluating designed proteins' stability and dynamic behavior. Widely used tools such as CHARMM, Amber, and Rosetta leverage advanced energy functions to optimize protein structures, facilitating accurate predictions of folding pathways and binding affinities. Additionally, the integration of machine learning (ML) and deep learning (DL) has significantly improved the speed and precision of energy-based modeling, enhancing the design and optimization process. This review systematically analyzes recent studies, provides quantitative benchmarking of major computational platforms, and presents a decision framework for method selection based on accuracy-cost-throughput trade-offs. By integrating classical force fields, quantum mechanical (QM) approaches, and AI-driven predictions with experimental validation, this work outlines a roadmap for advancing therapeutic and industrial protein design through synergistic physics-based and data-driven strategies.
{"title":"Energy-driven innovations in computational de novo protein engineering","authors":"Kevser Kübra Kırboğa , Ecir Uğur Küçüksille","doi":"10.1016/j.pbiomolbio.2026.01.005","DOIUrl":"10.1016/j.pbiomolbio.2026.01.005","url":null,"abstract":"<div><div>Energy models play a crucial role in the advancement of computational de novo protein engineering, enabling the design of novel proteins with tailored functionalities. Proteins serve as the foundation of biochemical processes, making their precise engineering essential for applications in biotechnology, medicine, and synthetic biology. Unlike traditional approaches that focus on modifying existing proteins, de novo engineering introduces entirely new constructs, a paradigm shift driven by energy-based strategies that guide protein folding, stability, and functionality through comprehensive simulations of energy landscapes. Computational techniques such as molecular dynamics (MD), thermodynamic integration, and Monte Carlo sampling are fundamental in evaluating designed proteins' stability and dynamic behavior. Widely used tools such as CHARMM, Amber, and Rosetta leverage advanced energy functions to optimize protein structures, facilitating accurate predictions of folding pathways and binding affinities. Additionally, the integration of machine learning (ML) and deep learning (DL) has significantly improved the speed and precision of energy-based modeling, enhancing the design and optimization process. This review systematically analyzes recent studies, provides quantitative benchmarking of major computational platforms, and presents a decision framework for method selection based on accuracy-cost-throughput trade-offs. By integrating classical force fields, quantum mechanical (QM) approaches, and AI-driven predictions with experimental validation, this work outlines a roadmap for advancing therapeutic and industrial protein design through synergistic physics-based and data-driven strategies.</div></div>","PeriodicalId":54554,"journal":{"name":"Progress in Biophysics & Molecular Biology","volume":"199 ","pages":"Pages 176-196"},"PeriodicalIF":4.5,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146030334","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}
Pub Date : 2026-01-19DOI: 10.1016/j.pbiomolbio.2026.01.004
Chunqin Li , Xige Dong , Mengxu Sun , Yuanfen Xie , Beilei Wang , Jiaxin Qin , Na Wang , Huanhuan Lv
Diabetes mellitus, a chronic metabolic disorder associated with high risk of cardiovascular disease, kidney disease, neuropathy and bone disorder, has emerged as a globally epidemic public health issue. Osteoporosis, the most common bone disease in middle-aged and elderly populations, demonstrates a particularly high prevalence in individuals with diabetes mellitus. This correlation underscores the urgent need to develop innovative strategies to improve the quality of life for patients with diabetic osteoporosis. Magnetic field-based physical therapy, a non-invasive therapeutic modality, presents distinct advantages over conventional treatments. Recent advances in biomagnetic research have unveiled novel biological and therapeutic effects of magnetic fields, with accumulating evidence supporting their potential clinical applications in bone-related disorders. This review critically examines the mechanistic links between diabetes mellitus and the deterioration of bone health, the therapeutic effects of both dynamic and static magnetic fields on diabetes-associated complications, with a specific focus on skeletal outcomes, and the prospective applications of magnetic fields intervention for maintaining bone health in diabetes mellitus. Ultimately, this review aims to propose novel therapeutic strategies for managing osteoporosis in diabetes mellitus through magnetic approaches.
{"title":"Modulating bone remodeling through magnetic field: Approach targeting metabolic dysregulation in diabetic osteoporosis","authors":"Chunqin Li , Xige Dong , Mengxu Sun , Yuanfen Xie , Beilei Wang , Jiaxin Qin , Na Wang , Huanhuan Lv","doi":"10.1016/j.pbiomolbio.2026.01.004","DOIUrl":"10.1016/j.pbiomolbio.2026.01.004","url":null,"abstract":"<div><div>Diabetes mellitus, a chronic metabolic disorder associated with high risk of cardiovascular disease, kidney disease, neuropathy and bone disorder, has emerged as a globally epidemic public health issue. Osteoporosis, the most common bone disease in middle-aged and elderly populations, demonstrates a particularly high prevalence in individuals with diabetes mellitus. This correlation underscores the urgent need to develop innovative strategies to improve the quality of life for patients with diabetic osteoporosis. Magnetic field-based physical therapy, a non-invasive therapeutic modality, presents distinct advantages over conventional treatments. Recent advances in biomagnetic research have unveiled novel biological and therapeutic effects of magnetic fields, with accumulating evidence supporting their potential clinical applications in bone-related disorders. This review critically examines the mechanistic links between diabetes mellitus and the deterioration of bone health, the therapeutic effects of both dynamic and static magnetic fields on diabetes-associated complications, with a specific focus on skeletal outcomes, and the prospective applications of magnetic fields intervention for maintaining bone health in diabetes mellitus. Ultimately, this review aims to propose novel therapeutic strategies for managing osteoporosis in diabetes mellitus through magnetic approaches.</div></div>","PeriodicalId":54554,"journal":{"name":"Progress in Biophysics & Molecular Biology","volume":"199 ","pages":"Pages 197-208"},"PeriodicalIF":4.5,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146020364","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}
The development of modern molecular biology helps us to identify the link between Kaposi's sarcoma-associated herpesvirus (KSHV) and multiple human malignancies by infecting B-lymphocyte or endothelial cells. Infection with KSHV plays a crucial role in stabilizing hypoxia-inducible factor-1 (HIF-1) and promoting its transcriptional activity. The association of KSHV and HIF-1 is essential for KSHV latency, reactivation, and associated disease phenotypes. In this review, we have discussed the detailed mechanisms of HIF-1 activation by KSHV infection. Based on the available evidence, we summarize the impact of HIF-1 activation on cellular metabolism, Angiogenesis, and lytic reactivation of KSHV in the proliferation and oncogenic progression of KSHV-infected B-lymphocyte or endothelial cells.
Furthermore, more studies reveal a deeper understanding of the interaction between KSHV and HIF-1. The modulatory impact of HIF-1 on the KSHV life cycle and oncogenic progression require further investigation. To advance this research, clinical trials targeting HIF-1 should commence in the near future.
{"title":"Impact of hypoxia-inducible factor 1 in the oncogenic progression of Kaposi's sarcoma-associated herpes virus","authors":"Koushik Chakraborty , Monalisha Ghosh , Dristi Majumdar , Tathagata Choudhuri","doi":"10.1016/j.pbiomolbio.2026.01.001","DOIUrl":"10.1016/j.pbiomolbio.2026.01.001","url":null,"abstract":"<div><div>The development of modern molecular biology helps us to identify the link between Kaposi's sarcoma-associated herpesvirus (KSHV) and multiple human malignancies by infecting B-lymphocyte or endothelial cells. Infection with KSHV plays a crucial role in stabilizing hypoxia-inducible factor-1 (HIF-1) and promoting its transcriptional activity. The association of KSHV and HIF-1 is essential for KSHV latency, reactivation, and associated disease phenotypes. In this review, we have discussed the detailed mechanisms of HIF-1 activation by KSHV infection. Based on the available evidence, we summarize the impact of HIF-1 activation on cellular metabolism, Angiogenesis, and lytic reactivation of KSHV in the proliferation and oncogenic progression of KSHV-infected B-lymphocyte or endothelial cells.</div><div>Furthermore, more studies reveal a deeper understanding of the interaction between KSHV and HIF-1. The modulatory impact of HIF-1 on the KSHV life cycle and oncogenic progression require further investigation. To advance this research, clinical trials targeting HIF-1 should commence in the near future.</div></div>","PeriodicalId":54554,"journal":{"name":"Progress in Biophysics & Molecular Biology","volume":"199 ","pages":"Pages 167-175"},"PeriodicalIF":4.5,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948877","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}
Pub Date : 2025-12-23DOI: 10.1016/j.pbiomolbio.2025.12.006
Eulália Rebeca Silva-Araújo , Raul Manhães-de-Castro , Ana Elisa Toscano , Henrique José Cavalcanti Bezerra Gouveia , Mônica Rodrigues de Sá , Gedeone Bezerra de Almeida Júnior , Assíria Natali da Silva , Eduardo Padrón-Hernández
Ultrastructural alterations in the central nervous system—such as synaptic dysfunction, axonal injury, and demyelination—contribute to the cognitive and sensorimotor deficits observed in neurological damage, in which TLR4-mediated neuroinflammation is a key pathological feature. This systematic review synthesizes evidence from 20 rodent studies employing transmission electron microscopy (TEM) to investigate central ultrastructural alterations induced by neuroinflammation, with a focus on the brain. A search was performed on Embase, PubMed, Scopus, and Web of Science databases. Study quality was assessed using the SYRCLE Risk of Bias tool for in vivo/ex vivo studies and an adapted QUIN tool for in vitro studies. Most studies have modeled neuroinflammation through LPS-infection or toxic insults, which have been implicated in disorders ranging from early brain injury to late-onset neurodegeneration, such as Alzheimer's disease. We observed that ultrastructural alterations originate from changes in glial morphology and function, subsequently affecting intracellular organelles and the extracellular space, thereby compromising cellular metabolism and neural integrity. TEM results show vascularized regions and protective barriers, enriched in glial cells, are particularly susceptible to early ultrastructural impairment. The damage extends to myelin architecture and axonal structure, which exhibit aberrant characteristics. Although the molecular mechanisms of neuroinflammation are well characterized, its ultrastructural consequences remain poorly explored. Elucidating these alterations through TEM studies provides a basis for targeted therapeutic strategies in neuroinflammation-related conditions.
中枢神经系统的超微结构改变,如突触功能障碍、轴突损伤和脱髓鞘,有助于神经损伤中观察到的认知和感觉运动缺陷,其中tlr4介导的神经炎症是一个关键的病理特征。本系统综述综合了来自20个啮齿动物研究的证据,利用透射电子显微镜(TEM)研究神经炎症引起的中枢超微结构改变,重点是大脑。在Embase、PubMed、Scopus和Web of Science数据库上进行了搜索。在体内/离体研究中使用sycle偏倚风险工具评估研究质量,在体外研究中使用经过调整的QUIN工具评估研究质量。大多数研究通过lps感染或毒性损伤来模拟神经炎症,这与从早期脑损伤到迟发性神经变性(如阿尔茨海默病)等疾病有关。我们观察到超微结构的改变源于胶质形态和功能的改变,随后影响细胞内细胞器和细胞外空间,从而损害细胞代谢和神经完整性。透射电镜结果显示,血管化区和保护屏障,丰富的胶质细胞,特别容易受到早期超微结构损伤。损伤扩展到髓鞘结构和轴突结构,表现出异常特征。尽管神经炎症的分子机制已被很好地表征,但其超微结构后果仍未得到充分探讨。通过透射电镜研究阐明这些改变为神经炎症相关疾病的靶向治疗策略提供了基础。
{"title":"Unraveling cerebral ultrastructural alterations in TLR4-mediated neuroinflammation via transmission electron microscopy: a systematic preclinical review","authors":"Eulália Rebeca Silva-Araújo , Raul Manhães-de-Castro , Ana Elisa Toscano , Henrique José Cavalcanti Bezerra Gouveia , Mônica Rodrigues de Sá , Gedeone Bezerra de Almeida Júnior , Assíria Natali da Silva , Eduardo Padrón-Hernández","doi":"10.1016/j.pbiomolbio.2025.12.006","DOIUrl":"10.1016/j.pbiomolbio.2025.12.006","url":null,"abstract":"<div><div>Ultrastructural alterations in the central nervous system—such as synaptic dysfunction, axonal injury, and demyelination—contribute to the cognitive and sensorimotor deficits observed in neurological damage, in which TLR4-mediated neuroinflammation is a key pathological feature. This systematic review synthesizes evidence from 20 rodent studies employing transmission electron microscopy (TEM) to investigate central ultrastructural alterations induced by neuroinflammation, with a focus on the brain. A search was performed on Embase, PubMed, Scopus, and Web of Science databases. Study quality was assessed using the SYRCLE Risk of Bias tool for in vivo/ex vivo studies and an adapted QUIN tool for in vitro studies. Most studies have modeled neuroinflammation through LPS-infection or toxic insults, which have been implicated in disorders ranging from early brain injury to late-onset neurodegeneration, such as Alzheimer's disease. We observed that ultrastructural alterations originate from changes in glial morphology and function, subsequently affecting intracellular organelles and the extracellular space, thereby compromising cellular metabolism and neural integrity. TEM results show vascularized regions and protective barriers, enriched in glial cells, are particularly susceptible to early ultrastructural impairment. The damage extends to myelin architecture and axonal structure, which exhibit aberrant characteristics. Although the molecular mechanisms of neuroinflammation are well characterized, its ultrastructural consequences remain poorly explored. Elucidating these alterations through TEM studies provides a basis for targeted therapeutic strategies in neuroinflammation-related conditions.</div></div>","PeriodicalId":54554,"journal":{"name":"Progress in Biophysics & Molecular Biology","volume":"199 ","pages":"Pages 146-161"},"PeriodicalIF":4.5,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145829166","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}
Cardiovascular disease (CVD) is a leading cause of mortality worldwide, and the mechanical behavior of arterial wall tissue (AWT) is central to its initiation and progression. This review surveys advances in constitutive models of AWT over the past two decades, with the aim of improving understanding of vascular mechanics and informing clinical practice. Five major computational frameworks are evaluated—elastic, viscoelastic, hyperelastic, structural solid models, and growth and remodeling (G&R) models—which collectively provide insights into stress–strain relationships and mechanobiological interactions under physiological and pathological conditions. Simple elastic formulations cannot capture the intrinsic nonlinearity of AWT. Nonlinear elastic and pseudo-elastic models are better suited for large deformations and anisotropy, especially under cyclic loading. Viscoelastic models effectively represent time-dependent responses to pulsatile blood flow. Structural solid models, including layered anisotropic, equivalent homogeneous, and generalized structure tensor formulations, predict the mechanical behavior of individual wall layers with high fidelity. Extending beyond instantaneous mechanics, G&R models embed these constitutive relations within higher-level frameworks to simulate long-term adaptations to altered hemodynamics, such as hypertension, aneurysm progression, or vascular graft remodeling. Future research should focus on developing dynamic models that more accurately simulate pulsatile loading, refining the characterization of AWT heterogeneity and anisotropy, and establishing multiscale and multi-physics frameworks to connect cellular processes with tissue-level behavior. Integrating big data and machine learning offers additional potential for robust parameter identification and predictive modeling. In conclusion, this review provides a comprehensive evaluation of AWT constitutive modeling, from fundamental elasticity-based approaches to advanced G&R frameworks. By identifying limitations and outlining future directions, it highlights the role of biomechanics in advancing personalized medicine, improving CVD diagnosis and treatment, and promoting deeper understanding of disease mechanisms.
{"title":"Progress in constitutive modeling of arterial wall tissue mechanics: from theoretical frameworks to clinical application","authors":"Qian Fan , Dezhong Qi , Qiang Xiao , Xiaoqiang Zhou","doi":"10.1016/j.pbiomolbio.2025.12.005","DOIUrl":"10.1016/j.pbiomolbio.2025.12.005","url":null,"abstract":"<div><div>Cardiovascular disease (CVD) is a leading cause of mortality worldwide, and the mechanical behavior of arterial wall tissue (AWT) is central to its initiation and progression. This review surveys advances in constitutive models of AWT over the past two decades, with the aim of improving understanding of vascular mechanics and informing clinical practice. Five major computational frameworks are evaluated—elastic, viscoelastic, hyperelastic, structural solid models, and growth and remodeling (G&R) models—which collectively provide insights into stress–strain relationships and mechanobiological interactions under physiological and pathological conditions. Simple elastic formulations cannot capture the intrinsic nonlinearity of AWT. Nonlinear elastic and pseudo-elastic models are better suited for large deformations and anisotropy, especially under cyclic loading. Viscoelastic models effectively represent time-dependent responses to pulsatile blood flow. Structural solid models, including layered anisotropic, equivalent homogeneous, and generalized structure tensor formulations, predict the mechanical behavior of individual wall layers with high fidelity. Extending beyond instantaneous mechanics, G&R models embed these constitutive relations within higher-level frameworks to simulate long-term adaptations to altered hemodynamics, such as hypertension, aneurysm progression, or vascular graft remodeling. Future research should focus on developing dynamic models that more accurately simulate pulsatile loading, refining the characterization of AWT heterogeneity and anisotropy, and establishing multiscale and multi-physics frameworks to connect cellular processes with tissue-level behavior. Integrating big data and machine learning offers additional potential for robust parameter identification and predictive modeling. In conclusion, this review provides a comprehensive evaluation of AWT constitutive modeling, from fundamental elasticity-based approaches to advanced G&R frameworks. By identifying limitations and outlining future directions, it highlights the role of biomechanics in advancing personalized medicine, improving CVD diagnosis and treatment, and promoting deeper understanding of disease mechanisms.</div></div>","PeriodicalId":54554,"journal":{"name":"Progress in Biophysics & Molecular Biology","volume":"199 ","pages":"Pages 114-145"},"PeriodicalIF":4.5,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145795380","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}