Pub Date : 2025-12-10DOI: 10.1016/j.pbiomolbio.2025.12.004
Martin Král , Olga Švecová , Pavel Jurák , Josef Halámek , Milena Šimurdová , Jiří Šimurda , Markéta Bébarová
The microelectrode array (MEA) is an easy, high-throughput method, ideal for obtaining a large amount of data from excitable cells, including cardiomyocytes. However, the analysis can be problematic, especially the analysis of the field potential duration (FPD). Several factors, including the differentiation protocol, culture duration, recording settings, and signal processing, may influence the results. In this paper, we focused on the MEA recording settings, analysis, and evaluation of FPD from cardiomyocytes, especially those derived from human pluripotent stem cells (hPSC). By examining more than 120 original articles using MEA and any cardiac preparation, we detected an inconsistency in the acquisition setting. It is striking that only one-third of the studies provided complete information about filtering of the signal, even though this may substantially influence the shape of the signal and, thus, FPD. The performed analysis emphasizes a thorough inspection of both the ‘raw’ and filtered signals to estimate proper FPD values, as well as a careful determination of the relationship between FPD and cycle length before using any correction formula.
{"title":"Field potential duration and its variability as essential parameters for revealing proarrhythmia: problematic aspects of analysis in cardiomyocytes derived from human pluripotent stem cells","authors":"Martin Král , Olga Švecová , Pavel Jurák , Josef Halámek , Milena Šimurdová , Jiří Šimurda , Markéta Bébarová","doi":"10.1016/j.pbiomolbio.2025.12.004","DOIUrl":"10.1016/j.pbiomolbio.2025.12.004","url":null,"abstract":"<div><div>The microelectrode array (MEA) is an easy, high-throughput method, ideal for obtaining a large amount of data from excitable cells, including cardiomyocytes. However, the analysis can be problematic, especially the analysis of the field potential duration (FPD). Several factors, including the differentiation protocol, culture duration, recording settings, and signal processing, may influence the results. In this paper, we focused on the MEA recording settings, analysis, and evaluation of FPD from cardiomyocytes, especially those derived from human pluripotent stem cells (hPSC). By examining more than 120 original articles using MEA and any cardiac preparation, we detected an inconsistency in the acquisition setting. It is striking that only one-third of the studies provided complete information about filtering of the signal, even though this may substantially influence the shape of the signal and, thus, FPD. The performed analysis emphasizes a thorough inspection of both the ‘raw’ and filtered signals to estimate proper FPD values, as well as a careful determination of the relationship between FPD and cycle length before using any correction formula.</div></div>","PeriodicalId":54554,"journal":{"name":"Progress in Biophysics & Molecular Biology","volume":"199 ","pages":"Pages 99-113"},"PeriodicalIF":4.5,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145745495","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 : 2025-12-04DOI: 10.1016/j.pbiomolbio.2025.12.003
Eugenio Frixione, Lourdes Ruiz-Zamarripa
Water, elected as Molecule of the Year by the American Society for Biochemistry and Molecular Biology, is the substance in which life originated on this planet and became then involved in numerous cell functions of all animal and vegetal tissues, up to being the most abundant component of all living systems. Despite its importance, however, the various conditions and roles of water in the protoplasm are mostly absent in current cell biology textbooks and common related reviews, so the subject demands consideration of how it should be now taught to graduate students interested in biochemistry and molecular biology. The present paper offers an overview of how knowledge about water involvement in cell structure and function has evolved from the mid 19th century up to our time, starting with early microscopic inspections of living cells, proceeding next to the emergence of notions about water distribution within them, including its various particular behaviors in the protoplasm and the roles it plays in cell function, plus succinct notes about recent reports of experimental approaches with their results and particular views on the topic for different types of cells.
{"title":"WATER roles in cells: Biological and biophysical perspectives","authors":"Eugenio Frixione, Lourdes Ruiz-Zamarripa","doi":"10.1016/j.pbiomolbio.2025.12.003","DOIUrl":"10.1016/j.pbiomolbio.2025.12.003","url":null,"abstract":"<div><div>Water, elected as Molecule of the Year by the American Society for Biochemistry and Molecular Biology, is the substance in which life originated on this planet and became then involved in numerous cell functions of all animal and vegetal tissues, up to being the most abundant component of all living systems. Despite its importance, however, the various conditions and roles of water in the protoplasm are mostly absent in current cell biology textbooks and common related reviews, so the subject demands consideration of how it should be now taught to graduate students interested in biochemistry and molecular biology. The present paper offers an overview of how knowledge about water involvement in cell structure and function has evolved from the mid 19th century up to our time, starting with early microscopic inspections of living cells, proceeding next to the emergence of notions about water distribution within them, including its various particular behaviors in the protoplasm and the roles it plays in cell function, plus succinct notes about recent reports of experimental approaches with their results and particular views on the topic for different types of cells.</div></div>","PeriodicalId":54554,"journal":{"name":"Progress in Biophysics & Molecular Biology","volume":"199 ","pages":"Pages 162-166"},"PeriodicalIF":4.5,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696329","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 : 2025-12-03DOI: 10.1016/j.pbiomolbio.2025.12.002
Amirhamzeh Farajollahi
The past decade has seen growing interest in injectable hydrogels for cancer therapy due to their tunable polymer backbones and high chemical versatility. Researchers are engineering injectable hydrogel platforms for chemotherapy, immunotherapy, and combination regimens to overcome limitations of conventional treatments. These materials enable localized, targeted delivery by encapsulating anti-tumor agents within a gel matrix, allowing sustained and controlled release that boosts efficacy while reducing systemic side effects. This review summarizes methods for preparing injectable hydrogels and highlights their key applications in cancer treatment, including strategies for payload loading, release modulation, and site-specific administration. We discuss how hydrogel composition, crosslinking chemistry, and microstructure govern therapeutic performance and biocompatibility, and we survey designs that integrate immune modulators, chemotherapeutics, or multi-modal agents for synergistic effects. Remaining challenges—such as predictable degradation, scalable manufacturing, in vivo stability, and regulatory translation—are examined, along with opportunities for improving targeting, responsiveness, and combination-therapy compatibility. Finally, we outline research directions needed to accelerate clinical translation, including standardized characterization, long-term safety studies, and optimized delivery protocols. By consolidating recent advances and identifying gaps, this review aims to guide future development of injectable hydrogels that can meaningfully enhance therapeutic outcomes for cancer patients.
{"title":"Injectable hydrogel: A promising frontier in cancer therapy","authors":"Amirhamzeh Farajollahi","doi":"10.1016/j.pbiomolbio.2025.12.002","DOIUrl":"10.1016/j.pbiomolbio.2025.12.002","url":null,"abstract":"<div><div>The past decade has seen growing interest in injectable hydrogels for cancer therapy due to their tunable polymer backbones and high chemical versatility. Researchers are engineering injectable hydrogel platforms for chemotherapy, immunotherapy, and combination regimens to overcome limitations of conventional treatments. These materials enable localized, targeted delivery by encapsulating anti-tumor agents within a gel matrix, allowing sustained and controlled release that boosts efficacy while reducing systemic side effects. This review summarizes methods for preparing injectable hydrogels and highlights their key applications in cancer treatment, including strategies for payload loading, release modulation, and site-specific administration. We discuss how hydrogel composition, crosslinking chemistry, and microstructure govern therapeutic performance and biocompatibility, and we survey designs that integrate immune modulators, chemotherapeutics, or multi-modal agents for synergistic effects. Remaining challenges—such as predictable degradation, scalable manufacturing, in vivo stability, and regulatory translation—are examined, along with opportunities for improving targeting, responsiveness, and combination-therapy compatibility. Finally, we outline research directions needed to accelerate clinical translation, including standardized characterization, long-term safety studies, and optimized delivery protocols. By consolidating recent advances and identifying gaps, this review aims to guide future development of injectable hydrogels that can meaningfully enhance therapeutic outcomes for cancer patients.</div></div>","PeriodicalId":54554,"journal":{"name":"Progress in Biophysics & Molecular Biology","volume":"199 ","pages":"46"},"PeriodicalIF":4.5,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145688681","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 : 2025-12-02DOI: 10.1016/j.pbiomolbio.2025.11.003
Jesse Oluwaseun Ayantoye , Baigao Yang , Hang Zhang , Jianhua Dong , Xiaomeng Zhang , Haoran Song , Muhammad Shahzad , Hubdar Ali Kolachi , Osamede Henry Osaiyuwu , Pengcheng Wan , Hongmei Pan , Xueming Zhao
Reproductive cryopreservation via vitrification is vital for livestock breeding and biodiversity conservation, as it enables ice-free storage of gametes and embryos. However, success increasingly depends on achieving rapid, uniform warming to avoid devitrification: the critical warming rate (CWR) required is often orders of magnitude higher than the critical cooling rate (CCR). Conventional convective thawing (e.g., water baths) produces edge-to-core thermal gradients that can lead to lethal ice formation in larger or more complex samples. Suboptimal warming disrupts cellular ultrastructure, leading to meiotic spindle collapse, mitochondrial depolarization, reactive oxygen species production, DNA damage, and apoptosis. These changes manifest as impaired embryo development and the formation of necrotic tissue cores. Notably, lipid-rich porcine oocytes and embryos are particularly susceptible to recrystallization during slow warming, with higher fragmentation and lower viability than their bovine and ovine counterparts. This review synthesizes thermophysical principles underlying the CWR requirement and biological evidence of the warming bottleneck across animal systems. This thermophysical imbalance means that rewarming, rather than cooling, is the decisive barrier to successful vitrification. We then discuss emerging volumetric rewarming technologies that uniformly deliver energy: magnetic nanoparticle-induced nanowarming, laser-driven photothermal heating, dielectric (radiofrequency/microwave) rewarming, and ultrafast Joule (ohmic) heating. These methods have demonstrably exceeded CWR thresholds in embryos, tissues, and organs, improving cell survival and function. We also highlight enabling tools such as microfluidic cryoprotectant (CPA) handling, automated vitrification platforms, artificial intelligence (AI)-guided protocol optimization, and isochoric (constant-volume) vitrification, which collectively enhance reproducibility and scalability of cryopreservation workflows. In conclusion, integrating volumetric heating modalities with these engineering innovations promises to transform animal cryopreservation: uniformly rapid warming will improve immediate post-thaw viability and preserve biological integrity, enabling routine, large-scale germplasm banking for livestock production and conservation.
{"title":"Overcoming the warming bottleneck in animal vitrification: Volumetric heating and enabling technologies for reproductive cryobanking","authors":"Jesse Oluwaseun Ayantoye , Baigao Yang , Hang Zhang , Jianhua Dong , Xiaomeng Zhang , Haoran Song , Muhammad Shahzad , Hubdar Ali Kolachi , Osamede Henry Osaiyuwu , Pengcheng Wan , Hongmei Pan , Xueming Zhao","doi":"10.1016/j.pbiomolbio.2025.11.003","DOIUrl":"10.1016/j.pbiomolbio.2025.11.003","url":null,"abstract":"<div><div>Reproductive cryopreservation via vitrification is vital for livestock breeding and biodiversity conservation, as it enables ice-free storage of gametes and embryos. However, success increasingly depends on achieving rapid, uniform warming to avoid devitrification: the critical warming rate (CWR) required is often orders of magnitude higher than the critical cooling rate (CCR). Conventional convective thawing (e.g., water baths) produces edge-to-core thermal gradients that can lead to lethal ice formation in larger or more complex samples. Suboptimal warming disrupts cellular ultrastructure, leading to meiotic spindle collapse, mitochondrial depolarization, reactive oxygen species production, DNA damage, and apoptosis. These changes manifest as impaired embryo development and the formation of necrotic tissue cores. Notably, lipid-rich porcine oocytes and embryos are particularly susceptible to recrystallization during slow warming, with higher fragmentation and lower viability than their bovine and ovine counterparts. This review synthesizes thermophysical principles underlying the CWR requirement and biological evidence of the warming bottleneck across animal systems. This thermophysical imbalance means that rewarming, rather than cooling, is the decisive barrier to successful vitrification. We then discuss emerging volumetric rewarming technologies that uniformly deliver energy: magnetic nanoparticle-induced nanowarming, laser-driven photothermal heating, dielectric (radiofrequency/microwave) rewarming, and ultrafast Joule (ohmic) heating. These methods have demonstrably exceeded CWR thresholds in embryos, tissues, and organs, improving cell survival and function. We also highlight enabling tools such as microfluidic cryoprotectant (CPA) handling, automated vitrification platforms, artificial intelligence (AI)-guided protocol optimization, and isochoric (constant-volume) vitrification, which collectively enhance reproducibility and scalability of cryopreservation workflows. In conclusion, integrating volumetric heating modalities with these engineering innovations promises to transform animal cryopreservation: uniformly rapid warming will improve immediate post-thaw viability and preserve biological integrity, enabling routine, large-scale germplasm banking for livestock production and conservation.</div></div>","PeriodicalId":54554,"journal":{"name":"Progress in Biophysics & Molecular Biology","volume":"199 ","pages":"Pages 31-45"},"PeriodicalIF":4.5,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145679604","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}
Quantum mechanics (QM) is emerging as a powerful framework for studying disease-related mutations at the atomic and subatomic levels, providing mechanistic insights beyond those of classical models. In this review, we examined primary research to evaluate the extent to which QM is used to understand mutational mechanisms across various disease contexts. Our search was conducted in PubMed using the keywords “quantum mechanics” AND “mutations.” We also reviewed the reference lists of the retrieved articles for relevant data. All review articles were excluded. The final number of selected articles was thirty-four. These studies were categorized into two main modules: QM applications in non-communicable diseases and QM-based approaches to infectious diseases. In non-communicable diseases, especially cancer and neurodegeneration, QM simulations help clarify how mutations influence enzymatic catalysis, protein dynamics, and drug-target interactions, thereby improving our understanding of DNA repair, metabolic reprogramming, and resistance to targeted therapies. In communicable diseases, QM approaches can reveal how alterations in pathogens' genetic material impact protein–receptor interactions, virulence, and treatment effectiveness. Our findings highlight QM's role in shifting from discovery to therapeutics and underscore its applications in biomedicine. These advances could speed up drug development and personalized medicine.
{"title":"Quantum mechanics as a tool to decipher the mutational landscape of human disease","authors":"Eustathia-Irene Zavitsanou , Argyris Dallis , Athanasios Balaskas , Sotirios Zarogiannis , Erasmia Rouka","doi":"10.1016/j.pbiomolbio.2025.11.004","DOIUrl":"10.1016/j.pbiomolbio.2025.11.004","url":null,"abstract":"<div><div>Quantum mechanics (QM) is emerging as a powerful framework for studying disease-related mutations at the atomic and subatomic levels, providing mechanistic insights beyond those of classical models. In this review, we examined primary research to evaluate the extent to which QM is used to understand mutational mechanisms across various disease contexts. Our search was conducted in PubMed using the keywords “quantum mechanics” AND “mutations.” We also reviewed the reference lists of the retrieved articles for relevant data. All review articles were excluded. The final number of selected articles was thirty-four. These studies were categorized into two main modules: QM applications in non-communicable diseases and QM-based approaches to infectious diseases. In non-communicable diseases, especially cancer and neurodegeneration, QM simulations help clarify how mutations influence enzymatic catalysis, protein dynamics, and drug-target interactions, thereby improving our understanding of DNA repair, metabolic reprogramming, and resistance to targeted therapies. In communicable diseases, QM approaches can reveal how alterations in pathogens' genetic material impact protein–receptor interactions, virulence, and treatment effectiveness. Our findings highlight QM's role in shifting from discovery to therapeutics and underscore its applications in biomedicine. These advances could speed up drug development and personalized medicine.</div></div>","PeriodicalId":54554,"journal":{"name":"Progress in Biophysics & Molecular Biology","volume":"199 ","pages":"Pages 69-78"},"PeriodicalIF":4.5,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145679623","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 : 2025-12-02DOI: 10.1016/j.pbiomolbio.2025.12.001
Isabella V. Gimón , Conner Sandefur , Santiago Schnell
Protein aggregation plays a dual role in cellular biology, enabling essential functions such as intracellular organization, signaling, and storage, while also contributing to pathological states associated with misfolding and toxicity. However, existing literature lacks an integrated framework for predicting when crowding will favor productive assembly versus drive pathological outcomes—a gap that has hindered both mechanistic understanding and therapeutic development. This review examines how macromolecular crowding—an intrinsic feature of the intracellular environment—shapes protein aggregation outcomes by modulating key physicochemical parameters: volume exclusion, electrostatic interactions, aggregate morphology, cytoplasmic viscosity, and liquid–liquid phase separation. We demonstrate that crowding acts not as a universal promoter or inhibitor of aggregation, but rather as a context-dependent modulator that amplifies latent vulnerabilities in proteins predisposed to misfolding while facilitating productive assembly in properly regulated systems. By analyzing the mechanistic continuum between functional and pathological aggregation, we provide a framework for interpreting how identical molecular forces yield divergent biological outcomes depending on protein properties, environmental conditions, and cellular regulation. This perspective clarifies how the intracellular milieu governs aggregation dynamics and identifies promising avenues for therapeutic intervention, including strategic modulation of crowding conditions to promote protective assemblies while suppressing toxic aggregates in misfolding-related diseases. We conclude by outlining future directions toward quantitative, predictive models that integrate molecular mechanism with physiological context, bridging the gap between in vitro biophysics and in vivo cellular function.
{"title":"Macromolecular crowding and protein aggregation: Friend, foe or contextual force?","authors":"Isabella V. Gimón , Conner Sandefur , Santiago Schnell","doi":"10.1016/j.pbiomolbio.2025.12.001","DOIUrl":"10.1016/j.pbiomolbio.2025.12.001","url":null,"abstract":"<div><div>Protein aggregation plays a dual role in cellular biology, enabling essential functions such as intracellular organization, signaling, and storage, while also contributing to pathological states associated with misfolding and toxicity. However, existing literature lacks an integrated framework for predicting when crowding will favor productive assembly versus drive pathological outcomes—a gap that has hindered both mechanistic understanding and therapeutic development. This review examines how macromolecular crowding—an intrinsic feature of the intracellular environment—shapes protein aggregation outcomes by modulating key physicochemical parameters: volume exclusion, electrostatic interactions, aggregate morphology, cytoplasmic viscosity, and liquid–liquid phase separation. We demonstrate that crowding acts not as a universal promoter or inhibitor of aggregation, but rather as a context-dependent modulator that amplifies latent vulnerabilities in proteins predisposed to misfolding while facilitating productive assembly in properly regulated systems. By analyzing the mechanistic continuum between functional and pathological aggregation, we provide a framework for interpreting how identical molecular forces yield divergent biological outcomes depending on protein properties, environmental conditions, and cellular regulation. This perspective clarifies how the intracellular milieu governs aggregation dynamics and identifies promising avenues for therapeutic intervention, including strategic modulation of crowding conditions to promote protective assemblies while suppressing toxic aggregates in misfolding-related diseases. We conclude by outlining future directions toward quantitative, predictive models that integrate molecular mechanism with physiological context, bridging the gap between in vitro biophysics and in vivo cellular function.</div></div>","PeriodicalId":54554,"journal":{"name":"Progress in Biophysics & Molecular Biology","volume":"199 ","pages":"Pages 79-98"},"PeriodicalIF":4.5,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145679540","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 : 2025-11-20DOI: 10.1016/j.pbiomolbio.2025.11.002
Dan Ni , Yuxuan Liu , Xiaofang Lin , Manqing Luo , Chuanhuan Deng , Jing Li , Pengfei Liang , Zhenguo Liu , Bimei Jiang
Carnitine palmitoyltransferase 1 (CPT1) serves as a critical gatekeeper in mitochondrial fatty acid oxidation and plays a central role in systemic energy homeostasis. The CPT1 family comprises three isoforms—CPT1A, CPT1B, and CPT1C—which exhibit distinct tissue distributions and regulatory features, enabling specialized metabolic functions in the liver, heart, skeletal muscle, and brain. CPT1 activity is tightly controlled through multiple mechanisms, including inhibition by malonyl-CoA, epigenetic modifications, and protein–protein interactions, all of which coordinate nutrient sensing and energy adaptation. Dysregulation of CPT1 has been implicated in the development of various metabolic disorders, including obesity, metabolic (dysfunction)-associated fatty liver disease (MAFLD), diabetic cardiomyopathy, and metabolic syndrome. This review summarizes recent advances in understanding the regulatory landscape and pathological roles of CPT1 and further discusses emerging therapeutic strategies. While CPT1-targeted interventions hold promise, challenges such as isoform specificity, off-target effects, and tissue-selective delivery must be addressed to achieve precision metabolic modulation.
{"title":"Rewiring lipid Metabolism: The central role of CPT1 in metabolic dysfunction","authors":"Dan Ni , Yuxuan Liu , Xiaofang Lin , Manqing Luo , Chuanhuan Deng , Jing Li , Pengfei Liang , Zhenguo Liu , Bimei Jiang","doi":"10.1016/j.pbiomolbio.2025.11.002","DOIUrl":"10.1016/j.pbiomolbio.2025.11.002","url":null,"abstract":"<div><div>Carnitine palmitoyltransferase 1 (CPT1) serves as a critical gatekeeper in mitochondrial fatty acid oxidation and plays a central role in systemic energy homeostasis. The CPT1 family comprises three isoforms—CPT1A, CPT1B, and CPT1C—which exhibit distinct tissue distributions and regulatory features, enabling specialized metabolic functions in the liver, heart, skeletal muscle, and brain. CPT1 activity is tightly controlled through multiple mechanisms, including inhibition by malonyl-CoA, epigenetic modifications, and protein–protein interactions, all of which coordinate nutrient sensing and energy adaptation. Dysregulation of CPT1 has been implicated in the development of various metabolic disorders, including obesity, metabolic (dysfunction)-associated fatty liver disease (MAFLD), diabetic cardiomyopathy, and metabolic syndrome. This review summarizes recent advances in understanding the regulatory landscape and pathological roles of CPT1 and further discusses emerging therapeutic strategies. While CPT1-targeted interventions hold promise, challenges such as isoform specificity, off-target effects, and tissue-selective delivery must be addressed to achieve precision metabolic modulation.</div></div>","PeriodicalId":54554,"journal":{"name":"Progress in Biophysics & Molecular Biology","volume":"199 ","pages":"Pages 20-30"},"PeriodicalIF":4.5,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145582827","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}
Threatening impact of tuberculosis (TB) on public health remains significant even after the global initiatives and emergence of multi-drug resistance (MDR) strains have made the situation complicated. Herein, the exploitation of the same medications for several decades, ineffective drug administration, and insufficient patient follow-up are some of the variables that have fuelled the resistance. As a result, the twenty-first century has seen the greatest number of multi-drug resistance TB cases. Nevertheless, nanotechnology has emerged as a promising tool against drug-resistant Mycobacterium tuberculosis, the bacterium responsible for TB. This seminal review highlights the most important findings from nanomaterials-related research to detect and counter TB. First, a deeper understanding of the essential molecular mechanisms underlying drug-resistance and drug-tolerance in Mycobacterium pathogen is provided along with biofilm formation and intracellular survival mechanisms. It is followed by detailed discussions about innovative nanomaterials-based drug delivery for antituberculosis medications, and different types of nanomaterials for direct antimicrobial actions. Then, nanotechnology-assisted diagnosis techniques and anti-biofilm possibilities for drug-resistant M. tuberculosis are elaborated. Finally, the challenges and perspectives related to nanomaterials-based theranostic for TB drug-resistance and treatment are provided with concluding remarks.
{"title":"Advances in nanomaterials-assisted drug delivery, diagnosis, and action towards drug-resistant Mycobacterium","authors":"Parikshana Mathur , Pinky Choudhary , Rajkuberan Chandrasekaran , Ragini Singh , Hemant Kumar Daima","doi":"10.1016/j.pbiomolbio.2025.11.001","DOIUrl":"10.1016/j.pbiomolbio.2025.11.001","url":null,"abstract":"<div><div>Threatening impact of tuberculosis (TB) on public health remains significant even after the global initiatives and emergence of multi-drug resistance (MDR) strains have made the situation complicated. Herein, the exploitation of the same medications for several decades, ineffective drug administration, and insufficient patient follow-up are some of the variables that have fuelled the resistance. As a result, the twenty-first century has seen the greatest number of multi-drug resistance TB cases. Nevertheless, nanotechnology has emerged as a promising tool against drug-resistant <em>Mycobacterium tuberculosis</em>, the bacterium responsible for TB. This seminal review highlights the most important findings from nanomaterials-related research to detect and counter TB. First, a deeper understanding of the essential molecular mechanisms underlying drug-resistance and drug-tolerance in <em>Mycobacterium</em> pathogen is provided along with biofilm formation and intracellular survival mechanisms. It is followed by detailed discussions about innovative nanomaterials-based drug delivery for antituberculosis medications, and different types of nanomaterials for direct antimicrobial actions. Then, nanotechnology-assisted diagnosis techniques and anti-biofilm possibilities for drug-resistant <em>M. tuberculosis</em> are elaborated. Finally, the challenges and perspectives related to nanomaterials-based theranostic for TB drug-resistance and treatment are provided with concluding remarks.</div></div>","PeriodicalId":54554,"journal":{"name":"Progress in Biophysics & Molecular Biology","volume":"199 ","pages":"Pages 1-19"},"PeriodicalIF":4.5,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145566385","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 : 2025-11-01DOI: 10.1016/j.pbiomolbio.2025.10.004
Amal Alachkar
L-3,4-dihydroxyphenylalanine (DOPA) is primarily defined by its role as the precursor to catecholamine neurotransmitters, a view substantiated by its status as the gold-standard treatment for Parkinson's disease. This framing obscures its profound evolutionary significance. This review reframes DOPA as a fundamental physicochemical scaffold whose core aromatic catechol-based properties: electron transfer, metal chelation, self-assembly, and polymerization into semiconducting biopolymers have been repeatedly repurposed throughout three billion years, from prebiotic Earth to the human brain.
From its plausible origins in prebiotic catalysis, these properties were leveraged by life to solve recurring challenges in survival and protection (e.g., microbial siderophores, protective melanins), settlement and colonization (e.g., marine bioadhesives), and competitive/cooperative communication (e.g., allelochemicals, social signaling). This evolutionary history of DOPA reveals a consistent pattern, a conserved 'Stress-Motion-Motivation-Action’ arc that links environmental challenges to the emergence of goal-directed behavior. I propose that DOPA's same ancient chemical logic was not discarded but repurposed in the mammalian brain. Beyond serving as a dopamine precursor, DOPA's non-canonical functions: adhesion, chelation, and polymerization into the semiconducting biopolymer neuromelanin, form a multiscale biophysical scaffold. This scaffold provides the structural and electrochemical stability necessary for the neural circuits and for the canonical dopamine signaling to execute not only motivation and movement but also the agency-related complex computations. This model thus bridges molecular biophysics with higher-order cognition, reframing DOPA as a fundamental material substrate for cognitive agency.
l -3,4-二羟基苯丙氨酸(DOPA)主要被定义为儿茶酚胺神经递质的前体,这一观点被其作为帕金森病的金标准治疗所证实。这种框架掩盖了其深刻的进化意义。这篇综述将DOPA重新定义为一种基本的物理化学支架,其核心的芳香儿茶酚性质:电子转移、金属螯合、自组装和聚合成半导体生物聚合物,在30亿年的时间里,从益生元地球到人类大脑,被反复地重新利用。从其可能的益生元催化起源来看,这些特性被生命利用来解决生存和保护(例如微生物铁载体,保护性黑色素),定居和定植(例如海洋生物粘合剂)以及竞争/合作通信(例如化感化学物质,社会信号)中反复出现的挑战。DOPA的进化史揭示了一个一致的模式,一个保守的“压力-运动-动机-行动”弧线,将环境挑战与目标导向行为的出现联系起来。我认为多巴同样古老的化学逻辑并没有被丢弃,而是在哺乳动物的大脑中被重新利用。除了作为多巴胺前体,多巴的非规范功能:粘附、螯合和聚合成半导体生物聚合物神经黑色素,形成了一个多尺度的生物物理支架。这种支架为神经回路和规范的多巴胺信号提供了必要的结构和电化学稳定性,不仅可以执行动机和运动,还可以执行与代理相关的复杂计算。因此,该模型将分子生物物理学与高阶认知联系起来,将多巴重构为认知代理的基本物质基质。
{"title":"The DOPA scaffold: Tracing catechol chemistry from prebiotic earth to cognitive agency","authors":"Amal Alachkar","doi":"10.1016/j.pbiomolbio.2025.10.004","DOIUrl":"10.1016/j.pbiomolbio.2025.10.004","url":null,"abstract":"<div><div>L-3,4-dihydroxyphenylalanine (DOPA) is primarily defined by its role as the precursor to catecholamine neurotransmitters, a view substantiated by its status as the gold-standard treatment for Parkinson's disease. This framing obscures its profound evolutionary significance. This review reframes DOPA as a fundamental physicochemical scaffold whose core aromatic catechol-based properties: electron transfer, metal chelation, self-assembly, and polymerization into semiconducting biopolymers have been repeatedly repurposed throughout three billion years, from prebiotic Earth to the human brain.</div><div>From its plausible origins in prebiotic catalysis, these properties were leveraged by life to solve recurring challenges in survival and protection (e.g., microbial siderophores, protective melanins), settlement and colonization (e.g., marine bioadhesives), and competitive/cooperative communication (e.g., allelochemicals, social signaling). This evolutionary history of DOPA reveals a consistent pattern, a conserved 'Stress-Motion-Motivation-Action’ arc that links environmental challenges to the emergence of goal-directed behavior. I propose that DOPA's same ancient chemical logic was not discarded but repurposed in the mammalian brain. Beyond serving as a dopamine precursor, DOPA's non-canonical functions: adhesion, chelation, and polymerization into the semiconducting biopolymer neuromelanin, form a multiscale biophysical scaffold. This scaffold provides the structural and electrochemical stability necessary for the neural circuits and for the canonical dopamine signaling to execute not only motivation and movement but also the agency-related complex computations. This model thus bridges molecular biophysics with higher-order cognition, reframing DOPA as a fundamental material substrate for cognitive agency.</div></div>","PeriodicalId":54554,"journal":{"name":"Progress in Biophysics & Molecular Biology","volume":"198 ","pages":"Pages 71-91"},"PeriodicalIF":4.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145439941","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 : 2025-10-31DOI: 10.1016/j.pbiomolbio.2025.10.003
Tina Karimian , Christoph Cremer , Julian Weghuber , Herbert Schneckenburger
Live-cell microscopy is gaining importance for studying cellular behavior in response to environmental cues. However, cell aging can result in modifications of various cellular structures and functions, affecting or distorting microscopy-based readouts. These changes include gene expression, nuclear architecture, energy metabolism, or changes in the mechanical properties of cell membranes and microtubules. In this mini-review, we briefly discuss how cell aging affects critical subcellular compartments and alters live-cell imaging outcomes. In contrast to many papers available on cell aging, here we are focusing on the influence of cell aging on the performance and outcome of advanced microscopy techniques such as super-resolution imaging, fluorescence lifetime imaging (FLIM), variable-angle total internal reflection fluorescence microscopy (VA-TIRFM), as well as micromanipulation techniques such as laser-assisted optoporation. Our findings highlight the importance of considering cell passage number and senescence markers in experimental design and data interpretation.
{"title":"Cell aging - a relevant factor in live cell microscopy (mini-review)","authors":"Tina Karimian , Christoph Cremer , Julian Weghuber , Herbert Schneckenburger","doi":"10.1016/j.pbiomolbio.2025.10.003","DOIUrl":"10.1016/j.pbiomolbio.2025.10.003","url":null,"abstract":"<div><div>Live-cell microscopy is gaining importance for studying cellular behavior in response to environmental cues. However, cell aging can result in modifications of various cellular structures and functions, affecting or distorting microscopy-based readouts. These changes include gene expression, nuclear architecture, energy metabolism, or changes in the mechanical properties of cell membranes and microtubules. In this mini-review, we briefly discuss how cell aging affects critical subcellular compartments and alters live-cell imaging outcomes. In contrast to many papers available on cell aging, here we are focusing on the influence of cell aging on the performance and outcome of advanced microscopy techniques such as super-resolution imaging, fluorescence lifetime imaging (FLIM), variable-angle total internal reflection fluorescence microscopy (VA-TIRFM), as well as micromanipulation techniques such as laser-assisted optoporation. Our findings highlight the importance of considering cell passage number and senescence markers in experimental design and data interpretation.</div></div>","PeriodicalId":54554,"journal":{"name":"Progress in Biophysics & Molecular Biology","volume":"198 ","pages":"Pages 61-70"},"PeriodicalIF":4.5,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145427166","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}