Pub Date : 2025-12-01DOI: 10.1016/j.biochi.2025.08.018
Wenbo Cao, Jun Tan
Comprehensive characterization of fatty acid (FA) structures has important value, as they are important components of cells and are crucial for cell structure and function. However, in view of the different structural possibilities of unsaturated FAs due to the carbon–carbon double bond (CC) location and its chemical configuration, there are still certain difficulties in characterizing unsaturated FAs with high structural specificity. In this work, we present a method based on nuclear magnetic resonance (NMR) spectroscopy for comprehensive characterization of unsaturated FAs. Combining 1D and 2D-NMR spectroscopy, it could provide diagnostic information specific to CC locations and stereochemistry of unsaturated FAs, facilitating FA isomers identification. Structural characterization of unsaturated FAs at the isomeric level has been validated by examination of multiple sample types through our proposed approach. The capability of the proposed method for relative quantitation of FA isomers utilizing its specific diagnostic peaks was also demonstrated. Unlike conventional approaches requiring both reference standards and extensive sample processing, the current proposed method represents a potential alternative by resolving unsaturated lipid structures at high structural level directly.
{"title":"Characterization of unsaturated fatty acids with high structural specificity by nuclear magnetic resonance spectroscopy","authors":"Wenbo Cao, Jun Tan","doi":"10.1016/j.biochi.2025.08.018","DOIUrl":"10.1016/j.biochi.2025.08.018","url":null,"abstract":"<div><div>Comprehensive characterization of fatty acid (FA) structures has important value, as they are important components of cells and are crucial for cell structure and function. However, in view of the different structural possibilities of unsaturated FAs due to the carbon–carbon double bond (C<img>C) location and its chemical configuration, there are still certain difficulties in characterizing unsaturated FAs with high structural specificity. In this work, we present a method based on nuclear magnetic resonance (NMR) spectroscopy for comprehensive characterization of unsaturated FAs. Combining 1D and 2D-NMR spectroscopy, it could provide diagnostic information specific to C<img>C locations and stereochemistry of unsaturated FAs, facilitating FA isomers identification. Structural characterization of unsaturated FAs at the isomeric level has been validated by examination of multiple sample types through our proposed approach. The capability of the proposed method for relative quantitation of FA isomers utilizing its specific diagnostic peaks was also demonstrated. Unlike conventional approaches requiring both reference standards and extensive sample processing, the current proposed method represents a potential alternative by resolving unsaturated lipid structures at high structural level directly.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"239 ","pages":"Pages 177-190"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982282","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 : 2025-12-01DOI: 10.1016/j.biochi.2025.10.001
Aditi Pathak , Ramanathan Sowdhamini
Gap junctions are multimeric intercellular channels that permit ions and small molecules to pass directly from one cell to another. Despite being fundamental to multicellular life, these channels are formed by distantly related protein families: innexins in invertebrates and connexins in vertebrates. Vertebrates also express pannexins, distant homologs of primordial innexins, which only form hemichannels. While these families have diverse sequences and different oligomeric states, their monomeric structures are highly similar. We generated structure-guided sequence alignments to establish equivalent residues across innexins, connexins, and pannexins. Further, computational approaches for determining protein-protein interaction hotspots, residue conservation, accessible surface area and local conformations of residues, provide insights into the relationships between residue positions and channel properties. We find that exposed transmembrane residues of TM1 and TM2 are more conserved than those in TM3 and TM4, especially in connexins and pannexins. Moreover, we see that residues in the extracellular extended hairpins of pannexins show more conformational flexibility, in variable protein blocks, than equivalent residues in connexins. This hints that the rigidity of this element could be a prerequisite for hemichannel docking. Finally, we identify inter- and intra-hemichannel interface hotspots that are positionally conserved across the families, implying their role in hemichannel and, ultimately, gap junction formation. Such analyses reveal a molecular grammar that underlies gap junction design and offer a basis for targeted perturbation of channel properties.
{"title":"Computational structural analysis sheds light on the molecular grammar of gap junction proteins","authors":"Aditi Pathak , Ramanathan Sowdhamini","doi":"10.1016/j.biochi.2025.10.001","DOIUrl":"10.1016/j.biochi.2025.10.001","url":null,"abstract":"<div><div>Gap junctions are multimeric intercellular channels that permit ions and small molecules to pass directly from one cell to another. Despite being fundamental to multicellular life, these channels are formed by distantly related protein families: innexins in invertebrates and connexins in vertebrates. Vertebrates also express pannexins, distant homologs of primordial innexins, which only form hemichannels. While these families have diverse sequences and different oligomeric states, their monomeric structures are highly similar. We generated structure-guided sequence alignments to establish equivalent residues across innexins, connexins, and pannexins. Further, computational approaches for determining protein-protein interaction hotspots, residue conservation, accessible surface area and local conformations of residues, provide insights into the relationships between residue positions and channel properties. We find that exposed transmembrane residues of TM1 and TM2 are more conserved than those in TM3 and TM4, especially in connexins and pannexins. Moreover, we see that residues in the extracellular extended hairpins of pannexins show more conformational flexibility, in variable protein blocks, than equivalent residues in connexins. This hints that the rigidity of this element could be a prerequisite for hemichannel docking. Finally, we identify inter- and intra-hemichannel interface hotspots that are positionally conserved across the families, implying their role in hemichannel and, ultimately, gap junction formation. Such analyses reveal a molecular grammar that underlies gap junction design and offer a basis for targeted perturbation of channel properties.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"239 ","pages":"Pages 82-96"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254148","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 : 2025-12-01DOI: 10.1016/j.biochi.2025.08.005
Alexandre G. de Brevern
Professor Serge Hazout, or Serge, as his friends and colleagues knew him, passed away on April 24, 2005 in Paris, France. Serge was a leading pioneer in the field of Bioinformatics in France. His work stretched over 30 years beginning with his graduate studies in 1975, and he impacted a large number of researches in this field. This in memoriam outlines both his professional career and personal life; highlighting his impact on bioinformatics at the training level in France and his numerous scientific contributions which both continue to flourish today.
{"title":"In memoriam of Professor Serge Hazout (1950–2005) – a bioinformatics pioneer in France","authors":"Alexandre G. de Brevern","doi":"10.1016/j.biochi.2025.08.005","DOIUrl":"10.1016/j.biochi.2025.08.005","url":null,"abstract":"<div><div>Professor Serge Hazout, or Serge, as his friends and colleagues knew him, passed away on April 24, 2005 in Paris, France. Serge was a leading pioneer in the field of Bioinformatics in France. His work stretched over 30 years beginning with his graduate studies in 1975, and he impacted a large number of researches in this field. This <em>in memoriam</em> outlines both his professional career and personal life; highlighting his impact on bioinformatics at the training level in France and his numerous scientific contributions which both continue to flourish today.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"239 ","pages":"Pages 1-7"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144818645","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 : 2025-12-01DOI: 10.1016/j.biochi.2025.08.011
Surbhi Dhingra , Stéphane Téletchéa , Ramanathan Sowdhamini , Yves-Henri Sanejouand , Alexandre G. de Brevern , Frédéric Cadet , Bernard Offmann
The remarkable structural diversity of modern proteins reflects millions of years of evolution, during which sequence space has expanded while many structural features remain conserved. This conservation is evident not only among homologous proteins but also in the recurrence of supersecondary motifs across unrelated proteins, underscoring the abundance and robustness of these structural units. Here, we present a novel pipeline for generating customized protein fragment libraries using protein blocks (PBs)—a structural alphabet that encodes local backbone conformations. Our method efficiently extracts structurally similar fragments from a curated, non-redundant protein structure database by converting three-dimensional structures into one-dimensional PB sequences. By integrating predicted PB sequences with the PB-ALIGN and PB-kPRED tools, our approach identifies relevant fragments independently of sequence homology. Fragment quality is further assessed using a new scoring function that combines secondary structure similarity and PB alignment metrics. The resulting libraries contain fragments of at least seven PBs (11 amino acid residues), covering over 70 % of the local backbone structure. Our results demonstrate that PBs enable efficient mining of high-quality structural fragments from diverse protein spaces, including proteins with disordered regions. The pipeline is accessible as an online tool (PB-Frag, http://pbpred-us2b.univ-nantes.fr/pbfrag).
{"title":"Using protein blocks to build custom fragment libraries from protein structures","authors":"Surbhi Dhingra , Stéphane Téletchéa , Ramanathan Sowdhamini , Yves-Henri Sanejouand , Alexandre G. de Brevern , Frédéric Cadet , Bernard Offmann","doi":"10.1016/j.biochi.2025.08.011","DOIUrl":"10.1016/j.biochi.2025.08.011","url":null,"abstract":"<div><div>The remarkable structural diversity of modern proteins reflects millions of years of evolution, during which sequence space has expanded while many structural features remain conserved. This conservation is evident not only among homologous proteins but also in the recurrence of supersecondary motifs across unrelated proteins, underscoring the abundance and robustness of these structural units. Here, we present a novel pipeline for generating customized protein fragment libraries using protein blocks (PBs)—a structural alphabet that encodes local backbone conformations. Our method efficiently extracts structurally similar fragments from a curated, non-redundant protein structure database by converting three-dimensional structures into one-dimensional PB sequences. By integrating predicted PB sequences with the PB-ALIGN and PB-kPRED tools, our approach identifies relevant fragments independently of sequence homology. Fragment quality is further assessed using a new scoring function that combines secondary structure similarity and PB alignment metrics. The resulting libraries contain fragments of at least seven PBs (11 amino acid residues), covering over 70 % of the local backbone structure. Our results demonstrate that PBs enable efficient mining of high-quality structural fragments from diverse protein spaces, including proteins with disordered regions. The pipeline is accessible as an online tool (PB-Frag, <span><span>http://pbpred-us2b.univ-nantes.fr/pbfrag</span><svg><path></path></svg></span>).</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"239 ","pages":"Pages 72-81"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859983","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}
Uncoupling proteins, as mitochondrial transporters, allow protons to enter the mitochondrial matrix without generating ATP, a process known as oxidative phosphorylation uncoupling. Mammalian UCPs have been demonstrated to regulate metabolism, modulate reactive oxygen species levels, and maintain calcium homeostasis, which is closely linked to cardiac disease. In Drosophila, four homologs of uncoupling protein have been identified, with only UCP5 being detected in the adult heart proteome by mass spectrometry. The essential role of Drosophila UCP5 in the heart remains unknown. Our results showed that cardiac-specific UCP5 overexpression increased the incidence of fibrillation in an age-dependent trend, while cardiac-specific UCP5 knockdown induced an age-dependent increase in the incidence of asystoles, likely due to tachycardia. Additionally, UCP5 RNA levels significantly decline with age, indicating a role of UCP5 in cardiac aging. Cardiac-specific UCP5 overexpression reduced the reactive oxygen species levels within the cardiomyocyte nuclei and extended the lifespan. UCP5 RNA levels increased under high-fat diet conditions, and systemic overexpression of UCP5 can lower triglyceride levels under such dietary conditions, indicating an adaptive role of UCP5 in metabolism.
{"title":"The role of UCP5 in cardiac aging and metabolism in Drosophila","authors":"Yanxu Zhang , Yiyuan Zhai , Ying Bai, Qun Zeng, Min Tang","doi":"10.1016/j.biochi.2025.09.012","DOIUrl":"10.1016/j.biochi.2025.09.012","url":null,"abstract":"<div><div>Uncoupling proteins, as mitochondrial transporters, allow protons to enter the mitochondrial matrix without generating ATP, a process known as oxidative phosphorylation uncoupling. Mammalian UCPs have been demonstrated to regulate metabolism, modulate reactive oxygen species levels, and maintain calcium homeostasis, which is closely linked to cardiac disease. In Drosophila, four homologs of uncoupling protein have been identified, with only UCP5 being detected in the adult heart proteome by mass spectrometry. The essential role of <em>Drosophila</em> UCP5 in the heart remains unknown. Our results showed that cardiac-specific UCP5 overexpression increased the incidence of fibrillation in an age-dependent trend, while cardiac-specific UCP5 knockdown induced an age-dependent increase in the incidence of asystoles, likely due to tachycardia. Additionally, UCP5 RNA levels significantly decline with age, indicating a role of UCP5 in cardiac aging. Cardiac-specific UCP5 overexpression reduced the reactive oxygen species levels within the cardiomyocyte nuclei and extended the lifespan. UCP5 RNA levels increased under high-fat diet conditions, and systemic overexpression of UCP5 can lower triglyceride levels under such dietary conditions, indicating an adaptive role of UCP5 in metabolism.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"239 ","pages":"Pages 252-260"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145180856","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 : 2025-12-01DOI: 10.1016/j.biochi.2025.10.009
Jean-Christophe Gelly
The classical concept of a protein domain has impacted structural and molecular biology, but geometric, evolutionary and functional criteria often result in conflicting domain boundaries. We proposed the “protein unit” (PU), an intermediate, evolutionarily conserved structural motif that connects secondary structures to complete domains. A hierarchical decomposition of protein structures identifies these compact units and their hierarchical arrangement, clarifying ambiguous boundaries and yielding multiple plausible domain organizations. Considering proteins as assemblies of modular PUs opens new perspectives and applications, such as structural comparison, by accounting for relative movements, insertions and circular permutations, as well as improved template detection in comparative modelling. Structural unit libraries also enable a modular design strategy in which new architectures arise from alternative combinations of existing units. The protein-unit framework redefines protein architecture as a hierarchy of reusable modules and opens new avenues of research for prediction, modelling and protein engineering.
{"title":"Beyond classical domains: The protein unit paradigm - from protein-architecture characterization to downstream applications","authors":"Jean-Christophe Gelly","doi":"10.1016/j.biochi.2025.10.009","DOIUrl":"10.1016/j.biochi.2025.10.009","url":null,"abstract":"<div><div>The classical concept of a protein domain has impacted structural and molecular biology, but geometric, evolutionary and functional criteria often result in conflicting domain boundaries. We proposed the “protein unit” (PU), an intermediate, evolutionarily conserved structural motif that connects secondary structures to complete domains. A hierarchical decomposition of protein structures identifies these compact units and their hierarchical arrangement, clarifying ambiguous boundaries and yielding multiple plausible domain organizations. Considering proteins as assemblies of modular PUs opens new perspectives and applications, such as structural comparison, by accounting for relative movements, insertions and circular permutations, as well as improved template detection in comparative modelling. Structural unit libraries also enable a modular design strategy in which new architectures arise from alternative combinations of existing units. The protein-unit framework redefines protein architecture as a hierarchy of reusable modules and opens new avenues of research for prediction, modelling and protein engineering.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"239 ","pages":"Pages 32-38"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145314180","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 : 2025-12-01DOI: 10.1016/j.biochi.2025.08.012
Leila E. Zyla , Flavia A. Bruna , Flavia E. Santiano , Silvina E. Gómez , Rocío Cano , Mariángeles Ávila Maniero , Elisa O. Pietrobon , Paula M. Ginevro , Fernando D. Cuello-Carrión , Virginia Pistone-Creydt , Rubén W. Carón , Constanza M. López Fontana
Thyroid hormones play a key role in adipose tissue development and function. Hypothyroidism (HypoT) can delay mammary tumor development in rats, possibly by altering mammary adipose tissue (MAT) and its interaction with epithelial cells. To explore this hypothesis, we evaluated the effects of conditioned media derived from mammary adipose tissue (MAT-CMs) of hypothyroid (HypoT) and euthyroid (EUT) rats, with and without mammary tumors, on the behavior of mammary epithelial cells. Specifically, we assessed cell viability, proliferation, apoptosis, adhesion, and migration in tumorigenic (MCF-7, MDA-MB-231) and non-tumorigenic (MCF-10A) human mammary epithelial cell lines exposed to the MAT-CMs. Mammary tumors were induced in female Sprague–Dawley rats using 7,12-dimethylbenz[a]anthracene (15 mg/rat), and animals were randomly assigned to HypoT (0.01 % 6-N-propyl-2-thiouracil in drinking water; n = 30) or EUT (tap water; n = 30) groups. MAT fragments were incubated in M199 medium for 24 h, and the resulting CMs were collected and applied to cell cultures. In vivo, HypoT rats exhibited larger mammary fat pads, reduced tumor incidence, volume, and growth rate, and extended tumor-free survival. In vitro, non-tumor MAT-CMs from HypoT rats promoted apoptosis in MCF-10A cells, reduced viability and adhesion of MCF-7 cells, and increased proliferation while decreasing adhesion in MDA-MB-231 cells. Tumor MAT-CMs from HypoT rats stimulated proliferation in tumorigenic cells and inhibited apoptosis in MCF-10A cells. In conclusion, these findings indicate that HypoT modifies the secretory profile of MAT, with tumor MAT-CMs from HypoT potentially enhancing tumorigenic behaviors in mammary tumor cells.
{"title":"Hypothyroidism impacts mammary tumor-associated adipose tissue and breast cancer epithelial cell dialogue","authors":"Leila E. Zyla , Flavia A. Bruna , Flavia E. Santiano , Silvina E. Gómez , Rocío Cano , Mariángeles Ávila Maniero , Elisa O. Pietrobon , Paula M. Ginevro , Fernando D. Cuello-Carrión , Virginia Pistone-Creydt , Rubén W. Carón , Constanza M. López Fontana","doi":"10.1016/j.biochi.2025.08.012","DOIUrl":"10.1016/j.biochi.2025.08.012","url":null,"abstract":"<div><div>Thyroid hormones play a key role in adipose tissue development and function. Hypothyroidism (HypoT) can delay mammary tumor development in rats, possibly by altering mammary adipose tissue (MAT) and its interaction with epithelial cells. To explore this hypothesis, we evaluated the effects of conditioned media derived from mammary adipose tissue (MAT-CMs) of hypothyroid (HypoT) and euthyroid (EUT) rats, with and without mammary tumors, on the behavior of mammary epithelial cells. Specifically, we assessed cell viability, proliferation, apoptosis, adhesion, and migration in tumorigenic (MCF-7, MDA-MB-231) and non-tumorigenic (MCF-10A) human mammary epithelial cell lines exposed to the MAT-CMs. Mammary tumors were induced in female Sprague–Dawley rats using 7,12-dimethylbenz[a]anthracene (15 mg/rat), and animals were randomly assigned to HypoT (0.01 % 6-N-propyl-2-thiouracil in drinking water; n = 30) or EUT (tap water; n = 30) groups. MAT fragments were incubated in M199 medium for 24 h, and the resulting CMs were collected and applied to cell cultures. <em>In vivo</em>, HypoT rats exhibited larger mammary fat pads, reduced tumor incidence, volume, and growth rate, and extended tumor-free survival. <em>In vitro,</em> non-tumor MAT-CMs from HypoT rats promoted apoptosis in MCF-10A cells, reduced viability and adhesion of MCF-7 cells, and increased proliferation while decreasing adhesion in MDA-MB-231 cells. Tumor MAT-CMs from HypoT rats stimulated proliferation in tumorigenic cells and inhibited apoptosis in MCF-10A cells. In conclusion, these findings indicate that HypoT modifies the secretory profile of MAT, with tumor MAT-CMs from HypoT potentially enhancing tumorigenic behaviors in mammary tumor cells.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"239 ","pages":"Pages 127-138"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144823414","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}
Particulate matter (PM) in air pollution has become a major environmental concern due to its potential health impacts, which vary seasonally and with human activities. While PM is often monitored for concentration, its chemical composition is equally important, especially regarding its effects on the immune system, which remain poorly understood. This study investigates the biological effects of PM2.5 on macrophages collected in different seasons and during COVID-19 restrictions in Taiwan. The experiments revealed significant seasonal variations in metal and polycyclic aromatic hydrocarbons (PAHs) content in PM2.5, with summer having the highest metal levels and winter the highest PAHs. Exposure to PM2.5 increased cell biotoxicity, correlating with higher PM2.5 concentrations. Further analysis showed that PM2.5 exposure polarized macrophages into the M1 type, triggering inflammatory cytokines, increased ROS levels, cell growth arrest, and apoptosis. Notably, PM2.5 from summer exhibited the highest biotoxicity. The study also identified four metals (Fe, Ti, Co, Sb) as key contributors to biotoxicity. PM2.5 collected during COVID-19 Level 2 Alert showed higher concentrations of these metals, resulting in greater toxicity to macrophages. This research underscores how seasonal changes and human activities influence PM2.5's impact on the immune system, contributing to air pollution control efforts.
{"title":"Evaluate the impact of PM2.5 in different macrophage types under the influence of seasonal changes and anthropogenic activities","authors":"Yung-Jui Chen , Meng-Hsin Li , Fang-Yi Gu , Yu-Cheng Chen , Hong-Lin Chan , Hsiu-Chuan Chou","doi":"10.1016/j.biochi.2025.08.010","DOIUrl":"10.1016/j.biochi.2025.08.010","url":null,"abstract":"<div><div>Particulate matter (PM) in air pollution has become a major environmental concern due to its potential health impacts, which vary seasonally and with human activities. While PM is often monitored for concentration, its chemical composition is equally important, especially regarding its effects on the immune system, which remain poorly understood. This study investigates the biological effects of PM2.5 on macrophages collected in different seasons and during COVID-19 restrictions in Taiwan. The experiments revealed significant seasonal variations in metal and polycyclic aromatic hydrocarbons (PAHs) content in PM2.5, with summer having the highest metal levels and winter the highest PAHs. Exposure to PM2.5 increased cell biotoxicity, correlating with higher PM2.5 concentrations. Further analysis showed that PM2.5 exposure polarized macrophages into the M1 type, triggering inflammatory cytokines, increased ROS levels, cell growth arrest, and apoptosis. Notably, PM2.5 from summer exhibited the highest biotoxicity. The study also identified four metals (Fe, Ti, Co, Sb) as key contributors to biotoxicity. PM2.5 collected during COVID-19 Level 2 Alert showed higher concentrations of these metals, resulting in greater toxicity to macrophages. This research underscores how seasonal changes and human activities influence PM2.5's impact on the immune system, contributing to air pollution control efforts.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"239 ","pages":"Pages 109-126"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144850017","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}
Trichomonas vaginalis, the causative agent of human trichomoniasis, relies on host-derived nutrients such as purines and glucose to support survival during infection. As an auxotrophic protozoan, T. vaginalis is incapable to synthesize purine nucleotides de novo and depends entirely on salvage mechanisms, particularly those involving adenosine. However, how nutrient availability modulates the parasite's virulence and purine metabolism remains unclear. Here, we demonstrate that serum and glucose limitation modulate the purine metabolism in T. vaginalis, enhancing extracellular nucleotide hydrolysis by ectonucleoside triphosphate diphosphohydrolase (NTPDase). Serum limitation, a condition that mimics reduced adenosine levels, increased the cytotoxicity of T. vaginalis towards human vaginal epithelial cells (HVECs). When adenosine was added to the culture, it reversed the increase in NTPDase activity and cytotoxicity caused by serum limitation. The protective effect promoted by adenosine during co-incubation of serum-limited T. vaginalis and HVECs was reduced by dipyridamole, possibly indicating a critical role for adenosine uptake by the parasites. Gene expression analysis revealed differential regulation of T. vaginalis equilibrative nucleoside transporter genes, with downregulation under serum limitation and upregulation under glucose restriction, suggesting an adaptative transcriptional response to stress in nutrient availability. These findings reveal that adenosine deprivation modulates purine metabolism in T. vaginalis and enhances parasite cytotoxicity. Furthermore, our results uncover adenosine as a pivotal regulator of T. vaginalis virulence under metabolic stress and highlight purine salvage pathways and nucleoside transport as promising targets for therapeutic intervention against trichomoniasis.
{"title":"Adenosine deprivation modulates purine metabolism and enhances Trichomonas vaginalis cytotoxicity","authors":"Saulo Almeida Menezes , Fernanda Gomes Cardoso , Caroline Rita Venturi , Amanda Thomas Barden , Tiana Tasca","doi":"10.1016/j.biochi.2025.08.015","DOIUrl":"10.1016/j.biochi.2025.08.015","url":null,"abstract":"<div><div><em>Trichomonas vaginalis</em>, the causative agent of human trichomoniasis, relies on host-derived nutrients such as purines and glucose to support survival during infection. As an auxotrophic protozoan, <em>T. vaginalis</em> is incapable to synthesize purine nucleotides <em>de novo</em> and depends entirely on salvage mechanisms, particularly those involving adenosine. However, how nutrient availability modulates the parasite's virulence and purine metabolism remains unclear. Here, we demonstrate that serum and glucose limitation modulate the purine metabolism in <em>T. vaginalis</em>, enhancing extracellular nucleotide hydrolysis by ectonucleoside triphosphate diphosphohydrolase (NTPDase). Serum limitation, a condition that mimics reduced adenosine levels, increased the cytotoxicity of <em>T. vaginalis</em> towards human vaginal epithelial cells (HVECs). When adenosine was added to the culture, it reversed the increase in NTPDase activity and cytotoxicity caused by serum limitation. The protective effect promoted by adenosine during co-incubation of serum-limited <em>T. vaginalis</em> and HVECs was reduced by dipyridamole, possibly indicating a critical role for adenosine uptake by the parasites. Gene expression analysis revealed differential regulation of <em>T. vaginalis</em> equilibrative nucleoside transporter genes, with downregulation under serum limitation and upregulation under glucose restriction, suggesting an adaptative transcriptional response to stress in nutrient availability. These findings reveal that adenosine deprivation modulates purine metabolism in <em>T. vaginalis</em> and enhances parasite cytotoxicity. Furthermore, our results uncover adenosine as a pivotal regulator of <em>T. vaginalis</em> virulence under metabolic stress and highlight purine salvage pathways and nucleoside transport as promising targets for therapeutic intervention against trichomoniasis.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"239 ","pages":"Pages 163-176"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982292","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}
Cellular senescence, a phenomenon believed to contribute significantly to aging and age-related diseases, can be readily achieved under cell culture conditions. Alterations in the N-glycosylation of human blood glycoproteins have emerged as promising biomarkers of aging. However, knowledge about the in vitro use of glycobiomarkers for assessing cellular senescence remains limited.
Our study utilized MALDI-TOF mass spectrometry to compare the alterations in the N-glycome of replicatively senescent human dermal fibroblasts and glyoxal- and H2O2-executed SIPS cells. In this regard, fibroblasts at both early and late stages of H2O2-induced SIPS were evaluated. In all models, the onset of senescence was marked by an increase in levels of paucimannose Hex2-3GlcNAc2Fuc1 species along with reductions in fucosylated di-galactosylated biantennary N-glycans (Hex5HexNAc4Fuc1-2), which coincided with an upregulation of β-galactosidase (β-gal) activities. A nearly 40 % and 30 % decline in complex sialylated N-glycans, and around a 60 % and 40 % reduction in free oligosaccharides were also observed in the terminal passage of RS fibroblasts and late-stage H2O2-induced SIPS, respectively.
Our findings suggest that the onset of RS and SIPS generally influenced the same types of N-glycans. However, the extent of influences varied and was more or less proportional to SA-β-gal expression levels. In contrast to standard markers of senescence, such as SA-β-gal, the MALDI-TOF MS glycomics analysis also allows for discrimination between the early onset and the late stages of senescence.
{"title":"Exploring glycobiomarkers beyond senescence-associated β-galactosidase for studying aging in vitro","authors":"Lucia Račková , Rebeka Kodríková , Marek Nemčovič , Erika Csekes , Zuzana Pakanová","doi":"10.1016/j.biochi.2025.09.005","DOIUrl":"10.1016/j.biochi.2025.09.005","url":null,"abstract":"<div><div>Cellular senescence, a phenomenon believed to contribute significantly to aging and age-related diseases, can be readily achieved under cell culture conditions. Alterations in the N-glycosylation of human blood glycoproteins have emerged as promising biomarkers of aging. However, knowledge about the <em>in vitro</em> use of glycobiomarkers for assessing cellular senescence remains limited.</div><div>Our study utilized MALDI-TOF mass spectrometry to compare the alterations in the N-glycome of replicatively senescent human dermal fibroblasts and glyoxal- and H<sub>2</sub>O<sub>2</sub>-executed SIPS cells. In this regard, fibroblasts at both early and late stages of H<sub>2</sub>O<sub>2</sub>-induced SIPS were evaluated. In all models, the onset of senescence was marked by an increase in levels of paucimannose Hex<sub>2-3</sub>GlcNAc<sub>2</sub>Fuc<sub>1</sub> species along with reductions in fucosylated di-galactosylated biantennary N-glycans (Hex<sub>5</sub>HexNAc<sub>4</sub>Fuc<sub>1-2</sub>), which coincided with an upregulation of β-galactosidase (β-gal) activities. A nearly 40 % and 30 % decline in complex sialylated N-glycans, and around a 60 % and 40 % reduction in free oligosaccharides were also observed in the terminal passage of RS fibroblasts and late-stage H<sub>2</sub>O<sub>2</sub>-induced SIPS, respectively.</div><div>Our findings suggest that the onset of RS and SIPS generally influenced the same types of N-glycans. However, the extent of influences varied and was more or less proportional to SA-β-gal expression levels. In contrast to standard markers of senescence, such as SA-β-gal, the MALDI-TOF MS glycomics analysis also allows for discrimination between the early onset and the late stages of senescence.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"239 ","pages":"Pages 218-235"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058772","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}
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