BBA Advances最新文献_第5页

Capturing the micro-communities: Insights into biogenesis and architecture of bacterial biofilms 捕获微群落：对细菌生物膜的生物发生和结构的见解。

BBA Advances Pub Date : 2025-01-01 Epub Date: 2024-12-21 DOI: 10.1016/j.bbadva.2024.100133

Harshita Agarwal , Bharat Gurnani , Bhumika Pippal , Neha Jain

{"title":"Capturing the micro-communities: Insights into biogenesis and architecture of bacterial biofilms","authors":"Harshita Agarwal , Bharat Gurnani , Bhumika Pippal , Neha Jain","doi":"10.1016/j.bbadva.2024.100133","DOIUrl":"10.1016/j.bbadva.2024.100133","url":null,"abstract":"<div><div>Biofilm is an assemblage of microorganisms embedded within the extracellular matrix that provides mechanical stability, nutrient absorption, antimicrobial resistance, cell-cell interactions, and defence against host immune system. Various biomolecules such as lipids, carbohydrates, protein polymers (amyloid), and eDNA are present in the matrix playing significant role in determining the distinctive properties of biofilm. The formation of biofilms contributes to resistance against antimicrobial therapy in most of the human infections and exacerbates existing diseases. Therefore, this field requires several state-of-the-art techniques to fully understand the 3-D organization of biofilms, their cell behaviour and responses to pharmaceutical treatments. Here, we explore the assembly and regulation of biofilm biogenesis in the context of matrix components and highlight the significance of high-resolution imaging and analysing techniques for monitoring complex biofilm architecture. Our review also emphasizes the novelty and advancements in techniques to visualise biofilm structure and composition, providing valuable insights to understand biofilm-related infections.</div></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"7 ","pages":"Article 100133"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143013140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Albumin does not induce IL-6 release and toll-like receptor activation in vitro: Role of endotoxin contamination and biochemical modifications 白蛋白不诱导IL-6释放和toll样受体的体外激活：内毒素污染和生化修饰的作用

IF 3

BBA Advances Pub Date : 2025-01-01 Epub Date: 2025-11-17 DOI: 10.1016/j.bbadva.2025.100174

Margret Paar , Vera H. Fengler , Martina Schweiger , Christine Rossmann , Christoph Nusshold , Martina Mairold , Doris Payerl , Gerhard Cvirn , Karl Oettl

{"title":"Albumin does not induce IL-6 release and toll-like receptor activation in vitro: Role of endotoxin contamination and biochemical modifications","authors":"Margret Paar , Vera H. Fengler , Martina Schweiger , Christine Rossmann , Christoph Nusshold , Martina Mairold , Doris Payerl , Gerhard Cvirn , Karl Oettl","doi":"10.1016/j.bbadva.2025.100174","DOIUrl":"10.1016/j.bbadva.2025.100174","url":null,"abstract":"<div><div>Human serum albumin (HSA) is widely used in both clinical and research settings, yet its potential to stimulate immune responses remains poorly understood. In this study, we systematically investigated various therapeutic, recombinant and plasma-derived albumin preparations for their ability to induce pro-inflammatory cytokine release by human peripheral blood mononuclear cells (PBMC) and activate Toll-like receptors (TLR) in HEK-Blue™ TLR4 and TLR2 reporter cell lines. All albumin preparations were characterized in terms of their redox state of cysteine-34, glycation level, non-esterified fatty acid content, and endotoxin contamination Therapeutic albumin, as may be expected, did not induce IL-6-release nor TLR activation. However, several commercial research grade albumins, including fatty acid-free, glycated, and recombinant preparations, significantly induced IL-6 release and activated TLR4 and TLR2 signaling. These inflammatory effects were strongly correlated with the endotoxin content, while no consistent associations were found with albumin redox state, degree of glycation, or fatty acid load. Albumins with more reduced cysteine-34 content showed lower pro-inflammatory activity, but this correlation was lost when controlling for endotoxin levels, suggesting confounding by endotoxin contamination. Direct testing of isolated albumin redox fractions and in vitro glycated albumins confirmed that neither oxidation nor glycation of albumin, in the absence of endotoxin, triggered inflammatory responses in PBMCs. Inducing effects were found to be related to contaminating ligands and not to albumin itself. Our findings emphasize the need for rigorous product characterization and highlight the critical importance of endotoxin as a confounding factor in immune assays involving research grade albumin preparations.</div></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"8 ","pages":"Article 100174"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145568661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Phosphorylation of N-glycans in the brain: The case for a non-canonical pathway? 大脑中 N-聚糖的磷酸化：非经典途径的案例？

BBA Advances Pub Date : 2025-01-01 Epub Date: 2024-12-19 DOI: 10.1016/j.bbadva.2024.100134

Lucija Sironić , Nikol Mraz , Gordan Lauc , Thomas S. Klarić

{"title":"Phosphorylation of N-glycans in the brain: The case for a non-canonical pathway?","authors":"Lucija Sironić , Nikol Mraz , Gordan Lauc , Thomas S. Klarić","doi":"10.1016/j.bbadva.2024.100134","DOIUrl":"10.1016/j.bbadva.2024.100134","url":null,"abstract":"<div><div>Asparagine-linked glycosylation (N-glycosylation) is a common co- and post-translational modification that refers to the addition of complex carbohydrates, called N-linked glycans (N-glycans), to asparagine residues within defined sequons of polypeptide acceptors. Some N-glycans can be modified by the addition of phosphate moieties to their monosaccharide residues, thus forming phospho-N-glycans (PNGs). The most prominent such carbohydrate modification is mannose-6-phosphate (M6P) which plays a well-established role in trafficking of acid hydrolases to lysosomes. However, comparatively little is known about potential alternative types of glycan phosphorylation, particularly when it comes to the brain which is especially rich in phosphorylated oligosaccharides. Combining data from the literature and novel insights derived from our own analyses of published datasets, here we present what is currently known about PNGs in the brain and the glycoproteins they modify. We show that brain PNGs exhibit several distinctive features that don't completely align with our current understanding of the canonical M6P pathway. Furthermore, we demonstrate that there are numerous differences in the way that lysosomal and non-lysosomal neural glycoproteins are modified by PNGs. Based on these observations, we put forward the hypothesis that, in addition to the conventional M6P pathway, the brain employs an alternative oligosaccharide phosphorylation mechanism for the modification of a discrete set of glycoproteins. Here we examine the evidence underpinning this hypothesis and discuss the implications that it raises. Overall, our work suggests that phosphorylation of N-glycans in the brain may be more complex and more diverse than previously recognised.</div></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"7 ","pages":"Article 100134"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

VDAC1 inhibitor DIDS uncouples respiration in isolated tissue mitochondria and induces mitochondrial hyperfusion in mammalian cells 在哺乳动物细胞中，VDAC1抑制剂DIDS解除离体组织线粒体的呼吸偶联并诱导线粒体低灌注

IF 3

BBA Advances Pub Date : 2025-01-01 Epub Date: 2025-10-08 DOI: 10.1016/j.bbadva.2025.100171

Surajit Das , Arpita Dutta , Minakshi Bedi , Arumay Pal , Shubhra Majumder , Alok Ghosh

{"title":"VDAC1 inhibitor DIDS uncouples respiration in isolated tissue mitochondria and induces mitochondrial hyperfusion in mammalian cells","authors":"Surajit Das , Arpita Dutta , Minakshi Bedi , Arumay Pal , Shubhra Majumder , Alok Ghosh","doi":"10.1016/j.bbadva.2025.100171","DOIUrl":"10.1016/j.bbadva.2025.100171","url":null,"abstract":"<div><div>Mitochondrial outer membrane protein, voltage-dependent anion channel 1 (VDAC1), is a gatekeeper of transport, metabolism, and cellular apoptosis. Ablation of VDAC1 or treatment with small molecular VDAC1 inhibitors often causes metabolic reprogramming in cells. However, the mechanism of VDAC1-mediated reprogramming of mitochondrial oxidative phosphorylation (OXPHOS) is still unclear. To address this problem, we tested how the high-affinity VDAC1 inhibitor, 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS), changes cell viability and mitochondrial functions. The IC50 value of DIDS was found 508 µM and 580 µM after 24 h of treatment on human osteosarcoma U2OS and mouse NIH-3T3 fibroblast cells. Moreover, when we inhibited mitochondrial OXPHOS by oligomycin A, 500 µM DIDS was found to uncouple the respiration like the conventional uncoupler CCCP in both the cells. Additionally, we observed that 50–200 µM DIDS, even after 2 h of treatment, depolarizes mitochondrial membrane potential. Also, brief DIDS treatment leads to an increase in cell population with hyperfused mitochondria and attenuation of DRP1 recruitment to mitochondria in U2OS cells. However, no significant alteration in the steady-state level of mitochondrial respiratory chain complex I and complex V subunits was noticed after DIDS treatment. Similar to cell lines, DIDS treatment also showed significant respiratory uncoupling in isolated mitochondria prepared from the normal muscle, liver, and sarcoma tumor tissues of mice. Finally, in silico modeling using AutoDock Vina and AlphaFold3 identified that DIDS binds inside the beta-barrel structure of VDAC1. Together, our findings directly demonstrate that DIDS binds to the VDAC1 inner pocket, uncouples OXPHOS, and promotes mitochondrial hyperfusion.</div></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"8 ","pages":"Article 100171"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145319581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Are cellulases slow? Kinetic and thermodynamic limitations for enzymatic breakdown of cellulose 纤维素酶慢吗？纤维素酶分解的动力学和热力学限制。

BBA Advances Pub Date : 2025-01-01 Epub Date: 2024-12-06 DOI: 10.1016/j.bbadva.2024.100128

Peter Westh , Jeppe Kari , Silke Badino , Trine Sørensen , Stefan Christensen , Nanna Røjel , Corinna Schiano-di-Cola , Kim Borch

{"title":"Are cellulases slow? Kinetic and thermodynamic limitations for enzymatic breakdown of cellulose","authors":"Peter Westh , Jeppe Kari , Silke Badino , Trine Sørensen , Stefan Christensen , Nanna Røjel , Corinna Schiano-di-Cola , Kim Borch","doi":"10.1016/j.bbadva.2024.100128","DOIUrl":"10.1016/j.bbadva.2024.100128","url":null,"abstract":"<div><div>Cellulases are of paramount interest for upcoming biorefineries that utilize residue from agriculture and forestry to produce sustainable fuels and chemicals. Specifically, cellulases are used for the conversion of recalcitrant plant biomass to fermentable sugars in a so-called saccharification process. The vast literature on enzymatic saccharification frequently refers to low catalytic rates of cellulases as a main bottleneck for industrial implementation, but such statements are rarely supported by kinetic or thermodynamic considerations. In this perspective, we first discuss activation barriers and equilibrium conditions for the hydrolysis of cellulose and how these parameters influence enzymatic turnover. Next, we propose a simple framework for kinetic description of cellulolytic enzyme reactions and show how this can pave the way for comparative biochemical analyses of cellulases acting on their native, insoluble substrate. This latter analysis emphasizes that cellulases are characterized by extraordinarily low off-rate constants, while other kinetic parameters including specificity constants and rate constants for association and bond cleavage are quite like parameters reported for related enzymes acting on soluble substrates.</div></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"7 ","pages":"Article 100128"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Protein recognition methods for diagnostics and therapy 用于诊断和治疗的蛋白质识别方法

BBA Advances Pub Date : 2025-01-01 Epub Date: 2025-02-14 DOI: 10.1016/j.bbadva.2025.100149

Ryne Montoya, Peter Deckerman, Mustafa O. Guler

{"title":"Protein recognition methods for diagnostics and therapy","authors":"Ryne Montoya, Peter Deckerman, Mustafa O. Guler","doi":"10.1016/j.bbadva.2025.100149","DOIUrl":"10.1016/j.bbadva.2025.100149","url":null,"abstract":"<div><div>The fundamental biological processes involving highly specific interactions between proteins and other biological motifs are the pillars of protein recognition mechanisms. These interactions are crucial for biological systems, often having significant implications within diagnostics and therapy development. Protein recognition and specificity are reliant on structural compatibility, dynamic conformational changes, and biochemical interactions—all of which are grounded in fundamental molecular forces like hydrogen bonding, ionic interactions, and van der Waals forces. Advanced characterization tools have improved our understanding of protein interactions, revealing the kinetics and thermodynamics of these recognition mechanisms. In parallel, new computing methods, including artificial intelligence, molecular docking, and dynamical simulations, have increased prediction accuracy for molecular interactions, leading to well-defined interaction sites and binding kinetics information. Protein recognition is pivotal in diagnostic methods including ELISAs and biosensors, which are crucial within disease detection applications. In therapeutics, protein recognition plays an important role in drug development, enabling the design of small molecules, peptides, and monoclonal antibodies. Despite recent progress, there are many challenges remaining to fully understand protein recognition, particularly within the complex cell environment. These challenges require future work in protein recognition studies to enhance diagnostic and therapeutic applications. The researchers are using improved detection and screening methods to identify, assess, and optimize interactions for clinical translation.</div></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"7 ","pages":"Article 100149"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

F-type lectins: Structural and functional aspects, and potential biomedical applications f型凝集素：结构和功能方面，以及潜在的生物医学应用

BBA Advances Pub Date : 2025-01-01 Epub Date: 2025-06-14 DOI: 10.1016/j.bbadva.2025.100166

Gerardo R. Vasta , Mario A. Bianchet

{"title":"F-type lectins: Structural and functional aspects, and potential biomedical applications","authors":"Gerardo R. Vasta , Mario A. Bianchet","doi":"10.1016/j.bbadva.2025.100166","DOIUrl":"10.1016/j.bbadva.2025.100166","url":null,"abstract":"<div><div>Among the multiple animal lectin families recognized to date, F-type lectins (FTLs), fucose-binding lectins characterized by an FTL domain (FTLD), constitute the most recent lectin family to be identified and structurally characterized. The structure of the FTL from the European eel <em>Anguilla anguilla</em> revealed a novel jellyroll lectin fold (the \"F-type\" fold) with unique fucose- and calcium-binding sequence motifs. The FTL lectin family comprises proteins that may exhibit single or multiple FTLD, in combination with structurally and functionally distinct domains, and can form oligomeric associations that display high-avidity multivalent binding. Differences in fine carbohydrate specificity among tandemly arrayed FTLDs present in any FTL polypeptide subunit, together with the expression of multiple FTL isoforms in a single individual supports a broad diversity in ligand recognition. Widely distributed in invertebrates, protochordates, ectothermic vertebrates, birds, and monotreme and marsupial mammals, the FTLD is also present in some bacterial proteins and viruses but absent in placental mammals. The taxonomically broad, and discontinuous distribution of the FTLD, suggests an extensive structural and functional diversification of this lectin family, including horizontal gene transfer in viruses and prokaryotic organisms, together with possible gene loss and/or cooption along the lineages leading to the mammals. FTLs’ biological roles range from pathogen recognition in innate immunity to fertilization, cell adhesion and cell aggregation, and as bacterial virulence factors, among others. The specificity of FTLs for fucosylated moieties should provide ample opportunities for novel applications in glycan and cell separation, and innovative diagnostic, preventive, and therapeutic approaches in cancer and infectious disease.</div></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"8 ","pages":"Article 100166"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144330350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Blending salmon gelatin with polyvinylidene fluoride using coaxial electrospinning 用同轴静电纺丝法将鲑鱼明胶与聚偏二氟乙烯混合

IF 3

BBA Advances Pub Date : 2025-01-01 Epub Date: 2025-07-19 DOI: 10.1016/j.bbadva.2025.100168

Martin Chavarria-Vidal , Dragica Bezjak , Maria Saavedra-Fredes , Benjamin Schleyer-Thiers , Javier Enrione , Cristian Acevedo , Jorge Tapia , Tomas P. Corrales

{"title":"Blending salmon gelatin with polyvinylidene fluoride using coaxial electrospinning","authors":"Martin Chavarria-Vidal , Dragica Bezjak , Maria Saavedra-Fredes , Benjamin Schleyer-Thiers , Javier Enrione , Cristian Acevedo , Jorge Tapia , Tomas P. Corrales","doi":"10.1016/j.bbadva.2025.100168","DOIUrl":"10.1016/j.bbadva.2025.100168","url":null,"abstract":"<div><div>Electrospinning is a technique that produces large quantities of nanofibers, that can be designed at the molecular level. Electrospun membranes can be designed to biomimic the chemical composition and morphological structure of the extracellular matrix. Here, we blend salmon gelatin with polyvinyl alcohol and chitosan, which are electrospun in a coaxial configuration with polyvinylidene fluoride, a piezoelectric polymer. We obtain membranes with two size distributions, a large nanofiber distribution with a mean diameter of 426 ±142 nm and a small nanofiber distribution with a diameter of 251 ±49 nm. Nanomechanical characterization of the large nanofibers reveals two Young’s moduli peaks centered at 1.77 ±0.05 GPa and 209±126 MPa. Small nanofibers also show a two component mechanical moduli distribution centered at 565 ±115 MPa and 1.33±0.31 GPa. This characterization indicates that the larger nanofibers are made mainly of polyvinylidene fluoride, while the smaller distribution consists of polyvinyl alcohol with polyvinylidene fluoride. Raman spectroscopy ensures the presence of all four polymers within the final membrane. This could indicate that polyvinylidene fluoride and the polyvinyl alcohol blend are separating during the coaxial electrospinning process, although we do not rule out the presence of core–shell nanofibers. These membranes have potential applications as scaffold for tissue engineering and regenerative medicine given the biochemical signaling of salmon gelatin and electromechanical properties of polyvinylidene fluoride.</div></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"8 ","pages":"Article 100168"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advances in total glycomic analysis including sialylated sub-glycan isomers by SALSA method SALSA法分析包括唾液化亚聚糖异构体的研究进展

BBA Advances Pub Date : 2025-01-01 Epub Date: 2025-01-28 DOI: 10.1016/j.bbadva.2025.100144

Masaki Kurogochi , Chiharu Suzuki , Hisatoshi Hanamatsu , Jun-ichi Furukawa

引用次数: 0

Therapeutic potential of 7-oxo-DHEA as an adjunctive host-directed therapy for pulmonary tuberculosis 7-氧-脱氢表雄酮作为辅助宿主治疗肺结核的治疗潜力

IF 3

BBA Advances Pub Date : 2025-01-01 Epub Date: 2025-10-14 DOI: 10.1016/j.bbadva.2025.100172

María Belén Vecchione , Jorge Barrios-Payán , Dulce Mata-Espinosa , Ricardo Márquez Velasco , Brenda Marquina-Castillo , Denise Anabella Giannone , Milagros Victoria Acevedo , Maria Florencia Quiroga , Rogelio Hernández-Pando

{"title":"Therapeutic potential of 7-oxo-DHEA as an adjunctive host-directed therapy for pulmonary tuberculosis","authors":"María Belén Vecchione , Jorge Barrios-Payán , Dulce Mata-Espinosa , Ricardo Márquez Velasco , Brenda Marquina-Castillo , Denise Anabella Giannone , Milagros Victoria Acevedo , Maria Florencia Quiroga , Rogelio Hernández-Pando","doi":"10.1016/j.bbadva.2025.100172","DOIUrl":"10.1016/j.bbadva.2025.100172","url":null,"abstract":"<div><div>Although anti-tuberculous therapy effectively eradicates <em>Mycobacterium tuberculosis</em> (<em>Mtb</em>) infection, it requires prolonged treatment with multiple drugs, often resulting in adverse effects and poor compliance. Therefore, novel immunotherapeutic strategies are needed to enhance host defense and improve disease management. In this study, we investigated the immunomodulatory and antimicrobial properties of 7-oxo-dehydroepiandrosterone (7-oxo-DHEA, 7-OD), a derivative of the endogenous hormone DHEA, using both <em>in vitro</em> and <em>in vivo</em> models of <em>Mtb</em> infection. In culture, 7-OD exerted a bacteriostatic effect on <em>Mtb</em> growth. In macrophage infection assays, it enhanced intracellular bacterial clearance and modulated cytokine secretion, favoring a pro-inflammatory profile. Notably, in a murine model of progressive pulmonary tuberculosis, 7-OD treatment significantly reduced bacterial burden and mitigated lung pathology. These findings indicate that 7-OD enhances host immune responses to control <em>Mtb</em> infection and limit tissue damage. Further studies are warranted to evaluate its applicability as an adjunctive host-directed therapy in combination with standard anti-TB drugs.</div></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"8 ","pages":"Article 100172"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145416104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0