Unveiling clinical applications of bacterial extracellular vesicles as natural nanomaterials in disease diagnosis and therapeutics

Acta Biomaterialia, Journal Year: 2024, Volume and Issue: 180, P. 18 - 45

Published: April 17, 2024

Bacterial extracellular vesicles (BEVs) are naturally occurring bioactive membrane-bound nanoparticles released by both gram-negative and gram-positive bacterial species, exhibiting a multifaceted role in mediating host-microbe interactions across various physiological conditions. Increasing evidence supports BEVs as essential mediators of cell-to-cell communicaiton, influencing pathogenicity, disease mechanisms, modulating the host immune response. However, extent to which these BEV-mediated actions can be leveraged predict onset, guide treatment strategies, determine clinical outcomes remains uncertain, particularly terms their translation potentials. This review briefly describes BEV biogenesis internalisation recipient cells summarises methods for isolation characterization, understanding composition cargo. Further, it discusses potential biofluid-associated biomarkers diseases, spanning cancer non-cancerous Following this, we outline ongoing human trials using vaccine development. In addition diagnostics, this explores emerging research natural or engineered smart nanomaterials applications anti-cancer therapy bone regeneration. discussion extends key factors unlocking BEVs, such standardization characterisation, well other hurdles translating findings setting. We propose that addressing through collaborative efforts well-designed holds fully harnessing BEVs. As field advances, suggests BEV-based nanomedicine has revolutionize management, paving way innovative diagnosis, therapeutics, personalized medicine approaches. STATEMENT OF SIGNIFICANCE: Extracellular (EVs) from bacteria serve multifunctional biomaterials fields biomedicine, bioengineering, biomaterials. majority current studies focus on host-derived EVs, leaving gap comprehensive bacteria-derived EVs (BEVs). Although offer an attractive option drug delivery systems, unique nanostructure easy-to-modify functions make them method diagnosis Our work among pioneering investigating nanobiomaterials plays crucial development diseases therapeutic interventions.

Language: Английский

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The intriguing strategies of Tannerella forsythia's host interaction

Frontiers in Oral Health, Journal Year: 2024, Volume and Issue: 5

Published: May 30, 2024

Tannerella forsythia , a member of the “red complex” bacteria implicated in severe periodontitis, employs various survival strategies and virulence factors to interact with host. It thrives as late colonizer oral biofilm, relying on its unique adaptation mechanisms for persistence. Essential are type 9 protein secretion system O -glycosylation proteins, crucial host interaction immune evasion. Virulence T. including sialidase proteases, facilitate pathogenicity by degrading glycoproteins respectively. Moreover, cell surface like S-layer BspA modulate responses bacterial adherence, influencing colonization tissue invasion. Outer membrane vesicles lipopolysaccharides further induce inflammatory responses, contributing periodontal destruction. Interactions specific types, epithelial cells, polymorphonuclear leukocytes macrophages, mesenchymal stromal highlight multifaceted nature forsythia's pathogenicity. Notably, it can invade cells impair PMN function, promoting dysregulated inflammation survival. Comparative studies periodontitis-associated Porphyromonas gingivalis reveal differences protease activity modulation, suggesting distinct roles disease progression. potential influence antimicrobial defense through protease-mediated degradation interactions other underscores significance pathogenesis. However, understanding precise role host-microbiome classification keystone pathogen requires investigation. Challenges translating research data stem from complexity microbiome biofilm dynamics, necessitating comprehensive elucidate clinical relevance therapeutic implications periodontitis management.

Language: Английский

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Integrating Aggregate Materials and Machine Learning Algorithms: Advancing Detection of Pathogen‐Derived Extracellular Vesicles

Aggregate, Journal Year: 2025, Volume and Issue: unknown

Published: March 27, 2025

ABSTRACT Extracellular vesicles (EVs) are essential for host–pathogen interactions, mediating processes such as immune modulation and pathogen survival. Pathogen‐derived EVs hold significant diagnostic potential because of their unique cargo, offering a wealth biomarkers. In this review, we first discuss the roles derived from various pathogens in interactions summarize latest advancements detection based on EVs. Then, highlight innovative strategies, including novel aggregate materials machine learning approaches, enhancing EV analysis. Finally, challenges field future directions advancing EV‐based diagnostics, aiming to translate these insights into clinical applications.

Language: Английский

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Immune-Mediated Bidirectional Causality Between Inflammatory Bowel Disease and Chronic Periodontitis: Evidence from Mendelian Randomization and Integrative Bioinformatics Analysis

Biomedicines, Journal Year: 2025, Volume and Issue: 13(2), P. 476 - 476

Published: Feb. 15, 2025

Background/Objectives: A bidirectional association between inflammatory bowel disease (IBD) and periodontitis has been observed, yet their causal relationship remains unclear. This study aimed to investigate the potential links these two conditions through comprehensive genetic molecular analyses. Methods: We conducted a Mendelian randomization (MR) analysis integrated with bioinformatics approaches. The relationships were primarily evaluated using inverse variance weighting (IVW), complemented by multiple sensitivity analyses assess robustness of findings. Additionally, we performed differential gene expression RNA sequencing data identify co-expressed genes shared mediators IBD periodontitis, followed pathway enrichment analysis. Results: Bidirectional MR revealed significant associations (p-value < 0.05). Sensitivity demonstrated consistency findings, no evidence heterogeneity or horizontal pleiotropy > Integrated identified key immune regulators, particularly interleukin 1 beta (IL1B) C-X-C motif chemokine receptor 4 (CXCR4), signaling pathways, including tumor necrosis factor (TNF-α) 17 (IL17), as mechanisms underlying conditions. Conclusions: Our findings provide supporting periodontitis. Transcriptomic pathological crucial regulatory factors common both diseases. These insights enhance our understanding interplay potentially informing new therapeutic strategies for

Language: Английский

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MiRNA Let-7i-5p-Contained Small Extracellular Vesicles from Macrophages Induce Nucleus Pulposus Cell Senescence via Targeting LIN28A

International Journal of Nanomedicine, Journal Year: 2025, Volume and Issue: Volume 20, P. 2163 - 2179

Published: Feb. 1, 2025

To investigate the role of macrophage-derived small extracellular vesicles (MΦ-sEVs) in nucleus pulposus (NP) cell (NPC) senescence and screen pro-senescent micro-RNA (miRNA) MΦ-sEVs potential mRNA targets. Bone marrow-derived macrophage (BMDM)-derived sEVs were isolated by differential centrifugation, phenotypes identified. NPCs treated with MΦ-sEVs, cellular levels examined senescence-associated β-galactosidase (SA‑β‑Gal) staining Western blotting (WB). Activation secretory phenotype (SASP) was tested using qRT-PCR cytometric bead arrays (CBA). LPS+IFNγ-MΦ-sEVs or IL-4-MΦ-sEVs injected into rat coccygeal NP tissues to determine vivo effects on intervertebral disc degeneration (IVDD) NPC senescence. The miRNA evaluated PANDORA sequencing. transfected mimics inhibitors miRNAs pro-senescence effects. displayed cup-shaped morphology, diameters mainly ranging from 40 200 nm. Both impaired viability accelerated expression SASP senescence-related proteins, including p16, p21, p53, elevated treatment. Animal experiments indicated that exacerbated IVDD increased p16-positive ratio activated SASP. sequencing revealed high let-7i-5p, which exerted downregulating LIN28A expression. Inhibiting silencing C1632 specific siRNAs also triggered induced delivering let-7i-5p inhibit LIN28A.

Language: Английский

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Bacterial Outer Membrane Vesicles: From Physics to Clinical

MedComm – Biomaterials and Applications, Journal Year: 2025, Volume and Issue: 4(2)

Published: May 7, 2025

ABSTRACT Bacterial outer membrane vesicles (OMVs) are nanoscale vesicular structures naturally produced by Gram‐negative bacteria during growth. These encapsulate a diverse array of bioactive molecules, including proteins, nucleic acids, and lipopolysaccharide, contributing to range bacterial processes such as toxin delivery, horizontal gene transfer, biofilm formation. OMVs play crucial roles in pathogenesis host immune modulation, their presence is implicated variety clinical conditions affecting the respiratory, gastrointestinal, immune, cardiovascular, urinary systems. The unique properties offer promising avenues for translation, use vaccines (against bacterial, viral, parasitic, tumor‐associated), diagnostic tools (for bioimaging molecular diagnostics), drug delivery vehicles antibiotics, anti‐cancer therapeutics, acids) regenerative medicine. However, several challenges hinder widespread adoption OMVs, heterogeneity composition depending on growth conditions, incompletely understood mechanisms cargo loading release, inherent immunogenicity potential toxicity, limitations scalable production. This review aims provide comprehensive overview biogenesis, composition, function, association with human disease, while also exploring current future development directions application.

Language: Английский

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Extracellular vesicle production by oral bacteria related to dental caries and periodontal disease: role in microbe-host and interspecies interactions

Critical Reviews in Microbiology, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 18

Published: Nov. 20, 2024

Extracellular vesicles (EVs) are cell membrane-derived structures between 20-400 nm in size. In bacteria, EVs play a crucial role molecule secretion, wall biogenesis, cell-cell communication, biofilm development, and host-pathogen interactions. Despite these increasing reports of bacterial-derived vesicles, there remains limited number studies that summarize oral bacterial EVs, their cargo, main biological functions. Therefore, the aim this review is to present latest research on bacteria-derived how they can modulate various physiological pathological processes cavity, including pathogenesis highly relevant diseases such as dental caries periodontitis systemic complications. Overall, caries-associated bacteria (such

Language: Английский

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Combination of Neovestitol and Vestitol Modifies the Profile of Periodontitis-Related Subgingival Multispecies Biofilm

Biomedicines, Journal Year: 2024, Volume and Issue: 12(6), P. 1189 - 1189

Published: May 27, 2024

The aim of this study was to evaluate the effect combination neovestitol–vestitol (CNV) compounds obtained from Brazilian red propolis on microbiological profile a mature multispecies subgingival biofilm. biofilm with 32 bacterial species associated periodontitis formed for seven days using Calgary device. Treatment CNV (1600, 800, 400, and 200 μg/mL), amoxicillin (54 vehicle control performed 24 h last day formation. Biofilm metabolic activity DNA–DNA hybridization (checkerboard) assays were performed. groups treated 1600 reduced 25 13 species, respectively, compared treatment (p ≤ 0.05); both P. gingivalis, while only T. forsythia. When data two treatments (CNV AMOXI) compared, statistically significant difference observed in particularly members Socransky’s orange complex. Our results showed that at μg/mL best regarding biofilms reduction disease, such as forsythia, showing better than amoxicillin. Therefore, seems be promising alternative eradicate reduce their pathogenicity.

Language: Английский

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Pathogenic mechanisms and potential applications of extracellular vesicles from periodontal pathogens in periodontitis

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 20, 2024

Periodontitis is a multifactorial disease characterized by chronic destruction of the periodontal supporting tissues and closely associated with dysbiosis plaque biofilm. It leading cause tooth loss in adults. Bacterial extracellular vesicles (BEVs) are released from bacteria, which range size 20 to 400 nm. These contain various components derived their parent including nucleic acids, proteins, lipids, other molecules, facilitate functions such as molecular transfer, metabolic regulation, bacterial interactions, biofilm formation, immune modulation. BEVs participated pathophysiological process periodontitis. Recently emerging evidence also showed that contents EVs saliva gingival crevicular fluid (miRNAs, mRNAs, proteins) could be used potential biomarkers for While most current research focuses on human-derived components, much less known about BEVs. Therefore, this review introduces formation mechanisms related Then, summarizes information mechanism, diagnostic theraputic value pathogen-derived development Furthermore, future challenges exploring role periodontitis discussed.

Language: Английский

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The association between polyunsaturated fatty acids and periodontitis: NHANES 2011–2014 and Mendelian randomisation analysis

Lipids in Health and Disease, Journal Year: 2024, Volume and Issue: 23(1)

Published: June 4, 2024

Abstract Background We aimed to explore the association and potential causality between polyunsaturated fatty acids concentrations risk of periodontal disease. Materials methods Data were collected from 2011–2014 National Health Nutrition Examination Survey (NHANES). Weighted logistic regression analysis restricted cubic spline (RCS) used analyse associations omega-3 omega-6 omega-6/omega-3 ratio with periodontitis. E-value propensity score matching (PSM) analyses for sensitivity analyses. In addition, two-sample Mendelian randomisation (MR) performed assess causal impact those on periodontitis risk. Results A total 2462 participants NHANES included. Logistic revealed that high levels negatively associated developing ( P < 0.05), while was positively 0.05). There no significant The findings mentioned above confirmed by following a 1:1 PSM. Furthermore, MR examination two samples indicated possible link or > Conclusion Although in cross-sectional studies, results did not support relationship them. Therefore, there is indication an increase concentration decrease may be beneficial preventing

Language: Английский

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