Unveiling the Wonders of Bacteria-Derived Extracellular Vesicles: From Fundamental Functions to Beneficial Applications

Heliyon, Journal Year: 2025, Volume and Issue: 11(4), P. e42509 - e42509

Published: Feb. 1, 2025

:Extracellular vesicles (EVs), are critical mediators of intercellular communication and exhibit significant potential across various biomedical domains. These nano-sized, membrane-encapsulated entities have captured substantial interest due to their diverse roles in pathogenesis promising therapeutic applications. EVs manage numerous physiological processes by transferring bioactive molecules, including proteins, lipids, nucleic acids, between cells. This review delves into the factors influencing properties EVs, such as temperature stress conditions, which collectively influence size, composition, functional attributes. We also describe emerging emphasizing involvement microbial interactions, immune modulation, antimicrobial resistance spread innovative diagnostic instruments. Despite applications, advancement EV-based therapies faces several challenges, will be discussed. By elucidating these elements, we aim provide a comprehensive overview transformative revolutionizing diagnostics therapeutics medicine.

Language: Английский

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In silico evidence of monkeypox F14 as a ligand for the human TLR1/2 dimer

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 17, 2025

Recent emergence of zoonotic monkeypox virus (Mpox) in human has triggered the virologists to develop plausible preventive measures. Hitherto, our understanding on mechanism immunopathogenesis Mpox infection is elusive. However, available experimental evidences suggest induction inflammation as main cause pathogenesis. Toll-like receptors (TLRs) are critical initiating and modulating host immune response pathogens. Inflammatory responses observed various poxvirus infections have, fact, been shown be mediated through TLR activation. Therefore, by silico approaches, this study seeks identify antigen(s) (MAg) that most likely interact with cell-surface TLRs. The proteomics data UniProt database contain 174 protein sequences, among which 105 immunoreactive proteins were modeled for 3D structure examined comparative protein-protein interactions TLRs molecular docking dynamics simulation. F14, an 8.28 kDa infective Mpox, was found exhibit strong binding affinity (ΔG=-12.5 Kcal mol-1) TLR1/2 dimer form a compact thermodynamically stable complex. Interestingly, significant level conformational change also both F14 TLR6 while forming F14-TLR1/2 Based these we propose putative ligand initiate proinflammatory signaling Mpox-infected host.

Language: Английский

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Myeloid‐Driven Immune Suppression Subverts Neutralizing Antibodies and T Cell Immunity in Severe COVID‐19

Journal of Medical Virology, Journal Year: 2025, Volume and Issue: 97(4)

Published: April 1, 2025

The objective of this study was to better understand immune failure mechanisms during severe acute respiratory syndrome coronavirus 2, SARS-CoV-2 infection, which are critical for developing targeted vaccines and effective treatments. We collected 34 cases representing different disease severities performed high-quality single-cell TCR/BCR sequencing analyze the peripheral cell profiles. Additionally, we assessed antibody-neutralizing activity through in vitro experiments. Our integrated multiomics analysis uncovers a profound paradox COVID-19: hyperinflammation coexists with immunosuppression, driven by distinct yet interconnected dysregulatory mechanisms. Severe patients develop robust humoral immunity, evidenced clonally expanded plasma cells producing neutralizing antibodies (e.g., IGHG1-dominated responses) antigen-specific T activation. However, these protective responses counteracted myeloid-driven particularly CD14+ HMGB2+ monocytes exhibiting metabolic reprogramming HLA-DR downregulation, coupled progressive exhaustion characterized IFN-γ/TNF-α hyperactivation impaired antigen presentation. Importantly, prolonged viral persistence arises from coordinate cellular immunity-antibody-mediated neutralization cannot compensate defective cytotoxic function monocyte-mediated suppression. These findings highlight necessity therapeutic strategies that simultaneously enhance antibody effector functions Fc optimization), restore exhausted cells, reverse myeloid They also importance designed elicit balanced B memory durable responses, preventing progression. By addressing dual challenges such approaches could coordination improve outcomes COVID-19.

Language: Английский

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Alleviating penicillin-resistant Streptococcus pneumoniae‑induced lung epithelial cell injury: mechanistic insights into effects of the optimized combination of main components from Yinhuapinggan granules

BMC Infectious Diseases, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 20, 2025

Penicillin-resistant Streptococcus pneumoniae (PRSP), for which novel treatment medicines are required, has expanded extensively due to the overuse of antibiotics. This study aimed detect optimal ratio combination main components based on Yinhuapinggan granules (YHPG) generate concepts PRSP-induced lung injury. Three representative components: chlorogenic acid (C), amygdalin (A), and puerarin (P) were selected, these three was determined by an orthogonal experiment. Investigations conducted potential mechanisms underlying protective effect this optimized against epithelial cell damage. Meanwhile, bacteriostatic further explored through natural products combined with penicillin G (PG). The CAP (C: 16 µg/mL, A: 24 P: µg/mL) screened experimental design reduced damage in a model human cells infected PRSP, PG had synergistic effect. At cellular level, attenuated injury modulating TLRs/MyD88 inflammatory pathway. bacterial modulated virulence drug resistance resulting enhanced inhibition PG. Taken together, our results suggest that can modulate or synergize pathway attenuate injury, be used as treating PRSP infection.

Language: Английский

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