Lactobacillus acidophilus extracellular vesicles-coated UiO-66-NH2@siRNA nanoparticles for ulcerative colitis targeted gene therapy and gut microbiota modulation

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 17, 2025

Ulcerative colitis (UC) is a complex and chronic inflammatory bowel disease whose pathogenesis involves genetic environmental factors, which poses challenge for treatment. Here, we have designed an innovative integrated therapeutic strategy using Lactobacillus acidophilus extracellular vesicles (EVs) to encapsulate UiO-66-NH2 nanoparticles bounded with TNF-α siRNA (EVs@UiO-66-NH2@siRNA) UC This system shows superior affinity inflammation-related cells due the EVs can maintain immune homeostasis by regulating secretion of cytokines in vitro. specifically target key silence its gene expression, thereby process response. After oral administration, EVs@UiO-66-NH2@siRNA demonstrates accurate delivery colonize colon site exerts effect inhibiting expression TNF-α, alleviates intestinal inflammation DSS-induced model. Moreover, this modulate types compositional structures gut microbiota metabolites achieve anti-inflammatory phenotype, helpful repair homeostasis. We also proved that exhibit high loading capacity good pH responsiveness, improving potent release tissue. Collectively, nano-delivery demonstrate feasible combination through microecology modulation, regulation silence, may provide potential targeted treatment approach disease.

Language: Английский

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Temperature control in sepsis

Frontiers in Medicine, Journal Year: 2023, Volume and Issue: 10

Published: Oct. 31, 2023

Fever can be viewed as an adaptive response to infection. Temperature control in sepsis is aimed at preventing potential harms associated with high temperature (tachycardia, vasodilation, electrolyte and water loss) therapeutic hypothermia may slowing metabolic activities protecting organs from inflammation. Although fever (>39.5°C) usually performed critically ill patients, available cohorts randomized controlled trials do not support its use improve prognosis. Finally, both spontaneous are poor outcomes sepsis.

Language: Английский

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Gut diversity and the resistome as biomarkers of febrile neutropenia outcome in paediatric oncology patients undergoing hematopoietic stem cell transplantation

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: March 6, 2024

Abstract The gut microbiota of paediatric oncology patients undergoing a conditioning regimen before hematopoietic stem cell transplantation is recently considered to play role in febrile neutropenia. Disruption commensal and evolution opportune pathogens community carrying plethora antibiotic-resistance genes crucial role. However, the impact, predictive association patient´s resistome course therapy still be elucidated. We analysed composition 18 transplantation, including 12 developing neutropenia, hospitalized at Bone Marrow Transplantation Unit National Institute Children´s disease Slovak Republic healthy individuals (n = 14). Gut microbiome stool samples obtained 3 time points, 16), one week after 16) four weeks 14) was investigated using shotgun metagenome sequencing bioinformatical analysis. identified significant decrease alpha-diversity nine msr(C), dfrG, erm(T), VanHAX, erm(B), aac(6)-aph(2), aph(3)-III, ant(6)-Ia aac(6)-Ii , associated with Multidrug-resistant ESKAPE, Enterococcus faecium Staphylococcus aureus Klebsiella pneumoniae Escherichia coli found carried subset patient’s resistome. Over 50% treated trimethoprim/sulfamethoxazole, piperacillin/tazobactam amikacin applied treatment. alpha diversity relevant predictor neutropenia outcome transplantation. Furthermore, interindividual multi-drug resistant opportunistic variable portfolios indicates necessity preventive, personalized approach.

Language: Английский

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Alleviation of DSS-induced colitis via bovine colostrum-derived extracellular vesicles with microRNA let-7a-5p is mediated by regulating Akkermansia and β -hydroxybutyrate in gut environments

Microbiology Spectrum, Journal Year: 2023, Volume and Issue: 11(6)

Published: Nov. 15, 2023

ABSTRACT Inflammatory bowel disease (IBD) is an inflammatory caused by the interaction of environmental and genetic factors, including diet microbiota. Recent studies have suggested effects extracellular vesicles (EVs) on controlling host intestinal immune responses, although specified mechanisms not yet been fully elucidated. In current study, we investigated EVs isolated from bovine colostrum attenuating dextran sodium sulfate-induced colitis in mice. Multiomic approaches were used to assess gene expression gut microbiota profiles explain roles modulating system. Transcriptomic analyses a possible immunoregulatory mechanism mediated cell cycle regulator CDK6 pro-inflammatory responses. The microbiome composition fecal metabolite showed that EV supplementation promoted microbial abundance Akkermansia short-chain fatty acid production mice with colitis. Further vivo analysis revealed β-hydroxybutyrate muciniphila , which are elevated administration EVs, involved lessening through Additionally, bta-let-7a-5p, one most abundant microRNAs colostrum-derived alleviated indications their immunity regulating cycle-related target Cdk6. Overall, these results suggest bta-let-7a-5p could be promising alternative strategies for preventing onset IBD. IMPORTANCE Even though studying involvement host-microbe interactions, how relationships mediate physiology has clarified yet. Our findings provide insights into encouraging benefits dietary source-derived (miRNAs) organic ultimately stimulating human health, suggesting miRNAs novel preventive strategy treatment disease.

Language: Английский

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Mucositis and Infection in Hematology Patients

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(11), P. 9592 - 9592

Published: May 31, 2023

Survival in patients with hematological malignancies has improved over the years, both due to major developments anticancer treatment, as well supportive care. Nevertheless, important and debilitating complications of intensive treatment regimens still frequently occur, including mucositis, fever bloodstream infections. Exploring potential interacting mechanisms directed therapies counteract mucosal barrier injury is utmost importance if we are continue improve care for this increasingly growing patient population. In perspective, I highlight recent advances our understanding relation mucositis infection.

Language: Английский

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Gastrointestinal mucositis: a sign of a (systemic) inflammatory response

Current Opinion in Supportive and Palliative Care, Journal Year: 2024, Volume and Issue: 18(2), P. 78 - 85

Published: April 23, 2024

Gastrointestinal mucositis (GIM) is a significant complication of cancer therapy. Whilst inflammation central feature GIM, studies attempting to mitigate mucosal damage via this mechanism are scarce. This review describes the relation between local and systemic inflammation, microbiome its metabolites, explores recent research on therapeutics that target relationship.

Language: Английский

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Akkermansia muciniphila ONE effectively ameliorates dextran sulfate sodium (DSS)-induced ulcerative colitis in mice

npj Science of Food, Journal Year: 2024, Volume and Issue: 8(1)

Published: Nov. 19, 2024

Akermansia muciniphila shows promise as a next-generation probiotic, however, its beneficial regulatory effects on mice ulcerative colitis (UC) has not been extensively investigated. We used an Akkermansia strain (AKK ONE) isolated from healthy human feces to study effect DSS-induced in mice. Our results demonstrate that AKK ONE supplementation significantly improves food intake, weight, colon length, disease activity index (DAI) score, organ index, and tissue damage of notably improved intestinal barrier integrity by enhancing expression occludin claudin-1. Additionally, reduced inflammation down-regulating IL-1β, IL-6, TNF-α, up-regulating IL-10. In addition reducing excessive inflammation, also increased the abundance decreased Bacteroides. Furthermore, intervention markedly SCFAs cecal contents. may be potential therapeutic agent for improving UC, based findings this study.

Language: Английский

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Fecal microbiota transplantation in hematopoietic cell transplant and cellular therapy recipients: lessons learned and the path forward

Gut Microbes, Journal Year: 2023, Volume and Issue: 15(1)

Published: June 29, 2023

Disruptions to the gut microbiota have been associated with adverse outcomes including graft-versus-host disease, infections, and mortality after hematopoietic cell transplantation cellular therapy. Evidence for causal links is accumulating, thus supporting therapeutic interventions targeting goal of preventing treating outcomes. One such intervention fecal (FMT) by which an entire community transferred patient dysbiosis. As this approach in transplant therapy recipients still its infancy, no best has defined many open questions need be addressed before FMT becomes a standard treatment. In review, we highlight microbiota-outcome associations highest level evidence, provide overview main trials, suggest some paths forward.

Language: Английский

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Bacteroides ovatus alleviates dysbiotic microbiota-induced intestinal graft-versus-host disease

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 31, 2023

Acute gastrointestinal intestinal GVHD (aGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation, and the microbiota known to impact on its severity. However, an association between treatment response aGI-GVHD has not been well-studied. In cohort patients with (n=37), we found that non-response standard therapy corticosteroids was associated prior carbapenem antibiotics loss

Language: Английский

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The Microbiome and Its Impact on Allogeneic Hematopoietic Cell Transplantation

The Cancer Journal, Journal Year: 2023, Volume and Issue: 29(2), P. 75 - 83

Published: March 1, 2023

Abstract Allogeneic hematopoietic cell transplantation (alloHCT) is a standard curative therapy for variety of benign and malignant hematological diseases. Previously, patients who underwent alloHCT were at high risk complications with potentially life-threatening toxicities, including opportunistic infections as well acute chronic manifestations graft-versus-host disease (GVHD), where the transplanted immune system can produce inflammatory damage to patient. With recent advances, newer conditioning regimens, advances in viral fungal infection prophylaxis, novel GVHD prophylactic treatment strategies, improvements clinical outcomes have steadily improved. One modality great potential that has yet be fully realized targeting microbiome further improve outcomes. In years, intestinal microbiota, which includes bacteria, fungi, viruses, other microbes reside within tract, become established potent modulator The composition particular, been found large multicenter prospective studies strongly associated GVHD, treatment-related mortality, overall survival. Murine demonstrated causal relationship between microbiota injury aggravated more recently, interventional repleting fecal emerged effective therapies GVHD. How bacterial often highly variable patients, modulate not understood. Recent studies, however, begun make substantial headway, identifying particular subsets and/or bacterial-derived metabolites mediate harm or benefit. Here, authors review improved our mechanistic understanding outcomes, are beginning establish strategies hope optimizing

Language: Английский

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