Neurotensin receptor agonist PD149163 modulates LPS-induced enterocyte apoptosis by downregulating TNFR pathway and executioner caspase 3 in endotoxemic mice: insights from in vivo and in silico study

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 15, 2025

Language: Английский

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A review of gut failure as a cause and consequence of critical illness

Critical Care, Journal Year: 2025, Volume and Issue: 29(1)

Published: Feb. 26, 2025

In critical illness, all elements of gut function are perturbed. Dysbiosis develops as the microbial community loses taxonomic diversity and new virulence factors appear. Intestinal permeability increases, allowing for translocation bacteria and/or bacterial products. Epithelial is altered at a cellular level homeostasis epithelial monolayer compromised by increased intestinal cell death decreased proliferation. Gut immunity impaired with simultaneous activation maladaptive pro- anti-inflammatory signals leading to both tissue damage susceptibility infections. Additionally, splanchnic vasoconstriction leads blood flow local ischemic changes. Together, these interrelated gastrointestinal dysfunction drive then perpetuate multi-organ syndrome. Despite clear importance maintaining homeostasis, there very few reliable measures in illness. Further, while multiple therapeutic strategies have been proposed, most not shown conclusively demonstrate benefit, care still largely supportive. The key role illness was subject tenth Perioperative Quality Initiative meeting, conference summarize current state literature identify knowledge gaps future study. This review product that conference.

Language: Английский

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Understanding dental pulp inflammation: from signaling to structure

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

Published: Oct. 29, 2024

The pulp is a unique tissue within each tooth that susceptible to painful inflammation, known as pulpitis, triggered by microbial invasion from carious lesions or trauma affect many individuals. host response involves complex immunological processes for pathogen defense and dentin apposition at the site of infection. interplay signaling between immune non-immune cells via cytokines, chemokines, neuropeptides, proteases, reactive nitrogen oxygen species leads reactions structural changes in escalate beyond certain threshold irreversible damage. If left untreated, which initially localized, can progress pulpal necrosis, requiring root canal treatment adversely affecting prognosis tooth. To preserve vitality dental health, deeper understanding molecular cellular mechanisms pulpitis imperative. In particular, elucidating links pathways, clinical symptoms, spatiotemporal spread essential develop novel therapeutic strategies push boundaries vital therapy.

Language: Английский

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Functional connectivity within sensorimotor cortical and striatal regions is regulated by sepsis in a sex-dependent manner

NeuroImage, Journal Year: 2025, Volume and Issue: unknown, P. 120995 - 120995

Published: Jan. 1, 2025

Sepsis is a state of systemic immune dysregulation and organ failure that frequently associated with severe brain disability. Epidemiological studies have indicated younger females better prognosis clinical outcomes relative to males, though the sex-dependent response sepsis during post-sepsis recovery remains largely uncharacterized. Using modified polymicrobial intra-abdominal murine model surgical sepsis, we characterized acute effects on peripheral inflammation, inflammation functional connectivity in young adult mice both sexes. Following male female survived procedure, regained body weight within 7 days showed reduced diversity their gut microbiome. Interestingly, compared sepsis-induced changes observed mice, post-septic exhibited comparatively robust profile splenic cell expansion intracerebral glial proliferation healthy counterparts. Analysis resting-state Magnetic Resonance Imaging (fMRI) data collected from revealed while somatosensory cortex were affected equally sexes, intra-network strength striatum preferentially increased males but remained near baseline mice. Additionally, network alterations projections periaqueductal gray superior colliculus as also between anterior cingulate striatum. Coupled sustained gliosis response, intra-striatal fMRI patterns could signify delayed sepsis. Together, our study provides evidence influences immunity, immunity manner, strongly indicating cognitive benefits recovering

Language: Английский

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Gut microbes of the cecum versus the colon drive more severe lethality and multi-organ damage

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 147, P. 114029 - 114029

Published: Jan. 9, 2025

Language: Английский

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Changes in Vitamin D and Gut Microbiota in Pediatric Hematopoietic Stem Cell Transplantation Patients with Bloodstream Infections

International Journal for Vitamin and Nutrition Research, Journal Year: 2025, Volume and Issue: 95(1)

Published: Feb. 12, 2025

Background: Vitamin D (VD) and gut microbiota (GM) are important variables in pediatric hematopoietic stem cell transplantation (HSCT) recipients with bloodstream infections (BSI). Both VD GM play significant roles immune regulation maintaining intestinal barrier function. Methods: This prospective case-control study included 48 consecutive patients who underwent HSCT, as well 20 healthy children from the community. Plasma samples were collected pre- post-HSCT, together post-HSCT fecal samples. Serum 25-hydroxyvitamin (25(OH)D) 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) measured using chemiluminescence enzyme linked immunosorbent assay, respectively. was analyzed by 16S rDNA next generation sequencing. Results: The incidence of BSI HSCT 33.3% (16/48). No differences serum 25(OH)D or 1,25(OH)2D3 levels observed between non-BSI groups either before after transplantation, control group. α-diversity significantly lower than subjects. Proteobacteria more abundant (p = 0.0434) controls 0.0193). Pediatric showed higher Staphylococcus < 0.001), Pseudomonas Enterococcus Clostridium innocuum 0.0175) Enterobacter 0.0394) compared to controls, whereas Firmicutes 0.009), Actinobacteria Bifidobacterium 0.001) Faecalibacterium lower. β-diversity analysis revealed population three groups. Conclusions: These results indicate there is no practical value monitoring patients. During BSI, experiences a loss probiotics an increase potential pathogens.

Language: Английский

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Intestinal Microbiota Dysbiosis Role and Bacterial Translocation as a Factor for Septic Risk

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 2028 - 2028

Published: Feb. 26, 2025

The human immune system is closely linked to microbiota such as a complex symbiotic relationship during the coevolution of vertebrates and microorganisms. transfer microorganisms from mother's newborn begins before birth gestation considered initial phase intestinal (IM). gut an important site where can establish colonies. IM contains polymicrobial communities, which show interactions with diet host immunity. tendency towards dysbiosis influenced by local but also extra-intestinal factors inflammatory processes, infections, or septic state that aggravate it. Pathogens could trigger response, proinflammatory responses. In addition, changes in influence community structure additional translocation pathogenic non-pathogenic bacteria. Finally, inflammation has been found be factor growth microorganisms, particularly its role sepsis. aim this article able detect current knowledge mechanisms lead cause bacterial risk infection vice versa.

Language: Английский

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A Novel Frontier in Gut–Brain Axis Research: The Transplantation of Fecal Microbiota in Neurodegenerative Disorders

Biomedicines, Journal Year: 2025, Volume and Issue: 13(4), P. 915 - 915

Published: April 9, 2025

The gut–brain axis (GBA) represents a sophisticated bidirectional communication system connecting the central nervous (CNS) and gastrointestinal (GI) tract. This interplay occurs primarily through neuronal, immune, metabolic pathways. Dysbiosis in gut microbiota has been associated with multiple neurodegenerative diseases, such as Parkinson’s disease (PD), Alzheimer’s (AD), sclerosis (MS), amyotrophic lateral (ALS). In recent years, fecal transplantation (FMT) gained attention an innovative therapeutic approach, aiming to restore microbial balance while influencing neuroinflammatory review explores mechanisms by which FMT impacts axis. Key areas of focus include its ability reduce neuroinflammation, strengthen barrier integrity, regulate neurotransmitter production, reinstate diversity. Both preclinical clinical studies indicate that can alleviate motor cognitive deficits PD AD, lower markers MS, enhance respiratory neuromuscular functions ALS. Despite these findings, several challenges remain, including donor selection complexities, uncertainties about long-term safety, inconsistencies outcomes. Innovations synthetic communities, engineered probiotics, AI-driven analysis microbiome hold potential improve precision effectiveness managing conditions. Although presents considerable promise development, widespread application for diseases requires thorough validation well-designed, large-scale trials. It is essential establish standardized protocols, refine processes, deepen our understanding molecular behind efficacy.

Language: Английский

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Pseudomonas aeruginosa population dynamics in a vancomycin-induced murine model of gastrointestinal carriage

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

Published: April 10, 2025

ABSTRACT Pseudomonas aeruginosa is a common nosocomial pathogen and major cause of morbidity mortality in hospitalized patients. Multiple reports highlight that P. gastrointestinal colonization may precede systemic infections by this pathogen. Gaining deeper insight into the dynamics carriage an essential step managing could contribute to preventing bacterial transmission progression infection. Here, we present clinically relevant mouse model relying on parenteral vancomycin pretreatment single orogastric gavage controlled dose . Robust was observed with multiple clinical isolates, persisted for up 60 days. Histological microbiological examination mice indicated indeed represented not We then used barcoded library along sequence tag-based analysis microbial populations (STAMPR) analytic pipeline quantify population bottlenecks during establishment carriage. Analysis most rapidly eliminated stomach, but few bacteria moved small intestine cecum expanded rapidly. Hence, stomach constitutes significant barrier against aeruginosa, which have implications IMPORTANCE While rarely part normal human microbiome, bacterium quite frequent patients residents long-term care facilities. precursor Options treating caused difficult-to-treat strains are dwindling, underscoring urgency better understand impede pre-infection stages, such as colonization. use vancomycin-treated antibiotic-treated who become colonized their tracts. identify These findings suggest efforts prevent should focus only judicious antibiotics also investigation how eliminates orally ingested

Language: Английский

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Accelerating and protective effects toward cancer growth in cGAS and FcgRIIb deficient mice, respectively, an impact of macrophage polarization

Inflammation Research, Journal Year: 2025, Volume and Issue: 74(1)

Published: April 24, 2025

Language: Английский

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