Released Bacterial ATP Shapes Local and Systemic Inflammation during Abdominal Sepsis DOI Creative Commons
Daniel Spari, Annina B. Schmid, Daniel Sánchez‐Taltavull

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: April 19, 2024

Sepsis causes millions of deaths per year worldwide and is a current global health priority declared by the WHO. Sepsis-related are result dysregulated inflammatory immune responses indicating need to develop strategies target inflammation. An important mediator inflammation extracellular adenosine triphosphate (ATP) that released inflamed host cells tissues, also bacteria in strain-specific growth-dependent manner. Here, we investigated mechanisms which release ATP. Using genetic mutant strains Escherichia coli ( E. ), demonstrate ATP dependent on synthase within inner bacterial membrane. In addition, impaired integrity outer membrane notably contributes associated with death. mouse model abdominal sepsis, local effects were analyzed using transformed bearing an arabinose-inducible periplasmic apyrase hydrolyzing be released. Abrogating shows suppresses responses, resulting reduced neutrophil counts survival. has systemic via its transport vesicles (OMV). ATP-loaded OMV quickly distributed throughout body upregulated expression genes activating degranulation neutrophils, potentially contributing exacerbation sepsis severity. This study reveals roles pathogenesis.

Language: Английский

IL-6 and PD-1 antibody blockade combination therapy regulate inflammation and T lymphocyte apoptosis in murine model of sepsis DOI Creative Commons
Song‐I Lee, Na Young Kim, Chaeuk Chung

et al.

BMC Immunology, Journal Year: 2025, Volume and Issue: 26(1)

Published: Jan. 14, 2025

Interleukin-6 (IL-6) plays a central role in sepsis-induced cytokine storm involving immune hyperactivation and early neutrophil activation. Programmed death protein-1 (PD-1) is associated with immunosuppression lymphocyte apoptosis. However, the effects of simultaneous blockade IL-6 PD-1 murine sepsis model are not well understood. In this study, was induced male C57BL/6 mice through cecal ligation puncture (CLP). blockade, or combination both administered 24 h after CLP. Peripheral blood count, level, apoptosis spleen, infiltration lungs liver, survival rate were measured. The mortality IL-6/PD-1 group lower, though statistically significant (p = 0.164), than that CLP (75.0% vs. 91.7%). had lower percentage platelet count compared group; no difference observed other levels. also showed reduced T spleen decreased liver lungs. dual reduces infiltration, apoptosis, bacterial burden while preserving tissue integrity sepsis. Although improvement significant, these findings highlight its potential as therapeutic approach

Language: Английский

Citations

1
Engineered Nanomicelles Delivering the Combination of Steroids and Antioxidants Can Mitigate Local and Systemic Inflammation, Including Sepsis DOI
Kajal Rana, Poonam Yadav,

Ruchira Chakraborty

et al.

ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 13, 2025

Chronic inflammation is mainly characterized by the release of proinflammatory cytokines (cytokine storm) and reactive oxygen/nitrogen species. Sepsis a life-threatening condition resulting from successive chronic inflammatory responses toward infection, leading to multiple organ failure and, ultimately, death. As oxidative stress are known nourish each other initiate an uncontrolled immune response, inhibiting cross-talk between response using anti-inflammatory drugs antioxidants can be promising strategy target sepsis. Here, we present engineering chimeric nanomicelles (NMs) ester-linked polyethylene glycol-derived lithocholic acid–drug conjugate dexamethasone (DEX), potent glucocorticoid possessing properties, vitamin E (VITE), antioxidant stress. Interestingly, these DEX-VITE NMs show enhanced accumulation at inflamed sites driven permeation retention effect mitigate localized acute in paw, lung, liver models. We further demonstrated efficacy mitigating LPS-induced endotoxemia CLP-induced microbial sepsis, conferring survival advantages. also modulate homeostasis decreasing infiltration total cells, neutrophils, overall macrophages. Finally, administration reduces prevents vascular damage, two critical factors sepsis pathogenesis. Therefore, this therapeutic approach effectively deliver steroids systemic inflammation.

Language: Английский

Citations

1
Evolving Paradigms in Sepsis Management: A Narrative Review DOI Creative Commons
Min‐Ji Kim, Eun Joo Choi,

Eun-Jung Choi

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(14), P. 1172 - 1172

Published: July 9, 2024

Sepsis, a condition characterized by life-threatening organ dysfunction due to dysregulated host response infection, significantly impacts global health, with mortality rates varying widely across regions. Traditional therapeutic strategies that target hyperinflammation and immunosuppression have largely failed improve outcomes, underscoring the need for innovative approaches. This review examines development of agents sepsis, focus on clinical trials addressing immunosuppression. It highlights frequent failures these trials, explores underlying reasons, outlines current research efforts aimed at bridging gap between theoretical advancements applications. Although personalized medicine phenotypic categorization present promising directions, this emphasizes importance understanding complex pathogenesis sepsis developing targeted, effective therapies enhance patient outcomes. By multifaceted nature future can pave way more precise individualized treatment strategies, ultimately improving management prognosis patients.

Language: Английский

Citations

4
Author response: Released Bacterial ATP Shapes Local and Systemic Inflammation during Abdominal Sepsis DOI Open Access
Daniel Spari, Annina B. Schmid, Daniel Sánchez‐Taltavull

et al.

Published: July 15, 2024

Sepsis causes millions of deaths per year worldwide and is a current global health priority declared by the WHO. Sepsis-related are result dysregulated inflammatory immune responses indicating need to develop strategies target inflammation. An important mediator inflammation extracellular adenosine triphosphate (ATP) that secreted inflamed host cells tissues, also bacteria in strain-specific growth phase-dependent manner. Here, we investigated mechanisms which release ATP. Using genetic mutant strains Escherichia coli (E. coli), demonstrate ATP dependent on synthase within inner bacterial membrane. In addition, impaired integrity outer membrane death notably contribute release. mouse model abdominal sepsis, local effects were analysed using transformed E. bearing an arabinose-inducible periplasmic apyrase hydrolyzing be released. Abrogating shows suppresses responses, resulting reduced neutrophil counts survival. has systemic via its transport vesicles (OMV). ATP-loaded OMV quickly distributed throughout body upregulated expression genes activating degranulation neutrophils, potentially contributing exacerbation sepsis severity. This study reveals roles pathogenesis.

Language: Английский

Citations

4
Pathological roles of ubiquitination and deubiquitination systems in sepsis-induced myocardial dysfunction DOI Creative Commons
Zhiping Wang,

Simiao Sun,

Lili Huang

et al.

Biomolecules and Biomedicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 7, 2025

Sepsis-induced myocardial dysfunction (SIMD) is a severe complication of sepsis, characterized by impaired cardiac function and high mortality rates. Despite significant advances in understanding sepsis pathophysiology, the molecular mechanisms underlying SIMD remain incompletely elucidated. Ubiquitination deubiquitination, critical post-translational modifications (PTMs) regulating protein stability, localization, activity, play pivotal roles cellular processes, such as inflammation, apoptosis, mitochondrial function, calcium handling. Dysregulation these systems has been increasingly implicated pathogenesis SIMD. This review provides comprehensive overview pathological driving SIMD, with focus on classification functions E3 ubiquitin ligases deubiquitinating enzymes (DUBs), their regulatory systems, involvement Dysfunction ubiquitin-proteasome system (UPS), often driven altered activity ligases, accelerates degradation proteins, thereby exacerbating oxidative stress, apoptosis. Concurrently, imbalances DUB disrupt homeostasis, further amplifying injury. Emerging research underscores therapeutic potential targeting systems. Strategies aimed at modulating ligase or restoring balance have shown promise preclinical studies. summarizes current findings ubiquitination deubiquitination pathogenesis, highlights key challenges advancing this field, proposes directions for future research.

Language: Английский

Citations

0
Drp1–associated genes implicated in sepsis survival DOI Creative Commons
Marissa D. Pokharel,

Anlin Feng,

Ying Liang

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 8, 2025

Sepsis is a severe and life-threatening medical syndrome that can lead to organ failure death. Despite advances in treatment, current therapies are often inadequate, with high septic mortality rates. Therefore, there critical need for reliable prognostic markers be used clinical settings improve the management outcomes of patients sepsis. Recent studies have suggested mitochondrial dynamics, including processes fission fusion, closely related severity sepsis status inflammation. By monitoring transcriptomic signals new biomarkers engineered more accurately predict survival risk. Such would invaluable settings, aiding healthcare providers early identification high-risk improving treatment strategies. To achieve this goal, we utilized major regulatory protein dynamin-related 1 (Drp1, gene code DNM1L) identified Drp1-associated genes enriched genes. A 12-gene signature (GS) was established as differentially expressed (DEG)-based GS. Next, compared proteins interact Drp1 7 common genes, establishing GS term protein-protein interaction (PPI)-based evaluate if these GSs survival, publicly available human blood datasets from patients. We confirmed both successfully discovery validation cohorts sensitivity specificity, PPI-based showing enhanced performance. Together, study engineers validated blood-borne biomarker (PPI-based 7-gene GS) risk prediction. This holds potential optimizing personalized strategies reduce mortality.

Language: Английский

Citations

0
Integrative bioinformatics analysis reveals CGAS as a ferroptosis-related signature gene in sepsis and screens the potential natural inhibitors of CGAS DOI
Jiaxi Chen,

Mingmei Feng,

Tianyao Zhang

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 139778 - 139778

Published: Jan. 1, 2025

Language: Английский

Citations

0
Immunotherapies for sepsis and the impact of study design DOI
John H. Powers, Charles Natanson

BMJ, Journal Year: 2025, Volume and Issue: unknown, P. r48 - r48

Published: Jan. 15, 2025

Language: Английский

Citations

0
Identification of circulating Tfh/Th subsets as a biomarker of developed hospital-acquired pneumonia DOI Creative Commons

Peng Yuan,

Tao Tao,

Ni-Wen Yu

et al.

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

Published: Jan. 22, 2025

Background This study aimed to explore the possible value of follicular helper T (Tfh) cells in hospital-acquired pneumonia (HAP). Methods Flow cytometry was used measure circulating Tfh and cell (Th) 62 HAP patients 16 healthy individuals. were further categorized into uncontrolled controlled groups, accordance with relevant guidelines. Subgroup analyses additionally conducted based on pathogen presence bloodstream infections (BSIs) incidence septic shock. Kaplan-Meier survival analysis ROC performed estimate prognostic combination Tfh/Th ratios PCT levels. Results The ratio notably higher than controls (P<0.05). Specifically, either Klebsiella pneumoniae (K.p) -positive or BSIs subgroups shock showed significantly increased level increased. However, there no significant differences between K.p-infected non-K.p-infected patients. So, is a good supplement for distinguishing K.p non-K.p groups. also demonstrated strong correlation procalcitonin (PCT) levels Accordingly, could serve as more effective predictive marker deterioration prediction. high along had lower 28-day rate. Conclusion ratio, instrumental gauging severity HAP, be employed biomarker HAP.

Language: Английский

Citations

0
Hyaluronic acid-silybin conjugate for the preparation of multifunctional, biomimetic, vancomycin-loaded self-assembled polymersomes against bacterial sepsis DOI
Mohammed A. Gafar, Calvin A. Omolo, Usri H. Ibrahim

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: 299, P. 140152 - 140152

Published: Jan. 22, 2025

Language: Английский

Citations

0