Cell Biochemistry and Biophysics, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 23, 2024
Language: Английский
Critical Care, Journal Year: 2024, Volume and Issue: 28(1)
Published: Sept. 3, 2024
Sepsis is a severe medical condition characterized by systemic inflammatory response, often culminating in multiple organ dysfunction and high mortality rates. In recent years, there has been growing recognition of the pivotal role played mitochondrial damage driving progression sepsis. Various factors contribute to impairment during sepsis, encompassing mechanisms such as reactive nitrogen/oxygen species generation, mitophagy inhibition, dynamics change, membrane permeabilization. Damaged mitochondria actively participate shaping milieu triggering key signaling pathways, including those mediated Toll-like receptors, NOD-like cyclic GMP-AMP synthase. Consequently, surge interest developing therapeutic strategies targeting mitigate septic pathogenesis. This review aims delve into intricate underpinning sepsis its significant impact on immune dysregulation. Moreover, we spotlight promising mitochondria-targeted interventions that have demonstrated efficacy preclinical models.
Language: Английский
Citations
14
Molecules, Journal Year: 2025, Volume and Issue: 30(3), P. 635 - 635
Published: Jan. 31, 2025
Acetic acid bacteria are single-celled organisms well-known for their ability to convert ethanol into acetic acid. Still, recent research suggests they may harbor another attractive characteristic—the production of proteins with remarkable similarities sirtuins. Sirtuins have been linked lifespan extension in various organisms, raising intriguing questions about the potential connection between and biology aging. This article delves characterization sirtuin homologs bacteria. Up three types identified 21% genomes deposited NCBI. All were present only genera Acetobacter Novacetimonas, which known survive harshest environmental conditions (high concentrations ethanol). Interestingly, two these (SirAAB-L SirAAB-S) constitute a separate group (SirAAB), distinctive from all other presently The results obtained silico thus encourage further studies function sirtuins interplay metabolic pathways industrially important
Language: Английский
Citations
1
Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)
Published: April 12, 2025
Abstract Disruption of nicotinamide adenine dinucleotide (NAD) biosynthesis and function during infection may impair host defenses aggravate inflammatory oxidative organ injury. Increasingly, studies are investigating whether niacin or NAD metabolite treatment is beneficial in sepsis animal models. We examined this preclinical experience supports clinical trials. A systematic review three data bases was conducted through 2/29/2024 a meta-analysis performed comparing to control adult models employing microbial challenges. Fifty-six met inclusion criteria, with 24 published after 2019. Most employed mouse (n = 40 studies) rat 12) administered either bacterial toxin 28) 19) challenge. Four viral fungal challenges respectively. Studies investigated an alone 44), 9), both 3), usually before within 24h challenge 50). Only four included standard antimicrobial support started > In similar patterns differing types (p ≥ 0.06), compared across those the parameter, decreased odds ratio mortality [95% confidence interval (CI)] [0.28 (0.17, 0.49)] blood tissue increased antioxidant levels [standardized mean differences (95%CI)] (SMD) [3.61 (2.20,5.02)] microbes [− 2.44 (− 3.34, − 1.55)], histologic permeability injury scoring 1.62 2.27, 0.98) 1.31(− 1.77, 0.86) respectively], TNFα, IL-6 IL-1β 2.47 3.30, 1.64), 3.17 4.74, 1.60) 8.44 12.4, 4.5) respectively] myeloperoxidase (MPO) 1.60 2.06, 1.14)], although significant, primarily quantitative heterogeneity for each (I 2 53%, p < 0.01) except MPO. Treatment + chemical measures oxidation markers but differently species ≤ 0.05). 9 survival described power analyses randomization respectively no study non-histologic outcome measure blinding. Among studies, Egger’s analysis 0.002) suggested publication bias. While suggestive, do not yet trials testing sepsis. Animal simulating conditions randomized, blinded designs needed investigate potentially promising therapeutic approach.
Language: Английский
Citations
1
Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)
Published: Aug. 30, 2024
Nicotinamide mononucleotide (NMN), a crucial intermediate in NAD + synthesis, can rapidly transform into within the body after ingestion. NMN plays pivotal role several important biological processes, including energy metabolism, cellular aging, circadian rhythm regulation, DNA repair, chromatin remodeling, immunity, and inflammation. has emerged as key focus of research fields biomedicine, health care, food science. Recent years have witnessed extensive preclinical studies on NMN, offering valuable insights pathogenesis age- aging-related diseases. Given sustained global interest substantial market expectations for future, here, we comprehensively review milestones biotherapy over past 10 years. Additionally, highlight current field digestive system diseases, identifying existing problems challenges research. The overarching aim this is to provide references further exploration spectrum
Language: Английский
Citations
6
Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15
Published: April 16, 2024
Sepsis is a life-threatening organ dysfunction caused by the host’s dysfunctional response to infection. Abnormal activation of immune system and disturbance energy metabolism play key role in development sepsis. In recent years, Sirtuins (SIRTs) family has been found an important pathogenesis SIRTs, as class histone deacetylases (HDACs), are widely involved cellular inflammation regulation, oxidative stress. The effects SIRTs on cells mainly reflected regulation inflammatory pathways. This helps balance may lessen cell damage terms metabolism, can immunophenotypic transformation regulating improve mitochondrial function, increase production, maintain balance. also regulate production reactive oxygen species (ROS), protecting from stress activating antioxidant defense pathways maintaining between oxidants reducing agents. Current studies have shown that several potential drugs, such Resveratrol melatonin, enhance activity SIRT. It help reduce response, stress, showing clinical application prospects for treatment review focuses SIRT cells, well its influence multiple sepsis, discusses summarizes related drugs compounds sepsis through pathway involving SIRTs. become new target resulting dysfunction, providing ideas possibilities this disease.
Language: Английский
Citations
5
Mediators of Inflammation, Journal Year: 2025, Volume and Issue: 2025(1)
Published: Jan. 1, 2025
Background and Aims: Plasma interleukin (IL)-27 is an important mediator of acute hepatic injury (AHI) associated with sepsis. Mitochondria contribute to the proper regulation macrophage phagocytosis. In this study, we investigated effect IL-27 on mitochondrial function antimicrobial response macrophages in sepsis-associated AHI. Methods: Wild-type (WT) receptor WSX-1 deficient (IL-27R-/-) mice underwent cecal ligation puncture (CLP). The severity injury, inflammatory cytokine levels, pyroptosis, bacterial load liver blood were assessed 24 h after CLP. vitro, RAW264.7 cells peritoneal treated lipopolysaccharide (LPS) and/or IL-27. phagocytosis killing functions detected. Mitochondrial mitophagy detected using western blot, glutathione (GSH)/malondialdehyde (MDA) content measurement, fluorescence staining, JC-1 staining vivo vitro. After treatment nicotinamide mononucleotide (NMN, NAD + precursor), a pharmacologic agent that improves function, response, pyroptosis assessed. Results: IL-27R-/- exhibited marked reduction (based cleaved GSDMD Caspases 1 protein levels), systemic inflammation serum IL-6, IL-10, TNF-α levels) compared WT following CLP, lacking IL-27R displayed significantly higher clearance greater local infection control. Subsequent studies demonstrated directly impaired LPS-induced phagocytosis, capacity, macrophages. Finally, enhanced NMN alleviated pathological inflammation. Conclusions: These findings indicated impairs capacity by aggravating dysfunction aggravate AHI during
Language: Английский
Citations
0
Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: 234, P. 86 - 99
Published: April 15, 2025
Language: Английский
Citations
0
Metabolites, Journal Year: 2024, Volume and Issue: 14(6), P. 341 - 341
Published: June 18, 2024
Recent years have seen a surge in research focused on NAD+ decline and potential interventions, despite significant progress, new discoveries continue to highlight the complexity of biology. Nicotinamide mononucleotide (NMN), well-established precursor, has garnered considerable interest due its capacity elevate levels induce promising health benefits preclinical models. Clinical trials investigating NMN supplementation yielded variable outcomes while shedding light intricacies metabolism revealing critical roles played by gut microbiota specific cellular uptake pathways. Individual variability factors such as lifestyle, conditions, genetics, microbiome composition likely contributes observed discrepancies clinical trial results. Preliminary evidence suggests that NMN’s effects may be context-dependent, varying based person’s physiological state. Understanding these nuances is for definitively assessing impact manipulating through supplementation. Here, we review metabolism, focusing current knowledge, pinpointing key areas where further needed, outlining future directions advance our understanding significance.
Language: Английский
Citations
3
Molecular Medicine, Journal Year: 2024, Volume and Issue: 30(1)
Published: Nov. 14, 2024
Abstract Background Sepsis-induced organ failure and high mortality are largely ascribed to the of bacterial clearance from infected tissues. Recently, probiotic bacteria-released extracellular vesicles (BEVs) have been implicated as critical mediators intercellular communication which widely involved in regulation inflammatory response. However, their functional role macrophage phagocytosis during sepsis has never explored. Methods BEVs were collected three different strains probiotics including Lactiplantibacillus plantarum WCFS1 (LP WCFS1), Lactobacillus rhamnosus Gorbach-Goldin (LGG), Escherichia coli Nissle 1917 (EcN), or LGG cultured under pH conditions (pH5-acid, pH6.5-standard, pH8-akaline) through differential centrifugation, filtration, ultracentrifugation culture supernatants. In vitro was measured Raw264.7 cells bone marrow-derived macrophages using pHrodo red E. BioParticles. The vivo therapeutic effects tested a feces-injection-in-peritoneum (FIP) model polymicrobial sepsis. Results LGG-derived EVs (BEV ) best among these stimulating take up bacteria. Furthermore, BEV pH8 condition exhibited strongest capacity phagocytosis, compared with pH5 pH6.5 . Treatment septic mice significantly prolonged animal survival; increased blood, peritoneal lavage fluid, multiple organs; decreased serum levels pro-inflammatory cytokines/chemokines, well reduced injuries, comparison control-treated mice. Mechanistically, RNA-seq bioinformatic analysis identified that FPR1/2 signaling remarkably activated, along its downstream pathways (PI3K-Akt-MARCO NADPH-ROS) -treated macrophages, control cells. Accordingly, pre-addition Boc2, specific antagonist FPR1/FPR2, attenuated -mediated controls. Conclusions This study demonstrates may against sepsis-induced injury enhancing FPR1/2-mediated phagocytosis.
Language: Английский
Citations
3
Published: March 28, 2024
Nicotinamide mononucleotide (NMN), a key NAD+ precursor, exhibits distinct metabolic characteristics and potential health benefits. Recent investigations underscore the pivotal role of gut bacteria specialized uptake mechanisms in NMN metabolism. While human trials demonstrate NMN's safety promising outcomes, challenges persist. Variability results is likely influenced by lifestyle, conditions, individual genetic microbiota differences. Understanding how these factors affect metabolism crucial for personalized approaches maximizing potential. Advances delivery systems show promise enhancing bioavailability, but further understanding optimal levels reliable measures effects necessary. This comprehensive approach to optimizing impact on longevity.
Language: Английский
Citations
1