Utilization of egg white powders to mitigate the astringency of Aronia berry juice and produce protein-Proanthocyanidin aggregates with enhanced stability during digestion

Article

Author: Huang, Rui ; Xu, Changmou ; Xie, Xiaoqing

Aronia berry has a strong unpleasant astringency, however, few approaches have been developed to modify it. This study aims to screen out the suitable proteins to mitigate astringency in aronia juice, elucidate the interaction mechanism, and evaluate the digestive stability of formed complexes. Among proteins tested, two egg white powders (original P-110 and modified M-200) were the optimal ones with 0.5 % (w/w) addition to effectively reduce astringency. At room temperature (25 °C), the interaction of proanthocyanidins (PAs) with both P-110 and M-200 was spontaneous, endothermic, and majorly driven by hydrophobic interaction. The binding affinity of PAs with M-200 is stronger than that with P-110. On the other hand, the egg white protein-PA aggregates enhanced the stability of PAs during digestion, allowing more PAs to reach gut microbiota to exert their bioactivities. This study improves fundamental understanding of egg white protein-PAs interaction and provides a practical processing approach for aronia industry.

01 Jun 2022·Critical Care Medicine

Drp1/Fis1-Dependent Pathologic Fission and Associated Damaged Extracellular Mitochondria Contribute to Macrophage Dysfunction in Endotoxin Tolerance

Article

Author: Joshi, Amit U. ; Haileselassie, Bereketeab ; Ostberg, Nicolai P. ; Gera, Kanika ; Mochly-Rosen, Daria ; Massis, Liliana M. ; Cornell, Timothy T. ; Hall, Mark W. ; Vijayan, Vijith ; Mukherjee, Riddhita ; Monack, Denise ; Tompkins, Carly A.

OBJECTIVES:Recent publications have shown that mitochondrial dynamics can govern the quality and quantity of extracellular mitochondria subsequently impacting immune phenotypes. This study aims to determine if pathologic mitochondrial fission mediated by Drp1/Fis1 interaction impacts extracellular mitochondrial content and macrophage function in sepsis-induced immunoparalysis.DESIGN:Laboratory investigation.SETTING:University laboratory.SUBJECTS:C57BL/6 and BALB/C mice.INTERVENTIONS:Using in vitro and murine models of endotoxin tolerance (ET), we evaluated changes in Drp1/Fis1-dependent pathologic fission and simultaneously measured the quantity and quality of extracellular mitochondria. Next, by priming mouse macrophages with isolated healthy mitochondria (MC) and damaged mitochondria, we determined if damaged extracellular mitochondria are capable of inducing tolerance to subsequent endotoxin challenge. Finally, we determined if inhibition of Drp1/Fis1-mediated pathologic fission abrogates release of damaged extracellular mitochondria and improves macrophage response to subsequent endotoxin challenge.MEASUREMENTS AND MAIN RESULTS:When compared with naïve macrophages (NMs), endotoxin-tolerant macrophages (ETM) demonstrated Drp1/Fis1-dependent mitochondrial dysfunction and higher levels of damaged extracellular mitochondria (Mitotracker-Green + events/50 μL: ETM = 2.42 × 106 ± 4,391 vs NM = 5.69 × 105 ± 2,478; p < 0.001). Exposure of NMs to damaged extracellular mitochondria (MH) induced cross-tolerance to subsequent endotoxin challenge, whereas MC had minimal effect (tumor necrosis factor [TNF]-α [pg/mL]: NM = 668 ± 3, NM + MH = 221 ± 15, and NM + Mc = 881 ± 15; p < 0.0001). Inhibiting Drp1/Fis1-dependent mitochondrial fission using heptapeptide (P110), a selective inhibitor of Drp1/Fis1 interaction, improved extracellular mitochondrial function (extracellular mitochondrial membrane potential, JC-1 [R/G] ETM = 7 ± 0.5 vs ETM + P110 = 19 ± 2.0; p < 0.001) and subsequently improved immune response in ETMs (TNF-α [pg/mL]; ETM = 149 ± 1 vs ETM + P110 = 1,150 ± 4; p < 0.0001). Similarly, P110-treated endotoxin tolerant mice had lower amounts of damaged extracellular mitochondria in plasma (represented by higher extracellular mitochondrial membrane potential, TMRM/MT-G: endotoxin tolerant [ET] = 0.04 ± 0.02 vs ET + P110 = 0.21 ± 0.02; p = 0.03) and improved immune response to subsequent endotoxin treatment as well as cecal ligation and puncture.CONCLUSIONS:Inhibition of Drp1/Fis1-dependent mitochondrial fragmentation improved macrophage function and immune response in both in vitro and in vivo models of ET. This benefit is mediated, at least in part, by decreasing the release of damaged extracellular mitochondria, which contributes to endotoxin cross-tolerance. Altogether, these data suggest that alterations in mitochondrial dynamics may play an important role in sepsis-induced immunoparalysis.

01 Jan 2020·Cellular and Molecular Gastroenterology and HepatologyQ1 · MEDICINE

Perturbed Mitochondrial Dynamics Is a Novel Feature of Colitis That Can Be Targeted to Lessen Disease

Q1 · MEDICINE

ArticleOA

Author: Al Rajabi, Ala ; van Tilburg Bernandes, Erik ; Goudie, Luke ; Rajeev, Sruthi ; Wang, Arthur ; Shearer, Jane ; Mancini, Nicole L ; McKay, Derek M ; Sabouny, Rasha ; Esquerre, Nicolas ; Jayme, Timothy S ; Ferraz, José G P ; Xu, Warren ; Nasser, Yasmin ; Shutt, Timothy

BACKGROUND & AIMSMitochondria exist in a constantly remodelling network, and excessive fragmentation can be pathophysiological. Mitochondrial dysfunction can accompany enteric inflammation, but any contribution of altered mitochondrial dynamics (ie, fission/fusion) to gut inflammation is unknown. We hypothesized that perturbed mitochondrial dynamics would contribute to colitis.METHODSQuantitative polymerase chain reaction for markers of mitochondrial fission and fusion was applied to tissue from dextran sodium sulfate (DSS)-treated mice. An inhibitor of mitochondrial fission, P110 (prevents dynamin related protein [Drp]-1 binding to mitochondrial fission 1 protein [Fis1]) was tested in the DSS and di-nitrobenzene sulfonic acid (DNBS) models of murine colitis, and the impact of DSS ± P110 on intestinal epithelial and macrophage mitochondria was assessed in vitro.RESULTSAnalysis of colonic tissue from mice with DSS-colitis revealed increased mRNA for molecules associated with mitochondrial fission (ie, Drp1, Fis1) and fusion (optic atrophy factor 1) and increased phospho-Drp1 compared with control. Systemic delivery of P110 in prophylactic or treatment regimens reduced the severity of DSS- or DNBS-colitis and the subsequent hyperalgesia in DNBS-mice. Application of DSS to epithelial cells or macrophages caused mitochondrial fragmentation. DSS-evoked perturbation of epithelial cell energetics and mitochondrial fragmentation, but not cell death, were ameliorated by in vitro co-treatment with P110.CONCLUSIONSWe speculate that the anti-colitic effect of systemic delivery of the anti-fission drug, P110, works at least partially by maintaining enterocyte and macrophage mitochondrial networks. Perturbed mitochondrial dynamics can be a feature of intestinal inflammation, the suppression of which is a potential novel therapeutic direction in inflammatory bowel disease.

100 Deals associated with P-110 (Stanford University)

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Indication	Highest Phase	Country/Location	Organization	Date
Alzheimer Disease	Phase 2	US	Stanford University	-
Huntington Disease	Phase 2	US	Stanford University	-
Parkinson Disease	Preclinical	US	Case Western Reserve University School of Medicine	01 Jan 2012

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