Macrophages are highly plastic cells of the innate immune system. Macrophages play central roles in immunity against microbes and contribute to a wide array of pathologies. The processes of macrophage activation and their functions have attracted considerable attention from life scientists. Although macrophages are highly resistant to many toxic stimuli, including oxidative stress, macrophage death has been reported in certain diseases, such as viral infections, tuberculosis, atherosclerotic plaque development, inflammation, and sepsis. While most studies on macrophage death focused on apoptosis, a significant body of data indicates that programmed necrotic cell death forms may be equally important modes of macrophage death. Three such regulated necrotic cell death modalities in macrophages contribute to different pathologies, including necroptosis, pyroptosis, and parthanatos. Various reactive oxygen and nitrogen species, such as superoxide, hydrogen peroxide, and peroxynitrite have been shown to act as triggers, mediators, or modulators in regulated necrotic cell death pathways. Here we discuss recent advances in necroptosis, pyroptosis, and parthanatos, with a strong focus on the role of redox homeostasis in the regulation of these events.
In breast cancer patients, the diversity of the microbiome decreases, coinciding with decreased production of cytostatic bacterial metabolites like lithocholic acid (LCA). We hypothesized that LCA can modulate oxidative stress to exert cytostatic effects in breast cancer cells. Treatment of breast cancer cells with LCA decreased nuclear factor-2 (NRF2) expression and increased Kelch-like ECH associating protein 1 (KEAP1) expression via activation of Takeda G-protein coupled receptor (TGR5) and constitutive androstane receptor (CAR). Altered NRF2 and KEAP1 expression subsequently led to decreased expression of glutathione peroxidase 3 (GPX3), an antioxidant enzyme, and increased expression of inducible nitric oxide synthase (iNOS). The imbalance between the pro- and antioxidant enzymes increased cytostatic effects via increased levels of lipid and protein oxidation. These effects were reversed by the pharmacological induction of NRF2 with RA839, tBHQ, or by thiol antioxidants. The expression of key components of the LCA-elicited cytostatic pathway (iNOS and 4HNE) gradually decreased as the breast cancer stage advanced. The level of lipid peroxidation in tumors negatively correlated with the mitotic index. The overexpression of iNOS, nNOS, CAR, KEAP1, NOX4, and TGR5 or the downregulation of NRF2 correlated with better survival in breast cancer patients, except for triple negative cases. Taken together, LCA, a metabolite of the gut microbiome, elicits oxidative stress that slows down the proliferation of breast cancer cells. The LCA–oxidative stress protective pathway is lost as breast cancer progresses, and the loss correlates with poor prognosis.
Male C57BL/6J mice were used to determine the possible therapeutic effects of our previously described tart cherry extract in a chronic obesity mouse model on metabolic parameters, glucose tolerance, inflammatory mediators, and antioxidant capacity. The control group received standard mouse chow, and the high fat control group was switched to a high fat diet and tap water supplemented with 5% sucrose. The high fat + anthocyanin group received the high fat and sucrose diet, but received the anthocyanin-rich tart cherry extract dissolved in their drinking water. After six weeks, an oral glucose tolerance test was performed, and the water-soluble antioxidant capacity (ACW), superoxide dismutase (SOD) activity, and the plasma levels of insulin, C-peptide, leptin, IL-6, MCP-1, adiponectin and resistin were measured. The high fat diet increased body weight, reduced glucose tolerance, and caused an elevation in leptin, IL-6, MCP-1, and resistin levels. Furthermore, antioxidant capacity was decreased with a significant elevation of SOD activity. Anthocyanin treatment failed to reverse the effects of the high fat diet on body weight and glucose tolerance, but significantly reduced the leptin and IL-6 levels. The tart cherry extract also made a significant enhancement in antioxidant capacity and SOD activity. Our results show that chronic anthocyanin intake has a potential to enhance redox status and alleviate inflammation associated with obesity.
The level of malondialdehyde, a stable end product of lipid peroxidation induced by reactive oxygen intermediates and the activity of two potent antioxidant enzymes, superoxide dismutase and glutathione peroxidase, was investigated in tissue homogenates of 22 surgical periapical granuloma specimens. Malondialdehyde levels were significantly higher and glutathione peroxidase activity was significantly lower in periapical granuloma samples than in healthy gingival tissue homogenates, which were used as controls. The activity of superoxide dismutase was similar in periapical granuloma and in control samples. Our results indicate an altered balance between the production and the elimination of toxic oxygen metabolites in chronic apical periodontitis. We hypothesize that reactive oxygen intermediates, which are being produced by activated phagocytic cells abundantly present in periapical granulomas, can contribute to periapical tissue injury and bone loss in this disease.
Active screening for resistant multidrug strain carriers remains an important component of infection control policy in any healthcare setting indifferent of financial and logistical costs. The objective of our study was to determine the spectrum of bacterial colonization individually among intensive care unit patients. A retrospective observational study was performed in the Intensive Care Unit of Emergency Clinical County Hospital of Oradea during 2017. Medical records of the patients were used for evaluation of source of ICU admission, previous antibiotic therapy, comorbidities, and length of hospital stay. Nasal and groin swabs for MRSA detection and rectal swabs for ESBL, VRE, and CRE detection were collected upon ICU admission of all patients in the first 24 hours and after 7 days. Swab samples were processed for isolation and identification of these resistant multidrug strains. Bacterial colonization on admission was detected in a quarter of patients included in the study. Carbapenemase-producing bacteria were the most common colonizers (21.16%). On admission, 12.06% of patients have been colonized by ESBL-producing members of the family Enterobacterales. Risk factors for colonization on admission to the ICU were chronic liver diseases and chronic renal failure for ESBL infection and chronic liver disease for CRE in male patients. Evaluation of Carmeli’s score for male patients showed association only with CRE colonization. Chronic renal failure was found as risk factor for ESBL colonization in female patients. The prevalence of MRSA was 5.23% and less than 1% for VRE. There was no association between any risk factors studied and the presence of S. aureus or VRE upon admission. The 7-day ICU stay also proved to be an increased risk for ESBL and CRE infection.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.