Immunometabolic Analysis of Mobiluncus mulieris and Eggerthella sp. Reveals Novel Insights Into Their Pathogenic Contributions to the Hallmarks of Bacterial Vaginosis

The cervicovaginal microbiome plays an important role in protecting women from dysbiosis and infection caused by pathogenic microorganisms. In healthy reproductive-age women the cervicovaginal microbiome is predominantly colonized by protective Lactobacillus spp. The loss of these protective bacteria leads to colonization of the cervicovaginal microenvironment by pathogenic microorganisms resulting in dysbiosis and bacterial vaginosis (BV). Mobiluncus mulieris and Eggerthella sp. are two of the many anaerobes that can contribute to BV, a condition associated with multiple adverse obstetric and gynecological outcomes. M. mulieris has been linked to high Nugent scores (relating to BV morphotypes) and preterm birth (PTB), whilst some bacterial members of the Eggerthellaceae family are highly prevalent in BV, and identified in ~85-95% of cases. The functional impact of M. mulieris and Eggerthella sp. in BV is still poorly understood. To determine the individual immunometabolic contributions of Eggerthella sp. and M. mulieris within the cervicovaginal microenvironment, we utilized our well-characterized human three-dimensional (3-D) cervical epithelial cell model in combination with multiplex immunoassays and global untargeted metabolomics approaches to identify key immune mediators and metabolites related to M. mulieris and Eggerthella sp. infections. We found that infection with M. mulieris significantly elevated multiple proinflammatory markers (IL-6, IL-8, TNF-α and MCP-1) and altered metabolites related to energy metabolism (nicotinamide and succinate) and oxidative stress (cysteinylglycine, cysteinylglycine disulfide and 2-hydroxygluatrate). Eggerthella sp. infection significantly elevated multiple sphingolipids and glycerolipids related to epithelial barrier function, and biogenic amines (putrescine and cadaverine) associated with elevated vaginal pH, vaginal amine odor and vaginal discharge. Our study elucidated that M. mulieris elevated multiple proinflammatory markers relating to PTB and STI acquisition, as well as altered energy metabolism and oxidative stress, whilst Eggerthella sp. upregulated multiple biogenic amines associated with the clinical diagnostic criteria of BV. Future studies are needed to evaluate how these bacteria interact with other BV-associated bacteria within the cervicovaginal microenvironment.

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‘Pera’ orange (Citrus sinensis) and ‘Moro’ orange juice (Citrus sinensis (L.) Osbeck) attenuates left ventricular dysfunction and oxidative stress and improves myocardial energy metabolism in acute doxorubicin-induced cardiotoxicity in rats

Nutrition ◽

10.1016/j.nut.2021.111350 ◽

2021 ◽

pp. 111350

Author(s):

Ana Paula Dantas Ribeiro ◽

Amanda Gomes Pereira ◽

Márcia Cristina Todo ◽

Anderson Seiji Soares Fujimori ◽

Priscila Portugal dos Santos ◽

...

Keyword(s):

Oxidative Stress ◽

Energy Metabolism ◽

Left Ventricular Dysfunction ◽

Orange Juice ◽

Citrus Sinensis ◽

Ventricular Dysfunction ◽

Left Ventricular ◽

Myocardial Energy Metabolism ◽

And Oxidative Stress

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Catechin and Procyanidin B2 Modulate the Expression of Tight Junction Proteins but Do Not Protect from Inflammation-Induced Changes in Permeability in Human Intestinal Cell Monolayers

Nutrients ◽

10.3390/nu11102271 ◽

2019 ◽

Vol 11 (10) ◽

pp. 2271 ◽

Cited By ~ 4

Author(s):

Massimiliano G. Bianchi ◽

Martina Chiu ◽

Giuseppe Taurino ◽

Furio Brighenti ◽

Daniele Del Rio ◽

...

Keyword(s):

Oxidative Stress ◽

Barrier Function ◽

Cell Model ◽

Intestinal Cell ◽

Epithelial Barrier ◽

Epithelial Barrier Function ◽

Inflammatory Stress ◽

Cell Monolayers ◽

Dietary Polyphenols ◽

Junctional Proteins

The possibility of counteracting inflammation-related barrier defects with dietary compounds such as (poly)phenols has raised much interest, but information is still scarce. We have investigated here if (+)-catechin (CAT) and procyanidin B2 (PB2), two main dietary polyphenols, protect the barrier function of intestinal cells undergoing inflammatory stress. The cell model adopted consisted of co-cultured Caco-2 and HT29-MTX cells, while inflammatory conditions were mimicked through the incubation of epithelial cells with the conditioned medium of activated macrophages (MCM). The epithelial barrier function was monitored through trans-epithelial electrical resistance (TEER), and ROS production was assessed with dichlorofluorescein, while the expression of tight-junctional proteins and signal transduction pathways were evaluated with Western blot. The results indicated that MCM produced significant oxidative stress, the activation of NF-κB and MAPK pathways, a decrease in occludin and ZO-1 expression, and an increase in claudin-7 (CL-7) expression, while TEER was markedly lowered. Neither CAT nor PB2 prevented oxidative stress, transduction pathways activation, ZO-1 suppression, or TEER decrease. However, PB2 prevented the decrease in occludin expression and both polyphenols produced a huge increase in CL-7 abundance. It is concluded that, under the conditions adopted, CAT and PB2 do not prevent inflammation-dependent impairment of the epithelial barrier function of intestinal cell monolayers. However, the two compounds modify the expression of tight-junctional proteins and, in particular, markedly increase the expression of CL-7. These insights add to a better understanding of the potential biological activity of these major dietary flavan-3-ols at intestinal level.

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Effects of Levosimendan on Inflammation and Oxidative Stress Pathways in a Lipopolysaccharide-Stimulated Human Endothelial Cell Model

Biological Research For Nursing ◽

10.1177/1099800419861694 ◽

2019 ◽

Vol 21 (5) ◽

pp. 466-472 ◽

Cited By ~ 1

Author(s):

Raquel Rodríguez-González ◽

Piero Pollesello ◽

Aurora Baluja ◽

Julián Álvarez

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Endothelial Cell ◽

Molecular Mechanisms ◽

Cell Model ◽

Acute Decompensated Heart Failure ◽

Umbilical Vein ◽

Organ Protection ◽

Endothelial Cell Death ◽

And Oxidative Stress

Levosimendan is a myocardial Ca2+sensitizer and opener of ATP-dependent potassium channels with inotropic, vasodilating, and cardioprotective properties. It was originally developed for the treatment of acute decompensated heart failure, but its complex mechanism of action means that it could also play a role in organ protection in response to infection. Using an in vitro approach, we explored whether levosimendan administration influenced cell responses to lipopolysaccharide (LPS). Primary human umbilical vein endothelial cells were stimulated with 1 µg/ml LPS from Escherichia coli ( E. coli). Cells were treated with levosimendan at 0, 0.1, 1, or 10 µM 3 hr later. Samples were taken 24 hr after treatment to measure cell necrosis, apoptosis, pro-inflammatory mediators (interleukin 6 [IL-6] and toll-like receptor 4 [TLR4]), and oxidative stress (total reactive oxygen species/reactive nitrogen species [ROS/RNS]). Levosimendan at 1 and 10 µM protected against LPS-induced endothelial cell death and reduced TLR4 expression ( p < .05). All doses reduced levels of IL-6 and ROS/RNS ( p < .05). Findings suggest that levosimendan may exert protective effects against endothelial cell death in this model via attenuation of inflammation and oxidative stress pathways. Future studies might explore the potential beneficial role of levosimendan in modulating molecular mechanisms triggered by infections.

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