CC16 deficiency in the context of early life Mycoplasma pneumoniae infection results in augmented airway responses in adult mice.

2021 ◽  
Author(s):  
Natalie Iannuzo ◽  
Michael Insel ◽  
Craig Marshall ◽  
William P. Pederson ◽  
Kenneth J. Addison ◽  
...  
Keyword(s):  
Lung Function ◽  
Mycoplasma Pneumoniae ◽  
Early Life ◽  
Defense Mechanisms ◽  
Airway Remodeling ◽  
Secretory Protein ◽  
Protective Role ◽  
Tracheal Epithelial Cells ◽  
Adult Mice ◽  
The Impact

Studies have shown that club cell secretory protein (CC16) plays important protective roles in the lungs, yet its complete biological functions are unclear. We devised a translational mouse model in order to investigate the impact of early life infections, in the context of CC16 deficiency, on lung function in adult mice. CC16 sufficient (WT) and deficient (CC16 -/- ) mice were infected with Mycoplasma pneumoniae (Mp) as weanlings and assessed as adults ( e arly l ife i nfection m odel; ELIM) and compared to adult mice infected for only three days ( a dult i nfection m odel; AIM). CC16 -/- Mp-infected mice had significantly increased airway hyperresponsiveness (AHR) in both models compared to WT mice. However, CC16 -/- mice infected in early life (ELIM) displayed significantly increased AHR compared to CC16 -/- mice infected in adulthood (AIM). In stark contrast, lung function in ELIM WT mice returned to levels similar to saline-treated controls. While WT mice cleared Mp infection in the ELIM, CC16 -/- mice remained colonized with Mp throughout the model, which likely contributed to increased airway remodeling and persistence of Muc5ac expression. When CC16 -/- mouse tracheal epithelial cells (MTECs) were infected with Mp, increased Mp colonization and collagen gene expression were also detected compared to WT cells, suggesting that CC16 plays a protective role during Mp infection, in part through epithelial-driven host defense mechanisms.

The impact of early-life stress on the expression of HPA-associated genes in the adult murine brain

Behaviour ◽  
2018 ◽  
Vol 155 (2-3) ◽  
pp. 181-203 ◽  
Author(s):  
V.V. Reshetnikov ◽  
A.A. Studenikina ◽  
J.A. Ryabushkina ◽  
T.I. Merkulova ◽  
N.P. Bondar
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Early Life Stress ◽  
Long Term Memory ◽  
Adult Mice ◽  
Specific Manner ◽  
Behavioural Phenotypes ◽  
The Impact

Abstract Early life is an important period for the development of the nervous system and for the programming of behavioural phenotypes in adulthood. In our study, two types of early-life stress were used: prolonged separation of pups from their mothers (for 3 h/day, maternal separation (MS)) and brief separation (for 15 min/day, handling (HD)). We analysed the effects of early-life stress on behaviour and the expression of HPA-associated genes in the hypothalamus, hippocampus, and frontal cortex of male mice. Adult mice in the MS group demonstrated reduced locomotor activity and deficiencies in spatial long-term memory, while the HD showed no significant changes. Additionally, early-life MS resulted in reduced hippocampal Crhr1 mRNA, increased MR/GR mRNA in the hippocampus and hypothalamus. Both groups, HD and MS, showed increased Avp mRNA in the hypothalamus. Thus, prolonged maternal separation but not brief leads to adverse behavioural changes and influences the expression of HPA-associated genes in a brain region-specific manner.

Epigenetic Memory Is Involved in the Persistent Alterations of Drug-Processing Genes in Adult Mice Due to PCN-Activated PXR During Early Life

2019 ◽  
Vol 172 (1) ◽  
pp. 98-108
Author(s):  
Pei Wang ◽  
Guangming Liu ◽  
Yali Nie ◽  
Shengna Han ◽  
Jiangfeng Li ◽  
...  
Keyword(s):  
Early Life ◽  
Pregnane X Receptor ◽  
Underlying Mechanism ◽  
Epigenetic Memory ◽  
Hepatic Expression ◽  
Adult Mice ◽  
Elevated Expression ◽  
High Doses ◽  
Long Term Impact ◽  
The Impact

Abstract Pregnane X receptor (PXR), which can be activated by xenobiotic chemicals (including pediatric drugs), plays a key role in the regulation of drug-processing genes (DPGs). The induction of DPGs due to PXR activation may reduce therapeutic efficacy or cause toxicity. This work aims to demonstrate the impact of pregnenolone 16α-carbonitrile (PCN)-mediated PXR activation during early life on DPGs expression and drug sensitivity in adulthood, as well as the underlying mechanism. In this study, mice were sacrificed at postnatal day 60 to detect the hepatic expression of selected DPGs and histone modifications in the Cyp3a11 promoter. We found that all doses of PCN treatment (50–200 mg/kg/day) at postnatal days 5–8 resulted in persistently increased CYP2B10 expression, whereas only high doses of PCN treatment (150 and 200 mg/kg/day) persistently induced the expression of CYP3A11, 1A2, and UGT1A1. We also demonstrated that PCN treatment before postnatal day 15 had a long-term impact on the expression of CYP3A11, 2B10, ABCC4, and PAPSS2. Additionally, elevated expression of CYP3A11, SULT2A1, UGT1A1, and PAPSS2 was observed in PCN-treated groups at days 25–28. Attenuated inducibility of CYP3A11 by PCN was seen in the primary hepatocytes derived from PCN-pretreated mice. Moreover, enhanced H3K4me3 level and reduced H3K27me3 level in the PXR response elements (PXREs) of the Cyp3a11 promoter may contribute to the persistent upregulation of CYP3A11 by neonatal PCN treatment. Overall, our study suggests that PXR activation during early life could persistently alter the hepatic expression of DPGs and epigenetic memory may be an underlying mechanism in mice.

The Impact of Plant Bioactive Compounds on Aging and Fertility of Diverse Organisms: A Review

2020 ◽  
Vol 20 (13) ◽  
pp. 1287-1299
Author(s):  
Muhammad Akram Mohd Noordin ◽  
Mahanem Mat Noor ◽  
Wan Mohd Aizat
Keyword(s):  
Clinical Trial ◽  
Bioactive Compounds ◽  
Defense Mechanisms ◽  
Healthy Aging ◽  
Antioxidant Defense ◽  
Senior Citizens ◽  
Aging Population ◽  
Human Clinical Trial ◽  
Fertility Reduction ◽  
The Impact

It is expected that in 2050, there will be more than 20% of senior citizens aged over 60 years worldwide. Such alarming statistics require immediate attention to improve the health of the aging population. Since aging is closely related to the loss of antioxidant defense mechanisms, this situation eventually leads to numerous health problems, including fertility reduction. Furthermore, plant extracts have been used in traditional medicine as potent antioxidant sources. Although many experiments had reported the impact of various bioactive compounds on aging or fertility, there is a lack of review papers that combine both subjects. In this review, we have collected and discussed various bioactive compounds from 26 different plant species known to affect both longevity and fertility. These compounds, including phenolics and terpenes, are mostly involved in the antioxidant defense mechanisms of diverse organisms such as rats, mites, fruit flies, roundworms, and even roosters. A human clinical trial should be considered in the future to measure the effects of these bioactive compounds on human health and longevity. Ultimately, these plant-derived compounds could be developed into health supplements or potential medical drugs to ensure a healthy aging population.

The Impact of L-Carnitine and Coenzyme Q10 as Protection Against Busulfan-Oxidative Stress in the Liver of Adult Rats

2020 ◽  
Vol 10 (5) ◽  
pp. 578-586
Author(s):  
Areeg M. Abdelrazek ◽  
Shimaa A. Haredy
Keyword(s):  
Oxidative Stress ◽  
Coenzyme Q10 ◽  
Protective Role ◽  
Albino Rats ◽  
Distilled Water ◽  
Negative Effects ◽  
Adult Rats ◽  
Stress Damage ◽  
The Impact ◽  
Liver Tissues

Background: Busulfan (Bu) is an anticancer drug with a variety of adverse effects for cancer patients. Oxidative stress has been considered as a common pathological mechanism and it has a key role in the initiation and progression of liver injury by Bu. Aim: The study aimed to evaluate the antioxidant impact of L-Carnitine and Coenzyme Q10 and their protective role against oxidative stress damage in liver tissues. Methods and Material: Thirty-six albino rats were divided equally into six groups. G1 (con), received I.P. injection of DMSO plus 1 ml of distilled water daily by oral gavages; G2 (Bu), received I.P. injection of Bu plus 1 ml of the distilled water daily; G3 (L-Car), received 1 ml of L-Car orally; G4 (Bu + L-Car) received I.P. injection of Bu plus 1 ml of L-Car, G5 (CoQ10) 1 ml of CoQ10 daily; and G6 (Bu + CoQ10) received I.P. injection of Bu plus 1 ml of CoQ10 daily. Results: The recent data showed that Bu induced significant (P<0.05) elevation in serum ALT, AST, liver GSSG, NO, MDA and 8-OHDG, while showing significant (P<0.05) decrease in liver GSH and ATP. On the other hand, L-Carnitine and Coenzyme Q10 ameliorated the negative effects prompted by Bu. Immunohistochemical expression of caspase-3 in liver tissues reported pathological alterations in Bu group while also showed significant recovery in L-Car more than CoQ10. Conclusion: L-Car, as well as CoQ10, can enhance the hepatotoxic effects of Bu by promoting energy production in oxidative phosphorylation process and by scavenging the free radicals.

scholarly journals Association of a PAI-1 Gene Polymorphism and Early Life Infections with Asthma Risk, Exacerbations, and Reduced Lung Function

PLoS ONE ◽  
2016 ◽  
Vol 11 (8) ◽  
pp. e0157848 ◽  
Author(s):  
Seong H. Cho ◽  
Jin-Young Min ◽  
Dong Young Kim ◽  
Sam S. Oh ◽  
Dara R. Torgerson ◽  
...  
Keyword(s):  
Lung Function ◽  
Gene Polymorphism ◽  
Early Life ◽  
Asthma Risk ◽  
Pai 1

scholarly journals Association of Genetic Polymorphisms in Oxidative Stress and Inflammation Pathways with Glaucoma Risk and Phenotype

2021 ◽  
Vol 10 (5) ◽  
pp. 1148
Author(s):  
Makedonka Atanasovska Velkovska ◽  
Katja Goričar ◽  
Tanja Blagus ◽  
Vita Dolžan ◽  
Barbara Cvenkel
Keyword(s):  
Oxidative Stress ◽  
Ocular Hypertension ◽  
Gene Deletion ◽  
Open Angle Glaucoma ◽  
Protective Role ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Gstm1 Gene ◽  
Stress Genes ◽  
The Impact

Oxidative stress and neuroinflammation are involved in the pathogenesis and progression of glaucoma. Our aim was to evaluate the impact of selected single-nucleotide polymorphisms in inflammation and oxidative stress genes on the risk of glaucoma, the patients’ clinical characteristics and the glaucoma phenotype. In total, 307 patients with primary open-angle glaucoma or ocular hypertension were enrolled. The control group included 339 healthy Slovenian blood donors. DNA was isolated from peripheral blood. Genotyping was performed for SOD2 rs4880, CAT rs1001179, GPX1 rs1050450, GSTP1 rs1695, GSTM1 gene deletion, GSTT1 gene deletion, IL1B rs1143623, IL1B rs16944, IL6 rs1800795 and TNF rs1800629. We found a nominally significant association of GSTM1 gene deletion with decreased risk of ocular hypertension and a protective role of IL1B rs16944 and IL6 rs1800629 in the risk of glaucoma. The CT and TT genotypes of GPX1 rs1050450 were significantly associated with advanced disease, lower intraocular pressure and a larger vertical cup–disc ratio. In conclusion, genetic variability in IL1B and IL6 may be associated with glaucoma risk, while GPX and TNF may be associated with the glaucoma phenotype. In the future, improved knowledge of these pathways has the potential for new strategies and personalised treatment of glaucoma.

Effects of dietary n-3 PUFA levels in early life on susceptibility to high-fat-diet-induced metabolic syndrome in adult mice

2020 ◽  
pp. 108578
Author(s):  
Dan-Dan Wang ◽  
Fang Wu ◽  
Ling-Yu Zhang ◽  
Ying-Cai Zhao ◽  
Cheng-Cheng Wang ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
High Fat Diet ◽  
Early Life ◽  
High Fat ◽  
Adult Mice

scholarly journals ROS Defense Systems and Terminal Oxidases in Bacteria

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 839
Author(s):  
Vitaliy B. Borisov ◽  
Sergey A. Siletsky ◽  
Martina R. Nastasi ◽  
Elena Forte
Keyword(s):  
Defense Mechanisms ◽  
Protective Role ◽  
Superoxide Dismutases ◽  
Oxygen Species ◽  
Ros Scavenging ◽  
Terminal Oxidases ◽  
Defense Systems ◽  
Respiratory Chains ◽  
Scavenging Enzymes

Reactive oxygen species (ROS) comprise the superoxide anion (O2·−), hydrogen peroxide (H2O2), hydroxyl radical (·OH), and singlet oxygen (1O2). ROS can damage a variety of macromolecules, including DNA, RNA, proteins, and lipids, and compromise cell viability. To prevent or reduce ROS-induced oxidative stress, bacteria utilize different ROS defense mechanisms, of which ROS scavenging enzymes, such as superoxide dismutases, catalases, and peroxidases, are the best characterized. Recently, evidence has been accumulating that some of the terminal oxidases in bacterial respiratory chains may also play a protective role against ROS. The present review covers this role of terminal oxidases in light of recent findings.

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