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Sexual dimorphism of gut microbiota dictates therapeutics efficacy of radiation injuries [miRNA-seq]

ABSTRACT: Accidental or iatrogenic ionizing radiation exposure precipitates acute and chronic radiation injuries. Traditional paradigm of mitigating radiotherapy-associated side effects has ignored the gender-specific dimorphism of patients. Here we examined the effects of sexual dimorphism on therapeutic agent efficiencies in murine models. High-throughput sequencing showed that different treatments preserved miRNA expression profile in small intestines of male or female mice, respectively. Collectively, our observations demonstrate that therapeutic strategy efficiencies for radiation toxicity might be dependent on the gender of patients. We aim to uncover the underlying mechanisms by which simvastatin or high fat diet fights against radiotherapy-induced gastrointestinal tract toxicity for male or female mice. The mice were exposed to 12 Gy total abdominal irradiation (TAI), then treated with simvastatin for male mice or fed with high fat diet for female mice. The small intestine tissues were extracted from male mice without TAI, exposed to TAI only, and exposed to TAI combined with simvastatin treatment as one cohort, and from female mice without TAI, exposed to TAI only, and exposed to TAI combined with high fat diet feeding as the other cohort.

ORGANISM(S): Mus musculus

PROVIDER: GSE126506 | GEO | 2020/01/25

REPOSITORIES: GEO

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Sexual dimorphism of gut microbiota dictates therapeutics efficacy of radiation injuries [RNA-seq]

Project description:Accidental or iatrogenic ionizing radiation exposure precipitates acute and chronic radiation injuries. Traditional paradigm of mitigating radiotherapy-associated side effects has ignored the gender-specific dimorphism of patients. Here we examined the effects of sexual dimorphism on therapeutic agent efficiencies in murine models. High-throughput sequencing of host mRNA showed that different treatments reprogrammed the spectrum of mRNA expression in small intestines of male or female mice, respectively. Collectively, our observations demonstrate that therapeutic strategy efficiencies for radiation toxicity might be dependent on the gender of patients. We aim to uncover the underlying mechanisms by which simvastatin or high fat diet fights against radiotherapy-induced gastrointestinal tract toxicity for male or female mice. The mice were exposed to 12 Gy total abdominal irradiation (TAI), then treated with simvastatin for male mice or fed with high fat diet for female mice. The small intestine tissues were extracted from male mice without TAI, exposed to TAI only, and exposed to TAI combined with simvastatin treatment as one cohort, and from female mice without TAI, exposed to TAI only, and exposed to TAI combined with high fat diet feeding as the other cohort.

2020-01-25 | GSE126507 | GEO

XX chromosome complement promotes, and w-3 fatty acid treatment prevents, adverse statin effects in mice

Project description:RNA-sequening of livers from male and female C57BL/6J mice fed either chow diet or chow diet + simvastatin (0.1g/kg body weight) for 4 weeks.

2024-02-01 | GSE184588 | GEO

Expression data from murine cardiac tissue

Project description:Gender dimorphism exists in the physiological response to diet and other environmental factors. Trans-hydrogenated fatty acid (TFA) intake is associated with an increase in coronary heart disease (CHD), and gender differences in the incidence of CHD are well documented. Neonatal administration of Monosodium Glutamate (MSG) causes stunted heart growth and hypoplasticity; and gender dimorphism at the growth hormone axis has been demonstrated in MSG-treated rodents. The identification of gender dimorphism in cardiac nutrigenomics may provide the basis for gender-specific medicine in the future. We used microarray analysis to examine changes in cardiac gene transcription in response to TFA and/or MSG feeding in male and female C57Bl/6J mice. Our study animals were bred from female C57Bl/6J mice fed a standard chow diet until 6 weeks of age whereupon they were placed on one of 4 different dietary regimens for a period of 3 weeks prior to mating. The four dietary regimens used in this study were: [1] Standard Chow (Control diet) with ad lib drinking water. [2] Standard Chow, with ad lib drinking water containing 0.64 g/L Monosodium Glutamate (MSG diet). [3] Trans fat diet of 20% (w/w) Partially Hydrogenated Vegetable Shortening containing 8.68% w/w Trans fatty acids(TFA diet). [4] Trans fat Diet #5C4M together with ad lib drinking water containing 0.64 g/L Monosodium Glutamate (TFA+MSG diet). Following mating, the 4 groups of dams were maintained on their respective diets throughout the gestation and nursing period. Male and female offspring used in the following experiments were weighed, weaned onto the same diets and maintained on their respective dietary regimens until they reached 32 weeks of age.Cardiac tissues (8 per diet group) were used at 32 weeks for RNA extraction and hybridization on Affymetrix microarrays.

2011-12-31 | E-GEOD-22881 | biostudies-arrayexpress

Developmental Exposure to a Perfluorooctanesulfonic acid, Perfluorooctanoic acid, Perfluorohexanesulfonic Mixture Alters the Neonatal Lung Proteome

Project description:This study aimed to assess PFAS distribution and lung proteome changes in CD-1 offspring after gestational and lactational exposure to PFOS, PFOA, PFHxS, or a PFAS mix. A secondary aim was to evaluate how maternal exposure to a high fat diet (HFD) affected the latter endpoints. Pregnant CD-1 mice received PFOA, PFOS, PFHxS (1 mg/kg), a PFAS mix (1 mg/kg each), or vehicle. Dams were fed standard diet (SD) or high fat diet (HFD), and PFAS were administered from gestation day 1 to postnatal day 20. At PND 21, lung PFAS concentration was measured using LC-MS/MS, and proteomic analysis was conducted. Results from LC-MS/MS analysis showed a significant overall difference in PFOS, PFOA, and PFHxS levels and the treatment groups with PFHxS concentration were significantly higher compared to PFOS and PFOA. Proteomic analysis determined female pups exposed to maternal HFD Mix (Mix HFD female) and PFOS (PFOS HFD female) had the most differentially expressed proteins followed by PFOS SD male, Mix SD female, and Mix SD male. Canonical pathways like EIF2 signaling, mTOR signaling, and mitochondrial dysfunction were differentially modulated. This study provides insights into PFAS distribution, the molecular mechanism, biomarkers on the neonatal lung in animal models following perinatal exposure.

2023-12-06 | MSV000093587 | MassIVE

Diet-induced Obesity Disturbs Epigenetic Responses to Ionizing Radiation in Mouse

Project description:Both exposure to ionizing radiation and obesity have been associated with various pathologies including cancer. There is a crucial need in better understanding the interactions between ionizing radiation effects (especially at low doses) and other risk factors, such as obesity. In order to evaluate radiation responses in obese animals, C3H and C57BL/6 mice fed a control low fat or a high fat (HF) diet were exposed to fractionated doses of X-rays (4×0.75 Gy). Bone marrow micronucleus assays did not suggest a modulation of radiation-induced genotoxicity by HF diet. Both HF diet and irradiation resulted in increased oxidative damage, H2AX levels and proliferation in C57BL/6 mouse liver. Using methylation-specific PCR, we observed that the promoters of p16 and Dapk genes were methylated in the livers of C57BL/6 mice fed a HF diet (irradiated and non-irradiated); Mgmt promoter was methylated in irradiated and/or HF diet-fed mice. In addition, methylation PCR arrays identified Ep300 and Socs1 (whose promoters exhibited higher methylation levels in non-irradiated HF diet-fed mice) as potential targets for further studies. We then compared microRNA regulations after radiation exposure in the livers of C57BL/6 mice fed a normal or an HF diet, using microRNA arrays. Interestingly, radiation-triggered microRNA regulations observed in normal mice were not observed in obese mice. All together, our results suggested the existence of dietary effects on radiation responses (especially epigenetic regulations) in mice, possibly in relationship with obesity-induced chronic oxidative stress. C57BL/6J mice were fed a normal or a high-fat diet and exposed to 4 x 0.75 Gy X-rays. miRNA expression was measured in the livers of 3 mice for each experimental group.

2013-11-09 | E-GEOD-47956 | biostudies-arrayexpress

Mice obesity associated circulating sEVs proteomics

Project description:This animal study was approved by the Ethics Committee at school of Chinese medicine,Hong Kong Baptist University. A total of 4 female and 4 male C57BL/6 mices were included in control diet group (BC); A total of 4 female and 4 male C57BL/6 mices were included in high fat diet group (BT).

2024-02-27 | PXD041294 | Pride

Effect of six different diets on liver gene expression

Project description:Male and female mice (Bl6/J) were fed a chow diet (control 1 and control 2) or a High fat diet (HFD) or a Choline deficient High fat diet (CD HFD) or a Western Diet (WD) or a Western Diet supplemented with glucose and fructose in drinking water (WD glucose fructose) for 15 weeks.

2022-10-31 | GSE159090 | GEO

Role of Cyp2b in diet-induced nonalcoholic steatohepatitis (NASH)

Project description:To investigate the role of hepatic CYP2B in diet-induced nonalcoholic steatohepatitis (NASH), a Cyp2b triple knockout mouse lacking Cyp2b9, Cyp2b10, and Cyp2b13 was developed using CRISPER/Cas9. Wildtype (WT) and Cyp2b-null mice were fed a normal diet (ND) or a choline-deficient, L-amino acid-defined high-fat diet (CDAHFD), containing 0.1% methionine and 62% fat for 8 weeks. RNA was extracted from the livers of female and male mice from all treatment groups and used for RNA seqencing. RNAseq data demonstrated that a lack of Cyp2b was protective in female but more harmful in male mice. Hepatic gene expression revealed a higher number of phase I-III xenobiotic metabolism and inflammatory response genes were down-regulated in CDAHFD-fed WT female and Cyp2b-null male mice.

2019-12-31 | GSE137449 | GEO

PolyA-enriched RNA-Seq of livers from male and female C57Bl/6J mice fed a control or high-fat diet and treated with estrogen receptor agonists

Project description:Metabolic dysfunction-associated fatty liver disease is the most prevalent liver disease and affects a quarter of the global population. Estrogens are associated to safeguard the liver from metabolic diseases. We fed male and female mice a control or high-fat diet for 13 weeks. Only male mice developed fatty livers. We injected a subset of male mice fed a high-fat diet with four different estrogen receptor (ER) agonists for the last three weeks of the high-fat diet, activating the nuclear ERalpha and ERbeta. Livers were collected and flash-frozen before RNA isolation, DNAse treatment, library preparation and sequencing on an Illumina NextSeq 500 instrument.

2024-02-22 | E-MTAB-11833 | biostudies-arrayexpress

Diet-induced Obesity Disturbs Epigenetic Responses to Ionizing Radiation in Mouse

2013-11-09 | GSE47956 | GEO

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