Local radiotherapy of exposed murine small bowel: Apoptosis and inflammation

Polistena, Andrea; Johnson, Louis Banka; Ohiami-Masseron, Salomé; Wittgren, Lena; Bäck, Sven; Thornberg, Charlotte; Gadaleanu, Virgil; Adawi, Diya; Jeppsson, Bengt

doi:10.1186/1471-2482-8-1

Cited by 27 publications

(21 citation statements)

References 26 publications

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“…The gastrointestinal (GI) system is particularly susceptible to radiation injury due to increased apoptosis of crypt epithelial cells, mucosal cell loss and by lymphocyte infiltration of the underlying tissue (4). In addition, cytotoxic effects of radiation exposure can also lead to defects in the intestinal epithelial barrier, which offers higher permeability to luminal bacteria and triggers immune responses (5).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, cytotoxic effects of radiation exposure can also lead to defects in the intestinal epithelial barrier, which offers higher permeability to luminal bacteria and triggers immune responses (5). Furthermore, while the severity of these histological changes tends to be dose dependent (4), there are also secondary adverse GI effects that are directly related to the radiation exposure such as bile salt malabsorption from terminal ileal damage (6, 7), malabsorption of lactose or other fermentable sugars (8), small bowel bacterial overgrowth (9, 10) and altered transit time (11). Therefore, to study the local biology and the perturbations in gut homeostasis, stool may be a valuable biofluid.…”

Section: Introductionmentioning

confidence: 99%

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An Integrated Multi-Omic Approach to Assess Radiation Injury on the Host-Microbiome Axis

Goudarzi¹,

Mak

Jacobs

et al. 2016

Radiation Research

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Medical responders to radiological and nuclear disasters currently lack sufficient high-throughput and minimally invasive biodosimetry tools to assess exposure and injury in the affected populations. For this reason, we have focused on developing robust radiation exposure biomarkers in easily accessible biofluids such as urine, serum and feces. While we have previously reported on urine and serum biomarkers, here we assessed perturbations in the fecal metabolome resulting from exposure to external X radiation in vivo. The gastrointestinal (GI) system is of particular importance in radiation biodosimetry due to its constant cell renewal and sensitivity to radiation-induced injury. While the clinical GI symptoms such as pain, bloating, nausea, vomiting and diarrhea are manifested after radiation exposure, no reliable bioindicator has been identified for radiation-induced gastrointestinal injuries. To this end, we focused on determining a fecal metabolomic signature in X-ray irradiated mice. There is overwhelming evidence that the gut microbiota play an essential role in gut homeostasis and overall health. Because the fecal metabolome is tightly correlated with the composition and diversity of the microorganism in the gut, we also performed fecal 16S rRNA sequencing analysis to determine the changes in the microbial composition postir-radiation. We used in-house bioinformatics tools to integrate the 16S rRNA sequencing and metabolomic data, and to elucidate the gut integrated ecosystem and its deviations from a stable host-microbiome state that result from irradiation. The 16S rRNA sequencing results indicated that radiation caused remarkable alterations of the microbiome in feces at the family level. Increased abundance of common members of Lactobacillaceae and Staphylococcaceae families, and decreased abundances of Lachnospiraceae, Ruminococcaceae and Clostridiaceae families were found after 5 and 12 Gy irradiation. The metabolomic data revealed statistically significant changes in the microbial-derived products such as pipecolic acid, glutaconic acid, urobilinogen and homogentisic acid. In addition, significant changes were detected in bile acids such as taurocholic acid and 12-ketodeoxycholic acid. These changes may be associated with the observed shifts in the abundance of intestinal microbes, such as R. gnavus, which can transform bile acids.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

An Integrated Multi-Omic Approach to Assess Radiation Injury on the Host-Microbiome Axis

Goudarzi¹,

Mak

Jacobs

et al. 2016

Radiation Research

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“…Previous investigators have focused on peri-operative events as important etiologic factors [4–6]. Growth failure during early infancy has been implicated in impaired development of executive function and worse school performance in children without congenital heart defects (CHD) [7–9]. In other “at risk” populations such as extreme prematurity, catch-up growth in weight and head circumference from birth to hospital discharge has been associated with better neurocognitive outcome at 5 years (10).…”

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confidence: 99%

Association of Impaired Linear Growth and Worse Neurodevelopmental Outcome in Infants with Single Ventricle Physiology: A Report from the Pediatric Heart Network Infant Single Ventricle Trial

Ravishankar

Zak

Williams

et al. 2013

The Journal of Pediatrics

123

109

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Objectives To describe neurodevelopmental outcomes in infants with single ventricle (SV) physiology and determine factors associated with worse outcomes. Study design Neurodevelopmental outcomes for infants with SV enrolled in a multicenter drug trial were assessed at 14 months of age using the Bayley Scales of Infant Development-II. Multivariable regression analysis was used to identify factors associated with worse outcomes. Results Neurodevelopmental testing was performed at 14±1 months in 170/185 subjects in the trial. Hypoplastic left heart syndrome was present in 59% and 75% had undergone the Norwood operation. Mean psychomotor (PDI) and mental developmental indices (MDI) were 80±18 and 96±14 respectively (normal 100±15, P<0.001 for each). Group-based trajectory analysis provided a two-group model (high” and “low”) for height z-score trajectory and brain type natriuretic peptide (BNP) trajectory. The predicted PDI scores were 15 points higher in the “high” height z-score trajectory compared with the “low” cluster (P<.001). A higher number of serious adverse events during the trial was associated with lower PDI scores (P=.02). The predicted MDI scores were 13–17 points lower in “low height trajectory- high BNP trajectory” group compared with the other three groups (P<.001). MDI scores were also lower in subjects who required extracorporeal membrane oxygenation during the neonatal hospitalization (P=.01) or supplemental oxygen at discharge (P=.01). Conclusions Neurodevelopmental outcome at 14 months of age is impaired in infants with SV physiology. Low height trajectory and high BNP trajectory were associated with worse neurodevelopmental outcomes. Efforts to improve nutritional status alone may not improve neurodevelopmental outcomes.

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“…TGFβ participates in the remodelling of the ECM, but has many other functions, such as suppression of the immune system and regulation of cell growth. It was also shown to act both as an inhibitor of tumour growth and as a promoter of tumour progression (37,38).…”

Section: Discussionmentioning

confidence: 99%

MMP7 Modulation by Short- and Long-term Radiotherapy in Patients with Rectal Cancer

Stene

Polistena

Gaber

et al. 2018

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Local radiotherapy of exposed murine small bowel: Apoptosis and inflammation

Cited by 27 publications

References 26 publications

An Integrated Multi-Omic Approach to Assess Radiation Injury on the Host-Microbiome Axis

An Integrated Multi-Omic Approach to Assess Radiation Injury on the Host-Microbiome Axis

Association of Impaired Linear Growth and Worse Neurodevelopmental Outcome in Infants with Single Ventricle Physiology: A Report from the Pediatric Heart Network Infant Single Ventricle Trial

MMP7 Modulation by Short- and Long-term Radiotherapy in Patients with Rectal Cancer

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