Dietary Modification of Mouse Response to Total-Body-Irradiation

Exposure to ionizing radiation (IR) could induce deleterious effects including cancer. Diet, as one of the major factors to influence susceptibility to many diseases, plays a critical role in maintaining human heath. It is known that unbalanced diet could result in health consequences, for example, high-calorie diet could lead to obesity, which could increase the risk of diabetes, heart disease, fatty liver, and some forms of cancer. Although the impact of diet on susceptibility to IR is thought to be big, the evidence is not clear due to lack of study. In this work, effects from dietary fat on modulation of mouse responses to total-body-irradiation (TBI) were studied. The mice were fed after weaning at postnatal age of 4 weeks with a standard diet (MB-1), a very high-fat diet (HFD32), and a very low-fat diet (CE-2 Low Fat), containing of 4.4%, 32.0%, and 0.4% of crude fat, respectively. A mouse model for radiation-induced adaptive response (AR) was applied to this work. The priming low-dose TBI at a dose of 0.5 Gy from X-rays was given at postnatal age of 6 weeks, and the challenge high dose of TBI was given at postnatal age of 8 weeks. The mouse response to low dose of TBI was evaluated by the efficacy of the priming low dose to rescue the animals from bone marrow death induced by the challenge high dose in the 30-day survival test. The mouse response to high dose of TBI was evaluated by comparing the LD50 in the 30-day survival test. In addition, dietary modulation of the residual (late) genotoxic effect from TBI was also evaluated by comparing the incidence of micronucleated erythrocytes in bone marrow using micronucleus test. Results showed that for the mice fed with the MB-1, a successful AR was demonstrated. While for the mice fed with either HFD32 or CE-2 Low Fat, no AR was observed, and all the animals died within 15 days after TBI with the challenge high dose at 7.5 Gy regardless the priming low dose at 0.5 Gy. When comparing the LD50 in the 30-day survival test, the LD50 values for the animals fed with the MB-1, HFD32 diet, and CE-2 Low Fat were 7.1 Gy, 6.0 Gy, and 6.2 Gy, respectively. As to the micronucleus test, for the mice fed with MB-1, the priming low dose at 0.5 Gy could significantly reduce the incidence of micronucleated erythrocytes in bone marrow that were caused by a challenge high dose at 4.0 Gy, while for the mice fed with either HFD32 or CE-2 Low Fat no such effect was observed. These findings indicated that under an unbalanced diet, namely, either of very high fat or of very low fat, alterations in mouse responses to TBI were induced. These findings confirmed that diet played a pivotal role in the response of the animals to radiation exposure, and suggested the possibility to modulate radiosensitivity through diet intervention in humans

Involvement of activated transcriptional process in efficient gene transfection using unmodified and mannose-modified bubble lipoplexes with ultrasound exposure.

Recently, our group developed ultrasound (US)-responsive and mannose-modified gene carriers (Man-PEG(2000) bubble lipoplexes), and successfully obtained a high level of gene expression in mannose receptor-expressing cells following gene transfection using Man-PEG(2000) bubble lipoplexes and US exposure. We also reported that large amounts of plasmid DNA (pDNA) were transferred into the cytoplasm of the targeted cells in the gene transfection using this method. In the present study, we investigated the involvement of transcriptional processes on enhanced gene expression obtained by unmodified and Man-PEG(2000) bubble lipoplexes with US exposure. The transcriptional process related to activator protein-1 (AP-1) and nuclear factor-κB (NFκB) was activated by US exposure, and was founded to be involved in enhanced gene expression obtained by gene transfection using unmodified and Man-PEG(2000) bubble lipoplexes with US exposure. On the other hand, activation of AP-1 and NFκB pathways followed by US exposure was hardly involved in the inflammatory responses in the gene transfection using this method. These findings suggest that activation of AP-1 and NFκB followed by US exposure is involved in the enhanced gene expression using unmodified and Man-PEG(2000) bubble lipoplexes with US exposure, and the selection of pDNAs activated by US exposure is important in this gene transfection method

Diallyl Disulfide Mitigates DNA Damage and Spleen Tissue Effects After Irradiation

BACKGROUND Several factors found in foods are beneficial to human health and they may contribute to radiation protection. Taking food factors could be an easy way to reduce the effects of radiation after nuclear accidents, as well as secondary radiation risks after cancer radiotherapy or space missions. Here, diallyl disulfide (DADS), a component of garlic oil, was studied for its ability to mitigate radiation damage. MATERIAL AND METHODS We investigated the effects of DADS on micronucleus (MN) formation and apoptosis in HepG2 cells by use of 4-Gy X-ray irradiation. We also assessed the effects of DADS on radiation damage in vivo by evaluating MN formation in bone marrow cells in mice (BALB/c, 8-week-old females) after oral intake of DADS prior to irradiation with 4 Gy. Several tissue effects were also investigated. RESULTS The presence of DADS inhibited MN formation, whereas DADS had no influence on the radiation-induced inhibition of cell cycle progression in HepG2 cells. An increase in apoptosis in HepG2 cells was induced after irradiation, and this effect was stronger in the presence of DADS than in its absence. In mice, when DADS was administered daily for 3 days prior to irradiation, MN formation in irradiated mice was decreased. The decrease in MN formation in mice was greater with 0.5% DADS compared to 1% DADS. Moreover, an increase in spleen weight observed 3 weeks after irradiation was suppressed in mice administered DADS. CONCLUSIONS DADS is a potential radiation-protective agent that effectively mitigates DNA damage, and its effects in the spleen observed after irradiation may be related to inflammation and carcinogenesis

A novel homozygous variant of the thrombomodulin gene causes a hereditary bleeding disorder

ArticleBlood Advances. 5(19): 3830-3838 (2021)journal articl

Case of three delayed complications of radiotherapy: Bilateral vocal cord immobility, esophageal obstruction and ruptured pseudoaneurysm of carotid artery

金沢大学医薬保健研究域医学系We report the first case of three delayed complications following irradiation for laryngeal carcinoma: bilateral vocal cord immobility, obstruction of esophagus and spontaneously ruptured pseudoaneurysm of common carotid artery. Medial fixation of bilateral vocal cords and stenosis of cervical esophagus were noted at 28 years after radiotherapy. Spontaneous rupture of a pseudoaneurysm bulging into the hypopharynx and obstruction of the esophagus occurred at 35 years after irradiation. The life-threatening hemorrhage was successfully treated by microcoil embolization of the common carotid artery. The relationship between these complications and irradiation is also discussed. © 2008 Elsevier Ireland Ltd. All rights reserved

Antitumor effect of nuclear factor-κB decoy transfer by mannose-modified bubble lipoplex into macrophages in mouse malignant ascites

Patients with malignant ascites (MAs) display several symptoms, such as dyspnea, nausea, pain, and abdominal tenderness, resulting in a significant reduction in their quality of life. Tumor-associated macrophages (TAMs) play a crucial role in MA progression. Because TAMs have a tumor-promoting M2 phenotype, conversion of the M2 phenotypic function of TAMs would be promising for MA treatment. Nuclear factor-κB (NF-κB) is a master regulator of macrophage polarization. Here, we developed targeted transfer of a NF-κB decoy into TAMs by ultrasound (US)-responsive, mannose-modified liposome/NF-κB decoy complexes (Man-PEG bubble lipoplexes) in a mouse peritoneal dissemination model of Ehrlich ascites carcinoma. In addition, we investigated the effects of NF-κB decoy transfection into TAMs on MA progression and mouse survival rates. Intraperitoneal injection of Man-PEG bubble lipoplexes and US exposure transferred the NF-κB decoy into TAMs effectively. When the NF-κB decoy was delivered into TAMs by this method in the mouse peritoneal dissemination model, mRNA expression of the Th2 cytokine interleukin (IL)-10 in TAMs was decreased significantly. In contrast, mRNA levels of Th1 cytokines (IL-12, tumor necrosis factor-α, and IL-6) were increased significantly. Moreover, the expression level of vascular endothelial growth factor in ascites was suppressed significantly, and peritoneal angiogenesis showed a reduction. Furthermore, NF-κB decoy transfer into TAMs significantly decreased the ascitic volume and number of Ehrlich ascites carcinoma cells in ascites, and prolonged mouse survival. In conclusion, we transferred a NF-κB decoy efficiently by Man-PEG bubble lipoplexes with US exposure into TAMs, which may be a novel approach for MA treatment. We demonstrated that the combinatorial use of mannose-modified bubble lipoplexes with ultrasound exposure achieved the efficient delivery of NF-κB decoy oligonucleotides into tumor-associated macrophages (TAM) in a mouse peritoneal dissemination model of Ehrlich ascites carcinoma. Using this method, NF-κB decoy transfer into TAM inhibited the malignant ascites progression significantly that may be the phenotypic conversion of TAM from M2 toward M1

Maggot debridement therapy with a direct dressing can cause compression injuries in patients with chronic limb ischemia

While there are no reports regarding dressing-associated iatrogenic skin ulcer as an adverse event of maggot debridement therapy (MDT), MDT is clinically used on patients with critical limb ischaemia with dermal fragility. Herein we report causes and counter measures for a case of iatrogenic skin ulcer induced by MDT dressing