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  1. Article ; Online: The serotonergic neurons derived from rhombomere 2 are localized in the median raphe and project to the dorsal pallium in zebrafish.

    Shibayama, Kotaro / Nakajo, Haruna / Tanimoto, Yuki / Kakinuma, Hisaya / Shiraki, Toshiyuki / Tsuboi, Takashi / Okamoto, Hitoshi

    Neuroscience research

    2024  

    Abstract: The serotonergic neurons in the raphe nucleus are implicated in various cognitive functions such as learning and emotion. In vertebrates, the raphe nucleus is divided into the dorsal raphe and the median raphe. In contrast to the abundance of knowledge ... ...

    Abstract The serotonergic neurons in the raphe nucleus are implicated in various cognitive functions such as learning and emotion. In vertebrates, the raphe nucleus is divided into the dorsal raphe and the median raphe. In contrast to the abundance of knowledge on the functions of the dorsal raphe, the roles of the serotonergic neurons in the median raphe are relatively unknown. The studies using zebrafish revealed that the median raphe serotonergic neurons receive input from the two distinct pathways from the habenula and the IPN. The use of zebrafish may reveal the function of the Hb-IPN-median raphe pathway. To clarify the functions of the median raphe serotonergic neurons, it is necessary to distinguish them from those in the dorsal raphe. Most median raphe serotonergic neurons originate from rhombomere 2 in mice, and we generated the transgenic zebrafish which can label the serotonergic neurons derived from rhombomere 2. In this study, we found the serotonergic neurons derived from rhombomere 2 are localized in the median raphe and project axons to the rostral dorsal pallium in zebrafish. This study suggests that this transgenic system has the potential to specifically reveal the function and information processing of the Hb-IPN-raphe-telencephalon circuit in learning.
    Language English
    Publishing date 2024-03-05
    Publishing country Ireland
    Document type Journal Article
    ZDB-ID 605842-5
    ISSN 1872-8111 ; 0168-0102 ; 0921-8696
    ISSN (online) 1872-8111
    ISSN 0168-0102 ; 0921-8696
    DOI 10.1016/j.neures.2024.03.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Elevated blood pressure in high-fat diet-exposed low birthweight rat offspring is most likely caused by elevated glucocorticoid levels due to abnormal pituitary negative feedback.

    Nemoto, Takahiro / Nakakura, Takashi / Kakinuma, Yoshihiko

    PloS one

    2020  Volume 15, Issue 8, Page(s) e0238223

    Abstract: Being delivered as a low birthweight (LBW) infant is a risk factor for elevated blood pressure and future problems with cardiovascular and cerebellar diseases. Although premature babies are reported to have low numbers of nephrons, some unclear questions ...

    Abstract Being delivered as a low birthweight (LBW) infant is a risk factor for elevated blood pressure and future problems with cardiovascular and cerebellar diseases. Although premature babies are reported to have low numbers of nephrons, some unclear questions remain about the mechanisms underlying elevated blood pressure in full-term LBW infants. We previously reported that glucocorticoids increased miR-449a expression, and increased miR-449a expression suppressed Crhr1 expression and caused negative glucocorticoid feedback. Therefore, we conducted this study to clarify the involvement of pituitary miR-449a in the increase in blood pressure caused by higher glucocorticoids in LBW rats. We generated a fetal low-carbohydrate and calorie-restricted model rat (60% of standard chow), and some individuals showed postnatal growth failure caused by growth hormone receptor expression. Using this model, we examined how a high-fat diet (lard-based 45kcal% fat)-induced mismatch between prenatal and postnatal environments could elevate blood pressure after growth. Although LBW rats fed standard chow had slightly higher blood pressure than control rats, their blood pressure was significantly higher than controls when exposed to a high-fat diet. Observation of glomeruli subjected to periodic acid methenamine silver (PAM) staining showed no difference in number or size. Aortic and cardiac angiotensin II receptor expression was altered with compensatory responses. Blood aldosterone levels were not different between control and LBW rats, but blood corticosterone levels were significantly higher in the latter with high-fat diet exposure. Administration of metyrapone, a steroid synthesis inhibitor, reduced blood pressure to levels comparable to controls. We showed that high-fat diet exposure causes impairment of the pituitary glucocorticoid negative feedback via miR-449a. These results clarify that LBW rats have increased blood pressure due to high glucocorticoid levels when they are exposed to a high-fat diet. These findings suggest a new therapeutic target for hypertension of LBW individuals.
    MeSH term(s) Animals ; Birth Weight/drug effects ; Birth Weight/physiology ; Blood Pressure/drug effects ; Blood Pressure/physiology ; Corticosterone/blood ; Diet, High-Fat/adverse effects ; Feedback, Physiological/physiology ; Female ; Glucocorticoids/blood ; Humans ; Hypertension/blood ; Hypertension/physiopathology ; Infant, Low Birth Weight/blood ; Infant, Low Birth Weight/physiology ; Infant, Newborn ; Male ; Metyrapone/therapeutic use ; Pituitary Diseases/blood ; Pituitary Diseases/drug therapy ; Pituitary Diseases/physiopathology ; Pituitary Gland/drug effects ; Pituitary Gland/physiology ; Pregnancy ; Prenatal Exposure Delayed Effects/blood ; Prenatal Exposure Delayed Effects/physiopathology ; Rats ; Rats, Wistar
    Chemical Substances Glucocorticoids ; Corticosterone (W980KJ009P) ; Metyrapone (ZS9KD92H6V)
    Language English
    Publishing date 2020-08-27
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0238223
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Cor triatriatum sinister with dextrocardia in association with ostium secundum atrial septal defect, subpulmonary ventricular septal defect and bicuspid pulmonary valve in a pig.

    Shiga, Takanori / Kamiya, Yumiko / Ohkubo, Mitsuharu / Miyamoto, Takashi / Kakinuma, Yoko / Kayanuma, Hideki / Aoki, Takuma / Fujii, Yoko / Aihara, Naoyuki / Kamiie, Junichi

    Journal of comparative pathology

    2023  Volume 206, Page(s) 13–16

    Abstract: Necropsy of a 52-day-old Camborough pig revealed numerous cardiac malformations. The positional relationship of the atria, ventricles and great vessels was a mirror image type (I, L and L): inverted arrangement of the atria, with a left-sided right ... ...

    Abstract Necropsy of a 52-day-old Camborough pig revealed numerous cardiac malformations. The positional relationship of the atria, ventricles and great vessels was a mirror image type (I, L and L): inverted arrangement of the atria, with a left-sided right atrium and right-sided left atrium (situs inversus); inverted arrangement of the ventricles, with a left-sided morphological right ventricle and right-sided morphological left ventricle (L-loop); and aortic valve to the front left relative to the pulmonary valve (L-malposed). The major malformations included an ostium secundum atrial septal defect, cor triatriatum sinister (CTS), a subpulmonary ventricular septal defect and a bicuspid pulmonary valve. Histological examination revealed myocyte hypertrophy, focal myocardial necrosis and calcification in the left morphological right ventricle of the heart. To the best of our knowledge, this is the first report of CTS in pigs. Although the individual malformations found in the present case are not unique, an unusual combination of these cardiac malformations has not been described in animals.
    MeSH term(s) Animals ; Swine ; Cor Triatriatum/complications ; Cor Triatriatum/diagnosis ; Cor Triatriatum/veterinary ; Pulmonary Valve ; Heart Defects, Congenital/veterinary ; Heart Septal Defects, Atrial/complications ; Heart Septal Defects, Atrial/diagnosis ; Heart Septal Defects, Atrial/veterinary ; Heart Septal Defects, Ventricular/complications ; Heart Septal Defects, Ventricular/diagnosis ; Heart Septal Defects, Ventricular/veterinary ; Dextrocardia/complications ; Dextrocardia/veterinary ; Swine Diseases
    Language English
    Publishing date 2023-09-22
    Publishing country England
    Document type Journal Article
    ZDB-ID 390920-7
    ISSN 1532-3129 ; 0021-9975
    ISSN (online) 1532-3129
    ISSN 0021-9975
    DOI 10.1016/j.jcpa.2023.08.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Elevated blood pressure in high-fat diet-exposed low birthweight rat offspring is most likely caused by elevated glucocorticoid levels due to abnormal pituitary negative feedback.

    Takahiro Nemoto / Takashi Nakakura / Yoshihiko Kakinuma

    PLoS ONE, Vol 15, Iss 8, p e

    2020  Volume 0238223

    Abstract: Being delivered as a low birthweight (LBW) infant is a risk factor for elevated blood pressure and future problems with cardiovascular and cerebellar diseases. Although premature babies are reported to have low numbers of nephrons, some unclear questions ...

    Abstract Being delivered as a low birthweight (LBW) infant is a risk factor for elevated blood pressure and future problems with cardiovascular and cerebellar diseases. Although premature babies are reported to have low numbers of nephrons, some unclear questions remain about the mechanisms underlying elevated blood pressure in full-term LBW infants. We previously reported that glucocorticoids increased miR-449a expression, and increased miR-449a expression suppressed Crhr1 expression and caused negative glucocorticoid feedback. Therefore, we conducted this study to clarify the involvement of pituitary miR-449a in the increase in blood pressure caused by higher glucocorticoids in LBW rats. We generated a fetal low-carbohydrate and calorie-restricted model rat (60% of standard chow), and some individuals showed postnatal growth failure caused by growth hormone receptor expression. Using this model, we examined how a high-fat diet (lard-based 45kcal% fat)-induced mismatch between prenatal and postnatal environments could elevate blood pressure after growth. Although LBW rats fed standard chow had slightly higher blood pressure than control rats, their blood pressure was significantly higher than controls when exposed to a high-fat diet. Observation of glomeruli subjected to periodic acid methenamine silver (PAM) staining showed no difference in number or size. Aortic and cardiac angiotensin II receptor expression was altered with compensatory responses. Blood aldosterone levels were not different between control and LBW rats, but blood corticosterone levels were significantly higher in the latter with high-fat diet exposure. Administration of metyrapone, a steroid synthesis inhibitor, reduced blood pressure to levels comparable to controls. We showed that high-fat diet exposure causes impairment of the pituitary glucocorticoid negative feedback via miR-449a. These results clarify that LBW rats have increased blood pressure due to high glucocorticoid levels when they are exposed to a high-fat diet. These findings suggest a ...
    Keywords Medicine ; R ; Science ; Q
    Subject code 610 ; 630
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Development and characterization of a unique anti-IgE mouse monoclonal antibody cross-reactive between human and canine IgE.

    Kumagai, Akiko / Nara, Takuya / Uematsu, Mizuho / Kakinuma, Yoko / Saito, Takashi / Masuda, Kenichi

    Immunity, inflammation and disease

    2021  Volume 9, Issue 4, Page(s) 1740–1748

    Abstract: Background: The efficacy assessment of human anti-IgE monoclonal antibodies (mAbs) in animal models before clinical trials is hampered due to the lack of cross-reactivity of anti-IgE mAbs between species.: Objective: We developed CRE-DR (an anti-dog ... ...

    Abstract Background: The efficacy assessment of human anti-IgE monoclonal antibodies (mAbs) in animal models before clinical trials is hampered due to the lack of cross-reactivity of anti-IgE mAbs between species.
    Objective: We developed CRE-DR (an anti-dog IgE monoclonal antibody), an anti-IgE mouse mAb that recognizes canine and human IgE, and then examined its IgE specificity and cross-reactivity between three animal and human species.
    Methods: After mouse immunization with a synthetic peptide derived from canine IgE (
    Results: CRE-DR is a monoclonal mouse IgG1κ specific for dog IgE, and the ELISA values in atopic dog sera were inhibited by dog IgE, but not dog IgG. The binding of CRE-DR to human IgE was relatively maintained, but not to rodent IgEs, which results were confirmed with the BSA-conjugated IgE peptides of the various species. The CRE-DR reactivity was supported by the comparison of amino acid sequence of CRE-DR epitope, DWIEGETYYC, in dog IgE; one, two, and three amino acids were substituted in the human, rat, and mouse IgE epitopes, respectively.
    Conclusions and clinical relevance: CRE-DR is a mAb cross-reactive to dog and human IgEs, which can allow the use of a dog model of allergy to test the efficacy of a CRE-DR-derived anti-IgE therapeutic mAb before human clinical trials.
    MeSH term(s) Animals ; Antibodies, Anti-Idiotypic ; Antibodies, Monoclonal ; Antibody Specificity ; Cross Reactions ; Dogs ; Humans ; Immunoglobulin E ; Mice ; Rats
    Chemical Substances Antibodies, Anti-Idiotypic ; Antibodies, Monoclonal ; anti-IgE antibodies ; Immunoglobulin E (37341-29-0)
    Language English
    Publishing date 2021-09-17
    Publishing country England
    Document type Journal Article
    ISSN 2050-4527
    ISSN (online) 2050-4527
    DOI 10.1002/iid3.531
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  6. Article ; Online: Groin and anterolateral thigh flaps for hemiglossectomy reconstruction: A comparison based on Japanese speech intelligibility.

    Watarai, Aya / Yasunaga, Yoshichika / Nakao, Junichi / Mori, Hiroaki / Araki, Jun / Ishii, Yoshitaka / Yonezawa, Minami / Kakinuma, Shota / Mukaigawa, Takashi / Kadomatsu, Koichi

    Auris, nasus, larynx

    2022  Volume 50, Issue 1, Page(s) 110–118

    Abstract: Objective: The differences in speech function between groin flap reconstruction and anterolateral thigh (ALT) flap reconstruction after hemiglossectomy have not been clarified to date. This study aimed to compare Japanese speech intelligibility after ... ...

    Abstract Objective: The differences in speech function between groin flap reconstruction and anterolateral thigh (ALT) flap reconstruction after hemiglossectomy have not been clarified to date. This study aimed to compare Japanese speech intelligibility after hemiglossectomy reconstruction using groin and ALT flaps of similar thickness.
    Methods: Data of patients who underwent hemiglossectomy reconstruction with groin or ALT flaps between April 2010 and March 2020 were collected from the medical chart database. The ALT flap was the first choice for hemiglossectomy reconstruction, and a groin flap was used when the ALT flap was >10 mm. Cases in which speech intelligibility assessments based on Hirose's 10-point scoring system, the TKR speech test, and the Japanese speech intelligibility test for 100 monosyllables were performed after 6 months postoperatively were extracted. The per-patient scores for each assessment were initially compared between the two flap groups. Then, the results of the Japanese speech intelligibility test for 100 monosyllables were reanalyzed on a syllable-by-syllable basis.
    Results: Among the 44 hemiglossectomy patients who underwent free-flap reconstruction during the study period, 14 (seven each in the groin flap and ALT flap groups) underwent all three conventional speech intelligibility assessments after 6 months postoperatively. The two groups showed no significant difference in postoperative speech intelligibility in any of the three patient assessment methods. However, in intergroup comparisons based on per-syllable accuracy for each of the 100 monosyllables, the groin flap group showed 19 syllables with a significantly higher accuracy, whereas the ALT flap group showed one such syllable. In particular, five out of the six alveolar consonants (/t/ and /d/) were more accurately articulated in the groin flap group. Per-syllable accuracy was significantly higher in the groin flap group (74.6% vs. 66.7%; 95% confidence interval: 4.6-11.1, p < 0.001).
    Conclusion: In patients undergoing hemiglossectomy reconstruction, our new analysis method, which compared intelligibility by syllables, showed that the groin flap yielded higher speech intelligibility than the ALT flap. This difference was evident at all four articulation points involving the tongue, whereas there was no significant difference at the two articulation points without tongue involvement.
    MeSH term(s) Humans ; Speech Intelligibility ; Thigh/surgery ; Groin ; East Asian People ; Tongue Neoplasms/surgery ; Free Tissue Flaps ; Deglutition
    Language English
    Publishing date 2022-05-19
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 604552-2
    ISSN 1879-1476 ; 0385-8146
    ISSN (online) 1879-1476
    ISSN 0385-8146
    DOI 10.1016/j.anl.2022.05.001
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  7. Article: Dog-specific hemorrhagic changes induced by liposomal formulations, in the liver and the gallbladder.

    Makita-Suzuki, Keiko / Kakinuma, Chihaya / Inomata, Akira / Shimada, Yasuhiro / Hara, Takefumi / Yao, Takashi

    Journal of toxicologic pathology

    2019  Volume 33, Issue 1, Page(s) 1–9

    Abstract: Although several liposomal drugs, including liposomal doxorubicin, have been approved, the etiology of the pathological responses caused by their physicochemical properties remains unknown. Herein, we investigated the pathological changes in the liver ... ...

    Abstract Although several liposomal drugs, including liposomal doxorubicin, have been approved, the etiology of the pathological responses caused by their physicochemical properties remains unknown. Herein, we investigated the pathological changes in the liver and the gallbladder of dogs following a single injection of liposomal doxorubicin (1 or 2.5 mg/kg) or an empty liposomal formulation (i.e., liposomal formulation without doxorubicin, ca. 21 mg/kg as lipid content). Injection of liposomal doxorubicin or the empty liposomal formulation induced hemorrhagic changes in the liver and the gallbladder. These changes were accompanied by minimal cellular infiltration with no obvious changes in the blood vessels. As there were no differences in the incidence and severity of hemorrhage between the groups administered comparable amounts of total lipid, the physicochemical properties of the liposomal formulation rather than an active pharmacological ingredient, doxorubicin, were associated with the hemorrhagic changes. Furthermore, decreased cytoplasmic granules with low electron density in mast cells beneath the endothelium of the hepatic vein were observed in the liver of dogs treated with liposomal doxorubicin or empty liposomal formulation. Injection of compound 48/80, a histamine releaser induced comparable hemorrhage in dogs, implying that hemorrhage caused by injection of liposomal doxorubicin or the empty liposomal formulation could be attributed to the histamine released from mast cells. The absence of similar hemorrhagic lesions in other species commonly used in toxicology studies (i.e., rats and monkeys), as well as humans, is due to the lack of mast cells beneath the endothelium of the hepatic vein in these species.
    Language English
    Publishing date 2019-09-12
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 2128461-1
    ISSN 1881-915X ; 0914-9198
    ISSN (online) 1881-915X
    ISSN 0914-9198
    DOI 10.1293/tox.2019-0029
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  8. Article: Establishment of a patient-derived xenograft mouse model of pleomorphic leiomyosarcoma.

    Shimada, Yasuhiro / Naito, Tomoharu / Hayashi, Takuo / Saito, Tsuyoshi / Suehara, Yoshiyuki / Kakinuma, Chihaya / Nozaki, Yuji / Takagi, Hisayoshi / Yao, Takashi

    Journal of toxicologic pathology

    2020  Volume 34, Issue 1, Page(s) 89–93

    Abstract: Soft tissue sarcomas are difficult to treat using chemotherapy owing to a current deficiency in candidate drugs for specific targets. Screening candidate compounds and analyzing therapeutic targets in sarcomas is insufficient, given the lack of an ... ...

    Abstract Soft tissue sarcomas are difficult to treat using chemotherapy owing to a current deficiency in candidate drugs for specific targets. Screening candidate compounds and analyzing therapeutic targets in sarcomas is insufficient, given the lack of an appropriate human sarcoma animal model to accurately evaluate their efficacy, as well as the lack of an adequate technical protocol for efficient transplantation and engraftment of sarcoma specimens in patient-derived xenograft (PDX) models. Accordingly, in this study, we sought to identify the optimal type of sarcoma and develop a protocol for generating a PDX model. We characterized a PDX mouse model using histopathological and immunohistochemical analyses to determine whether it would show pathological characteristics similar to those of human sarcomas. We achieved engraftment of one of the 10 transplanted sarcoma specimens, the xenografted tumor of which exhibited massive proliferation. Histologically, the engrafted sarcoma foci resembled a primary tumor of pleomorphic leiomyosarcoma and maintained their histological structure in all passages. Moreover, immunohistochemical analysis revealed the expression of specific markers of differentiation to smooth muscle, which is consistent with the features of leiomyosarcoma. We thus demonstrated that our pleomorphic leiomyosarcoma PDX mouse model mimics at least one aspect of human sarcomas, and we believe that this model will facilitate the development of novel therapies for sarcomas.
    Language English
    Publishing date 2020-12-12
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 2128461-1
    ISSN 1881-915X ; 0914-9198
    ISSN (online) 1881-915X
    ISSN 0914-9198
    DOI 10.1293/tox.2020-0061
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  9. Article ; Online: Discovery of Novel Pyrazolylpyridine Derivatives for 20-Hydroxyeicosatetraenoic Acid Synthase Inhibitors with Selective CYP4A11/4F2 Inhibition.

    Kawamura, Madoka / Kobashi, Yohei / Tanaka, Hiroaki / Bohno-Mikami, Ayako / Hamada, Makoto / Ito, Yuji / Hirata, Takashi / Ohara, Hiroki / Kojima, Naoki / Koretsune, Hiroko / Gunji, Emi / Fukunaga, Takuya / Inatani, Shoko / Hasegawa, Yoshitaka / Suzuki, Akinori / Takahashi, Teisuke / Kakinuma, Hiroyuki

    Journal of medicinal chemistry

    2022  Volume 65, Issue 21, Page(s) 14599–14613

    Abstract: 20-Hydroxyeicosatetraenoic acid (20-HETE) is one of the major oxidized arachidonic acid (AA) metabolites produced by cytochrome P450 (CYP) 4A11 and CYP4F2 isozymes in the human liver and kidney. Numerous studies have suggested the involvement of 20-HETE ... ...

    Abstract 20-Hydroxyeicosatetraenoic acid (20-HETE) is one of the major oxidized arachidonic acid (AA) metabolites produced by cytochrome P450 (CYP) 4A11 and CYP4F2 isozymes in the human liver and kidney. Numerous studies have suggested the involvement of 20-HETE in the pathogenesis of renal diseases, and suppression of 20-HETE production by inhibition of CYP4A11 and CYP4F2 may be an attractive therapeutic strategy for renal diseases. At first, we identified methylthiazole derivative
    MeSH term(s) Humans ; Animals ; Rats ; Rats, Sprague-Dawley ; Hydroxyeicosatetraenoic Acids/metabolism ; Cytochrome P-450 Enzyme System/metabolism ; Cytochrome P-450 CYP4A
    Chemical Substances 20-hydroxy-5,8,11,14-eicosatetraenoic acid (79551-86-3) ; Carbon-11 ; Hydroxyeicosatetraenoic Acids ; Cytochrome P-450 Enzyme System (9035-51-2) ; CYP4A11 protein, human (EC 1.14.15.3) ; Cytochrome P-450 CYP4A (EC 1.14.15.3)
    Language English
    Publishing date 2022-11-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/acs.jmedchem.2c01089
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  10. Article ; Online: An Enriched Environment Alters DNA Repair and Inflammatory Responses After Radiation Exposure.

    Sakama, Sae / Kurusu, Keisuke / Morita, Mayu / Oizumi, Takashi / Masugata, Shinya / Oka, Shohei / Yokomizo, Shinya / Nishimura, Mayumi / Morioka, Takamitsu / Kakinuma, Shizuko / Shimada, Yoshiya / Nakamura, Asako J

    Frontiers in immunology

    2021  Volume 12, Page(s) 760322

    Abstract: After the Fukushima Daiichi Nuclear Power Plant accident, there is growing concern about radiation-induced carcinogenesis. In addition, living in a long-term shelter or temporary housing due to disasters might cause unpleasant stress, which adversely ... ...

    Abstract After the Fukushima Daiichi Nuclear Power Plant accident, there is growing concern about radiation-induced carcinogenesis. In addition, living in a long-term shelter or temporary housing due to disasters might cause unpleasant stress, which adversely affects physical and mental health. It's been experimentally demonstrated that "eustress", which is rich and comfortable, has beneficial effects for health using mouse models. In a previous study, mice raised in the enriched environment (EE) has shown effects such as suppression of tumor growth and enhancement of drug sensitivity during cancer treatment. However, it's not yet been evaluated whether EE affects radiation-induced carcinogenesis. Therefore, to evaluate whether EE suppresses a radiation-induced carcinogenesis after radiation exposure, in this study, we assessed the serum leptin levels, radiation-induced DNA damage response and inflammatory response using the mouse model. In brief, serum and tissues were collected and analyzed over time in irradiated mice after manipulating the raising environment during the juvenile or adult stage. To assess the radiation-induced DNA damage response, we performed immunostaining for phosphorylated H2AX which is a marker of DNA double-strand break. Focusing on the polarization of macrophages in the inflammatory reaction that has an important role in carcinogenesis, we performed analysis using tissue immunofluorescence staining and RT-qPCR. Our data confirmed that EE breeding before radiation exposure improved the responsiveness to radiation-induced DNA damage and basal immunity, further suppressing the chronic inflammatory response, and that might lead to a reduction of the risk of radiation-induced carcinogenesis.
    MeSH term(s) Animals ; Arginase/genetics ; DNA Damage ; DNA Repair ; Environment ; Gene Expression Regulation/radiation effects ; Inflammation/blood ; Inflammation/genetics ; Inflammation/immunology ; Leptin/blood ; Macrophages/immunology ; Macrophages/radiation effects ; Male ; Mice ; Radiation Injuries, Experimental/blood ; Radiation Injuries, Experimental/genetics ; Radiation Injuries, Experimental/immunology ; Tumor Necrosis Factor-alpha/genetics ; X-Rays/adverse effects
    Chemical Substances Leptin ; Tnf protein, mouse ; Tumor Necrosis Factor-alpha ; Arg1 protein, mouse (EC 3.5.3.1) ; Arginase (EC 3.5.3.1)
    Language English
    Publishing date 2021-10-22
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2021.760322
    Database MEDical Literature Analysis and Retrieval System OnLINE

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