Yuuki Horii, Kanako Okadera, Shingo Miyawaki, T. Shiina, Y. Shimizu
{"title":"Suncus murinus as a novel model animal that is suitable for elucidating the mechanism of daily torpor.","authors":"Yuuki Horii, Kanako Okadera, Shingo Miyawaki, T. Shiina, Y. Shimizu","doi":"10.2220/biomedres.43.53","DOIUrl":"https://doi.org/10.2220/biomedres.43.53","url":null,"abstract":"Torpor, a state of lowered body temperature due to active reduction of the metabolic rate, has potential medical benefits. The aim of this study was to establish a novel laboratory animal that enter torpor without imposing complex conditions. When house musk shrews (Suncus murinus) were kept at an ambient temperature of 24°C, most of the animals did not enter daily torpor. However, when the ambient temperature was lowered to below 20°C, all of the shrews showed torpor in the absence of fasting and short-day photoperiod. The shrews that were exposed to a stepwise decrease in ambient temperature from 24°C to 8°C entered torpor even after returning them to a room kept at 24°C. In conclusion, this study indicates that Suncus murinus may be a suitable model animal for elucidating the mechanism of daily torpor. Elucidation of the mechanisms of torpor by using this model may be useful for inducing a state of artificial hibernation in various species including humans.","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":"43 2 1","pages":"53-57"},"PeriodicalIF":1.2,"publicationDate":"2022-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48454338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Consensus molecular subtyping improves the clinical usefulness of canonical tumor markers for colorectal cancer.","authors":"Hiroyasu Kagawa, Keiichi Hatakeyama, Akio Shiomi, Hitoshi Hino, Shoichi Manabe, Yusuke Yamaoka, Takeshi Nagashima, Keiichi Ohshima, Kenichi Urakami, Ken Yamaguchi","doi":"10.2220/biomedres.43.201","DOIUrl":"https://doi.org/10.2220/biomedres.43.201","url":null,"abstract":"<p><p>Transcriptome-based classification, such as consensus molecular subtyping, is expected to be applied to colorectal cancer (CRC). However, the relationship between molecular profiles and classical tumor markers, which are already used in clinical practice, has not been analyzed in a large cohort and remains unclear. We classified more than 1,500 Japanese patients with CRC based on consensus molecular subtyping and investigated the clinically available blood carcinoembryonic antigen (CEA) concentrations of each subgroup. To precisely distinguish CRCs, we allocated them to five subgroups, including tumors that were difficult to classify using the consensus molecular subtypes (CMSs), and extracted a heterogeneous population with somatic mutations and expression profiles that differed from those of the CMSs 1-4. For patients allocated to the CMS4 subgroup of stage III CRCs, elevated blood CEA concentrations may identify a subgroup with highly aggressive disease and contribute to improving therapeutic decisions. Furthermore, gene expression and pathway analyses of tumor and non-tumor tissues revealed that tumor immunity was \"cold\" in this subgroup with high CEA concentrations. The combination of emerging molecular profiling and classical tumor markers may have greater clinical utility than either used alone.</p>","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":"43 6","pages":"201-209"},"PeriodicalIF":1.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9591832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Neonatal isoflurane exposure disturbs granule cell migration in the rat dentate gyrus.","authors":"Yosuke Uchida, Toshikazu Hashimoto, Hitoshi Saito, Koichi Takita, Yuji Morimoto","doi":"10.2220/biomedres.43.1","DOIUrl":"https://doi.org/10.2220/biomedres.43.1","url":null,"abstract":"<p><p>It has been reported that neonatal isoflurane exposure causes behavioral abnormalities following neurodegeneration in animals and gamma-aminobutyric acid type A (GABA<sub>A</sub>) receptor activation during the synaptogenesis is considered to be one possible trigger. Additionally, the inhibitory effect of excitatory GABA<sub>A</sub> receptor signaling on the granule cell (GC) migration in the neonatal rat dentate gyrus (DG) was reported in a febrile seizure model. Then, we hypothesized that neonatal isoflurane exposure, which activates GABA<sub>A</sub> receptor, causes GC migration disturbances in the neonatal rat. Rat pups were injected with 5-bromo-2'-deoxyuridine (BrdU) and divided into five treatment groups, and double immunofluorescent staining targeting BrdU and homeobox prospero-like protein 1 (Prox1) was performed to examine the localization of BrdU/Prox1 colabeled cells, and then the GC migration was assessed. As a result, we found that the ectopic migration of GC after 2% isoflurane exposure on postnatal day 7 significantly increased after P21. The number of hilar ectopic GCs was influenced by the concentration of isoflurane and the exposure day but not by carbon dioxide exposure. Our main finding is that neonatal isoflurane anesthesia disturbs the migration of GCs in the rat DG, which may be one possible mechanism underlying the neurotoxicity following neonatal isoflurane anesthesia.</p>","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":"43 1","pages":"1-9"},"PeriodicalIF":1.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39930230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Anatomical background of the sensory function in the urethra: involvement of endocrine paraneurons and afferent nerves in divergent urogenital functions. A review.","authors":"Toshihiko Iwanaga, Hiromi Takahashi-Iwanaga","doi":"10.2220/biomedres.43.187","DOIUrl":"https://doi.org/10.2220/biomedres.43.187","url":null,"abstract":"<p><p>The urethra is ontogenetically derived from the cloaca together with distal parts of the large intestine, and serotonin cells are predominant among dispersed endocrine/paracrine cells in the epithelia of both tissues. Analysis of urethral endocrine cells thus helps us to understand the functions of gut endocrine cells and their communication with the nervous system, due to the fact that the urethra is a simple tubular organ, where only urine without microflora rapidly passes through. A certain number of urethral endocrine cells display unique, complicated shapes with dendritic processes, reminiscent of neurons. Characteristically, urethral endocrine cells-often called paraneurons-have direct contact with sensory nerves within the epithelium, unlike gut endocrine cells lacking in direct contact with nerves. These traits encourage us to focus on the urethral paraneurons as ideal endocrine/paracrine cells. A topographical complex of urethral paraneurons and afferent nerve fibers is sensitive to the passage of urine or the distention of the urethral lumen. The urethra-bladder excitatory reflex facilitates micturition via the release of serotonin from the paraneurons, ultimately ensuring complete voiding of the bladder. This reflex may also influence sexual behaviors such as ejaculation or the female orgasm. Urethral brush cells as well as paraneurons are responsible for continuous monitoring of the mucosal surface, especially for pathogens entering via the external urethral orifice.</p>","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":"43 6","pages":"187-199"},"PeriodicalIF":1.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10360797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"RIPK1 is a key factor in black carbon-induced cell death.","authors":"Xianyan Xu, Zhaojun Xu, Shiyong Zeng, Yuhui Ouyang","doi":"10.2220/biomedres.43.23","DOIUrl":"https://doi.org/10.2220/biomedres.43.23","url":null,"abstract":"<p><p>Air pollution is associated with increased morbidity and mortality and with cell death at a cellular level. However, the exact mechanism of particulate matter-induced cell death remains to be elucidated. The aim of the present in vitro study using human alveolar epithelial cells (A549) was to determine the cell death pathway(s) induced by black carbon (BC) and ozone oxidized-black carbon (O-BC). BC and O-BC induced A549 cell death and the cytotoxic effect was dose-dependent. Cell death was significantly abrogated by inhibitor of receptor protein interacting kinase 1 (RIPK1) but only mildly inhibited by apoptosis inhibitor and RIPK3. BC- and O-BC-treated cells showed RIPK1 and RIPK3 protein overexpression and high phosphorylated levels of these proteins, as well as detectable levels of caspase-8 active form. BC- and O-BC-triggered cell death was also fully rescued in A549 cells that under-expressed RIPK1 with RIPK1 siRNA. Our results indicated that BC and O-BC could induce cell death through a multitude of pathways including apoptotic and necroptotic pathways and that RIPK1 is the upstream signal protein of these cell death pathways, with an important role in the regulation of BC-induced cell death.</p>","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":"43 1","pages":"23-30"},"PeriodicalIF":1.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39626539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jing Qin, Wu-Shuang Huang, Hao-Ran DU, Chun-Qing Zhang, Peng Xie, Han Qin
{"title":"Ca<sup>2+</sup>-based neural activity recording for rapidly screening behavioral correlates of the claustrum in freely behaving mice.","authors":"Jing Qin, Wu-Shuang Huang, Hao-Ran DU, Chun-Qing Zhang, Peng Xie, Han Qin","doi":"10.2220/biomedres.43.81","DOIUrl":"https://doi.org/10.2220/biomedres.43.81","url":null,"abstract":"<p><p>The claustrum has been hypothesized to participate in high-order brain functions, but experimental studies to demonstrate these functions are currently lacking. Neural activity recording of the claustrum in freely-behaving animals allows for correlating claustral activities with specific behaviors. However, previously utilized methods for studying the claustrum make it difficult to monitor neural activity patterns of freely-behaving animals in real time. Here we applied fiber photometry to monitor Ca<sup>2+</sup> activity in the claustrum of freely-behaving mice. Using this method, we were able to achieve Ca<sup>2+</sup> activity recording in both anesthetized and freely-behaving mice. We found that the dynamics of Ca<sup>2+</sup> activity depended on anesthesia levels. As compared to the use of genetically encoded Ca<sup>2+</sup> indicators that requires a few weeks of virus-dependent expression, we used a synthetic fluorescent Ca<sup>2+</sup>-sensitive dye, Oregon green 488 BAPTA-1, that allows for rapidly screening neural activity of interest within a few hours that relates to certain behaviors. In this way, we found the correlation between Ca<sup>2+</sup> activity and specific behaviors, such as approaching an object. Our work offers an effective method for recording neural activity in the claustrum and thus for rapidly screening any behavioral relevance of the claustrum in freely-behaving mice.</p>","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":"43 3","pages":"81-89"},"PeriodicalIF":1.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39998564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Meis1 plays roles in cortical development through regulation of cellular proliferative capacity in the embryonic cerebrum.","authors":"Eriko Isogai, Kazuhiro Okumura, Megumi Saito, Yurika Tokunaga, Yuichi Wakabayashi","doi":"10.2220/biomedres.43.91","DOIUrl":"https://doi.org/10.2220/biomedres.43.91","url":null,"abstract":"<p><p>Meis1 (myeloid ecotropic insertion site 1) is known to be related to embryonic development and cancer. In this study, to analyze the function of Meis1 in neural stem cells, we crossed Meis1<sup>fl/fl</sup> (Meis1 floxed) mice with Nestin-Cre mice. The results showed that Meis1-conditional knockout mice showed cerebral cortex malformation. The mice had a significantly thinner cortex than wildtype mice. At E14.5, BrdU incorporation and Pax6-positive radial glial cells were significantly decreased in the cerebral cortex of Meis1 knockout embryos as compared with wild-type embryos, whereas Tbr2-positive intermediate progenitors and NeuN-positive differentiated neurons were not. Cell death detected by immunostaining with cleaved caspase3 antibody showed no difference in the cortex between knockout and wild-type embryos. Furthermore, knockout of Meis1 in embryo by in utero electroporation showed that cellular migration was disturbed during cortical development. Therefore, Meis1 could play important roles during cortical development through the regulation of cell proliferation and migration in the embryonic cerebral cortex.</p>","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":"43 3","pages":"91-97"},"PeriodicalIF":1.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39998565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Diet-related changes of basal lamina fenestrations in the villous epithelium of the rat small intestine: Statistical analysis on scanning electron microscopy.","authors":"Masatoshi Sato, Keisuke Morita, Rie Azumi, Yusuke Mizutani, Manabu Hayatsu, Tatsuo Ushiki, Shuji Terai","doi":"10.2220/biomedres.43.11","DOIUrl":"https://doi.org/10.2220/biomedres.43.11","url":null,"abstract":"<p><p>The epithelial basal lamina of the small intestine has numerous fenestrations for intraepithelial migration of leukocytes. We have reported dynamic changes of fenestrations in dietary conditions. To investigate this phenomenon, we performed statistical analyses using scanning electron microscopy images of the epithelial basal lamina of rat intestinal villi after removal of the villous epithelium by osmium maceration. We examined structural changes in the number and size of fenestrations in the rat jejunum and ileum under fasted and fed states for 24 h. Our findings revealed that, in the jejunum, the number of free cells migrating into the epithelium through fenestrations increased from 2 h after feeding, resulting in an increase in the fenestration size of intestinal villi; the number of free cells then tended to decrease at 6 h after feeding, and the fenestration size also gradually decreased. By contrast, the increase in the fenestration size by feeding was not statistically significant in the ileum. These findings indicate that the number of migrating cells increases in the upper part of the small intestine under dietary conditions, which may influence the absorption efficiency of nutrients including lipids, as well as the induction of nutrient-induced inflammation.</p>","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":"43 1","pages":"11-22"},"PeriodicalIF":1.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39930231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Structure and barrier functions of the perineurium and its relationship with associated sensory corpuscles: A review.","authors":"Toshihiko Iwanaga, Hiromi Takahashi-Iwanaga, Junko Nio-Kobayashi, Satomi Ebara","doi":"10.2220/biomedres.43.145","DOIUrl":"https://doi.org/10.2220/biomedres.43.145","url":null,"abstract":"<p><p>Peripheral nerves are provided with a blood-nerve barrier which prevents the invasion of harmful substances and pathogens, and also regulates metabolic and ionic homeostasis within nerve fascicles. The barrier functions are attributed to both the concentric layer of flattened cells in the perineurium and blood vessels running in the endoneurium. The perineurial cells develop continuous tight junctions as a diffusion barrier. In order to take up a predominant nutrient, glucose, the perineurium as well as endoneurial capillaries expresses GLUT1, a glucose transporter. An axon-Schwann cell complex within peripheral nerves utilizes glucose as a major energy source via the GLUT1, as does the brain. Under conditions of a reduced utilization of glucose, only the perineurial cells can transfer other nutrients, namely monocarboxylates such as ketone bodies and lactate via MCT1. Thus, MCT1 colocalizes with GLUT1 in the perineurium but not in endoneurial capillaries. To identify the cellular origins of the nerve sheath, marker proteins such as glial specific S100 protein, GLUT1, endoneurial CD34, and EMA (epithelial membrane antigen) are useful. Immunohistochemical findings for these markers are reviewed in this paper, focusing on the perineurium and endoneurium and their derivatives, Pacinian and Meissner corpuscles. Growing evidence throws light on the critical involvement of the nerve sheaths in the development, maintenance, and diseases of peripheral nerves.</p>","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":"43 5","pages":"145-159"},"PeriodicalIF":1.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33512963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Selective estrogen receptor modulators, acting as agonists of estrogen receptor α in osteoblasts, reduce the TGF-β-induced synthesis of macrophage colony-stimulating factor via inhibition of JNK signaling pathway.","authors":"Tomoyuki Hioki, Rie Matsusima-Nishiwaki, Haruhiko Tokuda, Osamu Kozawa","doi":"10.2220/biomedres.43.211","DOIUrl":"https://doi.org/10.2220/biomedres.43.211","url":null,"abstract":"<p><p>Selective estrogen receptor modulator (SERM) binds to estrogen receptors (ERs) and acts as both an agonist or an antagonist, depending on the target tissue. Raloxifene and bazedoxifene as SERMs are currently used hormone replacement medicines for postmenopausal osteoporosis. Macrophage colony-stimulating factor (M-CSF) secreted from osteoblasts promotes osteoclastogenesis. We have previously demonstrated that transforming growth factor (TGF)-β induces the synthesis of M-CSF via SMAD2/3, p38 mitogen-activated protein kinase (MAPK), p44/p42 MAPK and c-Jun N-terminal kinase (JNK) in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether SERM affects the M-CSF synthesis by TGF-β in MC3T3-E1 cells. Raloxifene and bazedoxifene significantly suppressed the synthesis of M-CSF. PPT, an ERα agonist, but not ERB041, an ERβ agonist, inhibited the release of M-CSF. MPP, an ERα antagonist, reversed the suppression by raloxifene of the M-CSF release. Raloxifene attenuated the TGF-β-induced phosphorylation of JNK but not SMAD3, p42 MAPK and p38 MAPK. Bazedoxifene and PPT also inhibited the phosphorylation of JNK. Furthermore, MPP, an ERα antagonist, reversed the suppression by both raloxifene and bazedoxifene of the phosphorylation of JNK. Our results strongly indicate that raloxifene and bazedoxifene, SERMs, suppress the TGF-β-induced synthesis of M-CSF through ERα-mediated inhibition of JNK pathway in osteoblasts.</p>","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":"43 6","pages":"211-221"},"PeriodicalIF":1.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10427662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}