{"title":"Calcium phosphate controls nucleation and growth of calcium oxalate crystal phases in kidney stones.","authors":"Uta Michibata, Mihoko Maruyama, Yutaro Tanaka, Masashi Yoshimura, Hiroshi Yoshikawa, Kazufumi Takano, Yoshihiro Furukawa, Koichi Momma, Rie Tajiri, Kazumi Taguchi, Shuzo Hamamoto, Atsushi Okada, Kenjiro Kohri, Takahiro Yasui, Shigeyoshi Usami, Masashi Imanishi, Yusuke Mori","doi":"10.2220/biomedres.45.103","DOIUrl":"https://doi.org/10.2220/biomedres.45.103","url":null,"abstract":"<p><p>Kidney stone disease is a serious disease due to the severe pain it causes, high morbidity, and high recurrence rate. Notably, calcium oxalate stones are the most common type of kidney stone. Calcium oxalate appears in two forms in kidney stones: the stable phase, monohydrate (COM), and the metastable phase, dihydrate (COD). Particularly, COM stones with concentric structures are hard and difficult to treat. However, the factor determining the growth of either COM or COD crystals in the urine, which is supersaturated for both phases, remains unclear. This study shows that calcium phosphate ingredients preferentially induce COM crystal nucleation and growth, by observing and analyzing kidney stones containing both COM and COD crystals. The forms of calcium phosphate are not limited to Randall's plaques (1-2 mm size aggregates, which contain calcium phosphate nanoparticles and proteins, and form in the renal papilla). For example, aggregates of strip-shaped calcium phosphate crystals and fields of dispersed calcium phosphate microcrystals (nano to micrometer order) also promote the growth of concentric COM structures. This suggests that patients who excrete urine with a higher quantity of calcium phosphate crystals may be more prone to forming hard and troublesome COM stones.</p>","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261429","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":"Identification of membrane proteins targeted by small-molecule compounds using nanomagnetic beads.","authors":"Yasufumi Kikuchi, Takayuki Ando, Tadashi Ashizawa, Akira Iizuka, Akari Kanematsu, Chie Maeda, Chikako Hozumi, Haruo Miyata, Kazue Yamashita, Tomoatsu Ikeya, Ken Yamaguchi, Yasuto Akiyama","doi":"10.2220/biomedres.45.179","DOIUrl":"https://doi.org/10.2220/biomedres.45.179","url":null,"abstract":"<p><p>In drug discovery research, it is important to identify target proteins of bioactive small-molecule compounds and analyse their functions. In this study, we examined whether target membrane proteins could be captured by compounds that bind to membrane proteins on the cell surface. For this purpose, we performed affinity purification using the compound-immobilized nanomagnetic beads. Affinity purification with nanomagnetic beads is known to be effective for determining the protein binding partners of small molecules. However, most previous studies have targeted proteins in the cytoplasm. As a model compound, we chose BMS-1166 (a representative small-molecule compound from Bristol Myers Squibb), a PD-1/PD-L1 immune checkpoint inhibitor that binds to PD- L1 and promotes PD-L1 dimerization. BMS-1166-immobilized beads were manufactured and incubated with extracts of cells with high PD-L1 protein expression. The bound protein was confirmed by western blotting and proteomic analysis to be PD-L1. BMS-1166-immobilized nano-magnetic beads were able to specifically bind and capture the membrane protein PD-L1. In addition, high-purity protein could be obtained from cell extracts in a single step. This is the first report of the purification of a membrane protein to high purity with nanobeads. Nanomagnetic beads with immobilized compounds are an effective tool for identifying the protein binding partners of small molecules, especially when the targets are membrane proteins.</p>","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380007","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":"Bone regeneration-enhancing effects of extremely low-frequency electromag- netic fields: Analysis using fish scales as a bone model.","authors":"Nobuo Suzuki, Makiko Kakikawa, Yuta Oda, Jingjing Kobayashi-Sun, Sotoshi Yamada, Kouhei Kuroda, Isao Kobayashi, Masato Honda, Hajime Matsubara, Yoshiaki Tabuchi, Nobuaki Shimizu, Kazuki Watanabe, Jun Hirayama, Atsuhiko Hattori","doi":"10.2220/biomedres.45.187","DOIUrl":"https://doi.org/10.2220/biomedres.45.187","url":null,"abstract":"<p><p>Electromagnetic fields (EMFs) noninvasively promote fracture healing, prevent osteoporosis, promote diaphyseal growth, enhance differentiation, and stimulate cell division. However, no good model systems for analyzing bone regeneration have been reported. In this study, we examined the in vivo regeneration of scales having osteoblasts and osteoclasts using a new magnetic field generator for exposing aquatic animals to EMFs at a sine-wave frequency of 60 Hz. Goldfish scales were put into a fish-breeding space with the developed magnetic field generator and exposed to extremely low-frequency electromagnetic fields (ELF-EMFs) of 60 Hz at an intensity of 1, 3, and 5 mT for 10 days while being regenerated the scales. After exposure, alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) activities in the goldfish scales were measured as markers of osteoblasts and osteoclasts, respectively. As a result, both ALP and TRAP activities in regenerating scales exposed to 3 mT ELF-EMFs were higher than those in regenerating scales exposed to 1 and 5 mT ELF-EMFs. Exposure of scales to 3 mT ELF-EMFs significantly enhanced the scale regeneration rate. Exposure of rat calvaria to 3 mT ELF-EMFs also increased both ALP and TRAP activities like in goldfish scales. Thus, we concluded that 3 mT ELF-EMFs contribute to the medical treatment of bone diseases.</p>","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380005","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":"Copper-induced renal toxicity controlled by period1 through modulation of Atox1 in mice.","authors":"Sarah Tominaga, Hiroki Yoshioka, Satoshi Yokota, Yosuke Tsukiboshi, Masumi Suzui, Makoto Nagai, Hirokazu Hara, Nobuhiko Miura, Tohru Maeda","doi":"10.2220/biomedres.45.143","DOIUrl":"10.2220/biomedres.45.143","url":null,"abstract":"<p><p>Copper (Cu) is known to induce oxidative stress and apoptosis in the liver, kidney, and brain. We previously demonstrated the molecular mechanism underlying the Cu-induced hepatic diurnal variation. However, the cellular molecule(s) involved in Cu-induced renal chronotoxicity remain unknown. In this study, we aimed to elucidate the molecular mechanisms underlying Cu-induced diurnal toxicity in the kidneys. We evaluated cell viability and clock gene expression levels in mouse renal cortex tubular cells (MuRTE61 cells) after Cu treatment. We also examined the Cu homeostasis- and apoptosis-related gene levels after period 1 (Per1) overexpression in MuRTE61 cells. Cu treatment decreased MuRTE61 cell viability in a dose-dependent manner. It increased the Per1 expression levels after 24 h. Notably, Per1 overexpression alleviated the Cu-induced inhibition of MuRTE61 cell viability. Moreover, Per1 overexpression downregulated the cleaved caspase-3 and reduced Cu levels by upregulating the antioxidant 1 copper chaperone (Atox1) levels. These results suggest that Cu-induced renal toxicity is associated with Per1 expression via the regulation of the copper chaperone, Atox1.</p>","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619324","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":"Effects of linalool on respiratory neuron activity in the brainstem-spinal cord preparation from newborn rats.","authors":"Yuka Shibuya, Kayo Tsuzawa, Hiroshi Onimaru, Masahiko Izumizaki","doi":"10.2220/biomedres.45.151","DOIUrl":"https://doi.org/10.2220/biomedres.45.151","url":null,"abstract":"<p><p>Linalool and linalyl acetate are major components of lavender essential oil. These substances possess many biological activities, such as anti-inflammatory activity, analgesic and anxiolytic effects, and anticonvulsant properties, and they also induce modulation of neuronal activity in the autonomic nervous system. However, there are no reports of the direct effects of linalool on respiratory activity. In the present study, we analyzed the effects of linalool and linalyl acetate on central respiratory activity in the brainstem-spinal cord preparation isolated from newborn rats. Linalool dose-dependently decreased the rate of respiratory activity. This effect was reversed by bicuculline, suggesting that linalool enhanced inhibitory synaptic connections via GABAA receptors. In addition, linalool reduced the coefficient of variation of inspiratory burst intervals and thus could work to stabilize the respiratory rhythm. Linalyl acetate did not cause inhibitory effects as observed in linalool treatment. Linalool depressed burst activity of pre-inspiratory neurons in the medullary respiratory networks and increased the amplitude of inspiratory inhibitory postsynaptic potentials of pre-inspiratory neurons. We concluded that linalool caused inhibitory effects on respiratory rhythm generation mainly through activation of presynaptic GABAA receptors of pre-inspiratory neurons.</p>","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619352","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":"Blockade of CD80/CD86-CD28 co-stimulation augments the inhibitory function of peptide antigen-specific regulatory T cells.","authors":"Yui Maehara, Kazuyoshi Takeda, Kyoko Tsuji-Yogo, Kodai Morimoto, Masaki Harada, Kyohei Kuriyama, Saori Hirota, Hideo Yagita, Ko Okumura, Koichiro Uchida","doi":"10.2220/biomedres.45.115","DOIUrl":"10.2220/biomedres.45.115","url":null,"abstract":"<p><p>Mixed lymphocyte culture under the blockade of CD80/CD86-CD28 co-stimulation induces anergic (completely hyporesponsive) T cells with immune suppressive function (inducible suppressing T cells: iTS cells). Previously, iTS cell therapy has demonstrated outstanding benefits in clinical trials for organ transplantation. Here, we examined whether peptide antigen-specific iTS cells are inducible. DO 11.10 iTS cells were obtained from splenocytes of BALB/c DO 11.10 mice by stimulation with OVA peptide and antagonistic anti-CD80/CD86 mAbs. When DO 11.10 iTS or Foxp3- DO 11.10 iTS cells were stimulated with OVA, these cells produced IL-13, but not IL-4. DO 11.10 iTS cells decreased IL-4 and increased IL-13 production from OVA-stimulated naïve DO 11.10 splenocytes. When Foxp3+ DO 11.10 iTS cells were prepared, these cells significantly inhibited the production of IL-4 and IL-13 compared with freshly isolated Foxp3+ DO 11.10 T cells. Moreover, an increase in the population expressing OX40, ICOS, and 4-1BB suggested activation of Foxp3+ DO 11.10 iTS cells. Thus, blockade of CD80/CD86-CD28 co-stimulation during peptide antigen stimulation augments the inhibitory function of Foxp3+ regulatory T cells, and does not induce anergic Foxp3- conventional T cells. Peptide-specific Foxp3+ regulatory iTS cells could be useful for the treatment of allergic and autoimmune diseases without adverse effects.</p>","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261390","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":"Indoxyl sulfate contributes to colorectal cancer cell proliferation and increased EGFR expression by activating AhR and Akt.","authors":"Yu Ichisaka, Shozo Yano, Kohji Nishimura, Toshimitsu Niwa, Hidehisa Shimizu","doi":"10.2220/biomedres.45.57","DOIUrl":"10.2220/biomedres.45.57","url":null,"abstract":"<p><p>Although patients with chronic kidney disease (CKD) have a higher risk of colorectal cancer (CRC) aggravation, the connection between these two diseases is not well understood. Recent studies have shown that both CKD and CRC aggravation are closely related to an increased abundance of indole-producing Fusobacterium nucleatum in the gut. The indole absorbed from the gut is eventually metabolized to indoxyl sulfate in the liver. Since indoxyl sulfate is involved not only in accelerating CKD progression but also in the initiation and development of its associated complications, the present study aimed to clarify whether indoxyl sulfate induces the proliferation of CRC cells. This study found that indoxyl sulfate induced the proliferation of CRC-derived HCT-116 cells by activating the aryl hydrocarbon receptor (AhR) and the proto-oncogene Akt. The AhR antagonist CH223191 and Akt inhibitor MK2206 suppressed indoxyl sulfate-induced proliferation of HCT-116 cells. We also found that indoxyl sulfate upregulated epidermal growth factor receptor (EGFR) expression, which is associated with poor prognosis of CRC, whereas CH223191 and MK2206 repressed EGFR expression. Furthermore, indoxyl sulfate increased the sensitivity of CRC cells to EGF by upregulating EGFR expression. These findings suggest that indoxyl sulfate may be an important link between CKD and CRC aggravation.</p>","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140331524","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":"Effects of inactivity and exercise intervention on brain-derived neurotrophic factor in mice: Comparison of kinetics in serum, skeletal muscle, and brain.","authors":"Azusa Miki, Masahiro Aihara, Hikaru Kawaguchi, Noboru Hirose, Hiroki Hagiwara","doi":"10.2220/biomedres.45.163","DOIUrl":"10.2220/biomedres.45.163","url":null,"abstract":"<p><p>Exercise training increases brain-derived neurotrophic factor (BDNF) expression and improves cognitive function. However, the dynamics of BDNF during inactivity and the effects of exercise intervention on BDNF levels have rarely been examined. Therefore, we aimed to examine changes in serum, skeletal muscle, and brain BDNF levels under these conditions. Mice were divided into control (Co), cast immobilization (CI), reloading (RL), and exercise (Ex) groups. Muscle atrophy was induced by cast immobilization for 2 weeks in the CI, RL, and Ex groups. After cast removal, the RL and Ex groups underwent regrounding and treadmill exercise, respectively, for 2 weeks. Serum, skeletal muscle, and brain BDNF levels showed a similar decreasing trend in the CI group, recovery in the RL group, and a further increase in the Ex group compared with those in the Co group. This indicates that BDNF levels change in parallel with the degree of activity. However, the magnitude of variation differed among the tissues in the order of serum > skeletal muscle > brain tissue. These results suggest that different mechanisms in different tissues regulate BDNF expression. BDNF could potentially act as an objective measure of the impact of both inactivity and exercise-based interventions.</p>","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619325","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":"Inhibition of skeletal muscle differentiation by calciprotein particles in human primary myoblasts.","authors":"Shohei Kohno, Eisuke Uno, Kazuto Goishi, Davood Kharaghani, Kenta Uchibe, Ryuji Terayama","doi":"10.2220/biomedres.45.173","DOIUrl":"https://doi.org/10.2220/biomedres.45.173","url":null,"abstract":"<p><p>Sarcopenia is a common complication of chronic kidney disease (CKD) and has a detrimental effect on prognosis. Previous studies have explored the role of secondary calciprotein particles (CPP2) in determining the progression of complications and poor outcomes in patients with CKD. However, no study has demonstrated that CPP2 impairs skeletal myogenesis. Our study revealed that CPP2 exposure inhibits skeletal myogenesis by suppressing myotube formation and expression of skeletal muscle-specific myosin heavy chain and actin in human primary myoblasts. Moreover, CPP2 exposure altered the expression patterns of lineage-determinative transcription factors responsible for regulating myotube differentiation marker genes. This study first demonstrated that CPP2 interferes with myoblast differentiation and myotube formation in vitro.</p>","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619353","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":"Epigenetic modification of histone acetylation in the sensorimotor cortex after intracerebral hemorrhage.","authors":"Taichi Nishio, Takahiro Inoue, Yasuyuki Takamatsu, Taiga Mishima, Hana Takamura, Kiho Soma, Yuki Kondo, Misato Okamura, Ryo Ikegami, Hiroshi Maejima","doi":"10.2220/biomedres.45.1","DOIUrl":"10.2220/biomedres.45.1","url":null,"abstract":"<p><p>Epigenetic regulation is involved in post-stroke neuroplasticity. We investigated the effects of intracerebral hemorrhage (ICH) on histone acetylation and gene expression related to neuronal plasticity in the bilateral sensorimotor cortices, which may affect post-stroke sensorimotor function. Wistar rats were randomly divided into the SHAM and ICH groups. We performed ICH surgery stereotaxically based on the microinjection of a collagenase solution in the ICH group. Foot fault and cylinder tests were performed to evaluate motor functions at 4-time points, including pre-ICH surgery. The amount of acetyl histones and the mRNA expression of neurotrophic factors crucial to neuroplasticity in the bilateral sensorimotor cortices were analyzed approximately 2 weeks after ICH surgery. Sensorimotor functions of the ICH group were inferior to those of the SHAM group during 2 weeks post-ICH. ICH increased the acetylation of histone H3 and H4 over the sham level in the ipsilateral and contralateral cortices. ICH increased the mRNA expression of IGF-1, but decreased the expression of BDNF compared with the sham level in the ipsilateral cortex. The present study suggests that histone acetylation levels are enhanced in bilateral sensorimotor cortices after ICH, presenting an altered epigenetic platform for gene expressions related to neuronal plasticity.</p>","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139701813","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}