المؤلفون: Hiroaki Inoue, Yuji Arai, S. Tsuchida, Yuta Fujii, Yoichiro Kamada, Toshiharu Shirai, Kazuya Ikoma, Shogo Toyama, Osam Mazda, Ryu Terauchi, Tsunao Kishida, Shuji Nakagawa, Kenta Kaihara, S. Shimomura, Yasuo Mikami

المصدر: International Journal of Molecular Sciences
Volume 20
Issue 20
International Journal of Molecular Sciences, Vol 20, Iss 20, p 5100 (2019)

مصطلحات موضوعية: Cartilage, Articular, rheumatoid arthritis, 0301 basic medicine, Osteoporosis, Arthritis, connexin 43, Arthritis, Rheumatoid, lcsh:Chemistry, 0302 clinical medicine, Treadmill running, Cathepsin K, Treadmill, lcsh:QH301-705.5, Spectroscopy, exercise therapy, exercise, Synovial Membrane, General Medicine, Computer Science Applications, Rheumatoid arthritis, Cytokines, Inflammation Mediators, musculoskeletal diseases, medicine.medical_specialty, collagen-induced arthritis, Article, Catalysis, Inorganic Chemistry, 03 medical and health sciences, Pharmacotherapy, Physical Conditioning, Animal, Internal medicine, medicine, Animals, treadmill running, articular cartilage, Bone Resorption, Physical and Theoretical Chemistry, Molecular Biology, 030203 arthritis & rheumatology, Tumor Necrosis Factor-alpha, business.industry, Body Weight, Organic Chemistry, medicine.disease, Arthritis, Experimental, osteoporosis, Rats, Disease Models, Animal, 030104 developmental biology, Endocrinology, lcsh:Biology (General), lcsh:QD1-999, pro-inflammatory cytokine, autoimmune disorder, business, Biomarkers, Immunostaining

الوصف: Exercise therapy inhibits joint destruction by suppressing pro-inflammatory cytokines. The efficacy of pharmacotherapy for rheumatoid arthritis differs depending on the phase of the disease, but that of exercise therapy for each phase is unknown. We assessed the differences in the efficacy of treadmill running on rheumatoid arthritis at various phases, using rat rheumatoid arthritis models. Rats with collagen-induced arthritis were used as rheumatoid arthritis models, and the phase after immunization was divided as pre-arthritis and established phases. Histologically, the groups with forced treadmill running in the established phase had significantly inhibited joint destruction compared with the other groups. The group with forced treadmill running in only the established phase had significantly better bone morphometry and reduced expression of connexin 43 and tumor necrosis factor &alpha
in the synovial membranes compared with the no treadmill group. Furthermore, few cells were positive for cathepsin K immunostaining in the groups with forced treadmill running in the established phase. Our results suggest that the efficacy of exercise therapy may differ depending on rheumatoid arthritis disease activity. Active exercise during phases of decreased disease activity may effectively inhibit arthritis and joint destruction.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::502d77c185a008be432bd59e39fea747Test
https://doi.org/10.3390/ijms20205100Test

المؤلفون: Yuta Fujii, Toshikazu Kubo, S. Tsuchida, Osam Mazda, Shuji Nakagawa, Toshiharu Shirai, Kazuya Ikoma, Yuji Arai, Hiroaki Inoue, Tsunao Kishida, S. Shimomura, S. Ichimaru

المصدر: International Journal of Molecular Sciences
International Journal of Molecular Sciences, Vol 19, Iss 6, p 1653 (2018)
Volume 19
Issue 6

مصطلحات موضوعية: 0301 basic medicine, Cartilage, Articular, Male, rheumatoid arthritis, Osteoporosis, Arthritis, Osteoclasts, Running, lcsh:Chemistry, Arthritis, Rheumatoid, Treadmill, skin and connective tissue diseases, lcsh:QH301-705.5, Spectroscopy, Synovitis, exercise, General Medicine, musculoskeletal system, Computer Science Applications, medicine.anatomical_structure, Rheumatoid arthritis, musculoskeletal diseases, medicine.medical_specialty, Pannus, collagen-induced arthritis, Catalysis, Bone and Bones, Article, Inorganic Chemistry, 03 medical and health sciences, Internal medicine, medicine, Animals, treadmill running, articular cartilage, Physical and Theoretical Chemistry, Molecular Biology, business.industry, Organic Chemistry, medicine.disease, osteoporosis, Rats, cnnexin43, 030104 developmental biology, Endocrinology, lcsh:Biology (General), lcsh:QD1-999, pro-inflammatory cytokine, Synovial membrane, Ankle, business

الوصف: We analyzed the influence of treadmill running on rheumatoid arthritis (RA) joints using a collagen-induced arthritis (CIA) rat model. Eight-week-old male Dark Agouti rats were randomly divided into four groups: The control group, treadmill group (30 min/day for 4 weeks from 10-weeks-old), CIA group (induced CIA at 8-weeks-old), and CIA + treadmill group. Destruction of the ankle joint was evaluated by histological analyses. Morphological changes of subchondral bone were analyzed by &mu
CT. CIA treatment-induced synovial membrane invasion, articular cartilage destruction, and bone erosion. Treadmill running improved these changes. The synovial membrane in CIA rats produced a large amount of tumor necrosis factor-&alpha
and Connexin 43
production was significantly suppressed by treadmill running. On &mu
CT of the talus, bone volume fraction (BV/TV) was significantly decreased in the CIA group. Marrow star volume (MSV), an index of bone loss, was significantly increased. These changes were significantly improved by treadmill running. Bone destruction in the talus was significantly increased with CIA and was suppressed by treadmill running. On tartrate-resistant acid phosphate and alkaline phosphatase (TRAP/ALP) staining, the number of osteoclasts around the pannus was decreased by treadmill running. These findings indicate that treadmill running in CIA rats inhibited synovial hyperplasia and joint destruction.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8edddafa23c403b6e2fb878d7681b73bTest
https://pubmed.ncbi.nlm.nih.gov/29865282Test

المؤلفون: Masabumi Shibuya, Masashi Muramatsu, S Tsuchida, Takashi Takahashi, Takafumi Inoue, F Wang, R Nishii, Takashi Minami, Youichiro Wada, Rika Tsuchida, Bikul Das, Tsuyoshi Osawa, Yasuhito Yuasa

المصدر: Oncogene. 33:3803-3811

مصطلحات موضوعية: Smad5 Protein, Cancer Research, animal structures, Angiogenesis, Melanoma, Experimental, Bone Morphogenetic Protein 4, Biology, Vascular endothelial growth inhibitor, Smad1 Protein, Thrombospondin 1, Mice, chemistry.chemical_compound, Cancer stem cell, Cell Line, Tumor, Neoplasms, Paracrine Communication, Genetics, Animals, Humans, Molecular Biology, Cell Proliferation, Tumor microenvironment, Neovascularization, Pathologic, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Endothelial Cells, Tumor Burden, Vascular endothelial growth factor, HIF1A, chemistry, embryonic structures, Immunology, Cancer cell, Cancer research, HeLa Cells, Signal Transduction

الوصف: Bone morphogenetic protein 4 (BMP4) has potential as an anticancer agent. Recent studies have suggested that BMP4 inhibits the survival of cancer stem cells (CSCs) of neural and colon cancers. Here, we showed that BMP4 paracrinically inhibited tumor angiogenesis via the induction of Thrombospondin-1 (TSP1), and consequently suppressed tumor growth in vivo. Although HeLa (human cervical cancer), HCI-H460-LNM35 (highly metastatic human lung cancer) and B16 (murine melanoma) cells did not respond to the BMP4 treatment in vitro, the growth of xeno- and allografts of these cells was suppressed via reductions in tumor angiogenesis after intraperitoneal treatment with BMP4. When we assessed the mRNA expression of major angiogenesis-related factors in grafted tumors, we found that the expression of TSP1 was significantly upregulated by BMP4 administration. We then confirmed that BMP4 was less effective in suppressing the tumor growth of TSP1-knockdown cancer cells. Furthermore, we found that BMP4 reduced vascular endothelial growth factor (VEGF) expression in vivo in a TSP1-dependent manner, which indicates that BMP4 interfered with the stabilization of tumor angiogenesis. In conclusion, the BMP4/TSP1 loop paracrinically suppressed tumor angiogenesis in the tumor microenvironment, which subsequently reduced the growth of tumors. BMP4 may become an antitumor agent and open a new field of antiangiogenic therapy.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1670ea0a088f0c4b773dde1b92bf3caeTest
https://doi.org/10.1038/onc.2013.358Test

المؤلفون: Masaharu Shin-Ya, S. Tsuchida, S. Shimomura, Tsunao Kishida, Shuji Nakagawa, Hiroaki Inoue, Kuniaki Honjo, Yuji Arai, S. Ichimaru, Osam Mazda, Hiroyoshi Fujiwara, Toshikazu Kubo

المصدر: International Journal of Molecular Sciences; Volume 17; Issue 7; Pages: 1013
International Journal of Molecular Sciences, Vol 17, Iss 7, p 1013 (2016)
International Journal of Molecular Sciences

مصطلحات موضوعية: 0301 basic medicine, Cartilage, Articular, Male, Anabolism, hypoxia-inducible factor 1 α, Extracellular matrix, lcsh:Chemistry, chemistry.chemical_compound, 0302 clinical medicine, Hyaluronic acid, hyaluronic acid, CD44, Receptor, lcsh:QH301-705.5, Spectroscopy, Cells, Cultured, Extracellular Matrix Proteins, General Medicine, Transfection, Cell Hypoxia, Computer Science Applications, Blot, Hyaluronan Receptors, Biochemistry, medicine.symptom, medicine.medical_specialty, extracellular matrix, Type II collagen, Catalysis, Article, Inorganic Chemistry, 03 medical and health sciences, Internal medicine, medicine, Animals, articular cartilage, Physical and Theoretical Chemistry, Rats, Wistar, Molecular Biology, 030203 arthritis & rheumatology, Organic Chemistry, Hypoxia (medical), Hypoxia-Inducible Factor 1, alpha Subunit, Rats, Oxygen, 030104 developmental biology, Endocrinology, chemistry, lcsh:Biology (General), lcsh:QD1-999

الوصف: Hyaluronic acid (HA) is used clinically to treat osteoarthritis (OA), but its pharmacological effects under hypoxic conditions remain unclear. Articular chondrocytes in patients with OA are exposed to a hypoxic environment. This study investigated whether hypoxia could potentiate the anabolic effects of exogenous HA in rat articular cartilage and whether these mechanisms involved HA receptors. HA under hypoxic conditions significantly enhanced the expression of extracellular matrix genes and proteins in explant culture, as shown by real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and dimethylmethylene blue (DMMB) assays. Staining with Safranin-O and immunohistochemical staining with antibody to type II collagen were also enhanced in pellet culture. The expression of CD44 was increased by hypoxia and significantly suppressed by transfection with siRNAs targeting hypoxia-inducible factor 1 alpha (siHIF-1α). These findings indicate that hypoxia potentiates the anabolic effects of exogenous HA by a mechanism in which HIF-1α positively regulates the expression of CD44, enhancing the binding affinity for exogenous HA. The anabolic effects of exogenous HA may increase as OA progresses.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::edb249264e05e3e350745423a2741f09Test

المؤلفون: L, Ling, T, Higashi, S, Tsuchida, K, Sato, T, Tsuji

المصدر: Acta Medica Okayama. 47(5):293-298

مصطلحات موضوعية: Male, indocyanine green, Staining and Labeling, genetic structures, Liver Neoplasms, hepatocarcinogenesis, Immunohistochemistry, eye diseases, Rats, body regions, Animals, Rats, Wistar, glutathione-S-transferase-?, Glutathione Transferase

الوصف: Reduced indocyanine green (ICG) uptake is one of the functional changes of human hepatocellular carcinoma (HCC). To clarify the mechanisms of loss of ICG uptake, and determine which subunit of glutathione-S-transferase (GST), alpha or pi, plays a role in ICG transport in hepatocytes, an experimental HCC model was developed that used nodules induced by 2-acetylamino-fluorene (2-AAF) administration. Many of the ICG stained nodules, which consisted of benign and borderline lesions, were GST-alpha positive. However, the percentage of GST-alpha positive cells tended to decrease according to the disappearance of ICG staining in the process of hepatocarcinogenesis. HCCs unstained by ICG were also GST-alpha negative. GST-pi, not detected in normal rat hepatocytes, appeared in an earlier stage of hepatocarcinogenesis before the disappearance of GST-alpha, and was not observed in HCCs. No significant relationship between ICG staining and GST-pi was recognized. These results suggest that GST-alpha synthesis is disturbed in the process of hepatocarcinogenesis and results in loss of ICG uptake in HCCs, and also indicate that GST-pi may be useful for early diagnosis of preneoplastic hepatocytes showing no roles in ICG transport.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::4846c63fa51d1e4201d1d48dfcb02e82Test
https://ousar.lib.okayama-u.ac.jp/31584Test

المؤلفون: T, Takahashi, I, Takahashi, S, Tsuchida, K, Oyama, M, Komatsu, H, Saito, G, Takada

المصدر: Clinical genetics. 61(4)

مصطلحات موضوعية: Male, X Chromosome, Adolescent, Membrane Transport Proteins, Osteochondrodysplasias, Pedigree, Japan, COS Cells, Mutation, Animals, Humans, Female, Carrier Proteins, Child, Transcription Factors

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::2d5d9ff03f0c6492c090fe29ddcf6f59Test
https://pubmed.ncbi.nlm.nih.gov/12030902Test

المؤلفون: T, Endo, K, Ookawa, M, Tanaka, S, Nakaji, S, Tsuchida, K, Sugawara

المصدر: Digestive diseases and sciences. 46(1)

مصطلحات موضوعية: Methylnitronitrosoguanidine, Genes, APC, Genes, ras, Time Factors, Carcinoma, Colonic Neoplasms, Mutation, Carcinogens, Animals, Rats, Inbred F344, 1,2-Dimethylhydrazine, Rats

الوصف: To clarify the carcinogenic factors--whether it is the kind of carcinogen or their length of exposure--that determine whether colorectal cancer develops from an adenoma or develops de novo in the absence of an adenoma, we histopathologically analyzed a total of 229 rat colon tumors induced by administration of 1,2-dimethyl-hydrazine (DMH) or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) for three or 15 weeks. In the three-week-exposure groups, 71% of DMH-induced carcinomas and 82% of MNNG-induced carcinomas coexisted with low-grade dysplasia (adenomatous remnant). However, in the 15-week-exposure groups, lowgrade dysplasia was observed in only 10% of DMH-induced and 27% of MNNG-induced carcinomas. Even in the tumors smaller than 20 mm3, it was observed in only 10% of DMH-induced and 32% of MNNG-induced carcinomas. Furthermore, carcinomas without low-grade dysplasia predominated from the initial period of tumor occurrence. Next, we investigated association of K-ras and APC gene mutations with these carcinogenesis patterns in 80 tumors. K-ras mutations were not detected in any tumors induced by three weeks of exposure. However, in the 15-week-exposure groups, this mutation was observed in 57% of DMH-induced tumors and 13% of MNNG-induced tumors. APC mutations in the region homologous to the human mutation cluster region were observed in only 6% of tumors. Thus, our results suggest that the carcinogenesis patterns in rat colon are dependent on the length of exposure to carcinogen and that K-ras mutations were partly involved in a subset of them.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::153efbde2d316cedf892e96eef84c7e6Test
https://pubmed.ncbi.nlm.nih.gov/11270774Test

المؤلفون: T, Omi, S, Tsuchida, A, Onishi, T, Amano, K, Tanaka, S, Iwamoto, E, Kajii

المصدر: Animal genetics. 31(6)

مصطلحات موضوعية: Polymorphism, Genetic, Base Sequence, Reverse Transcriptase Polymerase Chain Reaction, Swine, Molecular Sequence Data, Animals, Carboxylic Ester Hydrolases, Carboxylesterase, DNA Primers

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::56fc71e2b55a943eace6a6bc5cdc2169Test
https://pubmed.ncbi.nlm.nih.gov/11167536Test

المؤلفون: S, Tsuchida, J, Kimura, M, Hayakari, T, Ishikawa

المصدر: Rinsho byori. The Japanese journal of clinical pathology. 45(12)

مصطلحات موضوعية: Drug Resistance, Neoplasm, Neoplasms, Biomarkers, Tumor, Animals, Humans, Chemoprevention, Glutathione Transferase

الوصف: The glutathione S-transferases (GSTs), a family of multifunctional proteins, catalyze the glutathione conjugation reaction with electrophilic compounds biotransformed from xenobiotics, including carcinogens, and are grouped into four classes, Alpha, Mu, Pi and Theta. Some of these forms are suggested to act to prevent carcinogenesis by detoxifying proximate or ultimate carcinogens. In neoplastic cells, specific forms are known to be expressed and have been known to participate in their resistance to anticancer drugs. In this article, we review recent findings regarding the respective molecular forms involved in carcinogenesis and their usefulness as tumor markers. GST M1 and GST T1 genes are polymorphic in the population and losses of these genes have been suggested as possible markers for greater susceptibility to lung cancer among smokers and several other cancers. Since many GST inducers prevent rodent chemical carcinogenesis, potential chemopreventive agents have been screened by their induction capabilities. However, reliable markers useful to predict results of prospective chemopreventive trials in populations are not established. Immunohistochemical studies have revealed that many cancers, histologically classified as adenocarcinomas or squamous cell carcinomas, express GST P1-1. Its expression is regulated at transcriptional level and regulatory elements of the gene have been clarified. However, transacting factors responsible for expression in cancer tissues remain to be clarified. In addition, stability of GST P1 mRNA is suggested to be partly responsible in some cell lines. Plasma or serum GST P1-1 levels are increased in 30-50% of patients with cancers of the gastrointestinal tract. This form is also suggested to participate in resistance to anticancer drugs such as cisplatin and daunorubicin, and its expression in cancer tissues may be of prognostic value in cancer patients. Further studies on this enzyme family are clearly needed to obtain a better understanding of cancer prevention and therapy.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::74657bdd08c3db079262088e0a6c68a5Test
https://pubmed.ncbi.nlm.nih.gov/9437892Test

المؤلفون: H, Moro, K, Hanzawa, O, Namura, S, Nakazawa, H, Ozeki, J, Hayashi, H, Miyamura, S, Eguchi, S, Tsuchida

المصدر: [Zasshi] [Journal]. Nihon Kyobu Geka Gakkai. 42(6)

مصطلحات موضوعية: Perfusion, Extracorporeal Circulation, Oxygen Consumption, Swine, Cerebrovascular Circulation, Hemodynamics, Animals, Brain, Body Temperature

الوصف: In order to study the protective effect and problem of retrograde perfusion (RCP), cerebral hemodynamics and cerebral metabolism were evaluated in fourteen pigs weighing 25-30 kg. Intracranial pressure, carotid arterial flow and pressure, and internal jugular venous pressure as cerebral hemodynamics; pyruvate, lactate, and oxygen consumption as cerebral metabolism; and brain temperature were measured. The animal was cooled to electrical cerebral silence on electroencephalogram under cardiopulmonary bypass. Then, animals were divided into three groups: group I (n = 4); circulatory arrest; group II (n = 3); RCP through superior vena cava (SVC); group III (n = 7); RCP through bilateral internal jugular vein (IJV). Retrograde perfusion flow was regulated to maintain the SVC pressure or IJV pressure of 30 mmHg, for 90 minutes. The variations in brain temperature were least in group III. As perfusion flow increased, intracranial pressure, and inferior vena cava (IVC) pressure increased. But, cerebral perfusion pressure, which was calculated from the difference of intracranial arteriovenous pressure, did not increase and, SVC pressure and returned blood flow through the aorta did not increase in group III. In group II, there was no significant relation between pump flow, SVC pressure, and intracranial pressure, but SVC pressure had a positive correlation with the pressure gradient of SVC-IJV. The uptake of cerebral lactate, cerebral pyruvate, and lactate-pyruvate ratio, and cerebral oxygen consumption were superior in group III than other groups. In conclusion, RCP through IJV was advantageous to maintain hypothermia and aerobic metabolism of the brain during systemic hypothermic circulatory arrest.(ABSTRACT TRUNCATED AT 250 WORDS)

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::ee4d2f05035505ef0fbef8cbe44b0fc0Test
https://pubmed.ncbi.nlm.nih.gov/8057018Test