Biomedical Research-tokyo最新文献

{"title":"Analgesic effect of voluntary exercise in a rat model of persistent pain via suppression of microglial activation in the spinal cord.","authors":"Risa Takahara-Yamauchi,&nbsp;Hideshi Ikemoto,&nbsp;Takayuki Okumo,&nbsp;Fatma Zahra Sakhri,&nbsp;Hiroyuki Horikawa,&nbsp;Akiou Nakamura,&nbsp;Satoshi Sakaue,&nbsp;Mami Kato,&nbsp;Naoki Adachi,&nbsp;Masataka Sunagawa","doi":"10.2220/biomedres.42.67","DOIUrl":"https://doi.org/10.2220/biomedres.42.67","url":null,"abstract":"<p><p>In this study, we employed a rodent model for persistent allodynia and hyperalgesia to determine whether voluntary exercise could exert analgesic effects on these pain symptoms. Rats were subcutaneously injected with formalin into the plantar surface of the right hind paw to induce mechanical allodynia and hyperalgesia. We assessed the analgesic effects of a voluntary wheel running (VWR) using the von Frey test and investigated microglial proliferation in the dorsal horn of the spinal cord. We also determined the effect of formalin and VWR on the protein expression levels of brain-derived neurotrophic factor (BDNF), its receptor TrkB, and K⁺-Cl^- cotransporter 2 (KCC2), which play a key role in inducing allodynia and hyperalgesia. Rats with access to the running wheels showed beneficial effects on persistent formalin-induced mechanical allodynia and hyperalgesia. The effects of VWR were elicited through the suppression of formalin-induced microglial proliferation, TrkB up-regulation, and KCC2 down-regulation in the spinal cord. BDNF, however, might not contribute to the beneficial effects of VWR. Our results show an analgesic effect of voluntary physical exercise in a rodent model with persistent pain, possibly through the regulation of microglial proliferation and TrkB and KCC2 expression in the spinal cord.</p>","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25579581","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":"Deletion of the lysyl oxidase-like 1 gene induces impaired elastin fiber synthesis and inefficient urethral closure in rats.","authors":"Katsumi Kadekawa,&nbsp;Saori Nishijima,&nbsp;Katsuhiko Noguchi,&nbsp;Shiho Okitsu,&nbsp;Kennosuke Karube,&nbsp;Seiji Matsumoto,&nbsp;Hideyuki Yamamoto,&nbsp;Kimio Sugaya","doi":"10.2220/biomedres.42.23","DOIUrl":"https://doi.org/10.2220/biomedres.42.23","url":null,"abstract":"<p><p>We investigated the bladder and urethral function in a rat model lacking the protein lysyl oxidase-like 1 (Loxl1). Female nulliparous rats of Loxl1^-/- or age-matched wild type (WT) rats had leak-point pressure testing, cystometry, histopathological analyses of lower urinary tract, and contractile response of isolated detrusor strips to carbachol and electric field stimulation. The Loxl1^-/- rats showed increased looseness and redundancy of the skin, the decreased intercontraction interval and voided volume in cystometry, the lower leak-point pressure, thinner elastic fibers of the mesentery, bladder, urethra and vagina, and smaller contractile response of detrusor strips to carbachol when compared to the WT rats. Thus, the insufficient hydrostatic mechanism of urethra via submucosal impaired elastin synthesis might reduce the resting urethral closure pressure and the diminished cholinergic contractile response of detrusor smooth muscle might be involved in bladder activity in the Loxl1^-/- rats.</p>","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25353634","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":"CLN6's luminal tail-mediated functional interference between CLN6 mutants as a novel pathomechanism for the neuronal ceroid lipofuscinoses.","authors":"Yuki Shiro,&nbsp;Arisa Yamashita,&nbsp;Kana Watanabe,&nbsp;Tetsuo Yamazaki","doi":"10.2220/biomedres.42.129","DOIUrl":"https://doi.org/10.2220/biomedres.42.129","url":null,"abstract":"<p><p>CLN6 (Ceroid Lipofuscinosis, Neuronal, 6) is a 311-amino acid protein spanning the endoplasmic reticulum membrane. Mutations in CLN6 are linked to CLN6 disease, a hereditary neurodegenerative disorder categorized into the neuronal ceroid lipofuscinoses. CLN6 disease is an autosomal recessive disorder and individuals affected with this disease have two identical (homozygous) or two distinct (compound heterozygous) CLN6 mutant alleles. Little has been known about CLN6's physiological roles and the disease mechanism. We recently found that CLN6 prevents protein aggregate formation, pointing to impaired CLN6's anti-aggregate activity as a cause for the disease. To comprehensively understand the pathomechanism, overall anti-aggregate activity derived from two different CLN6 mutants needs to be investigated, considering patients compound heterozygous for CLN6 alleles. We focused on mutant combinations involving the S132CfsX18 (132fsX) prematurely terminated protein, produced from the most frequent mutation in CLN6. The 132fsX mutant nullified anti-aggregate activity of the P299L CLN6 missense mutant but not of wild-type CLN6. Wild-type CLN6's resistance to the 132fsX mutant was abolished by replacement of amino acids 297-301, including Pro297 and Pro299, with five alanine residues. Given that removal of CLN6's C-terminal fifteen amino acids 297-311 (luminal tail) did not affect the resistance, we suggested that CLN6's luminal tail, when unleashed from Pro297/299-mediated conformational constraints, is improperly positioned by the 132fsX mutant, thereby blocking the induction of anti- aggregate activity. We here reveal a novel mechanism for dissipating CLN6 mutants' residual functions, providing an explanation for the compound heterozygosity-driven pathogenesis.</p>","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39301594","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":"A mathematical model of kinetochore-microtubule attachment regulated by Aurora A activity gradient describes chromosome oscillation and correction of erroneous attachments.","authors":"Manuel Alejandro Campos Medina,&nbsp;Kenji Iemura,&nbsp;Akatsuki Kimura,&nbsp;Kozo Tanaka","doi":"10.2220/biomedres.42.203","DOIUrl":"https://doi.org/10.2220/biomedres.42.203","url":null,"abstract":"<p><p>Chromosome oscillation during metaphase is attenuated in cancer cell lines, concomitant with the reduction of Aurora A activity on kinetochores, which results in reduced mitotic fidelity. To verify the correlation between Aurora A activity, chromosome oscillation, and error correction efficiency, we developed a mathematical model of kinetochore-microtubule dynamics, based on stochastic attachment/detachment events regulated by Aurora A activity gradient centered at spindle poles. The model accurately reproduced the oscillatory movements of chromosomes, which were suppressed not only when Aurora A activity was inhibited, but also when it was upregulated, mimicking the situation in cancer cells. Our simulation also predicted efficient correction of erroneous attachments through chromosome oscillation, which was hampered by both inhibition and upregulation of Aurora A activity. Our model provides a framework to understand the physiological role of chromosome oscillation in the correction of erroneous attachments that is intrinsically related to Aurora A activity.</p>","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39434001","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":"Histochemical characteristics on minimodeling-based bone formation induced by anabolic drugs for osteoporotic treatment.","authors":"Tomomaya Yamamoto,&nbsp;Tomoka Hasegawa,&nbsp;Paulo Henrique Luiz de Fraitas,&nbsp;Hiromi Hongo,&nbsp;Shen Zhao,&nbsp;Tsuneyuki Yamamoto,&nbsp;Alireza Nasoori,&nbsp;Miki Abe,&nbsp;Haruhi Maruoka,&nbsp;Keisuke Kubota,&nbsp;Yasuhito Morimoto,&nbsp;Mai Haraguchi,&nbsp;Tomohiro Shimizu,&nbsp;Masahiko Takahata,&nbsp;Norimasa Iwasaki,&nbsp;Minqi Li,&nbsp;Norio Amizuka","doi":"10.2220/biomedres.42.161","DOIUrl":"https://doi.org/10.2220/biomedres.42.161","url":null,"abstract":"<p><p>Modeling, the changes of bone size and shape, often takes place at the developmental stages, whereas bone remodeling-replacing old bone with new bone-predominantly occurs in adults. Unlike bone remodeling, bone formation induced by modeling i.e., minimodeling (microscopic modeling in cancellous bone) is independent of osteoclastic bone resorption. Although recently-developed drugs for osteoporotic treatment could induce minimodeling-based bone formation in addition to remodeling-based bone formation, few reports have demonstrated the histological aspects of minimodeling-based bone formation. After administration of eldecalcitol or romosozumab, unlike teriparatide treatment, mature osteoblasts formed new bone by minimodeling, without developing thick preosteoblastic layers. The histological characteristics of minimodeling-based bone formation is quite different from remodeling, as it is not related to osteoclastic bone resorption, resulting in convex-shaped new bone and smooth cement lines called arrest lines. In this review, we will show histological properties of minimodeling-based bone formation by osteoporotic drugs.</p>","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39434573","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":"Overexpressed exocyst complex component 3-like 1 spontaneously induces apoptosis.","authors":"Shunichi Matsumoto,&nbsp;Junichi Okada,&nbsp;Eijiro Yamada,&nbsp;Tsugumichi Saito,&nbsp;Kazuya Okada,&nbsp;Takuya Watanabe,&nbsp;Yasuyo Nakajima,&nbsp;Atsushi Ozawa,&nbsp;Shuichi Okada,&nbsp;Masanobu Yamada","doi":"10.2220/biomedres.42.109","DOIUrl":"https://doi.org/10.2220/biomedres.42.109","url":null,"abstract":"<p><p>Exocyst complex component 3-like 1 (EXOC3L1), which regulates insulin secretion, is ubiquitously present in heart, lung, liver, spleen, kidney, muscle, cerebellum, pituitary, adrenal grand, and pancreatic islets. Its deduced amino acid sequence has 31% identity and 53% similarity with Sec6, so they are considered isoforms. Since Sec6 suppresses apoptosis via HSP27, we investigated the involvement of EXOC3L1 expression in apoptosis. We found that overexpressed EXOC3L1 in Chinese hamster ovary cells significantly reduced cultured cell numbers. It also significantly increased apoptotic DNA ladder, caspase 3 activity, and cleavage of caspase 3 compared with the control. Thus, although Sec6 reduces apoptosis by increasing HSP27 phosphorylation, overexpressed EXOC3L1 alone can spontaneously induce apoptosis without apoptotic stimulators or inducers.</p>","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39082693","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 Rauwolfia Vomitoria extracts on monoamine oxidase activity in wistar rats","authors":"I. AsoroIroghama, Ebuehi Osaretin At, N. Igwo-EzikpeMiriam","doi":"10.35841/0970-938X.32.5.104-107","DOIUrl":"https://doi.org/10.35841/0970-938X.32.5.104-107","url":null,"abstract":"Monoamine Oxidase (MAO; EC 1.4.3.4.) is a widely distributed mitochondrial enzyme with two isoforms: MAO-A and MAO-B. It has high expression levels in gastro-intestinal and hepatic as well as neuronal tissues. The enzyme catalyzes the oxidative deamination of a variety of monoamines, both endogenous and exogenous, and has major roles in metabolizing released neurotransmitters, and in detoxification of a large variety of endogenous and exogenous amines. Drugs which inhibit MAO are currently in clinical use for treatment of affective disorders. Major Depressive Disorder (MDD), the most prevalent mood disorder is the leading cause of worldwide disability. Core symptoms of MDD include depressed mood, irritability, anhedonia (defined as the reduced ability to experience pleasure from previously rewarding activities), difficulty concentrating, and disrupted appetite and sleep habits. Several clinical studies report a high prevalence of MDD comorbidity with inflammatory diseases including cardiovascular diseases, diabetes, metabolic disorders, asthma, and rheumatoid arthritis. Medicinal plant play a significant role in providing primary health care services to rural people serving as therapeutic agents as well as important raw materials for the manufacture of traditional and modern medicine. A large number of medicinal plants are claimed to possess the antidepressant properties in the traditional system and are also used extensively by people worldwide R. Vomitoria, a shrub of the family Apocynaceae is commonly called serpent wood or swizzler stick and is used locally in the treatment of mental disorders, nervous disorders and insomnia.The aim of this article is to review the findings of the studies on antidepressant effects, mechanism of action of medicinal plants with emphasis on monoamine oxidase enzyme. Ninety male Wistar rats were orally administered 125, 250 and 500 mg/kg body weight of aqueous and ethanol root extract of Rauwolfia vomitoria for 14 and 28 days. Animals were sacrificed by cervical dislocation and monoamine oxidase activity was determined spectrophotometrically. Rauwolfia vomitoria root decreased MAO significantly compared to standard imipramine, citalopram and control.","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77423650","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":"Principles and effectiveness of microbiological containment measures in COVID-19 pandemic induced by SARS-CoV-2.","authors":"Ayesha Rafiq, Abeer Kazmi, Amir Ali, Sher Mohammad, Naeem Shah, K. Shabir, Sumaiya Khatoon","doi":"10.35841/0970-938X.S36-S42","DOIUrl":"https://doi.org/10.35841/0970-938X.S36-S42","url":null,"abstract":"An outbreak of deadly clinical syndrome COVID-19 in Wuhan, China has spread rapidly across the world. It is currently required to develop methods and principle of containment measures with risk assessment, categorize the laboratory design, approaches the training and procedures to evaluated compliance. Considering the transmission dynamics of coronavirus pathogen (physical contact, droplet, or aerosol), certaineffectivemeasuresshould be followed to reducetheexposure of risk. Theseguidelinesareeffective, not only for thehealthworkers but also forgeneralpublic to encouragethemforadapting protectivebehaviours whichwill help to overcomethis pandemicsituation. The rationalandoptimizeduse of PPEs willserve as an initiative measure in solving theirglobal crisis.","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83611381","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":"Understanding molecular ultrastructure Coronavirus 2019 (nCoVs).","authors":"S. Baharuddin","doi":"10.35841/0970-938X.S43-S44","DOIUrl":"https://doi.org/10.35841/0970-938X.S43-S44","url":null,"abstract":"Coronaviruses (CoVs) have two main parts on their ultrastructure. First is the capsid (envelope). Second is the core part (core). These two sections are synthesized and incorporated in eukaryotic (host) cells. In this case the host cell is the epithelial cells in the respiratory system. If the molecular classification on the body of the virus, it will be obtained two major macromolecules: proteins and nucleic acids and little of carbohydrate complex.","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86205248","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":"Expression of tartrate-resistant acid phosphatase and cathepsin K during osteoclast differentiation in developing mouse mandibles.","authors":"Megumi Nakamura,&nbsp;Naoki Aoyama,&nbsp;Satoshi Yamaguchi,&nbsp;Yasuyuki Sasano","doi":"10.2220/biomedres.42.13","DOIUrl":"https://doi.org/10.2220/biomedres.42.13","url":null,"abstract":"<p><p>The present study was designed to test the hypothesis that osteoclasts appear after or at the same time as the initiation of bone mineralization in developing intramembranous bones. We examined mineral deposition via Von Kossa staining to determine when bone mineralization begins, tartrate-resistant acid phosphatase (TRAP) activity and cathepsin K immunoreactivity to identify the presence of osteoclasts, and their mRNA expression levels to assess osteoclastic differentiation in the embryonic mouse mandible. Cathepsin K-immunopositive cells were detected around the same time as the onset of bone mineralization, whereas TRAP-positive cells appeared prior to bone mineralization. Cathepsin K protein was expressed only in multinucleated osteoclasts, whereas TRAP activity was identified in both mono- and multinucleated cells. During bone development, TRAP-positive cells altered their morphology, which was related to the number of their nuclei. The elevated mRNA levels of TRAP and cathepsin K were consistent with the increased percentage of multinucleated osteoclasts and the progression of bone development. Our study revealed that TRAP-positive cells appear prior to bone mineralization, and TRAP- and cathepsin K-positive multinucleated osteoclasts appear at the same time as the initiation of bone mineralization in embryonic mouse mandibles, suggesting that osteoclasts contribute to bone matrix maturation during intramembranous ossification.</p>","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25353633","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}