{"title":"Secondary bile acid lithocholic acid attenuates neurally evoked ion transport in the rat distal colon.","authors":"Kohei Takahashi, Yuko Kuwahara, Ikuo Kato, Shinji Asano, Takaharu Kozakai, Yoshinori Marunaka, Atsukazu Kuwahara","doi":"10.2220/biomedres.43.223","DOIUrl":"https://doi.org/10.2220/biomedres.43.223","url":null,"abstract":"<p><p>The inhibitory action of the secondary bile acid lithocholic acid (LCA) on neurally evoked Cl<sup>-</sup>/HCO<sub>3</sub><sup>-</sup> secretion was investigated using the Ussing-chambered mucosal-submucosal preparation from the rat distal colon. Electrical field stimulation (EFS) evoked cholinergic and noncholinergic secretory responses in the rat distal colon. The responses were almost completely blocked by TTX (10<sup>-6</sup> M) but not atropine (10<sup>-5</sup> M) or hexamethonium (10<sup>-4</sup> M). The selective antagonist for VIP receptor 1 (VPAC1) greatly reduced the EFS-evoked response. Thus, the rat distal colon may be predominantly innervated by noncholinergic VIP secretomotor neurons. Basolateral addition of 6 × 10<sup>-5</sup> M LCA inhibited the EFS-evoked response. The inhibitory action of LCA was partly rescued by the Y2R antagonist BIIE0246. The bile acid receptor TGR5 agonist INT-777 mimicked the LCA-induced inhibitory action. Immunohistochemical staining showed the colocalization of TGR5 and PYY on L cells. TGR5 immunoreactivity was also found in VIP-immunoreactive submucosal neurons which also expressed the PYY receptor, Y2R. These results suggest that LCA inhibits neurally evoked Cl<sup>-</sup>/HCO<sub>3</sub><sup>-</sup> secretion through the activation of TGR5 on L cells and cholinergic- and VIP-secretomotor neurons in the submucosal plexus. Furthermore, the inhibitory mechanism may involve TGR5-stimulated PYY release from L cells and Y2R activation in VIP-secretomotor neurons.</p>","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":"43 6","pages":"223-239"},"PeriodicalIF":1.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10355112","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":"Disposal of intestinal apoptotic epithelial cells and their fate via divergent routes.","authors":"Toshihiko Iwanaga, Hiromi Takahashi-Iwanaga","doi":"10.2220/biomedres.43.59","DOIUrl":"https://doi.org/10.2220/biomedres.43.59","url":null,"abstract":"<p><p>Gut epithelial cells are characterized by rapid, constant cell renewal. The disposal of aging epithelial cells around the villus tips of the small intestine occurs so regularly that it has been regarded as a consequence of well-controlled cell death, designated as apoptosis. However, the notion of live cell extrusion in the intestine has been intensively built among researchers, and the disposal processes of effete epithelial cells display species and regional differences. Chemical mediators and mechanical forces rising from surrounding cells contribute to the regulated cell replacement. Cytotoxic intraepithelial lymphocytes and lamina propria macrophages play a leading role in the selection of disposal cells and their extrusion to maintain fully the epithelial homeostasis in tandem with the dynamic reconstruction of junctional devices. Lymphocyte-mediated cell killing is predominant in the mouse and rat, while the disposal of epithelial cells in the guinea pig, monkey, and human is characterized by active phagocytosis by subepithelially gathering macrophages. The fenestrated basement membrane formed by immune cells supports their involvement and explains species differences in the disposal of epithelial cells. Via these fenestrations, macrophages and dendritic cells can engulf apoptotic epithelial cells and debris and convey substantial information to regional lymph nodes. In this review, we attempt to focus on morphological aspects concerning the apoptosis and disposal process of effete epithelial cells; in vitro or ex vivo analyses using cultured monolayer has become predominant in recent studies concerning the exfoliation of apoptotic enterocytes. Furthermore, we give attention to their species differences, which is controversial but crucial to our understanding.</p>","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":"43 3","pages":"59-72"},"PeriodicalIF":1.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39997753","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":"CD44 as a pathological marker for the early detection of calcineurin inhibitor-induced nephrotoxicity post kidney transplantation.","authors":"Asako Hayashi, Takayuki Okamoto, Junko Nio-Kobayashi, Naoya Iwahara, Ryota Suzuki, Yasuhiro Ueda, Toshiyuki Takahashi, Yasuyuki Sato, Toshihiko Iwanaga, Kiyohiko Hotta","doi":"10.2220/biomedres.43.181","DOIUrl":"https://doi.org/10.2220/biomedres.43.181","url":null,"abstract":"<p><p>Long-term calcineurin inhibitor (CNI) administration causes irreversible nephrotoxicity. Therefore, early CNI-induced nephrotoxicity detection is necessary for patients who will need long-term CNI administration. There is no pathological indicator for early CNI-induced nephrotoxicity. Here, serial protocol kidney biopsy specimens from five kidney-transplant patients with severe CNI-induced nephrotoxicity were examined. We observed that the increase in CD44 expression in glomerular parietal epithelial cells (PECs) preceded the chronic pathological changes of CNI-induced nephrotoxicity such as tubular atrophy/interstitial fibrosis, arterial hyaline thickening, and focal segmental glomerulosclerosis (FSGS). This result suggests that CD44-positive PECs have pivotal roles in FSGS development in human CNI-induced nephrotoxicity as well as rodent models. CD44 could be useful as a pathological marker for early CNI-induced nephrotoxicity detection post kidney transplantation.</p>","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":"43 5","pages":"181-186"},"PeriodicalIF":1.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33512931","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 ANP and BNP on the generation of respiratory rhythms in brainstem-spinal cord preparation isolated from newborn rats.","authors":"Shino Katsuki, Shinichiro Ota, Shunya Yoda, Hiroshi Onimaru, Kenji Dohi, Masahiko Izumizaki","doi":"10.2220/biomedres.43.127","DOIUrl":"https://doi.org/10.2220/biomedres.43.127","url":null,"abstract":"<p><p>Natriuretic peptides (NPs) are a family of peptide hormones produced in cardiac muscle cells and consist mainly of three types: atrial NP (ANP), B-type (or brain) NP (BNP), and C-type NP. We herein report the effects of ANP and BNP on central respiratory activity in brainstem-spinal cord preparation isolated from newborn rats. Bath application of these peptides (100 nM) induced a weak transient depression of the respiratory rhythm followed by recovery. Respiratory-related neurons in the rostral ventrolateral medulla showed a tendency for transient hyperpolarization followed by recovery during the application of ANP or BNP. The application of a membrane-permeable cGMP, 8-Br-cGMP (10 or 20 μM), did not induce significant effects on respiratory rhythm, suggesting no involvement of guanylyl cyclase in effects of ANP or BNP. We also examined effects of BNP on respiratory depression induced by the sedative dexmedetomidine, which exerts an inhibitory influence on respiratory rhythm. When pretreated with 50 nM BNP, the inhibitory effect of 100 nM dexmedetomidine was significantly reduced. Our findings suggest that ANP and BNP act as mild excitatory agents with sustained effects on respiratory rhythm after an initial transient depression.</p>","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":"43 4","pages":"127-135"},"PeriodicalIF":1.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10442158","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":"Shotgun proteomic investigation of methyltransferase and methylation profiles in lipopolysaccharide stimulated RAW264.7 murine macrophages.","authors":"Yumi Aizawa, Masaru Mori, Tsukasa Suzuki, Akihiro Saito, Hirofumi Inoue","doi":"10.2220/biomedres.43.73","DOIUrl":"https://doi.org/10.2220/biomedres.43.73","url":null,"abstract":"<p><p>Arginine methylation is a common post-translational modification which functions as an epigenetic regulator of transcription and plays a key role in various cell signaling pathways. The methylation of arginine residues is catalyzed by protein arginine methyltransferase (PRMT). However, the expression pattern and underlying mechanism of PRMTs and protein methylation profile in lipopolysaccharide (LPS)-induced innate immune responses are poorly understood. Using a shotgun proteomic approach, we found that LPS stimulation increased arginine and proline metabolism and responses to inflammation and bacterial infections. In comparison, cysteine and methionine metabolism, the pentose phosphate pathway, purine metabolism, and protein methylation factors were also decreased in LPS stimulated murine macrophage cell lines. We revealed that LPS stimulation downregulated PRMT1, PRMT5, and protein arginine methylation profiles in RAW264.7 cells using western blot analysis. Additionally, this phenomenon occurred in parallel with nitric oxide accumulation in LPS-induced macrophages. Using inflammation models, we demonstrate for the first time that LPS stimulation decreases PRMTs, leading to the decreasing of arginine methylation in macrophages.</p>","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":"43 3","pages":"73-80"},"PeriodicalIF":1.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39998563","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":"Activation of STAT3 (signal transducer and activator of transcription 3) in synovial tissues from the hip joint in the early stage of rapidly destructive coxopathy.","authors":"Tadashi Yasuda, Shigeo Hara, Shinnosuke Yamashita, Sadaki Mitsuzawa, Yoshihiro Tsukamoto, Hisataka Takeuchi, Satoshi Ota, Eijiro Onishi","doi":"10.2220/biomedres.43.173","DOIUrl":"https://doi.org/10.2220/biomedres.43.173","url":null,"abstract":"<p><p>Interleukin-6 signaling activates signal transducer and activator of transcription 3 (STAT3), resulting in matrix metalloproteinase-3 (MMP-3) production. The hip joints with rapidly destructive coxopathy (RDC) show rapid chondrolysis, probably by increased MMP-3. This study aimed to elucidate STAT3 activation in the synovial tissues with joint destruction in the early stage of RDC. Synovial tissues within 7 months from the disease onset were obtained from four RDC patients with femoral head destruction and high serum levels of MMP-3. RDC synovial tissues demonstrated the synovial lining hyperplasia with an increase of CD68-positive macrophages and CD3-positive T lymphocytes. STAT3 activation was found in the synovial tissues by immunohistochemistry using anti-phospho-STAT3 antibody. The majority of phospho-STAT3-positive cells were the synovial lining cells and exhibited negative expression of the macrophage or T cell marker. Treatment with CP690,550, a Janus Kinase inhibitor, resulted in a decrease in phospho-STAT3-positive cells, especially with high intensity, indicating effective suppression of STAT3 activation in RDC synovial tissues. Inhibitory effect of CP690,550 could work through the Janus Kinase/STAT3 axis in the synovial tissues in the early stage of RDC. Thus, STAT3 may be a potential therapeutic target for prevention of joint structural damage in RDC.</p>","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":"43 5","pages":"173-180"},"PeriodicalIF":1.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33512930","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":"Pathological examination of Ym1, a chitinase family protein, in Mesocestoides corti-infected mice.","authors":"Junko Nio-Kobayashi, Makoto Owhashi, Toshihiko Iwanaga","doi":"10.2220/biomedres.43.161","DOIUrl":"https://doi.org/10.2220/biomedres.43.161","url":null,"abstract":"<p><p>Mammals express a set of chitinase family proteins, comprising chitinases, which can hydrolyze chitin, and chitinase-like proteins without the chitinase activity but possessing chitin-binding properties. They act as endogenous lectins, regulating various physiological/pathological events. Ym1, originally identified as an eosinophil chemotactic factor or a macrophage-derived protein in parasite-infected mice, is a rodent-specific chitinase-like protein. Ym1 is also purified from eosinophilic crystals formed in the lung and urinary system in various disease models. We previously reported that major cellular sources of murine Ym1 are alveolar macrophages in the lung and neutrophils/monocytes lineage cells of the spleen and bone marrow under normal conditions. We here analyzed the detailed cellular expression of Ym1 in Mesocestoides corti (M. corti)-infected mice. Ym1 was significantly increased in the liver containing the larvae, lung, and peritoneal exudate cells in M. corti-infected mice, where activated macrophages expressed Ym1. Characteristic needle-shaped eosinophilic crystals appeared in the larvae-free lung, and Ym1 was localized to endoplasmic reticulum of activated alveolar macrophages. Moreover, swollen mesothelial cells covering the liver, spleen, and heart expressed Ym1 abundantly. Although the role of Ym1 in parasitic infection remains unclear, our findings focusing on an endogenous lectin may help in better understanding defense mechanism against parasites.</p>","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":"43 5","pages":"161-171"},"PeriodicalIF":1.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33512964","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}
S. Harrak, S. Lemsanes, S. Razine, S. Najem, H. Mrabti, S. Jaba, S. ElMajjaoui, N. Benjaafar, H. Errihani
{"title":"Cutaneous angiosarcoma of the scalp: A case report and literature review","authors":"S. Harrak, S. Lemsanes, S. Razine, S. Najem, H. Mrabti, S. Jaba, S. ElMajjaoui, N. Benjaafar, H. Errihani","doi":"10.35841/0970-938X.32.4.79-83","DOIUrl":"https://doi.org/10.35841/0970-938X.32.4.79-83","url":null,"abstract":"Angiosarcoma (AS) is a rare aggressive sarcoma that occurs mostly in the skin of the head and neck in the elderly population. AS of the scalp is associated with high rates of local recurrence and a poor prognosis. Patients with typical presenting symptoms can be diagnosed clinically, but the precise pathological diagnosis should be performed by an expert pathologist. Angiosarcoma requires aggressive and comprehensive treatment by a multidisciplinary team, because a multimodal approach improves survival. The mainstay of treatment is surgical resection and adjuvant radiation therapy, but failure rates following local therapy are high. The chemotherapy is used in cases of metastatic or unresectable scalp angiosarcoma. We describe the case of a 38-year-old woman who presented with lesions nodular on the scalp. The biopsy with histological study demonstrated an angiosarcoma. A computed tomography scan revealed multiple pulmonary metastasis, she received intravenous paclitaxel, the scalp and lung lesions significantly diminished after 3 month of treatment.","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":"35 1","pages":"79-83"},"PeriodicalIF":1.2,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90678435","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":"RNA impacts formation of biomolecular condensates in the nucleus.","authors":"Saho Matsui, Ryu-Suke Nozawa","doi":"10.2220/biomedres.42.153","DOIUrl":"https://doi.org/10.2220/biomedres.42.153","url":null,"abstract":"<p><p>Biomolecular condensates are membrane-less compartments that are formed through an assembly of proteins and nucleic acids in the cell. Dysregulation of biological condensates has been implicated in diseases such as neurodegeneration and cancer. Ribonucleic acid (RNA) is known to affect the assembly of proteins in vitro, if and how RNA is involved in regulating biomolecular condensates in cells is not well investigated. Here we examined two nuclear proteins, FUS and HP1α, in which RNA was found to have an opposite contribution for the assembly of these proteins. Reduction of nuclear RNA, by inhibiting the transcription, triggered assembly of FUS that had been distributed in the nucleoplasm, whereas it dispersed spontaneously formed HP1α assembly. Notably, the cell cycle-dependent phosphorylation-mimicking substitutions in HP1α promoted its assembly formation. These transcription inhibitor experiments are versatile to examine diverse roles of nuclear RNA in regulating biomolecular condensates, in both physiological and pathological conditions.</p>","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":"42 4","pages":"153-160"},"PeriodicalIF":1.2,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39301596","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":"Assessment of role of pharmacists in managing ailments and ensuring medication safety at Dire Dawa town, East Ethiopia","authors":"Zeray Deresse, Teshome Sosengo, Eyassu Mathewos","doi":"10.35841/0970-938X.32.5.97-103","DOIUrl":"https://doi.org/10.35841/0970-938X.32.5.97-103","url":null,"abstract":"Background: Community pharmacistsare the most accessible healthprofessionals to the general public and pharmacistsareincreasinglybeingrecognized as a source of professionalhealth-relatedadvice. Objective:Theaimofthestudyis to assessroleofpharmacistsin managingailmentsandensuringmedication safety at Dire Dawatown, East Ethiopiafrom Feb20, 2021 to Mar 20, 2021.. Method: Community pharmacy based cross-sectional study was conducted with interview and structured self-administered questionnaires. All community pharmacists found in Dire Dawa town and willing to participate in the study were included. Data was collected from Feb 20, 2021 to Mar 20, 2021. The data is analyzed and presented using tables. Result: In the current study 50 study participants was included. The 87% of the respondents are graduated with first degree and 13% are graduated with masters. All of the respondents replied that they respond effectively to patient’s disease symptoms in their pharmacy and have responsibility to respond to patient’s symptom. The 67% of the respondents replied that that lack of knowledge and influence of pharmaceutical industry is the main factor for inappropriate symptom management in community pharmacy. Disease symptoms managed by the community pharmacists were cold/flue 37[73%], cough 20[40%], diarrhea 14[27%], and inflammation 10[20%]. The 33[67%] of respondents manage disease symptoms by giving medication, while 33[67%] and 14[27%] manage symptoms by advising the patient to visit doctor and to usehomeremediesrespectively. The 33[67%] of respondentsrepliedthatthey ask if thepatienthaveadverse drug reaction before they dispense medication.","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":"338 1","pages":"97-103"},"PeriodicalIF":1.2,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76567299","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}