Analysis of bone regeneration based on the relationship between the orientations of collagen and apatite in mouse femur

In this study, we focused on the preferential orientation of the extracellular matrix (ECM) of bone, since ECM orientation has been shown to significantly affect the mechanical functions of bones. Bone analysis is in most cases based on the premise that the apatite crystallizes on the collagen template such that its c-axis is parallel with the running direction of the collagen fibril. Bone regeneration analysis has also been discussed assuming that the apatite c-axis orientation reflects collagen orientation. To understand the regeneration processes of both collagen and apatite individually, the preferential orientations of apatite and collagen in regenerated bone were simultaneously analyzed using a bone regeneration model of mouse femur with an 0.8-mm drill hole defect. The defects in mouse femur were filled with mineralized bone matrix, which shows an intact mineral density. However, the directions of orientation of the collagen and apatite deviate from the femur longitudinal axis in the regenerated bone. Moreover, electron diffraction analysis revealed that the apatite c-axis aligned along the extended axis of a collagen fibril both in regenerated and intact bones, indicating that the direction of the apatite c-axis is regulated by collagen fibril orientation even in the regenerated bone. In conclusion, the less-oriented apatite crystallite observed in the regenerated bone was shown to be formed due to the less-oriented collagen fibrils.Ozasa R., Nakatsu M., Moriguchi A., et al. Analysis of bone regeneration based on the relationship between the orientations of collagen and apatite in mouse femur. Materials Transactions 61, 381 (2020); https://doi.org/10.2320/matertrans.MT-M2019341

The Quantitative Changes of the Plasma Fibronectin (FN) with Aging

Using an enzyme linked immunosorbent assay (ELISA), we investigated the changes in the amount of human plasma fibronectin (FN) with aging. The increase of plasma FN concentration with aging was slight up to about 50 years of age. Between 60 and 100 years there was a marked increase of plasma FN concentration with aging. The plasma FN concentration from three patients with Werner\u27s syndrome showed higher value than the average of their age group

Case Report Ovarian Seromucinous Borderline Tumor and Clear Cell Carcinoma: An Unusual Combination

Ovarian seromucinous borderline tumors (SMBTs) are rare. They architecturally resemble serous borderline tumors but are much more frequently associated with endometriosis. The coexistence of other tumors with seromucinous tumors is also extremely rare. Here, we report an unusual combination of bilateral ovarian SMBT and clear cell carcinoma associated with polypoid endometriosis of the colon, in a 62-year-old woman. There was no transitional lesion between the two tumors. Immunohistochemistry showed different staining patterns in tumor components. Seromucinous tumor cells were positive for estrogen receptor (ER) and progesterone receptor (PgR) but negative for Napsin A, p504S, and HNF1B. Clear cell tumor cells were positive for Napsin A and p504S and focally positive for HNF1B but negative for ER and PgR. Loss of ARID1A expression was not observed in SMBTs, clear cell tumors, or endometriosis. These findings suggest that these tumors arose from separate endometriosis foci and collided within the same ovary. To the best of our knowledge, this is the first case of this unusual combination of ovarian seromucinous tumor and clear cell carcinoma to be reported in the English literature

Disease modeling of pulmonary fibrosis using human pluripotent stem cell-derived alveolar organoids

iPS細胞を用いて作製した肺胞オルガノイドで間質性肺炎の病態再現に成功 --治療満足度の低い間質性肺炎の治療薬開発に向けて前進--. 京都大学プレスリリース. 2021-11-19.Although alveolar epithelial cells play a critical role in the pathogenesis of pulmonary fibrosis, few practical in vitro models exist to study them. Here, we established a novel in vitro pulmonary fibrosis model using alveolar organoids consisting of human pluripotent stem cell-derived alveolar epithelial cells and primary human lung fibroblasts. In this human model, bleomycin treatment induced phenotypes such as epithelial cell-mediated fibroblast activation, cellular senescence, and presence of alveolar epithelial cells in abnormal differentiation states. Chemical screening performed to target these abnormalities showed that inhibition of ALK5 or blocking of integrin αVβ6 ameliorated the fibrogenic changes in the alveolar organoids. Furthermore, organoid contraction and extracellular matrix accumulation in the model recapitulated the pathological changes observed in pulmonary fibrosis. This human model may therefore accelerate the development of highly effective therapeutic agents for otherwise incurable pulmonary fibrosis by targeting alveolar epithelial cells and epithelial-mesenchymal interactions

Erythropoietin Receptor Signaling Mitigates Renal Dysfunction-Associated Heart Failure by Mechanisms Unrelated to Relief of Anemia

ObjectivesWe examined the effect of asialoerythropoietin (asialoEPO), a nonerythrogenic derivative of erythropoietin (EPO), on renal dysfunction-associated heart failure.BackgroundAlthough EPO is known to exert beneficial effects on cardiac function, the clinical benefits in patients with chronic kidney disease are controversial. It remains to be addressed whether previously reported outcomes were the result of relief of the anemia, adverse effects of EPO, or direct cardiovascular effects.MethodsMice underwent 5/6 nephrectomy to cause renal dysfunction. Eight weeks later, when renal dysfunction was established, anemia and cardiac dysfunction and remodeling were apparent. Mice were then assigned to receive saline (control), recombinant human erythropoietin (rhEPO) at 5,000 IU (714 pmol)/kg, or asialoEPO at 714 pmol/kg, twice/week for 4 weeks.ResultsAlthough only rhEPO relieved the nephrectomy-induced anemia, both rhEPO and asialoEPO significantly and similarly mitigated left ventricular dilation and dysfunction. The hearts of rhEPO- or asialoEPO-treated mice showed less hypertrophy, reflecting decreases in cardiomyocyte hypertrophy and degenerative subcellular changes, as well as significant attenuation of fibrosis, leukocyte infiltration, and oxidative deoxyribonucleic acid damage. These phenotypes were accompanied by restored expression of GATA-4, sarcomeric proteins, and vascular endothelial growth factor and decreased inflammatory cytokines and lipid peroxidation. Finally, myocardial activation was observed of extracellular signal-regulated protein kinase and signal transducer and activator of transcription pathways in the treated mice.ConclusionsEPO receptor signaling exerts direct cardioprotection in an animal model of renal dysfunction-associated heart failure, probably by mitigating degenerative, pro-fibrosis, inflammatory, and oxidative processes but not through relief of anemia

Ecological traits and their diversities of five Zostera marina populations in and around Hiroshima Bay, the Seto Inland Sea, Japan

広島湾および周辺海域の5カ所の生育地のアマモZostera marinaの生態的特性を2004年の繁茂期に調査した。調査場所は広島湾奥部の阿品（St.1），同湾央部の大黒神島（St.2），同湾口部の屋代島（St.3），柳井湾奥部の伊保庄（St.4），および同湾外部に位置する平郡島（St.5）である。アマモの分布水深は生育地により異なり，St.1，St.2では海底でのアオサ類等の堆積により，分布下限水深は1-2m（C.D.L. 基準）までである一方，他の生育地では4-6mまで分布した。アマモの平均現存量は120-180g DWm-2の範囲にあったが，アマモの株のサイズと密度は生育地により異なっていた。平均株密度は生育地により88-278 shoots m-2の範囲であり，St.3およびSt.5では特に浅所で小型の株が密生した。これらの群落では，総現存量に占める地下部現存量の割合が相対的に大きかった。一方，湾奥部に位置するSt.1とSt.4では，アマモの株は大型である一方生育密度は低かった。群落内の底質の粒度組成の相違から，波浪流動等の物理的環境が生育地間で異なることが示唆され，それぞれの場所のアマモの生態的特性はその影響を受けていると考えられた。Ecological traits of five Zostera marina populations in and around Hiroshima Bay were investigated in a luxuriant season of 2004. Study sites were located at the most inner (Ajina; St.1), center (O-kurokami-jima; St. 2) and near the mouth area (northern coast of Yahiro-jima; St. 3) of Hiroshima Bay, and at the inner area (Ihono-sho; St. 4) and the outside (Heigun-jima; St.5) of Yanai Bay which is the strait adjacent to Hiroshima Bay. The distribution depth (C.D.L.) was different among the populations. The lower depth of Zostera distribution was limited to 1-2 m at St.1 and 2 by algal-mat of Ulva spp. and other macroalgae, though it was 4-6 m at St. 3-5. Mean biomass was ranged in 120-180g DWm-2, but shoot size and density was different among the populations. Mean density ranged between 88-278 shoots m-2, and the populations at St.3 and 5 exhibited higher densities with smaller shoots especially in shallow stands of the two population. These stands also exhibited higher proportion of below-ground biomass to total biomass. On the contrary, populations in inner areas (St. 1 and 4) exhibited lower density with larger shoots. Physical conditions such as water motion induced by waves were different among the habitats which were shown in grain size compositions of the sediments, and this could affect the ecological traits of each Z. marina population.本調査は，水産庁委託「生物多様性に配慮したアマモ場造成技術開発調査事業」（平成16～18年度）の一環として実施されたものである

Identification of 45 New Neutron-Rich Isotopes Produced by In-Flight Fission of a 238U Beam at 345 MeV/nucleon

A search for new isotopes using in-flight fission of a 345 MeV/nucleon 238U beam has been carried out at the RI Beam Factory at the RIKEN Nishina Center. Fission fragments were analyzed and identified by using the superconducting in-flight separator BigRIPS. We observed 45 new neutron-rich isotopes: 71Mn, 73,74Fe, 76Co, 79Ni, 81,82Cu, 84,85Zn, 87Ga, 90Ge, 95Se, 98Br, 101Kr, 103Rb, 106,107Sr, 108,109Y, 111,112Zr, 114,115Nb, 115,116,117Mo, 119,120Tc, 121,122,123,124Ru, 123,124,125,126Rh, 127,128Pd, 133Cd, 138Sn, 140Sb, 143Te, 145I, 148Xe, and 152Ba

Management of Hepatocellular Carcinoma in Japan : JSH Consensus Statements and Recommendations 2021 Update

The Clinical Practice Manual for Hepatocellular Carcinoma was published based on evidence confirmed by the Evidence-based Clinical Practice Guidelines for Hepatocellular Carcinoma along with consensus opinion among a Japan Society of Hepatology (JSH) expert panel on hepatocellular carcinoma (HCC). Since the JSH Clinical Practice Guidelines are based on original articles with extremely high levels of evidence, expert opinions on HCC management in clinical practice or consensus on newly developed treatments are not included. However, the practice manual incorporates the literature based on clinical data, expert opinion, and real-world clinical practice currently conducted in Japan to facilitate its use by clinicians. Alongside each revision of the JSH Guidelines, we issued an update to the manual, with the first edition of the manual published in 2007, the second edition in 2010, the third edition in 2015, and the fourth edition in 2020, which includes the 2017 edition of the JSH Guideline. This article is an excerpt from the fourth edition of the HCC Clinical Practice Manual focusing on pathology, diagnosis, and treatment of HCC. It is designed as a practical manual different from the latest version of the JSH Clinical Practice Guidelines. This practice manual was written by an expert panel from the JSH, with emphasis on the consensus statements and recommendations for the management of HCC proposed by the JSH expert panel. In this article, we included newly developed clinical practices that are relatively common among Japanese experts in this field, although all of their statements are not associated with a high level of evidence, but these practices are likely to be incorporated into guidelines in the future. To write this article, coauthors from different institutions drafted the content and then critically reviewed each other’s work. The revised content was then critically reviewed by the Board of Directors and the Planning and Public Relations Committee of JSH before publication to confirm the consensus statements and recommendations. The consensus statements and recommendations presented in this report represent measures actually being conducted at the highest-level HCC treatment centers in Japan. We hope this article provides insight into the actual situation of HCC practice in Japan, thereby affecting the global practice pattern in the management of HCC

Essential Role of Neuron-Enriched Diacylglycerol Kinase (DGK), DGKβ in Neurite Spine Formation, Contributing to Cognitive Function

BACKGROUND: Diacylglycerol (DG) kinase (DGK) phosphorylates DG to produce phosphatidic acid (PA). Of the 10 subtypes of mammalian DGKs, DGKbeta is a membrane-localized subtype and abundantly expressed in the cerebral cortex, hippocampus, and caudate-putamen. However, its physiological roles in neurons and higher brain function have not been elucidated. METHODOLOGY/PRINCIPAL FINDINGS: We, therefore, developed DGKbeta KO mice using the Sleeping Beauty transposon system, and found that its long-term potentiation in the hippocampal CA1 region was reduced, causing impairment of cognitive functions including spatial and long-term memories in Y-maze and Morris water-maze tests. The primary cultured hippocampal neurons from KO mice had less branches and spines compared to the wild type. This morphological impairment was rescued by overexpression of DGKbeta. In addition, overexpression of DGKbeta in SH-SY5Y cells or primary cultured mouse hippocampal neurons resulted in branch- and spine-formation, while a splice variant form of DGKbeta, which has kinase activity but loses membrane localization, did not induce branches and spines. In the cells overexpressing DGKbeta but not the splice variant form, DGK product, PA, was increased and the substrate, DG, was decreased on the plasma membrane. Importantly, lower spine density and abnormality of PA and DG contents in the CA1 region of the KO mice were confirmed. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that membrane-localized DGKbeta regulates spine formation by regulation of lipids, contributing to the maintenance of neural networks in synaptic transmission of cognitive processes including memory