Publications by authors named "Yosuke Mizuno"

118 Publications

Contact Co-culture of Osteoblasts and Sympathetic Neuronal Cells Promotes Differentiation of Both Cell Types.

In Vivo 2022 Jul-Aug;36(4):1608-1614

Department of Oral and Maxillofacial Surgery, Saitama Medical University, Saitama, Japan;

Background/aim: Bone and nerve reconstruction is crucial for treating various diseases of the oral and maxillofacial region. However, the relationship between bone and nervous system has not yet been fully elucidated. Therefore, we aimed to examine the interaction between osteoblasts and neuronal cells in contact co-culture.

Material And Methods: Osteoblasts and sympathetic neuronal cells were grown in contact co-culture. Microscopic observation, a mineralization assay, immunofluorescence staining, and DNA microarray analysis were performed.

Results: Microscopic observation revealed morphological changes in the osteoblasts that were cocultured with sympathetic neuronal cells. Contact co-culture enhanced osteoblast calcification and upregulated a neuronal marker. Not only osteoblast differentiation signals, but also neuronal signals were increased in murine osteoblasts that were co-cultured with rat sympathetic neuronal cells. We also found that not only rat neuron differentiation signals, but also osteoblast differentiation signals were increased in rat sympathetic neuronal cells that were co-cultured with murine osteoblasts.

Conclusion: In the contact co-culture with osteoblasts and sympathetic neuronal cells, the sympathetic neuronal cells promoted osteoblast differentiation, and the osteoblasts promoted neuron differentiation.
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http://dx.doi.org/10.21873/invivo.12871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301437PMC
June 2022

Familial Hyperaldosteronism Type 3 with a Rapidly Growing Adrenal Tumor: An In Situ Aldosterone Imaging Study.

Curr Issues Mol Biol 2021 Dec 28;44(1):128-138. Epub 2021 Dec 28.

Department of Urology and Andrology, Kansai Medical University, Osaka 573-1191, Japan.

Primary aldosteronism is most often caused by aldosterone-producing adenoma (APA) and bi-lateral adrenal hyperplasia. Most APAs are caused by somatic mutations of various ion channels and pumps, the most common being the inward-rectifying potassium channel . Germ line mutations of cause familial hyperaldosteronism type 3 (FH3), which is associated with severe hyperaldosteronism and hypertension. We present an unusual case of FH3 in a young woman, first diagnosed with primary aldosteronism at the age of 6 years, with bilateral adrenal hyperplasia, who underwent unilateral adrenalectomy (left adrenal) to alleviate hyperaldosteronism. However, her hyperaldosteronism persisted. At the age of 26 years, tomography of the remaining adrenal revealed two different adrenal tumors, one of which grew substantially in 4 months; therefore, the adrenal gland was removed. A comprehensive histological, immunohistochemical, and molecular evaluation of various sections of the adrenal gland and in situ visualization of aldosterone, using matrix-assisted laser desorption/ionization imaging mass spectrometry, was performed. Aldosterone synthase (CYP11B2) immunoreactivity was observed in the tumors and adrenal gland. The larger tumor also harbored a somatic β-catenin activating mutation. Aldosterone visualized in situ was only found in the subcapsular regions of the adrenal and not in the tumors. Collectively, this case of FH3 presented unusual tumor development and histological/molecular findings.
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http://dx.doi.org/10.3390/cimb44010010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8929039PMC
December 2021

Dynamic strain measurement in Brillouin optical correlation-domain sensing facilitated by dimensionality reduction and support vector machine.

Opt Express 2022 Apr;30(9):15616-15633

Brillouin optical correlation-domain sensing enables high-speed Brillouin gain spectrum (BGS) measurement at random positions along the optical fiber. To extract the Brillouin frequency shift (BFS) that reflects the real-time strain information, machine learning methods of principal components analysis (PCA) and support vector machine (SVM) are used in the signal processing for the BGSs. The performances of dimensionality reduction by PCA and SVM based on classification and regression are analyzed and compared. The experiment demonstrates an 8 kHz BGS acquisition repetition rate and an average BFS extraction time of 0.0104 ms, which is 27.3 times faster than the conventional method with no PCA. The proposed methods realize a real-time dynamic strain measurement at the frequency of 40 Hz.
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http://dx.doi.org/10.1364/OE.455454DOI Listing
April 2022

Analysis of Masticatory Muscle Tendon-aponeurosis Hyperplasia by Using Next-generation Sequencing.

In Vivo 2022 Mar-Apr;36(2):563-569

Department of Oral and Maxillofacial Surgery, Saitama Medical University, Saitama, Japan;

Background/aim: Masticatory muscle tendon-aponeurosis hyperplasia (MMTAH) is a disease associated with a mouth opening limitation. Here, we conducted a bioinformatics analysis to examine gene expression patterns in patients with MMTAH in comparison to those with facial deformity (FD).

Materials And Methods: Seven MMTAH patients and three FD patients were recruited. We conducted RNA sequencing analysis, quantitative reverse transcription polymerase chain reaction and immunoblot analysis.

Results: Of the identified 19,767 mapped read tags that showed clear differential expression, 2,471 genes were significantly up-regulated and 2,849 genes were significantly down-regulated in patients with MMTAH compared to those in patients with FD. Among the up-regulated genes, ten genes were significantly increased. The distribution of up-regulated and down-regulated genes at different ages tended to be similar. Moreover, the protein levels of Ankyrin Repeat Domain 2, Troponin T1 and myosin heavy chain 7, which are associated with slow twitch fibers and mechanical loading, were strongly expressed in patients with MMTAH compared to those in patients with FD.

Conclusion: The gene expression pattern in MMTAH patients was similar regardless of age. As the transition of fast-to-slow twitch in the skeletal muscle is induced by mechanical loading, and up-regulation of slow twitch molecules was observed in MMTAH patients, mechanical loading is suggested to be implicated in MMTAH.
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http://dx.doi.org/10.21873/invivo.12738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8931884PMC
March 2022

Leriche syndrome diagnosed due to polytrauma: a case report.

Int J Emerg Med 2022 Feb 4;15(1). Epub 2022 Feb 4.

Advanced Critical Care Center, Gifu University Hospital, 1-1 Yanagido, Gifu, 501-1194, Japan.

Background: Leriche syndrome is caused by atherosclerosis and is often characterized by symptoms such as intermittent claudication and numbness and coldness of the lower limbs. Its exact prevalence and incidence are unknown because it is a rare disease. We report a case of Leriche syndrome diagnosed incidentally on trauma pan-scan computed tomography (CT).

Case Presentation: A 61-year-old Asian male was driving a passenger car and had a head-on collision with a dump truck that required an emergency call. The patient was transported to our hospital in a doctor's helicopter. Physical examination revealed the following vital signs: respiratory rate, 23 breaths per min; SpO, 98% under a 10-L administration mask; pulse rate, 133 beats per min; blood pressure, 142/128 mmHg; Focused Assessment with Sonography for Trauma, positive; Glasgow Coma Scale assessment, E3V5M6; and body temperature, 35.9 °C. Trauma pan-scan CT showed bilateral mandibular fractures, bilateral multiple rib fractures, bilateral pneumothorax, sternal fractures, hematoma around thoracic spine, small bowel perforation, mesenteric injury, right clavicle fracture, right ankle debridement injury, and thrombotic occlusion from just above the abdominal aortic bifurcation to the bilateral common iliac arteries. Although thrombotic occlusion needed to be differentiated from traumatic aortic injury, the presence of collateral blood vessels led to the diagnosis of Leriche syndrome, and conservative treatment was performed. Damage control surgery was required for the small bowel injuries. From the second day of admission, the patient was treated with continuous intravenous heparin and prostaglandin preparations. However, impaired blood flow and reperfusion injury in the right lower extremity progressed. On the fifth day of admission, right thigh amputation was performed. The patient required renal replacement therapy for 2 weeks starting from the third day of admission.

Conclusions: In this case, conservative therapy was initially chosen for Leriche syndrome. However, the complex factors in the acute phase of trauma led to development of hemorrhagic necrosis, requiring amputation of the lower extremity. Our findings indicate the need to carefully consider the unique factors affecting Leriche syndrome patients when considering treatment indications and choices for trauma.
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http://dx.doi.org/10.1186/s12245-022-00411-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8903668PMC
February 2022

Induction of memory-like CD8+ T cells and CD4+ T cells from human naive T cells in culture.

Clin Exp Immunol 2022 01;207(1):95-103

Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, Saitama, Japan.

Memory T cells are crucial players in vertebrate adaptive immunity but their development is incompletely understood. Here, we describe a method to produce human memory-like T cells from naive human T cells in culture. Using commercially available human T-cell differentiation kits, both purified naive CD8+ T cells and purified naive CD4+ T cells were activated via T-cell receptor signaling and appropriate cytokines for several days in culture. All the T-cell activators were then removed from the medium and the cultures were continued in hypoxic condition (1% O2 atmosphere) for several more days; during this period, most of the cells died, but some survived in a quiescent state for a month. The survivors had small round cell bodies, expressed differentiation markers characteristic of memory T cells and restarted proliferation when the T-cell activators were added back. We could also induce memory-like T cells from naive human T cells without hypoxia, if we froze the activated T cells or prepared the naive T cells from chilled filter buffy coats.
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http://dx.doi.org/10.1093/cei/uxab012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8802181PMC
January 2022

Measuring the Concentration of Serum Syndecan-1 to Assess Vascular Endothelial Glycocalyx Injury During Hemodialysis.

Front Med (Lausanne) 2021 23;8:791309. Epub 2021 Dec 23.

Department of Pharmacy, Gifu University Hospital, Gifu, Japan.

Glycocalyx is present on the surface of healthy endothelium, and the concentration of serum syndecan-1 can serve as an injury marker. This study aimed to assess endothelial injury using serum syndecan-1 as a marker of endothelial glycocalyx injury in patients who underwent hemodialysis. In this single-center, retrospective, observational study, 145 patients who underwent hemodialysis at the Gifu University Hospital between March 2017 and December 2019 were enrolled. The median dialysis period and time were 63 months and 3.7 h, respectively. The serum syndecan-1 concentration significantly increased from 124.6 ± 107.8 ng/ml before hemodialysis to 229.0 ± 138.1 ng/ml after hemodialysis ( < 0.001). Treatment with anticoagulant nafamostat mesylate inhibited hemodialysis-induced increase in the levels of serum syndecan-1 in comparison to unfractionated heparin. Dialysis time and the change in the syndecan-1 concentration were positively correlated. Conversely, the amount of body fluid removed and the changes in the syndecan-1 concentration were not significantly correlated. The reduction in the amount of body fluid removed and dialysis time inhibited the change in the syndecan-1 levels before and after hemodialysis. In conclusion, quantitative assessment of the endothelial glycocalyx injury during hemodialysis can be performed by measuring the serum syndecan-1 concentration, which may aid in the selection of appropriate anticoagulants, reduction of hemodialysis time, and the amount of body fluid removed.
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http://dx.doi.org/10.3389/fmed.2021.791309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8733596PMC
December 2021

Comparative study of hydrophobically modified gelatin-based sealant with commercially available sealants.

J Biomed Mater Res A 2022 04 5;110(4):909-915. Epub 2021 Dec 5.

Graduate School of Science and Technology, University of Tsukuba, Ibaraki, Japan.

Air leakage is one of the major complications related to pulmonary surgeries. To reduce this complication, we developed a decyl group (C10)-modified Alaska pollock gelatin (ApGltn) (C10-ApGltn) sealant and evaluated its practical performance against commercially available sealants, Beriplast® and DuraSeal®. C10-ApGltn was synthesized by reductive amination of the amino groups in ApGltn with decanal. C10-ApGltn was crosslinked with a poly(ethylene glycol)-based crosslinker to form a tissue sealant. The crosslinking time of the C10-ApGltn sealant was fast enough for curing on tissue and application as a spray system. Although the percent swelling of C10-ApGltn and DuraSeal was significantly greater than Beriplast, C10-ApGltn and DuraSeal exhibited excellent tissue sealing properties on pleura tissue under a long-term moist condition. Additionally, C10-ApGltn and DuraSeal did not cause severe inflammatory responses in a rat subcutaneous example. Therefore, C10-ApGltn sealant had comparable tissue sealing properties to DuraSeal under a moist condition, indicating the potential of C10-ApGltn sealant for pulmonary surgeries.
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http://dx.doi.org/10.1002/jbm.a.37339DOI Listing
April 2022

Neural network-assisted signal processing in Brillouin optical correlation-domain sensing for potential high-speed implementation.

Opt Express 2021 Oct;29(22):35474-35489

The general neural networks (NNs) based on classification convert the Brillouin frequency shift (BFS) extraction in Brillouin-based distributed sensing to a problem in which the possible BFS output of the sensing system belongs to a finite number of discrete values. In this paper, we demonstrate a method of applying NNs with adaptive BFS incremental steps to signal processing for Brillouin optical correlation-domain sensing and achieve higher accuracy and operation speed. The comparison with the conventional curving fitting method shows that the NN improves the BFS measurement accuracy by 2-3 times and accelerates the signal processing speed by 1000 times for simulated signals. The experimental results demonstrate the NN provides 1.6-2.7 times enhancement for BFS measurement accuracy and 5000 times acceleration for the BFS extraction speed. This method supplies a potential solution to online signal processing for real-time Brillouin sensing.
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http://dx.doi.org/10.1364/OE.439215DOI Listing
October 2021

PIC methods in astrophysics: simulations of relativistic jets and kinetic physics in astrophysical systems.

Living Rev Comput Astrophys 2021 8;7(1). Epub 2021 Jul 8.

Tsung-Dao Lee Institute and School of Physics and Astronomy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240 People's Republic of China.

The Particle-In-Cell (PIC) method has been developed by Oscar Buneman, Charles Birdsall, Roger W. Hockney, and John Dawson in the 1950s and, with the advances of computing power, has been further developed for several fields such as astrophysical, magnetospheric as well as solar plasmas and recently also for atmospheric and laser-plasma physics. Currently more than 15 semi-public PIC codes are available which we discuss in this review. Its applications have grown extensively with increasing computing power available on high performance computing facilities around the world. These systems allow the study of various topics of astrophysical plasmas, such as magnetic reconnection, pulsars and black hole magnetosphere, non-relativistic and relativistic shocks, relativistic jets, and laser-plasma physics. We review a plethora of astrophysical phenomena such as relativistic jets, instabilities, magnetic reconnection, pulsars, as well as PIC simulations of laser-plasma physics (until 2021) emphasizing the physics involved in the simulations. Finally, we give an outlook of the future simulations of jets associated to neutron stars, black holes and their merging and discuss the future of PIC simulations in the light of petascale and exascale computing.
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http://dx.doi.org/10.1007/s41115-021-00012-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8549980PMC
July 2021

A Novel Alaska Pollock Gelatin Sealant Shows Higher Bonding Strength and Nerve Regeneration Comparable to That of Fibrin Sealant in a Cadaveric Model and a Rat Model.

Plast Reconstr Surg 2021 Nov;148(5):742e-752e

From the Department of Orthopedic Surgery, Electron Microscope Laboratory, and Department of Neuropsychiatry, Keio University School of Medicine; Graduate School of Pure and Applied Sciences, University of Tsukuba; and Polymers and Biomaterials Field, Research Center for Functional Materials, National Institute for Materials Science.

Background: A novel biocompatible sealant composed of Alaska pollock-derived gelatin (ApGltn) has recently shown good burst strength and biocompatibility in a porcine aorta. The purpose of this study was to investigate the bonding strength and biocompatibility of the ApGltn sealant in transected digital nerves of fresh frozen cadavers and in the sciatic nerves of a rat model.

Methods: Eighty human digital nerves of fresh frozen cadavers were transected for biomechanical traction testing. They were treated with four surgical interventions: (1) suture plus ApGltn sealant; (2) suture; (3) ApGltn sealant; and (4) fibrin sealant. Forty-three sciatic nerves of male Wistar rats were used for functional and histopathologic evaluation. They were treated with six surgical interventions: (1) suture plus ApGltn sealant; (2) suture; (3) ApGltn sealant; (4) fibrin sealant; (5) resection with a 5-mm gap (10 rats per group); and (6) sham operation (three rats). Macroscopic confirmation, muscle weight measurement, and histopathologic findings including G-ratio were examined 8 weeks after the procedure.

Results: The maximum failure load of the ApGltn sealant was significantly higher than that of a fibrin sealant (0.22 ± 0.05 N versus 0.06 ± 0.04 N). The maximum failure load of the ApGltn sealant was significantly lower that of suture plus ApGltn sealant (1.37 N) and suture (1.27 N). Functional evaluation and histologic examination showed that sciatic nerves repaired with ApGltn sealant showed similar nerve recovery compared to repair with the suture and fibrin sealant.

Conclusion: The ApGltn sealant showed higher bonding strength and equal effect of nerve regeneration when compared with the fibrin sealant.
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http://dx.doi.org/10.1097/PRS.0000000000008489DOI Listing
November 2021

Fish Gelatin-Based Absorbable Dural Sealant with Anti-inflammatory Properties.

ACS Biomater Sci Eng 2021 10 1;7(10):4991-4998. Epub 2021 Oct 1.

Graduate School of Science and Technology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan.

Cerebrospinal fluid (CSF) leakage from the dura mater during craniotomy is a common complication, which is associated with infection, meningitis, pneumocephalus, and delayed wound healing. In the present study, we developed an absorbable fish gelatin-based anti-inflammatory sealant for dura mater sealing to prevent CSF leakage. Gelatin derived from Alaska pollock (ApGltn) was modified with α-linolenic acid (ALA), an omega-3 fatty acid that exhibits anti-inflammatory properties, and cross-linked with a poly(ethylene glycol)-based cross-linker to develop ALA-ApGltn sealant (ALA-Seal). ALA-Seal demonstrated a higher storage modulus and tangent delta (tan δ) compared with those of the original ApGltn sealant (Org-Seal). The swelling ratio of ALA-Seal was markedly lower than that of DuraSeal, a commercially available dural sealant. Ex vivo burst strength measurements using porcine dura mater indicated that there was no significant difference between DuraSeal and ALA-Seal, despite ALA-Seal having an order of magnitude lower storage modulus. The anti-inflammatory properties of ALA-Seal, evaluated using brain microglial cells, were considerably higher than those of DuraSeal and Org-Seal, with a minimal adverse effect on cell viability. Therefore, compared to DuraSeal, ALA-Seal is a potential dural sealant with a lower swelling ratio, similar burst strength, and higher anti-inflammatory properties, which may prevent CSF leakage.
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http://dx.doi.org/10.1021/acsbiomaterials.1c00734DOI Listing
October 2021

Effect of cryoprecipitate transfusion therapy in patients with postpartum hemorrhage: a retrospective cohort study.

Sci Rep 2021 09 16;11(1):18458. Epub 2021 Sep 16.

Advanced Critical Care Center, Gifu University Hospital, 1-1 Yanagido, Gifu, 501-1194, Japan.

To evaluate the effect of cryoprecipitate (CRYO) transfusion in women referred for postpartum hemorrhage (PPH). This retrospective cohort study included patients with primary PPH referred to Gifu University Hospital between April 2013 and March 2020. We analyzed the effect of CRYO transfusion on fluid balance 24 h after the initial examination using a multivariable linear regression model adjusted for several confounding variables. To evaluate whether outcomes were modified by active bleeding, an interaction term of CRYO*active bleeding was incorporated into the multivariable model. We identified 157 women: 38 in the CRYO group (cases) and 119 in the control group. Fluid balance in the aforementioned period tended to decrease in the CRYO group compared with that in the control group (coefficient - 398.91; 95% CI - 1298.08 to + 500.26; p = 0.382). Active bleeding on contrast-enhanced computed tomography affected the relationship between CRYO transfusion and fluid balance (p = 0.016). Other outcomes, except for the overall transfusion requirement, were not significantly different; however, the interaction effect of active bleeding was significant (p = 0.016). CRYO transfusion may decrease the fluid balance in the first 24 h in PPH patients, especially in those without active bleeding.
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http://dx.doi.org/10.1038/s41598-021-97954-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8445974PMC
September 2021

Postmortem diagnosis of pulmonary tumor thrombotic microangiopathy with rapid exacerbation in a patient with gastric cancer: a case report.

Int J Emerg Med 2021 Sep 15;14(1):53. Epub 2021 Sep 15.

Advanced Critical Care Center, Gifu University Hospital, 1-1 Yanagido, Gifu, 501-1194, Japan.

Background: Pulmonary tumor thrombotic microangiopathy (PTTM) is a condition that involves the development of pulmonary hypertension due to the presence of microscopic tumor emboli of the peripheral pulmonary arteries. Here, we report a case of rapidly exacerbating PTTM associated with gastric cancer that was identified postmortem through pathological autopsy.

Case Presentation: A 52-year-old Asian woman who experienced anterior chest pain while coughing visited the orthopedic department of the Gifu University Hospital. She was diagnosed as having multiple osteolytic bone metastases throughout her body and was subsequently scheduled to undergo combined positron emission tomography and computed tomography (CT) to search for a primary lesion. However, 4 days after her visit to the orthopedic department, she was unable to stand up and thus visited the emergency department. At the time of admission, physical examination results revealed that she had a percutaneous oxygen saturation level of 90% (on room air) and cyanosis and that she was in a state of hemodynamic shock. Laboratory test results revealed elevated levels of fibrin degradation products and D-dimer in her blood. Chest CT results were normal. She was admitted to the hospital's general ward for follow-up but soon entered a gradually worsening state of shock and respiratory failure. Electrocardiography revealed findings associated with right heart strain; however, contrast-enhanced CT did not reveal the presence of pulmonary embolism. She was admitted to the intensive care unit and was treated for pulmonary hypertension; however, 45 h after her arrival at the hospital, she died of respiratory failure. A pathological autopsy revealed the presence of gastric cancer, tumor microemboli, and fibrous intimal thickening of the peripheral arteries of both lungs; thus, a diagnosis of PTTM was made.

Conclusions: In patients with carcinoma of unknown primary site and pulmonary hypertension with pulmonary embolism ruled out by CT, emergency physicians and intensivists must consider the possibility of PTTM, which represents an oncologic emergency, and initiate chemotherapy administration as soon as possible.
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http://dx.doi.org/10.1186/s12245-021-00377-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444540PMC
September 2021

Two DNA binding domains of MGA act in combination to suppress ectopic activation of meiosis-related genes in mouse embryonic stem cells.

Stem Cells 2021 11 14;39(11):1435-1446. Epub 2021 Jul 14.

Division of Biomedical Sciences, Research Center for Genomic Medicine, Saitama Medical University, Yamane Hidaka, Saitama, Japan.

Although the physiological meaning of the high potential of mouse embryonic stem cells (ESCs) for meiotic entry is not understood, a rigid safeguarding system is required to prevent ectopic onset of meiosis. PRC1.6, a non-canonical PRC1, is known for its suppression of precocious and ectopic meiotic onset in germ cells and ESCs, respectively. MGA, a scaffolding component of PRC1.6, bears two distinct DNA-binding domains termed bHLHZ and T-box. However, it is unclear how this feature contributes to the functions of PRC1.6. Here, we demonstrated that both domains repress distinct sets of genes in murine ESCs, but substantial numbers of meiosis-related genes are included in both gene sets. In addition, our data demonstrated that bHLHZ is crucially involved in repressing the expression of Meiosin, which plays essential roles in meiotic entry with Stra8, revealing at least part of the molecular mechanisms that link negative and positive regulation of meiotic onset.
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http://dx.doi.org/10.1002/stem.3433DOI Listing
November 2021

A population of neurons that produce hugin and express the diuretic hormone 44 receptor gene projects to the corpora allata in Drosophila melanogaster.

Dev Growth Differ 2021 May 17;63(4-5):249-261. Epub 2021 Jun 17.

Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Tsukuba, Japan.

The corpora allata (CA) are essential endocrine organs that biosynthesize and secrete the sesquiterpenoid hormone, namely juvenile hormone (JH), to regulate a wide variety of developmental and physiological events in insects. CA are directly innervated with neurons in many insect species, implying the innervations to be important for regulating JH biosynthesis. Although this is also true for the model organism Drosophila melanogaster, neurotransmitters produced in the CA-projecting neurons are yet to be identified. In this study on D. melanogaster, we aimed to demonstrate that a subset of neurons producing the neuropeptide hugin, the invertebrate counterpart of the vertebrate neuromedin U, directly projects to the adult CA. A synaptic vesicle marker in the hugin neurons was observed at their axon termini located on the CA, which were immunolabeled with a newly-generated antibody to the JH biosynthesis enzyme JH acid O-methyltransferase. We also found the CA-projecting hugin neurons to likely express a gene encoding the specific receptor for diuretic hormone 44 (Dh44). Moreover, our data suggest that the CA-projecting hugin neurons have synaptic connections with the upstream neurons producing Dh44. Unexpectedly, the inhibition of CA-projecting hugin neurons did not significantly alter the expression levels of the JH-inducible gene Krüppel-homolog 1, which implies that the CA-projecting neurons are not involved in JH biosynthesis but rather in other known biological processes. This is the first study to identify a specific neurotransmitter of the CA-projecting neurons in D. melanogaster, and to anatomically characterize a neuronal pathway of the CA-projecting neurons and their upstream neurons.
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http://dx.doi.org/10.1111/dgd.12733DOI Listing
May 2021

Brillouin optical correlation-domain reflectometry based on arbitrary waveform modulation: a theoretical study.

Opt Express 2021 Apr;29(9):13794-13805

We put forward a new theory on Brillouin optical correlation-domain reflectometry (BOCDR) based on arbitrary waveform modulation. We derive a universal representation for the spatial resolution using the foot convexity of the beat spectrum. This result well explains the previous results based on sinusoidal modulation, and thus our theory is the consistent extension of the conventional theory on BOCDR. This representation is also applicable to the spatial resolution evaluation of more complicated modulation schemes, such as the combined use of intensity and frequency modulations even with some phase delay. We also discuss what kinds of modulation waveforms should not be employed for distributed measurement to ensure high spatial resolution.
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http://dx.doi.org/10.1364/OE.422873DOI Listing
April 2021

Disseminated intravascular coagulation as a complication of bursitis: angiogenesis and repetitive bleeding as potential factors for disseminated intravascular coagulation: a case report.

J Med Case Rep 2021 Apr 10;15(1):155. Epub 2021 Apr 10.

Department of Anesthesia and Perioperative Medicine, Ehime University Graduate School of Medicine, Toon, Ehime, 791-0295, Japan.

Background: Malignant tumors, such as acute leukemia and solid cancers, frequently cause disseminated intravascular coagulation. However, cases of disseminated intravascular coagulation as a complication of bursitis were not reported previously.

Case Presentation: A 72-year-old Japanese woman was scheduled to undergo resection of a rapidly growing subcutaneous tumor-like lesion on her left back. Preoperative blood tests suggested disseminated intravascular coagulation. The resected lesion was cystic tumor containing a hematoma. After the operation, the patient completely recovered from disseminated intravascular coagulation, indicating that disseminated intravascular coagulation in this case was caused by the tumor. Pathological examination of the resected tumor revealed considerable fibrin deposition and angiogenesis on the cyst wall, which was presumably a response to inflammation and indicated presence of repetitive intratumoral bleeding, subsequently leading to a diagnosis of chronic hemorrhagic bursitis.

Conclusions: Clinicians should note that, despite being benign, soft-tissue tumors accompanied by inflammation with angiogenesis and repetitive intratumoral bleeding can cause disseminated intravascular coagulation, albeit rarely.
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http://dx.doi.org/10.1186/s13256-021-02773-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035724PMC
April 2021

Correction: Prevention of pulmonary air leaks using a biodegradable tissue-adhesive fiber sheet based on Alaska pollock gelatin modified with decanyl groups.

Biomater Sci 2021 Feb;9(3):1044-1046

Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan and Polymers and Biomaterials Field, Research Center for Functional Materials, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan.

Correction for 'Prevention of pulmonary air leaks using a biodegradable tissue-adhesive fiber sheet based on Alaska pollock gelatin modified with decanyl groups' by Hiroaki Ichimaru et al., Biomater. Sci., 2021, DOI: 10.1039/d0bm01302a.
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http://dx.doi.org/10.1039/d0bm90116dDOI Listing
February 2021

Evaluation of an octyl group-modified Alaska pollock gelatin-based surgical sealant for prevention of postoperative adhesion.

Acta Biomater 2021 02 14;121:328-338. Epub 2020 Dec 14.

Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan; Polymers and Biomaterials Field, Research Center for Functional Materials, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan. Electronic address:

Postoperative adhesion can lead to an increase in the number of surgeries required, longer operation times, and high medical costs, resulting in the quality of life of the patient being lowered. To address these clinical problems, we developed a surgical sealant with anti-adhesion properties for the prevention of postoperative adhesion following application to the large intestine surface. The developed sealant was composed of octyl (C8) group-modified Alaska pollock-derived gelatin (C8-ApGltn) and a poly(ethylene)glycol-based 4-armed crosslinker (4S-PEG) (C8-ApGltn/4S-PEG sealant). Hydrophobic modification of the ApGltn molecule with C8 groups effectively enhanced both the burst strength on the large intestine surface and the bulk modulus. An in vitro anti-adhesion test indicated that cured C8-ApGltn/4S-PEG sealant adhered to the large intestine surface showed low adhesive strength compared with commercial anti-adhesion film. Besides, cured C8-ApGltn/4S-PEG sealant effectively inhibited albumin permeation and penetration of L929 fibroblasts. In vivo experiments using a rat peritoneal anti-adhesion model showed that C8-ApGltn/4S-PEG sealant acted as a sealing barrier on the target cecum surface and also provided an anti-adhesion barrier to prevent postoperative adhesion between the peritoneum and cecum. C8-ApGltn/4S-PEG sealant showed sufficient cytocompatibility and biodegradability and therefore has potential for use in gastroenterological surgery.
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http://dx.doi.org/10.1016/j.actbio.2020.12.025DOI Listing
February 2021

Prevention of pulmonary air leaks using a biodegradable tissue-adhesive fiber sheet based on Alaska pollock gelatin modified with decanyl groups.

Biomater Sci 2021 Feb 25;9(3):861-873. Epub 2020 Nov 25.

Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan.

Tissue adhesives have been widely used in surgery to treat pulmonary air leaks. However, conventional adhesives have poor interfacial strength under wet conditions. To overcome this clinical problem, we modified Alaska pollock-derived gelatin to include decanyl (C10) groups (C10-ApGltn) and used electrospinning to create a tissue-adhesive fiber sheet (AdFS). C10-AdFS showed higher burst strength when adhering to porcine pleura compared with a sheet of original ApGltn (Org-ApGltn). Hematoxylin-eosin-stained sections after burst experiments reveal that a dense C10-AdFS layer remained on the surface of the porcine pleura. The effect of the degree of C10 modification of ApGltn on the burst strength was evaluated. ApGltn with a C10 modification ratio of 13 mol% amino groups (13C10-AdFS) exhibited the highest burst strength. Furthermore, from ex vivo experiments with extracted rat lung, 13C10-AdFS exhibited a higher burst strength (41 cm HO) than Org-AdFS. The decanyl groups in 13C10-AdFS interacted with the hydrophobic proteins and the lipid bilayers of the cells, resulting in the high interfacial strength between 13C10-AdFS and the pleura. Moreover, 13C10-AdFS samples implanted subcutaneously in the backs of rats were completely degraded within 21 days without any severe inflammation. These results show that 13C10-AdFS is a promising adhesive material for the treatment of pulmonary air leaks.
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http://dx.doi.org/10.1039/d0bm01302aDOI Listing
February 2021

Gravitational Test beyond the First Post-Newtonian Order with the Shadow of the M87 Black Hole.

Phys Rev Lett 2020 Oct;125(14):141104

Shanghai Astronomical Observatory, Chinese Academy of Sciences, 80 Nandan Road, Shanghai 200030, People's Republic of China.

The 2017 Event Horizon Telescope (EHT) observations of the central source in M87 have led to the first measurement of the size of a black-hole shadow. This observation offers a new and clean gravitational test of the black-hole metric in the strong-field regime. We show analytically that spacetimes that deviate from the Kerr metric but satisfy weak-field tests can lead to large deviations in the predicted black-hole shadows that are inconsistent with even the current EHT measurements. We use numerical calculations of regular, parametric, non-Kerr metrics to identify the common characteristic among these different parametrizations that control the predicted shadow size. We show that the shadow-size measurements place significant constraints on deviation parameters that control the second post-Newtonian and higher orders of each metric and are, therefore, inaccessible to weak-field tests. The new constraints are complementary to those imposed by observations of gravitational waves from stellar-mass sources.
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http://dx.doi.org/10.1103/PhysRevLett.125.141104DOI Listing
October 2020

Anti-Inflammatory and Tissue Adhesion Properties of an α-Linolenic Acid-Modified Gelatin-Based In Situ Hydrogel.

ACS Appl Bio Mater 2020 Sep 9;3(9):6204-6213. Epub 2020 Sep 9.

Graduate School of Science and Technology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan.

Poly unsaturated fatty acids (PUFAs)-natural chemicals derived from fish and nuts-have anti-inflammatory and antioxidative properties that are attributed to the inhibition of inflammatory pathways and the radical scavenging activity of their double bonds. In this study, Alaska pollock-derived gelatin (ApGltn), which has a low sol-gel transition temperature, was modified with α-linolenic acid (ALA) to obtain ALA-ApGltn, which was subsequently cross-linked to give a hydrogel (ALA-gel). Although the elastic modulus of ALA-gel and nonmodified ApGltn gel (Org-gel) was almost the same, ALA-gel exhibited a higher tan δ as well as a lower swelling ratio and enzymatic degradation rate than Org-gel. Moreover, ALA-gel showed enhanced tissue adhesive strength compared with a commercial fibrin adhesive. The concentration of a tumor necrosis factor (TNF)-α secreted from macrophage-like cells and the intracellular mitochondrial activity indicated that ALA-ApGltn exerted anti-inflammatory effects and maintained cell viability compared with the higher toxicity nonconjugated ALA. In addition, ALA-gel demonstrated suppressed formation of lamellipodia and secretion of TNF-α. ALA-gel therefore has potential as an adhesive biomaterial for wound sealing and treating burn injuries.
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http://dx.doi.org/10.1021/acsabm.0c00737DOI Listing
September 2020

Tissue-sealing and anti-adhesion properties of an in situ hydrogel of hydrophobically-modified Alaska pollock-derived gelatin.

Int J Biol Macromol 2020 Nov 15;163:2365-2373. Epub 2020 Sep 15.

Graduate School of Science and Technology, Degree Programs in Pure and Applied Sciences, University of Tsukuba, Japan; Polymers and Biomaterials Field, Research Center for Functional Materials, National Institute for Materials Science, Japan. Electronic address:

Anastomotic leakage and tissue adhesion are significant complications associated with colorectal surgeries, such as the resection of colorectal cancer. However, an effective biomedical apparatus has yet to be developed to address both complications. In the present study, we developed a tissue-sealing, anti-adhesive hydrogel composed of decyl group-modified gelatin (C10-ApGltn) and a poly (ethylene glycol)-based crosslinker. C10-ApGltn based hydrogel (C10-gel) demonstrated increased elastic modulus and suppressed swelling ratio compared with the unmodified ApGltn. Furthermore, C10-gel effectively sealed a water leakage model of intestine tissue and prevented contact between two intestinal tissue samples. In vivo experiments revealed that C10-gel degraded almost entirely in 28 days and prevented cell infiltration for 14 days, which effectively inhibits tissue adhesion. Therefore, C10-gel is a biocompatible hydrogel that can be used to mitigate or prevent anastomotic leakage and prevent tissue adhesion in colorectal surgery.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.09.084DOI Listing
November 2020

Asia-Pacific Optical Sensors Conference: focus issue introduction.

Opt Express 2020 Jul;28(15):21745-21748

This feature issue of Optics Express contains 17 articles expanding on recent advances in optical sensors presented at the eighth Asia-Pacific Optical Sensors Conference (APOS 2019) held in Auckland, New Zealand, from November 19 to 22, 2019. These articles span sensing for real-time positioning, refractive indices, strain, gas, and temperature using a variety of methods including photoacoustic computed tomography, coherent optical frequency-modulated continuous-wave interferometry, enhanced Bragg gratings, and phase-sensitive optical frequency-domain reflectometry.
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http://dx.doi.org/10.1364/OE.401277DOI Listing
July 2020

Intracranial anaplastic solitary fibrous tumor/hemangiopericytoma: immunohistochemical markers for definitive diagnosis.

Neurosurg Rev 2021 Jun 15;44(3):1591-1600. Epub 2020 Jul 15.

Department of Neurosurgery, Ehime University Graduate School of Medicine, 454 Shitsukawa, Toon, Ehime, 791-0295, Japan.

Intracranial anaplastic hemangiopericytoma (AHPC) is a rare and malignant subset of solitary fibrous tumor/hemangiopericytoma (SFT/HPC) as per the WHO 2016 Classification of Tumors of the Central Nervous System. AHPC portends a poor prognosis and is associated with higher rates of recurrence/metastasis in comparison with SFT/HPC. Accordingly, it is critical to continue to define the clinical course of patients with AHPC and in so doing further refine clinicopathologic/immunohistochemical (IHC) criteria needed for definitive diagnosis. Herein, we describe clinical/histological characteristics of six patients with AHPC. In addition, we reviewed and analyzed the expression of various IHC markers reported within the literature (i.e., a total of 354 intracranial SFT/HPCs and 460 meningiomas). Histologically, tumors from our six patients were characterized by a staghorn-like vascular pattern, mitotic cells, and strong nuclear atypia. Immunohistochemically, all tumors displayed positive nuclear staining for STAT6; other markers, including CD34 and Bcl-2, were expressed only in three patients. Analysis of IHC expression patterns for SFT/HPC and meningioma within the literature revealed that nuclear expression of STAT6 had the highest specificity (100%) for SFT/HPC, followed by ALDH1 (97.2%) and CD34 (93.6%). Of note, SSTR2A (95.2%) and EMA (85%) displayed a high specificity for meningioma. Anaplastic SFT/HPC is a tumor with poor prognosis that is associated with higher rates of recurrence and metastasis in comparison with SFT/HPC. Given that anaplastic SFT/HPC requires more aggressive treatment than meningioma despite of a similar presentation on imaging, it is crucial to be able to distinguish between these tumors.
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http://dx.doi.org/10.1007/s10143-020-01348-6DOI Listing
June 2021

A hydrophobic gelatin fiber sheet promotes secretion of endogenous vascular endothelial growth factor and stimulates angiogenesis.

RSC Adv 2020 Jun 30;10(42):24800-24807. Epub 2020 Jun 30.

Graduate School of Science and Technology, University of Tsukuba 1-1-1 Tennodai Tsukuba Ibaraki 305-8577 Japan.

In tissue engineering and regenerative medicine, the formation of vascular beds is an effective method to supply oxygen and nutrients to implanted cells or tissues to improve their survival and promote normal cellular functions. Various types of angiogenic materials have been developed by incorporating growth factors, such as vascular endothelial growth factor, in biocompatible materials. However, these exogenous growth factors suffer from instability and inactivation under physiological conditions. In this study, we designed a novel angiogenic electrospun fiber sheet (C16-FS) composed of Alaska pollock-derived gelatin (ApGltn) modified with hexadecyl (C16) groups to induce localized and sustained angiogenesis without growth factors. C16-FS was thermally crosslinked to enhance its stability. We demonstrated that C16-FS swells in phosphate-buffered saline for over 24 h and resists degradation. Laser doppler perfusion imaging showed that C16-FS induced increased blood perfusion when implanted subcutaneously in rats compared with unmodified ApGltn-fiber sheets (Org-FS) and the sham control. Furthermore, angiogenesis was sustained for up to 7 days following implantation. Immunohistochemical studies revealed elevated nuclear factor-κB and CD31 levels around the C16-FS implantation site compared with the Org-FS implantation site and the control incision site. These results demonstrate that C16-FS is a promising angiogenic material to promote the formation of vascular beds for cell and tissue transplantation without the need for growth factors.
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http://dx.doi.org/10.1039/d0ra03593aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9055140PMC
June 2020

Endometrial microRNAs and their aberrant expression patterns.

Med Mol Morphol 2020 Sep 29;53(3):131-140. Epub 2020 Apr 29.

Department of Obstetrics and Gynecology, Saitama Medical University, 38 Morohongo, Moroyama, Iruma-gun, Saitama, Japan.

MicroRNAs (miRNAs) are a class of small noncoding RNAs that regulate gene expression. They play fundamental roles in several biological processes, including cell differentiation and proliferation, embryo development, organ development, and organ metabolism. Besides regulating the physiological processes, miRNAs regulate various pathological conditions such as tumors, metastases, metabolic diseases, and osteoporosis. Although several studies have been performed on miRNAs, only few studies have described the miRNA expression and functions in human reproductive tract tissues. During menstruation, the human endometrium undergoes extensive cyclic morphological and biochemical modifications before embryo implantation. In addition to the ovarian steroid hormones (estrogen and progesterone), endometrial autocrine or paracrine factors and embryo-derived signals play a significant role in endometrial functions. miRNAs are considered key regulators of gene expression in the human endometrium and implantation process, and their aberrant expression levels are associated with the development of various disorders, including tumorigenesis. In this review, we summarize the studies that show the role of miRNAs in regulating the physiological conditions of the endometrium and the implantation process and discuss the aberrant expression of miRNAs in ectopic pregnancy, endometriosis, and endometrial cancer.
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http://dx.doi.org/10.1007/s00795-020-00252-8DOI Listing
September 2020

Mid-term predictive value of calciprotein particles in maintenance hemodialysis patients based on a gel-filtration assay.

Atherosclerosis 2020 06 21;303:46-52. Epub 2020 Mar 21.

Division of Anti-Ageing Medicine, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan.

Background And Aims: Calciprotein particles (CPPs), nano-aggregates containing fetuin-A-bound calcium-phosphate, are associated with aortic stiffness and coronary calcification in maintenance hemodialysis patients. A novel gel-filtration assay can detect low-density small CPPs, which are actually a major form of circulating CPPs in vivo. We sought to investigate whether circulating CPP levels measured by gel-filtration method would accurately predict hard endpoints in maintenance hemodialysis patients.

Methods: This study used a prospective, multicenter, longitudinal, and observational design. One-hundred eight patients enrolled in this study were followed-up for about 2 years. We reported all-cause death and cardiovascular events, which included major adverse cardiac, cerebrovascular, and limb events.

Results: Kaplan-Meier analysis showed no significant difference between patients with the higher (>median) and lower (
Conclusions: This finding suggests a potential predictive value of CPPs in maintenance hemodialysis patients.
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http://dx.doi.org/10.1016/j.atherosclerosis.2020.03.016DOI Listing
June 2020
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