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Article ; Online: Efficacy of comprehensive group-based education in lowering body weight, uric acid levels, and diuretic use in patients with chronic kidney disease: a retrospective study.

Hotta, Azumi / Iwatani, Hirotsugu

2023 Volume 24, Issue 1, Page(s) 272

Abstract: Background: Patient education for the management of chronic kidney disease (CKD) is attracting attention. Therefore, this study aimed to analyze changes in body weight, uric acid, and estimated-glomerular filtration rate (eGFR) in patients with CKD ... ...

Abstract	Background: Patient education for the management of chronic kidney disease (CKD) is attracting attention. Therefore, this study aimed to analyze changes in body weight, uric acid, and estimated-glomerular filtration rate (eGFR) in patients with CKD after a group-based education during admission. Methods: Overall, 157 patients with CKD, who were discharged from the nephrology department of our hospital between January 2015 and October 2019, received group-based education or individual-based education by nurses at admission. Deltas of body weight, uric acid, and eGFR, 6 months from baseline, were compared between group- and individual-based education using the Wilcoxon rank sum test. Results: In total, 60 patients receiving group-based education (G group, n =35) or individual-based education (I group, n =25) during admission were included in this retrospective study. The patient characteristics at baseline were as follows: age mean, 72 ± SD 9; 16 females and 44 males; body weight, 62 ± 17 kg; eGFR median, 21 (IQR: 14, 29) mL/min/1.73 m Conclusions: A comprehensive group-based education in patients with CKD may effectively suppress body weight and uric acid in 6 months along with less frequent diuretic use.
MeSH term(s)	Female ; Male ; Humans ; Retrospective Studies ; Uric Acid ; Diuretics/therapeutic use ; Body Weight ; Renal Insufficiency, Chronic/drug therapy
Chemical Substances	Uric Acid (268B43MJ25) ; Diuretics
Language	English
Publishing date	2023-09-14
Publishing country	England
Document type	Journal Article
ZDB-ID	2041348-8
ISSN	1471-2369 ; 1471-2369
ISSN (online)	1471-2369
ISSN	1471-2369
DOI	10.1186/s12882-023-03293-0
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Hiding from allogeneic NK cells and macrophages by a synthetic receptor.

Hotta, Akitsu / Lee, Joseph

Cell stem cell

2023 Volume 30, Issue 11, Page(s) 1393–1394

Abstract: Immune attack by natural killer (NK) cells is a major hurdle for allogeneic off-the-shelf cell therapy, especially when HLA molecules are removed. Gravina et al. ...

Abstract	Immune attack by natural killer (NK) cells is a major hurdle for allogeneic off-the-shelf cell therapy, especially when HLA molecules are removed. Gravina et al.
MeSH term(s)	Receptors, Artificial ; Killer Cells, Natural ; Hematopoietic Stem Cell Transplantation ; Macrophages
Chemical Substances	Receptors, Artificial
Language	English
Publishing date	2023-10-31
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2375354-7
ISSN	1875-9777 ; 1934-5909
ISSN (online)	1875-9777
ISSN	1934-5909
DOI	10.1016/j.stem.2023.10.005
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Article ; Online: iMSC-mediated delivery of ACVR2B-Fc fusion protein reduces heterotopic ossification in a mouse model of fibrodysplasia ossificans progressiva.

Gao, Pan / Inada, Yoshiko / Hotta, Akitsu / Sakurai, Hidetoshi / Ikeya, Makoto

Stem cell research & therapy

2024 Volume 15, Issue 1, Page(s) 83

Abstract: Background: Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease caused by a gain-of-function mutation in ACVR1, which is a bone morphogenetic protein (BMP) type I receptor. Moreover, it causes progressive heterotopic ossification (HO) ... ...

Abstract	Background: Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease caused by a gain-of-function mutation in ACVR1, which is a bone morphogenetic protein (BMP) type I receptor. Moreover, it causes progressive heterotopic ossification (HO) in connective tissues. Using FOP patient-derived induced pluripotent stem cells (FOP-iPSCs) and mouse models, we elucidated the underlying mechanisms of FOP pathogenesis and identified a candidate drug for FOP. Methods: In the current study, healthy mesenchymal stem/stromal cells derived from iPSCs (iMSCs) expressing ACVR2B-Fc (iMSC Results: We found that secreted ACVR2B-Fc attenuated BMP signaling initiated by Activin-A and BMP-9 in both iMSCs and FOP-iMSCs in vitro. Transplantation of ACVR2B-Fc-expressing iMSCs reduced primary HO in a transgenic mouse model of FOP. Notably, a local injection of ACVR2B-Fc-expressing iMSCs and not an intraperitoneal injection improved the treadmill performance, suggesting compound effects of ACVR2B-Fc and iMSCs. Conclusions: These results offer a new perspective for treating FOP through stem cell therapy.
MeSH term(s)	Female ; Humans ; Mice ; Animals ; Myositis Ossificans/genetics ; Myositis Ossificans/therapy ; Ossification, Heterotopic/therapy ; Ossification, Heterotopic/genetics ; Bone Morphogenetic Proteins/genetics ; Bone Morphogenetic Proteins/metabolism ; Bone Morphogenetic Proteins/pharmacology ; Signal Transduction ; Mice, Transgenic ; Mutation ; Activin Receptors, Type II/genetics ; Activin Receptors, Type II/metabolism ; Activin Receptors, Type II/pharmacology
Chemical Substances	Bone Morphogenetic Proteins ; ACVR2B protein, human (EC 2.7.11.30) ; Activin Receptors, Type II (EC 2.7.11.30)
Language	English
Publishing date	2024-03-18
Publishing country	England
Document type	Journal Article
ZDB-ID	2548671-8
ISSN	1757-6512 ; 1757-6512
ISSN (online)	1757-6512
ISSN	1757-6512
DOI	10.1186/s13287-024-03691-7
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Article ; Online: Multifunctionality of Iodinated Halogen-Bonded Polymer: Biodegradability, Radiopacity, Elasticity, Ductility, and Self-Healing Ability.

Oyama, Yuya / Kurokawa, Naruki / Hotta, Atsushi

ACS biomaterials science & engineering

2023 Volume 9, Issue 11, Page(s) 6094–6102

Abstract: A polymer with high contents of ester bonds and iodine atoms was synthesized, exhibiting sufficient biodegradability and radioactivity for biomedical applications. The iodine moieties of the synthesized polyester can generate halogen bonding between ... ...

Abstract	A polymer with high contents of ester bonds and iodine atoms was synthesized, exhibiting sufficient biodegradability and radioactivity for biomedical applications. The iodine moieties of the synthesized polyester can generate halogen bonding between molecules, which may develop additional functional properties through the bonding. In this study, poly(glycerol adipate) (PGA) was selected and synthesized as a polyester, which was then adequately conjugated with three different types of iodine compounds via the hydroxy groups of PGA. It was found that the iodine compounds could effectively work as donors of halogen bonding. The thermal analysis by differential scanning calorimetry (DSC) revealed that the glass transition temperature increased with the increase in the strength of interactions caused by π-π stacking and halogen bonding, eventually reaching 49.6 °C for PGA with triiodobenzoic groups. An elastomeric PGA with monoiodobenzoic groups was also obtained, exhibiting a high self-healing ability at room temperature because of the reconstruction of halogen bonding. Such multifaceted performance of the synthesized polyester with controllable thermal/mechanical properties was realized by halogen bonding, leading to a promising biomaterial with multifunctionality.
MeSH term(s)	Halogens/chemistry ; Polymers/chemistry ; Iodine/chemistry ; Iodine Compounds ; Polyesters/chemistry ; Elasticity
Chemical Substances	Halogens ; Polymers ; Iodine (9679TC07X4) ; Iodine Compounds ; Polyesters
Language	English
Publishing date	2023-10-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2373-9878
ISSN (online)	2373-9878
DOI	10.1021/acsbiomaterials.3c01075
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Article: Corrigendum to "Relationship between growth and food avoidance with food allergy at age 3 years: The Japan Environment and Children's Study (JECS)" [World Allergy Organ J (2023) 100826].

Saito, Midori / Hasunuma, Hideki / Okuda, Masumi / Hotta, Aki / Fujino, Tetsuro / Takeshima, Yasuhiro / Shima, Masayuki

The World Allergy Organization journal

2024 Volume 17, Issue 2, Page(s) 100872

Abstract: This corrects the article DOI: 10.1016/j.waojou.2023.100826.]. ...

Abstract	[This corrects the article DOI: 10.1016/j.waojou.2023.100826.].
Language	English
Publishing date	2024-01-27
Publishing country	United States
Document type	Published Erratum
ZDB-ID	2581968-9
ISSN	1939-4551
ISSN	1939-4551
DOI	10.1016/j.waojou.2024.100872
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Article ; Online: Thermally Reversible Gel-Sol Transition of Hydrogels via Dissociation and Association of an Artificial Protein Nanocage.

Nasu, Erika / Kawakami, Norifumi / Takamura, Shuhei / Hotta, Atsushi / Arai, Ryoichi / Miyamoto, Kenji

Biomacromolecules

2024 Volume 25, Issue 4, Page(s) 2358–2366

Abstract: Oligomeric protein nanocages often disassemble into their subunits and reassemble by external stimuli. Thus, using these nanocages as cross-linkers for hydrogel network structures is a promising approach to allow hydrogels to undergo stimuli-responsive ... ...

Abstract	Oligomeric protein nanocages often disassemble into their subunits and reassemble by external stimuli. Thus, using these nanocages as cross-linkers for hydrogel network structures is a promising approach to allow hydrogels to undergo stimuli-responsive gel-sol transitions or self-healing. Here, we report hydrogels that show a reversible gel-sol transition resulting from the heat-induced dissociation and reassociation of protein nanocages. The hydrogel contained the 60-mer artificial protein nanocage, TIP60, as a supramolecular cross-linker for polyethylene glycol network structures. The hydrogel showed a gel-to-sol transition upon heating at a temperature above the melting point of TIP60 and immediately returned to a gel state upon cooling to room temperature. During the heating and cooling treatment of the hydrogel, small-angle X-ray scattering analysis suggested the dissociation and reassociation of TIP60. Furthermore, we demonstrated redox-responsive cargo release from TIP60 in the hydrogel. These results showed the potential of TIP60 as a component of multi-stimuli-responsive hydrogels.
MeSH term(s)	Hydrogels/chemistry ; Polyethylene Glycols/chemistry ; Hot Temperature ; Temperature
Chemical Substances	Hydrogels ; Polyethylene Glycols (3WJQ0SDW1A)
Language	English
Publishing date	2024-03-06
Publishing country	United States
Document type	Journal Article
ISSN	1526-4602
ISSN (online)	1526-4602
DOI	10.1021/acs.biomac.3c01285
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Article ; Online: Neutralization sensitivity of SARS-CoV-2 Omicron variants FL.1 and GE.1 by therapeutic antibodies and XBB sera.

Lee, Joseph / Naoe, Youichi / Bang, Uikyu / Nakagama, Yu / Saito, Akatsuki / Kido, Yasutoshi / Hotta, Akitsu

Virology

2024 Volume 595, Page(s) 110067

Abstract: Two SARS-CoV-2 XBB sub-variants, FL.1 and GE.1, have been increasing in prevalence worldwide, but limited information is available about their ability to evade the immune system. FL.1 and GE.1 are emerging Omicron XBB variants possessing additional ... ...

Abstract	Two SARS-CoV-2 XBB sub-variants, FL.1 and GE.1, have been increasing in prevalence worldwide, but limited information is available about their ability to evade the immune system. FL.1 and GE.1 are emerging Omicron XBB variants possessing additional mutations in the spike RBD raising concerns of increased neutralization escape. In this study, we assessed the neutralizing ability of eleven FDA-approved monoclonal antibody combinations against different Omicron variants, including BA.2.75, BA.2.76, BA.4/5, XBB.1.5, and CH.1.1. Among the eleven antibodies, Sotrovimab was the only antibody to show broad neutralization ability against XBB.1.5. However, Sotrovimab showed attenuated neutralization efficiency against recently emerging XBB sub-lineages EG.5, FL.1, and GE.1 compared to XBB.1.5. Additionally, XBB.1.5 seropositive convalescent sera displayed lower neutralization activity against EG.5, FL.1, and GE.1. Overall, our findings present enhanced immune evasion capacity of emerging XBB variants and emphasize the importance of continued monitoring of novel variants.
MeSH term(s)	Humans ; SARS-CoV-2/immunology ; SARS-CoV-2/genetics ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; Neutralization Tests ; COVID-19/immunology ; COVID-19/virology ; Antibodies, Monoclonal/immunology ; Spike Glycoprotein, Coronavirus/immunology ; Spike Glycoprotein, Coronavirus/genetics ; Antibodies, Monoclonal, Humanized/immunology ; Antibodies, Monoclonal, Humanized/therapeutic use ; Mutation
Chemical Substances	sotrovimab ; spike protein, SARS-CoV-2
Language	English
Publishing date	2024-04-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	200425-2
ISSN	1096-0341 ; 0042-6822
ISSN (online)	1096-0341
ISSN	0042-6822
DOI	10.1016/j.virol.2024.110067
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Article: Genome Editing Gene Therapy for Duchenne Muscular Dystrophy.

Hotta, Akitsu

Journal of neuromuscular diseases

2015 Volume 2, Issue 4, Page(s) 343–355

Abstract: Duchenne muscular dystrophy (DMD) is a severe genetic disorder caused by loss of function of the dystrophin gene on the X chromosome. Gene augmentation of dystrophin is challenging due to the large size of the dystrophin cDNA. Emerging genome editing ... ...

Abstract	Duchenne muscular dystrophy (DMD) is a severe genetic disorder caused by loss of function of the dystrophin gene on the X chromosome. Gene augmentation of dystrophin is challenging due to the large size of the dystrophin cDNA. Emerging genome editing technologies, such as TALEN and CRISPR-Cas9 systems, open a new erain the restoration of functional dystrophin and are a hallmark of bona fide gene therapy. In this review, we summarize current genome editing approaches, properties of target cell types for ex vivo gene therapy, and perspectives of in vivo gene therapy including genome editing in human zygotes. Although technical challenges, such as efficacy, accuracy, and delivery of the genome editing components, remain to be further improved, yet genome editing technologies offer a new avenue for the gene therapy of DMD.
Language	English
Publishing date	2015-09-22
Publishing country	Netherlands
Document type	Journal Article
ISSN	2214-3599
ISSN	2214-3599
DOI	10.3233/JND-150116
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Article ; Online: Compensation for Orientation Birefringence of PMMA by Blending Bottlebrush Polymers Composed of Well-Controlled Graft Chains.

Tamura, Masaki / Kurokawa, Naruki / Hotta, Atsushi

ACS macro letters

2022 Volume 11, Issue 6, Page(s) 799–804

Abstract: The birefringence of optical polymers is a great issue in optical devices, inhibiting major applications of polymers to optical lenses and films. In this study, we have synthesized effective bottlebrush polymers with which we could attain almost zero ... ...

Abstract	The birefringence of optical polymers is a great issue in optical devices, inhibiting major applications of polymers to optical lenses and films. In this study, we have synthesized effective bottlebrush polymers with which we could attain almost zero birefringence when mixed with optical poly(methyl methacrylate) (PMMA). In detail, the PMMA bottlebrush polymers (PMMA-BBP) were synthesized by the ring-opening metathesis polymerization (ROMP) of norbornene-terminated PMMA macromonomers prepared via atom transfer radical polymerization (ATRP). Linear PMMA and PMMA-BBP were mixed to fabricate blend-film samples (PMMA/PMMA-BBP), which were uniaxially drawn to introduce molecular orientations. Linear PMMA possessed a negative value for its orientation birefringence, while the value of PMMA/PMMA-BBP increased as the PMMA-BBP content increased, whose orientation birefringence could reach almost zero when the ratio of the linear PMMA to PMMA-BBP became 73:27, regardless of the magnitude of the strain. The results reveal that the orientation birefringence of PMMA can be effectively controlled and removed by blending the appropriate content of PMMA-BBP.
MeSH term(s)	Birefringence ; Polymerization ; Polymers ; Polymethyl Methacrylate
Chemical Substances	Polymers ; Polymethyl Methacrylate (9011-14-7)
Language	English
Publishing date	2022-06-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2161-1653
ISSN (online)	2161-1653
DOI	10.1021/acsmacrolett.2c00270
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Article ; Online: Preparation of NanoMEDIC Extracellular Vesicles to Deliver CRISPR-Cas9 Ribonucleoproteins for Genomic Exon Skipping.

Watanabe, Kei / Gee, Peter / Hotta, Akitsu

Methods in molecular biology (Clifton, N.J.)

2022 Volume 2587, Page(s) 427–453

Abstract: The CRISPR-Cas9 system has quickly become the standard tool for genome editing. To deliver this system to target cells, adeno-associated virus (AAV) vectors are commonly used. In fact, AAV vectors have been utilized to deliver the CRISPR-Cas9 system to ... ...

Abstract	The CRISPR-Cas9 system has quickly become the standard tool for genome editing. To deliver this system to target cells, adeno-associated virus (AAV) vectors are commonly used. In fact, AAV vectors have been utilized to deliver the CRISPR-Cas9 system to induce genomic exon skipping and restore the dystrophin protein in various Duchenne muscular dystrophy model animals. Despite the high transduction efficiency, AAV vector-mediated delivery has several limitations, such as the packaging size, prolonged overexpression of Cas9, immunogenicity against the AAV capsid, and the risk of integrating a part of the AAV genomic sequence into the host cell. To overcome these issues, we have recently engineered a transient delivery system utilizing VSV-G pseudotyped extracellular vesicles (EVs) termed NanoMEDIC (nanomembrane-derived extracellular vesicles for the delivery of macromolecular cargo). NanoMEDIC utilizes an HIV-derived Gag protein to package Cas9 protein and gRNA into EVs. The Cas9 and Gag proteins are fused to a heterodimerizer and conditionally dimerized by the addition of an inducible chemical ligand to recruit Cas9 protein into EVs. sgRNA is packaged into EVs through an HIV-derived RNA packaging signal and is subsequently released by two self-cleaving ribozymes. Utilizing these features, NanoMEDIC can achieve highly efficient packaging of the Cas9 protein and gRNA for genome editing into a variety of target cells and in vivo. Here, we describe a step-by-step protocol, including the gRNA-expressing vector construction and large-scale NanoMEDIC production, for in vivo genome editing.
MeSH term(s)	Animals ; CRISPR-Associated Protein 9/genetics ; CRISPR-Cas Systems/genetics ; Exons/genetics ; Extracellular Vesicles/genetics ; Genomics ; HIV Infections/genetics ; Ribonucleoproteins/genetics ; RNA, Guide, CRISPR-Cas Systems/genetics
Chemical Substances	CRISPR-Associated Protein 9 (EC 3.1.-) ; Ribonucleoproteins ; RNA, Guide, CRISPR-Cas Systems
Language	English
Publishing date	2022-12-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-2772-3_22
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