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Article ; Online: Small-molecule inhibitor cocktail promotes the proliferation of pre-existing liver progenitor cells.

Fu, Qingjie / Ohnishi, Shunsuke / Suda, Goki / Sakamoto, Naoya

2022 Volume 17, Issue 7, Page(s) 1589–1603

Abstract: A recent study showed that a cocktail of three small molecules, Y-27632, A83-01, and CHIR99021 (YAC), converts mature hepatocytes (MHs) into proliferative bipotent cells that can be induced into MHs and cholangiocytes in rats. However, when we reproduced ...

Abstract	A recent study showed that a cocktail of three small molecules, Y-27632, A83-01, and CHIR99021 (YAC), converts mature hepatocytes (MHs) into proliferative bipotent cells that can be induced into MHs and cholangiocytes in rats. However, when we reproduced these experiments, it was found that bipotent cells may be derived from resident liver progenitor cells (LPCs), whose proliferative activity was promoted by YAC. A simple and efficient sorting scheme was also developed in this study to harvest high-purity and high-yield LPCs. The inducible bipotency of purified LPCs was verified; in addition, they were found to spontaneously differentiate into hepatocytes and cholangiocytes due to changes in proliferative status even without induction. Moreover, during the differentiation process, some hepatocytes spontaneously reconverted to LPCs under certain conditions, such as the release of contact inhibition. These findings may improve our understanding of LPCs and provide a cell source for regenerative medicine.
MeSH term(s)	Animals ; Cell Differentiation ; Cell Proliferation ; Hepatocytes ; Liver ; Rats ; Stem Cells
Language	English
Publishing date	2022-06-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2720528-9
ISSN	2213-6711 ; 2213-6711
ISSN (online)	2213-6711
ISSN	2213-6711
DOI	10.1016/j.stemcr.2022.05.023
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Ghrelin Enhancer, the Latest Evidence of Rikkunshito.

Yamada, Chihiro / Hattori, Tomohisa / Ohnishi, Shunsuke / Takeda, Hiroshi

Frontiers in nutrition

2021 Volume 8, Page(s) 761631

Abstract: Rikkunshito is a Japanese herbal medicine (Kampo) that has been attracting attention and researched by many researchers not only in Japan but also worldwide. There are 214 rikkunshito articles that can be searched on PubMed by August 2021. The reason why ...

Abstract	Rikkunshito is a Japanese herbal medicine (Kampo) that has been attracting attention and researched by many researchers not only in Japan but also worldwide. There are 214 rikkunshito articles that can be searched on PubMed by August 2021. The reason why rikkunshito has attracted so much attention is due to an epoch-making report (Gastroenterology, 2008) discovered that rikkunshito promotes the secretion of the orexigenic peptide ghrelin. Since then, many researchers have discovered that rikkunshito has a direct effect on the ghrelin receptor, GHS-R1a, and an effect of enhancing the ghrelin signal to the brain. Additionally, a lot of evidence that rikkunshito is expected to be effective for various gastrointestinal diseases have also been demonstrated. Numerous basic and clinical studies have suggested that rikkunshito affects (i) various discomforts caused by anticancer drugs, gastroesophageal reflux disease, functional dyspepsia, (ii) various stress-induced anorexia, (iii) hypophagia in the elderly, and (iv) healthy lifespan. In this review, as one who discovered the ghrelin enhancer effect of rikkunshito, we will review the research of rikkunshito so far and report on the latest research results.
Language	English
Publishing date	2021-12-09
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2776676-7
ISSN	2296-861X
ISSN	2296-861X
DOI	10.3389/fnut.2021.761631
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Article ; Online: The TLR4-TRIF-type 1 IFN-IFN-γ pathway is crucial for gastric MALT lymphoma formation after

Yamamoto, Koji / Kondo, Yasuyuki / Ohnishi, Shunsuke / Yoshida, Masaru / Sugiyama, Toshiro / Sakamoto, Naoya

iScience

2021 Volume 24, Issue 9, Page(s) 103064

Abstract: Helicobacter ... ...

Abstract	Helicobacter suis
Language	English
Publishing date	2021-08-30
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2021.103064
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Article: Conditioned Medium from Human Amnion-Derived Mesenchymal Stem Cells Regulates Activation of Primary Hepatic Stellate Cells.

Fu, Qingjie / Ohnishi, Shunsuke / Sakamoto, Naoya

Stem cells international

2018 Volume 2018, Page(s) 4898152

Abstract: Mesenchymal stem cells (MSCs), or multipotent mesenchymal stromal cells, are present in almost all organs and tissues, including the amnion. Human amnion-derived mesenchymal stem cell (hAMSC) transplantation has been reported to ameliorate liver fibrosis ...

Abstract	Mesenchymal stem cells (MSCs), or multipotent mesenchymal stromal cells, are present in almost all organs and tissues, including the amnion. Human amnion-derived mesenchymal stem cell (hAMSC) transplantation has been reported to ameliorate liver fibrosis in animal models. However, the mechanism for the prevention of liver fibrosis is poorly understood. In this study, we investigated the effects, and underlying mechanisms, of a conditioned medium obtained from hAMSC cultures (hAMSC-CM) on a primary culture of rat hepatic stellate cells (HSCs). We observed that in routine culture, hAMSC-CM in HSCs significantly inhibited the expression of alpha-smooth muscle actin (α-SMA), an activation marker of HSCs, and the production of collagen type 1 (COL1), a dominant component of the extracellular matrix (ECM) in the culture medium. In addition, hAMSC-CM upregulated the expression of ECM degradation-related genes, such as metalloproteinase- (
Language	English
Publishing date	2018-10-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2573856-2
ISSN	1687-9678 ; 1687-966X
ISSN (online)	1687-9678
ISSN	1687-966X
DOI	10.1155/2018/4898152
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Article: Decline in Liver Mitochondria Metabolic Function Is Restored by Hochuekkito Through Sirtuin 1 in Aged Mice With Malnutrition.

Nahata, Miwa / Fujitsuka, Naoki / Sekine, Hitomi / Shimobori, Chika / Ohbuchi, Katsuya / Iizuka, Seiichi / Mogami, Sachiko / Ohnishi, Shunsuke / Takeda, Hiroshi

Frontiers in physiology

2022 Volume 13, Page(s) 848960

Abstract: Malnutrition impairs basic daily activities and leads to physical frailty, which is aggravated in the elderly compared with young adults. It is also well-known that the elderly are more vulnerable to metabolic stress. Therefore, in this study, using a ... ...

Abstract	Malnutrition impairs basic daily activities and leads to physical frailty, which is aggravated in the elderly compared with young adults. It is also well-known that the elderly are more vulnerable to metabolic stress. Therefore, in this study, using a food restricted (FR) mouse, we aimed to evaluate the effect of aging on locomotor activity and liver metabolic function. Further, we also investigated the involvement of hepatic mitochondria in liver metabolic function during aging, as well as the therapeutic benefit of the traditional Japanese medicine, hochuekkito (HET). Our findings indicated that following food restriction provided as 30% of
Language	English
Publishing date	2022-03-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2022.848960
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Article: Herbal medicines for the treatment of cancer chemotherapy-induced side effects.

Ohnishi, Shunsuke / Takeda, Hiroshi

Frontiers in pharmacology

2015 Volume 6, Page(s) 14

Abstract: Accumulating evidence suggests that Japanese herbal medicines, called Kampo, have beneficial effects on cancer chemotherapy-induced side effects. Rikkunshito ameliorates cisplatin-induced anorexia through an antagonistic effect on the 5-HT receptors and ... ...

Abstract	Accumulating evidence suggests that Japanese herbal medicines, called Kampo, have beneficial effects on cancer chemotherapy-induced side effects. Rikkunshito ameliorates cisplatin-induced anorexia through an antagonistic effect on the 5-HT receptors and by increasing the serum ghrelin levels. Hangeshashinto improves irinotecan-induced diarrhea and chemotherapy-induced mucositis by inhibiting the activity of β-glucuronidase as well as the synthesis of prostaglandin E2. Goshajinkigan prevents oxaliplatin-induced neurotoxicity, possibly through suppressing functional alterations of the transient receptor potential channels. In this review, we will summarize the currently available literature regarding the clinical efficacy and potential mechanisms of Kampo medicines in the treatment of cancer chemotherapy-induced side effects.
Language	English
Publishing date	2015-02-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2015.00014
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Article ; Online: Intracerebral transplantation of MRI-trackable autologous bone marrow stromal cells for patients with subacute ischemic stroke.

Kawabori, Masahito / Kuroda, Satoshi / Shichinohe, Hideo / Kahata, Kaoru / Shiratori, Souichi / Ikeda, Satoshi / Harada, Taisuke / Hirata, Kenji / Tha, Khin Khin / Aragaki, Masato / Terasaka, Shunsuke / Ito, Yoichi M / Nishimoto, Naoki / Ohnishi, Shunsuke / Yabe, Ichiro / Kudo, Kohsuke / Houkin, Kiyohiro / Fujimura, Miki

Med (New York, N.Y.)

2024 Volume 5, Issue 5, Page(s) 432–444.e4

Abstract: Background: Ischemic stroke is one of the leading causes of death and neurological disability worldwide, and stem cell therapy is highly expected to reverse the sequelae. This phase 1/2, first-in-human study evaluated the safety, feasibility, and ... ...

Abstract	Background: Ischemic stroke is one of the leading causes of death and neurological disability worldwide, and stem cell therapy is highly expected to reverse the sequelae. This phase 1/2, first-in-human study evaluated the safety, feasibility, and monitoring of an intracerebral-transplanted magnetic resonance imaging (MRI)-trackable autologous bone marrow stromal cell (HUNS001-01) for patients with subacute ischemic stroke. Methods: The study included adults with severe disability due to ischemic stroke. HUNS001-01 cultured with human platelet lysates and labeled with superparamagnetic iron oxide was stereotactically transplanted into the peri-infarct area 47-64 days after ischemic stroke onset (dose: 2 or 5 × 10 Findings: All seven patients who met the inclusion criteria successfully achieved cell expansion, underwent intracerebral transplantation, and completed 1 year of follow-up. No product-related adverse events were observed. The median National Institutes of Health Stroke Scale and modified Rankin scale scores before transplantation were 13 and 4, which showed improvements of 1-8 and 0-2, respectively. Cell tracking proved that the engrafted cells migrated toward the infarction border area 1-6 months after transplantation, and the quantitative susceptibility mapping revealed that cell signals at the migrated area constantly increased throughout the follow-up period up to 34% of that of the initial transplanted site. Conclusions: Intracerebral transplantation of HUNS001-01 was safe and well tolerated. Cell tracking shed light on the therapeutic mechanisms of intracerebral transplantation. Funding: This work was supported by the Japan Agency for Medical Research and Development (AMED; JP17bk0104045 and JP20bk0104011).
MeSH term(s)	Humans ; Male ; Middle Aged ; Female ; Aged ; Magnetic Resonance Imaging ; Ischemic Stroke/therapy ; Ischemic Stroke/diagnostic imaging ; Ischemic Stroke/surgery ; Transplantation, Autologous/methods ; Mesenchymal Stem Cell Transplantation/methods ; Treatment Outcome ; Adult ; Feasibility Studies
Language	English
Publishing date	2024-03-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Clinical Trial, Phase I ; Clinical Trial, Phase II
ISSN	2666-6340
ISSN (online)	2666-6340
DOI	10.1016/j.medj.2024.02.009
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Article ; Online: Pitfalls and promises of bile duct alternatives: A narrative review.

Miyazawa, Mitsuo / Aikawa, Masayasu / Takashima, Junpei / Kobayashi, Hirotoshi / Ohnishi, Shunsuke / Ikada, Yoshito

World journal of gastroenterology

2020 Volume 28, Issue 39, Page(s) 5707–5722

Abstract: Biliodigestive anastomosis between the extrahepatic bile duct and the intestine for bile duct disease is a gastrointestinal reconstruction that abolishes duodenal papilla function and frequently causes retrograde cholangitis. This chronic inflammation ... ...

Abstract	Biliodigestive anastomosis between the extrahepatic bile duct and the intestine for bile duct disease is a gastrointestinal reconstruction that abolishes duodenal papilla function and frequently causes retrograde cholangitis. This chronic inflammation can cause liver dysfunction, liver abscess, and even bile duct cancer. Although research has been conducted for over 100 years to directly repair bile duct defects with alternatives, no bile duct substitute (BDS) has been developed. This narrative review confirms our understanding of why bile duct alternatives have not been developed and explains the clinical applicability of BDSs in the near future. We searched the PubMed electronic database to identify studies conducted to develop BDSs until December 2021 and identified studies in English. Two independent reviewers reviewed studies on large animals with 8 or more cases. Four types of BDSs prevail: Autologous tissue, non-bioabsorbable material, bioabsorbable material, and others (decellularized tissue, 3D-printed structures,
MeSH term(s)	Animals ; Bile Ducts/surgery ; Bile Ducts, Extrahepatic/surgery ; Bile Duct Diseases ; Cholangitis ; Anastomosis, Surgical ; Constriction, Pathologic
Language	English
Publishing date	2020-09-15
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2185929-2
ISSN	2219-2840 ; 1007-9327
ISSN (online)	2219-2840
ISSN	1007-9327
DOI	10.3748/wjg.v28.i39.5707
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Article ; Online: Mesenchymal stem cell therapy for acute and chronic pancreatitis.

Kawakubo, Kazumichi / Ohnishi, Shunsuke / Kuwatani, Masaki / Sakamoto, Naoya

Journal of gastroenterology

2017 Volume 53, Issue 1, Page(s) 1–5

Abstract: Mesenchymal stem cells (MSCs) have attracted attention as a cell source for regenerative medicine. In particular, MSCs have an anti-inflammatory effect by secreting several kinds of bioactive molecules. MSC therapy is now being applied to various ... ...

Abstract	Mesenchymal stem cells (MSCs) have attracted attention as a cell source for regenerative medicine. In particular, MSCs have an anti-inflammatory effect by secreting several kinds of bioactive molecules. MSC therapy is now being applied to various gastrointestinal diseases, such as graft-versus-host disease, inflammatory bowel disease, and liver cirrhosis. Therefore, MSC therapy has the potential to be a novel treatment for acute and chronic pancreatitis by suppressing inflammation. Several studies have investigated the effect of MSC therapy on acute and chronic pancreatitis, but the underlying mechanisms remain unknown. In this review, we summarize the present status of MSC therapy for acute and chronic pancreatitis.
MeSH term(s)	Acute Disease ; Animals ; Humans ; Inflammation/physiopathology ; Inflammation/therapy ; Mesenchymal Stem Cell Transplantation/methods ; Pancreatitis/physiopathology ; Pancreatitis/therapy ; Pancreatitis, Chronic/physiopathology ; Pancreatitis, Chronic/therapy ; Regenerative Medicine/methods
Language	English
Publishing date	2017-06-23
Publishing country	Japan
Document type	Journal Article ; Review
ZDB-ID	1186495-3
ISSN	1435-5922 ; 0944-1174
ISSN (online)	1435-5922
ISSN	0944-1174
DOI	10.1007/s00535-017-1363-9
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Zs.A 620: Show issues

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Article ; Online: Application of polyglycolic acid sheets and basic fibroblast growth factor to prevent esophageal stricture after endoscopic submucosal dissection in pigs.

Nishimura, Yusuke / Ono, Masayoshi / Okubo, Naoto / Sone, Takayuki / Higashino, Masayuki / Matsumoto, Shogo / Kubo, Marina / Yamamoto, Keiko / Ono, Shoko / Ohnishi, Shunsuke / Sakamoto, Naoya

Journal of gastroenterology

2023 Volume 58, Issue 11, Page(s) 1094–1104

Abstract: Background: Endoscopic submucosal dissection (ESD) has been the first-line treatment for early-stage esophageal cancer. However, it often causes postoperative stricture in cases requiring wide dissection. Basic fibroblast growth factor (bFGF) reportedly ...

Abstract	Background: Endoscopic submucosal dissection (ESD) has been the first-line treatment for early-stage esophageal cancer. However, it often causes postoperative stricture in cases requiring wide dissection. Basic fibroblast growth factor (bFGF) reportedly has anti-scarring effects during cutaneous wound healing. We hypothesized that suppressing myofibroblast activation will prevent stricture after esophageal ESD. Methods: We resected a complete porcine esophagus circumference section by ESD. To investigate the preventive effect of bFGF on esophageal stricture formation after ESD, we endoscopically applied bFGF-soaked poly-glycolic acid (PGA) sheets onto the wound bed after ESD and fixed them by spraying fibrin glue (PGA + bFGF group), PGA sheets alone onto the wound bed and fixed them by spraying fibrin glue (PGA group), or nothing (control group). After removing the esophagus on day 22, we evaluated the mucosal constriction rate. Results: Compared with those in the control group, esophageal stricture was significantly reduced in the PGA + bFGF group, and the areas stained with α-SMA and calponin-1 antibodies were significantly inhibited in the PGA + bFGF and PGA groups. The thickness of the fibrous layer in the PGA + bFGF group was uniform compared to that of the other groups. Thus, PGA + bFGF inhibited the development of unregulated fibroblasts in the acute phase, leading to uniform wound healing. Conclusions: Stenosis after esophageal ESD is related to fibrosis in the acute phase. Administration of PGA and bFGF suppresses myofibroblast activation in the acute phase, thereby preventing esophageal constriction in pigs.
Language	English
Publishing date	2023-08-27
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1186495-3
ISSN	1435-5922 ; 0944-1174
ISSN (online)	1435-5922
ISSN	0944-1174
DOI	10.1007/s00535-023-02032-4
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