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Article: [Role of NO-cGMP-PKG axis in pulmonary arterial hypertension].

Watanabe, Hiroshi

Nihon yakurigaku zasshi. Folia pharmacologica Japonica

2022 Volume 157, Issue 4, Page(s) 221–225

Abstract: The nitric oxide (NO) - cyclic guanosine monophosphate (cGMP) - protein kinase G (PKG) axis is a critical signaling cascade in the development of pulmonary arterial hypertension (PAH). Dysregulation of the NO-cGMP-PKG axis results in pulmonary vascular ... ...

Abstract	The nitric oxide (NO) - cyclic guanosine monophosphate (cGMP) - protein kinase G (PKG) axis is a critical signaling cascade in the development of pulmonary arterial hypertension (PAH). Dysregulation of the NO-cGMP-PKG axis results in pulmonary vascular inflammation, thrombosis and constriction, and ultimately leads to PAH. The PDE5 inhibitors such as sildenafil and tadalafil block the breakdown of cGMP. The resultant increase in cGMP concentration leads to relaxation of the smooth muscle and vasodilation. These effects are dependent on NO availability and sGC activity. The sGC stimulator riociguat has a dual mode of action, sensitizing sGC to endogenous NO by stabilizing NO-sGC binding and directly stimulating sGC via a different binding site. While there are clear pharmacokinetic and pharmacodynamic differences between these agents, it is still difficult to determine which agent is most appropriate for a specific PAH patient. Some patients respond better to sGC stimulator than a PDE5 inhibitor and vice versa. This chapter describes the role of the NO-cGMP-PKG pathway in PAH, potential and established treatment modalities to target this pathway, and their clinical applications.
MeSH term(s)	Cyclic GMP/metabolism ; Cyclic GMP-Dependent Protein Kinases ; Humans ; Nitric Oxide ; Phosphodiesterase 5 Inhibitors/pharmacology ; Phosphodiesterase 5 Inhibitors/therapeutic use ; Pulmonary Arterial Hypertension ; Tadalafil/pharmacology ; Tadalafil/therapeutic use
Chemical Substances	Phosphodiesterase 5 Inhibitors ; Nitric Oxide (31C4KY9ESH) ; Tadalafil (742SXX0ICT) ; Cyclic GMP-Dependent Protein Kinases (EC 2.7.11.12) ; Cyclic GMP (H2D2X058MU)
Language	Japanese
Publishing date	2022-07-04
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1097532-9
ISSN	1347-8397 ; 0015-5691
ISSN (online)	1347-8397
ISSN	0015-5691
DOI	10.1254/fpj.22018
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Zs.A 439: Show issues

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Article ; Online: Oxidized Albumin: Evaluation of Oxidative Stress as a Marker for the Progression of Kidney Disease.

Watanabe, Hiroshi

Biological & pharmaceutical bulletin

2022 Volume 45, Issue 12, Page(s) 1728–1732

Abstract: Oxidative stress has been reported to be associated with the progression of renal pathology as well as with the onset of complications associated with this condition. Bardoxolone methyl, a nuclear factor-erythroid 2-related factor 2 (Nrf2) activator with ...

Abstract	Oxidative stress has been reported to be associated with the progression of renal pathology as well as with the onset of complications associated with this condition. Bardoxolone methyl, a nuclear factor-erythroid 2-related factor 2 (Nrf2) activator with anti-oxidative and inflammatory modulation effects, has been reported to improve renal function in clinical trials. As of this writing, there have been no systems for the quantitative evaluation of oxidative stress that could be applied as a clinical test. We recently reported on post-translational modifications of albumin using electrospray-ionization time-of-flight mass spectrometry (ESI-TOF MS) and the results indicated that oxidized albumin (cysteinylated albumin: a molecule that was oxidatively cysteinylated at Cys34) was found to increase with the progression of renal pathology. A clinical study demonstrated that monitoring the levels of oxidized albumin could be useful for the early diagnosis of diabetic kidney disease and for predicting renal prognosis. Higher levels of serum oxidized albumin were also associated with cardiovascular complications or sarcopenia in patients who were undergoing hemodialysis. The overall findings indicate that oxidized albumin could also be an index of therapeutic efficacy against kidney disease. Oxidized albumin is not only a marker for kidney disease but also a nephrotoxic substance. This suggests that measuring the levels of oxidized albumin could be a biomarker for diagnosing the progression of and complications associated with renal disease in addition to evaluating the efficacy of therapeutic drugs.
MeSH term(s)	Humans ; Biomarkers ; Oxidative Stress ; Albumins ; Diabetic Nephropathies
Chemical Substances	bardoxolone (7HT68L8941) ; Biomarkers ; Albumins
Language	English
Publishing date	2022-11-30
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1150271-x
ISSN	1347-5215 ; 0918-6158
ISSN (online)	1347-5215
ISSN	0918-6158
DOI	10.1248/bpb.b22-00586
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Article ; Online: Editorial for "Integrating Postradiotherapy MRI-Detected Lymph Node Necrosis and Pre- and Posttreatment Epstein-Barr Virus-DNA for Risk Stratification in Nasopharyngeal Carcinoma".

Watanabe, Hiroshi

Journal of magnetic resonance imaging : JMRI

2022 Volume 58, Issue 1, Page(s) 120–121

MeSH term(s)	Humans ; Nasopharyngeal Carcinoma ; Herpesvirus 4, Human/genetics ; Epstein-Barr Virus Infections/diagnostic imaging ; Epstein-Barr Virus Infections/pathology ; Nasopharyngeal Neoplasms/diagnostic imaging ; Nasopharyngeal Neoplasms/radiotherapy ; Nasopharyngeal Neoplasms/pathology ; DNA ; Lymph Nodes/pathology ; Necrosis ; Risk Assessment ; Prognosis
Chemical Substances	DNA (9007-49-2)
Language	English
Publishing date	2022-10-31
Publishing country	United States
Document type	Editorial
ZDB-ID	1146614-5
ISSN	1522-2586 ; 1053-1807
ISSN (online)	1522-2586
ISSN	1053-1807
DOI	10.1002/jmri.28514
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Zs.A 3648: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 236: Show issues

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Article: Neuromuscular organization of the benthic ctenophore, Vallicula multiformis.

Mohri, Kurato / Watanabe, Hiroshi

Zoological letters

2024 Volume 10, Issue 1, Page(s) 3

Abstract: Ctenophora is the earliest metazoan taxon with neurons and muscles. Recent studies have described genetic, physiological, and cellular characteristics of the neural and muscular systems of this phylogenically important lineage. However, despite the ... ...

Abstract	Ctenophora is the earliest metazoan taxon with neurons and muscles. Recent studies have described genetic, physiological, and cellular characteristics of the neural and muscular systems of this phylogenically important lineage. However, despite the ecological diversity of ctenophore niches, including both pelagic and benthic forms, studies have focused predominantly on pelagic species. In the present study, we describe the neural and muscular architectures of the benthic ctenophore, Vallicula multiformis (Order Platyctenida), employing immunohistochemical analysis using antibodies against amidated neuropeptides with the C-terminal sequences VWYa, NPWa, FGLa, or WTGa to compare it to pelagic species. In V. multiformis, which lacks the characteristic comb rows seen in pelagic ctenophores, neural structures that develop beneath the comb were not detected, whereas the subepithelial and tentacle neural networks showed considerable similarity to those of pelagic species. Despite significant differences in morphology and lifestyle, muscle organization in V. multiformis closely resembles that of pelagic species. Detailed analysis of neurons that express these peptides unveiled a neural architecture composed of various neural subtypes. This included widely distributed subepithelial neural networks (SNNs) and neurosecretory cells located primarily in the peripheral region. The consistent distribution patterns of the VWYa-positive SNN and tentacle nerves between V. multiformis and the pelagic species, Bolinopsis mikado, suggest evolutionarily conserved function of these neurons in the Ctenophora. In contrast, NPWa-positive neurons, which extend neurites connecting the apical organ and comb rows in B. mikado, showed a neurite-less neurosecretory cell morphology in this flattened, sessile species. Evaluation of characteristics and variations in neural and muscular architectures shared by benthic and pelagic ctenophore species may yield valuable insights for unraveling the biology of this rapidly evolving yet enigmatic metazoan lineage. These findings also provide important insight into neural control modalities in early metazoan evolution.
Language	English
Publishing date	2024-01-30
Publishing country	England
Document type	Journal Article
ZDB-ID	2809936-9
ISSN	2056-306X
ISSN	2056-306X
DOI	10.1186/s40851-024-00225-0
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Book ; Online: On coexistence of decentralized system (blockchain) and central management in Internet-of-Things

Watanabe, Hiroshi

2022

Abstract: Networks are composed of logical nodes and edges for communications. The atomistic component of things connected to the network is a memory chip. Accordingly, the unique linkage of a memory chip and a logical node can be promising to resolve the root-of- ... ...

Abstract	Networks are composed of logical nodes and edges for communications. The atomistic component of things connected to the network is a memory chip. Accordingly, the unique linkage of a memory chip and a logical node can be promising to resolve the root-of-trust problem on the Internet-of-Things. For this aim, we propose a protocol of challenge-response using a memory chip. For the central management, a central node controls the entry of electronic appliances with a memory chip into the network, and excludes a fake node (e.g., the spoofing entity) from the network that the central node manages. For the decentralized communications, Merkle's tree turns out to be composed of memory chips to which the logical nodes are uniquely linked, respectively. The root of Merkle turns out to be the memory chip that stores the latest record of data transactions. We can register this memory chip as a new block by satisfying the requirement of the proof-of-consensus. After blocks are chained, it gets harder for even the central node to manipulate transaction record among memory chips. By this way, the decentralized system (e.g., blockchain) and the central management can coexist. A new idea of security state is also discussed briefly. Comment: 6 pages, 10 figures, accepted and presented in the 2022 IEEE 1st Global Emerging Technology Blockchain Forum, 7-11 November 2022 \| Virtual Event (Whova); https://getblockchain.events.whova.com/Agenda/2759385
Keywords	Computer Science - Distributed ; Parallel ; and Cluster Computing ; Computer Science - Cryptography and Security ; Computer Science - Networking and Internet Architecture
Subject code	303
Publishing date	2022-12-10
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Analysis of cnidarian Gcm suggests a neuronal origin of glial EAAT1 function.

Sheloukhova, Larisa / Watanabe, Hiroshi

Scientific reports

2023 Volume 13, Issue 1, Page(s) 14790

Abstract: In bilaterian central nervous systems, coordination of neurotransmission by glial cells enables highly sophisticated neural functions. The diversity of transcription factors (TFs) involved in gliogenesis suggests multiple evolutionary origins of various ... ...

Abstract	In bilaterian central nervous systems, coordination of neurotransmission by glial cells enables highly sophisticated neural functions. The diversity of transcription factors (TFs) involved in gliogenesis suggests multiple evolutionary origins of various glial cell types of bilaterians. Many of these TFs including the glial cells missing (Gcm) are also present in genomes of Cnidaria, the closest outgroup to Bilateria, but their function remains to be elucidated. In this study, we analyzed the function of Gcm, a multifunctional TF involved in development of glial and non-glial cell types, in the sea anemone, Nematostella vectensis. siRNA-mediated knockdown of Nematostella Gcm altered expression of cell adhesion proteins, glutamate and GABA transporters, ion channels, metabolic enzymes, and zinc finger and Ets-related TFs. NvGcm and mRNAs of downstream genes are expressed in broad neural cell clusters. However, immunostaining of a NvGcm target protein, the glutamate transporter, NvEAAT1, visualized a novel class of cells with flat cell bodies and no clear processes. Together with the finding of unique morphological features of NvEAAT1-functioning cells, these data suggest that extracellular glutamate metabolism, one of major glial functions, is deployed downstream of Gcm in specific neural cell types in Cnidaria.
MeSH term(s)	Animals ; Neuroglia ; Neurons ; Sea Anemones/genetics ; Glutamic Acid
Chemical Substances	SLC1A3 protein, human ; Glutamic Acid (3KX376GY7L)
Language	English
Publishing date	2023-09-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-42046-9
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Article ; Online: Energy spectrum analysis on a red blood cell model.

Yamamoto, Tetsuya / Watanabe, Hiroshi

The Journal of chemical physics

2023 Volume 159, Issue 23

Abstract: It is important to understand the dynamics of red blood cells (RBCs) in blood flow. This requires the formulation of coarse-grained RBC models that reproduce the hydrodynamic properties of blood accurately. One of the models that successfully reproduces ... ...

Abstract	It is important to understand the dynamics of red blood cells (RBCs) in blood flow. This requires the formulation of coarse-grained RBC models that reproduce the hydrodynamic properties of blood accurately. One of the models that successfully reproduces the rheology and morphology of blood has been proposed by Fedosov et al. [Comput. Methods Appl. Mech. Eng. 199, 1937-1948 (2010)]. The proposed RBC model contains several parameters whose values are determined by either various experiments or physical requirements. In this study, we developed a new method of determining parameter values precisely from the fluctuations of the RBC membrane. Specifically, we studied the relationship between the spectra of the fluctuations and model parameters. Characteristic peaks were observed in the spectra, whose peak frequencies were dependent on the parameter values. In addition, we investigated the spectra of the radius of gyration. We identified the peaks originating from the spring potential and the volume-conserving potential appearing in the spectra. These results lead to the precise experimental determination of the parameters used in the RBC model.
MeSH term(s)	Erythrocytes/metabolism ; Rheology/methods ; Spectrum Analysis
Language	English
Publishing date	2023-12-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	3113-6
ISSN	1089-7690 ; 0021-9606
ISSN (online)	1089-7690
ISSN	0021-9606
DOI	10.1063/5.0169467
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Article: Usefulness of pre-travel medical examination and vaccination.

Watanabe, Hiroshi

Nihon rinsho. Japanese journal of clinical medicine

2019 Volume 74, Issue 12, Page(s) 2047–2051

Abstract: At present, both the number of Japanese travelers to foreign countries and foreign travel- ers who visit Japan are remarkably increasing. Travel clinic for travelers is well-known in western countries and medical consultation, vaccination, prescription, ... ...

Abstract	At present, both the number of Japanese travelers to foreign countries and foreign travel- ers who visit Japan are remarkably increasing. Travel clinic for travelers is well-known in western countries and medical consultation, vaccination, prescription, etc are performed, but that is not popular in Japan yet. Most Japanese travelers to foreign countries do not necessa- rily collect any information concerning the infectious diseases which are endemic in the des- tination and security related with their travel and hesitates to receive the recommended vac- cines or prophylactic for malaria. Recently, travel clinics in Japan are gradually increasing due to the support project by Japanese society of travel and health, etc.
MeSH term(s)	Humans ; Malaria/prevention & control ; Malaria Vaccines/therapeutic use ; Travel ; Vaccination
Chemical Substances	Malaria Vaccines
Language	Japanese
Publishing date	2019-01-15
Publishing country	Japan
Document type	Journal Article
ZDB-ID	390903-7
ISSN	0047-1852
ISSN	0047-1852
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Zs.A 429: Show issues

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Book: Pharmacological research on traditional herbal medicines

Watanabe, Hiroshi

1999

Author's details	ed. by Hiroshi Watanabe
Language	English
Size	X, 247 S. : Ill., graph. Darst.
Publisher	Harwood Academic
Publishing place	Amsterdam
Publishing country	Netherlands
Document type	Book
HBZ-ID	HT010842094
ISBN	90-5702-054-8 ; 978-90-5702-054-4
Database	Catalogue ZB MED Medicine, Health

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Shelf mark	Loan status	Location
1999 A 5005	order for loan	Magazin

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Article ; Online: Treatment Selection in Pulmonary Arterial Hypertension: Phosphodiesterase Type 5 Inhibitors versus Soluble Guanylate Cyclase Stimulator.

Watanabe, Hiroshi

European cardiology

2018 Volume 13, Issue 1, Page(s) 35–37

Abstract: Pulmonary arterial hypertension is a chronic and life-threatening disease that if left untreated is fatal. Current therapies include stimulating the nitric oxide-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate axis, improving the ... ...

Abstract	Pulmonary arterial hypertension is a chronic and life-threatening disease that if left untreated is fatal. Current therapies include stimulating the nitric oxide-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate axis, improving the prostacyclin pathway and inhibiting the endothelin pathway. Phosphodiesterase type 5 inhibitors, such as sildenafil, and the sGC stimulator riociguat are currently used in the treatment of pulmonary arterial hypertension. This article discusses the similarities and differences between phosphodiesterase type 5 inhibitors and sGC stimulator based on pharmacological action and clinical trials, and considers which is better for the treatment of pulmonary arterial hypertension.
Language	English
Publishing date	2018-09-17
Publishing country	England
Document type	Journal Article ; Review
ISSN	1758-3764
ISSN (online)	1758-3764
DOI	10.15420/ecr.2017:22:2
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