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Article ; Online: Rapamycin vs TORin-1 or Gleevec vs Nilotinib: Simple chemical evolution that converts PAK1-blockers to TOR-blockers or vice versa?

Maruta, Hiroshi / He, Hong

2024

Abstract: Both PAK1 (RAC/CDC42-activating kinase 1) and TOR (Target of Rapamycin) are among the major oncogenic/ageing kinases. However, they play the opposite role in our immune system, namely immune system is suppressed by PAK1, while it requires TOR. Thus, PAK1- ...

Abstract	Both PAK1 (RAC/CDC42-activating kinase 1) and TOR (Target of Rapamycin) are among the major oncogenic/ageing kinases. However, they play the opposite role in our immune system, namely immune system is suppressed by PAK1, while it requires TOR. Thus, PAK1-blockers, would be more effective for therapy of cancers, than TOR-blockers. Since 2015 when we discovered genetically that PDGF-induced melanogenesis depends on "PAK1", we are able to screening a series of PAK1-blockers as melanogenesis-inhibitors which could eventually promote longevity. Interestingly, rapamycin, the first TOR-inhibitor, promotes melanogenesis, clearly indicating that TOR suppresses melanogenesis. However, a new TOR-inhibitor called TORin-1 no longer suppresses immune system, and blocks melanogenesis in cell culture. These observations strongly indicate that TORin-1 acts as PAK1-blockers, instead of TOR-blockers, in vivo. Thus, it is most likely that melanogenesis in cell culture could enable us to discriminate PAK1-blockers from TORblockers.
Language	English
Publishing date	2024-04-04
Publishing country	Japan
Document type	Journal Article
ZDB-ID	2568828-5
ISSN	1881-784X ; 1881-784X
ISSN (online)	1881-784X
ISSN	1881-784X
DOI	10.5582/ddt.2023.01097
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Book: Tumor-suppressing viruses, genes, and drugs

Maruta, Hiroshi

innovative cancer therapy approaches

2002

Title variant	Tumor-suppressing viruses, genes, and drugs
Author's details	ed. by Hiroshi Maruta
Language	English
Size	XV, 425 S. : Ill., graph. Darst.
Publisher	Acad. Press
Publishing place	San Diego u.a.
Publishing country	United States
Document type	Book
HBZ-ID	HT013236936
ISBN	0-12-476249-2 ; 978-0-12-476249-7
Database	Catalogue ZB MED Medicine, Health

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Shelf mark	Loan status	Location
2002 A 356	order for loan	Magazin

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Article ; Online: Probiotic microbes: Are their anti-melanogenicity and longevity promoting activities closely linked through the major "pathogenic" kinase PAK1?

Maruta, Hiroshi / Ahn, Mok-Ryeon

Drug discoveries & therapeutics

2022 Volume 16, Issue 1, Page(s) 43–46

Abstract: PAK1-deficient mutant of C. elegans lives 60% longer than the wild-type. Interestingly, PAK1-deficient mutant of melanocytes produces less melanin (only a half compared with the wild-type) in the presence of either serum (PDGF) or α-MSH (alpha-melanocyte ...

Abstract	PAK1-deficient mutant of C. elegans lives 60% longer than the wild-type. Interestingly, PAK1-deficient mutant of melanocytes produces less melanin (only a half compared with the wild-type) in the presence of either serum (PDGF) or α-MSH (alpha-melanocyte stimulating hormone). These observations indicate that the major "pathogenic" kinase PAK1 is responsible for both shortening the healthy lifespan, and PDGF/α-MSH-dependent melanogenesis. For screening of PAK1-blocking probiotic bacteria or their products, their anti-melanogenic as well as longevity promoting properties were examined. Recently it was found that C. elegans fed with Lactobacillus rhamnosus in Xinjiang cheese lives 40% longer than the worm fed with the standard E. coli. Interestingly, a Chinese traditional medicine called "ChiBai" fermented with the Lactobacillus rhamnosus also inhibited the α-MSH-induced melanogenesis, and this bacteria itself produces butyric acid that blocks the oncogenic HDAC (histone deacetylase)-PAK1 signaling pathway. These findings strongly suggest, if not proven, that anti-melanogenic activity of Lactobacillus and many other probiotic bacteria might serve as a reliable indicator for their longevity promoting activity. In this context, a popular Japanese Lactobacillus-fermented milk drink called "Calpis", developed a century ago, and recently proven to inhibit the melanogenesis by suppressing the PAK1-dependent tyrosinase gene expression, may potentially prolong our healthy lifespan.
MeSH term(s)	Animals ; Caenorhabditis elegans/metabolism ; Escherichia coli/metabolism ; Longevity ; Melanins/metabolism ; Melanocytes/metabolism ; Monophenol Monooxygenase/metabolism ; Probiotics/pharmacology ; p21-Activated Kinases
Chemical Substances	Melanins ; Monophenol Monooxygenase (EC 1.14.18.1) ; p21-Activated Kinases (EC 2.7.11.1)
Language	English
Publishing date	2022-03-09
Publishing country	Japan
Document type	Journal Article
ZDB-ID	2568828-5
ISSN	1881-784X ; 1881-784X
ISSN (online)	1881-784X
ISSN	1881-784X
DOI	10.5582/ddt.2022.01013
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Article: RETRACTED: Lactobacillus and other probiotic bacteria: Their anti-melanogenicity and longevity promoting activities are closely linked through the major ‘pathogenic’ kinase PAK1

Maruta, Hiroshi / Ahn, Mok-Ryeon

Lebensmittel-Wissenschaft + Technologie. 2022 Apr. 01,

2022

Abstract: PAK1-deficient mutant of Caenorhabditis elegans lives 60% longer than the wild-type. Interestingly, PAK1-deficient mutant of melanocytes produces less melanin (only a half compared with the wild-type) in the presence of either serum (PDGF) or α-MSH ( ... ...

Abstract	PAK1-deficient mutant of Caenorhabditis elegans lives 60% longer than the wild-type. Interestingly, PAK1-deficient mutant of melanocytes produces less melanin (only a half compared with the wild-type) in the presence of either serum (PDGF) or α-MSH (alpha-melanocyte stimulating hormone). These observations clearly indicate that the major “pathogenic” kinase PAK1 is responsible for both shortening the healthy lifespan, and PDGF/α-MSH-dependent melanogenesis. For screening of PAK1-blocking probiotic bacteria or their products, their anti-melanogenic as well as longevity promoting properties were examined. Recently it was found that C. elegans fed with Lactobacillus rhamnosus in Xinjiang cheese lives 40% longer than the worm fed with the standard Escherichia coli. Interestingly, a Chinese traditional medicine called “ChiBai” fermented with the L. rhamnosus also inhibited the α-MSH-induced melanogenesis, and this bacteria itself produces butyric acid that blocks the oncogenic HDAC (histone deacetylase)-PAK1 signaling pathway. These findings strongly suggest, if not proven, that anti-melanogenic activity of Lactobacillus and many other probiotic bacteria could serve as a reliable indicator for their longevity promoting activity. In this context, a popular Japanese Lactobacillus-fermented milk drink called “Calpis”, developed a century ago, and recently proven to inhibit the melanogenesis by suppressing the PAK1-dependent Tyrosinase gene expression, could potentially prolong our healthy lifespan.
Keywords	Caenorhabditis elegans ; Escherichia coli ; Lactobacillus rhamnosus ; Oriental traditional medicine ; blood serum ; butyric acid ; cheeses ; gene expression ; histone deacetylase ; longevity ; melanin ; melanocytes ; melanogenesis ; milk ; mutants ; probiotics ; China
Language	English
Dates of publication	2022-0401
Publishing place	Elsevier Ltd
Document type	Article
Note	Pre-press version
ZDB-ID	241369-3
ISSN	0460-1173 ; 0023-6438
ISSN	0460-1173 ; 0023-6438
DOI	10.1016/j.lwt.2022.113424
Database	NAL-Catalogue (AGRICOLA)

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Book ; Conference proceedings: Anticancer molecules

Maruta, Hiroshi

structure, function, and design ; [... papers from a Conference Entitled Anti-Cancer Proteins and Drugs: Structure, Function and Design

(Annals of the New York Academy of Sciences ; 886)

1999

Institution	New York Academy of Sciences
Event/congress	Conference Entitled Anti-Cancer Proteins and Drugs: Structure, Function and Design (1998, NewYorkNY)
Author's details	which was held by the New York Academy of Sciences in New York, New York on November 6 - 9, 1998]. Ed. by Hiroshi Maruta
Series title	Annals of the New York Academy of Sciences ; 886
Collection
Keywords	Cytostatikum ; Arzneimittelentwicklung
Subject	Arzneimittel ; Drug Development ; Zytostatikum ; Cancerotoxischer Stoff ; Carcinostatikum ; Krebsmittel ; Antineoplastikum ; Anticarcinogen ; Antikarzinogen ; Anticancerogen ; Antineoplastisches Mittel
Language	English
Size	XII, 303 S. : Ill., graph. Darst.
Publishing place	New York, N.Y
Publishing country	United States
Document type	Book ; Conference proceedings
HBZ-ID	HT011248107
ISBN	1-57331-184-7 ; 1-57331-185-5 ; 978-1-57331-184-7 ; 978-1-57331-185-4
Database	Catalogue ZB MED Medicine, Health

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Se 110 -886-	verfügbar in Königswinter	Königswinter

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Article ; Online: Torsional Vibration Tests of Extruded Polystyrene with Improved Accuracy in Determining the Shear Modulus.

Yoshihara, Hiroshi / Wakahara, Momoka / Yoshinobu, Masahiro / Maruta, Makoto

Polymers

2022 Volume 14, Issue 6

Abstract: Recently, extruded polystyrene (XPS) foam has been used as a component of construction materials; therefore, it is important to characterize its mechanical properties, including shear modulus. Despite the importance, it is often difficult to determine ... ...

Abstract	Recently, extruded polystyrene (XPS) foam has been used as a component of construction materials; therefore, it is important to characterize its mechanical properties, including shear modulus. Despite the importance, it is often difficult to determine the shear modulus accurately by using many of the conventional methods; therefore, it is desirable to establish another method to measure the shear modulus with a high accuracy. Among various methods, torsional vibration test is advantageous because it can be performed easily under the pure shear stress condition in the test sample and both the in-plane and out-of-plane shear moduli can be obtained. However, it is difficult to find any examples performing the torsional vibration tests. In this study, the in-plane and out-of-plane shear moduli of XPS were determined through torsional vibration tests using samples of various widths. In addition, the shear moduli were also determined through flexural vibration tests and compared with those obtained from the torsional vibration tests. In the torsional vibration tests, the anisotropy in these shear moduli became an obstacle, and the in-plane shear modulus determined using a single sample was often dependent on the width/thickness ratio of the sample. In this condition, the coefficient of variation of the in-plane shear modulus value was often close to 10%. However, when using data obtained from the samples with various width/thickness ratios, both the in-plane and out-of-plane shear moduli could be obtained while reducing the abovementioned dependence. Additionally, the coefficients of variation were restricted to those below 2% and 7% for the in-plane and out-of-plane shear moduli, respectively, and these values were obviously lower than those obtained from the flexural vibration tests (approximately 20%). In the proposed method, both the in-plane and out-of-plane shear moduli can be obtained accurately without using any numerical analyses, which are often required in the standardized methods to improve the accuracy. Thus, for accurate measurement of both types of shear moduli of XPS, we recommend performing torsional vibration tests using a range of samples of various width/thickness ratios.
Language	English
Publishing date	2022-03-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527146-5
ISSN	2073-4360 ; 2073-4360
ISSN (online)	2073-4360
ISSN	2073-4360
DOI	10.3390/polym14061148
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Article ; Online: PAK1-blockers: Potential Therapeutics against COVID-19.

Maruta, Hiroshi / He, Hong

Medicine in drug discovery

2020 Volume 6, Page(s) 100039

Abstract: PAK1 (RAC/CDC42-activated kinase 1) is the major "pathogenic" kinase whose abnormal activation causes a wide variety of diseases/disorders including cancers, inflammation, malaria and pandemic viral infection including influenza, HIV and COVID-19. Since ... ...

Abstract	PAK1 (RAC/CDC42-activated kinase 1) is the major "pathogenic" kinase whose abnormal activation causes a wide variety of diseases/disorders including cancers, inflammation, malaria and pandemic viral infection including influenza, HIV and COVID-19. Since Louis Pasteur who developed a vaccine against rabies in 1885, in general a series of "specific" vaccines have been used for treatment of viral infection, mainly because the majority of pre-existing antibiotics are either anti-bacterial or anti-fungal, thereby being ineffective against viruses in general. However, it takes 12-18 months till the effective vaccine becomes available. Until then ventilator (O
Keywords	covid19
Language	English
Publishing date	2020-04-19
Publishing country	Netherlands
Document type	Journal Article ; Review
ISSN	2590-0986
ISSN (online)	2590-0986
DOI	10.1016/j.medidd.2020.100039
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Article ; Online: Chemical evolution for taming the 'pathogenic kinase' PAK1.

Maruta, Hiroshi / Kittaka, Atsushi

Drug discovery today

2020 Volume 25, Issue 6, Page(s) 959–964

Abstract: To celebrate the 25th anniversary of the cloning of the first mammalian p21-activated kinases (PAKs) (RAC/CDC42-activated kinases) by Ed Manser, the first international PAK symposium was held in NYC in October 2019. Among six distinct PAKs in mammals, ... ...

Abstract	To celebrate the 25th anniversary of the cloning of the first mammalian p21-activated kinases (PAKs) (RAC/CDC42-activated kinases) by Ed Manser, the first international PAK symposium was held in NYC in October 2019. Among six distinct PAKs in mammals, PAK1 is the major 'pathogenic kinase', the abnormal activation of which is responsible for a wide variety of diseases and disorders including cancers, ageing processes and infectious and inflammatory diseases such as pandemic coronaviral infection. Recently, for a clinical application, a few potent (highly cell-permeable and water-soluble) PAK1 blockers have been developed from natural or synthetic PAK1 blockers (triptolide, vitamin D3 and ketorolac) via a series of 'chemical evolutions' that boost pharmacological activities >500 times.
MeSH term(s)	Aging/drug effects ; Aging/metabolism ; Animals ; Enzyme Inhibitors/pharmacology ; Evolution, Chemical ; Humans ; Inflammation/drug therapy ; Inflammation/metabolism ; Mammals/metabolism ; Neoplasms/drug therapy ; Neoplasms/metabolism ; p21-Activated Kinases/antagonists & inhibitors
Chemical Substances	Enzyme Inhibitors ; p21-Activated Kinases (EC 2.7.11.1)
Keywords	covid19
Language	English
Publishing date	2020-04-26
Publishing country	England
Document type	Journal Article
ZDB-ID	1324988-5
ISSN	1878-5832 ; 1359-6446
ISSN (online)	1878-5832
ISSN	1359-6446
DOI	10.1016/j.drudis.2020.03.008
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Article: Critical load for buckling of solid wood elements with a high slenderness ratio determined based on elastica theory

Yoshihara, Hiroshi / Maruta, Makoto

Holzforschung. 2022 Feb. 23, v. 76, no. 2

2022

Abstract: Buckling tests were conducted using slender specimens of western hemlock. In the tests, the slenderness ratio was varied from 132 to 418 in which elastic buckling was induced, and the values of the critical load for buckling were obtained. When the ... ...

Abstract	Buckling tests were conducted using slender specimens of western hemlock. In the tests, the slenderness ratio was varied from 132 to 418 in which elastic buckling was induced, and the values of the critical load for buckling were obtained. When the deflection of the specimen was calculated from the loading-line displacement based on elastica theory, the value of deflection/load initially decreased because the compressive deformation was more dominant than the bending deformation. In contrast, when the load increased, the bending deformation became dominant, and the deflection/load-deflection relation exhibited linearity. These tendencies indicated that the transition from compression to bending was induced around the minimum value of the deflection/load. Therefore, it was recommended to determine the critical load for buckling using the load at the minimum value of the deflection/load where the deflection was calculated from the loading-line displacement.
Keywords	critical load ; deformation ; wood
Language	English
Dates of publication	2022-0223
Size	p. 179-187.
Publishing place	De Gruyter
Document type	Article
ZDB-ID	1466072-6
ISSN	1437-434X ; 0018-3830
ISSN (online)	1437-434X
ISSN	0018-3830
DOI	10.1515/hf-2021-0108
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Herbal therapeutics that block the oncogenic kinase PAK1: a practical approach towards PAK1-dependent diseases and longevity.

Maruta, Hiroshi

Phytotherapy research : PTR

2014 Volume 28, Issue 5, Page(s) 656–672

Abstract: Over 35 years research on PAKs, RAC/CDC42(p21)-activated kinases, comes of age, and in particular PAK1 has been well known to be responsible for a variety of diseases such as cancer (mainly solid tumors), Alzheimer's disease, acquired immune deficiency ... ...

Abstract	Over 35 years research on PAKs, RAC/CDC42(p21)-activated kinases, comes of age, and in particular PAK1 has been well known to be responsible for a variety of diseases such as cancer (mainly solid tumors), Alzheimer's disease, acquired immune deficiency syndrome and other viral/bacterial infections, inflammatory diseases (asthma and arthritis), diabetes (type 2), neurofibromatosis, tuberous sclerosis, epilepsy, depression, schizophrenia, learning disability, autism, etc. Although several distinct synthetic PAK1-blockers have been recently developed, no FDA-approved PAK1 blockers are available on the market as yet. Thus, patients suffering from these PAK1-dependent diseases have to rely on solely a variety of herbal therapeutics such as propolis and curcumin that block PAK1 without affecting normal cell growth. Furthermore, several recent studies revealed that some of these herbal therapeutics significantly extend the lifespan of nematodes (C. elegans) and fruit flies (Drosophila), and PAK1-deficient worm lives longer than the wild type. Here, I outline mainly pathological phenotypes of hyper-activated PAK1 and a list of herbal therapeutics that block PAK1, but cause no side (harmful) effect on healthy people or animals.
MeSH term(s)	Animals ; Antineoplastic Agents, Phytogenic/pharmacology ; Communicable Diseases/drug therapy ; Curcumin/pharmacology ; Humans ; Inflammation/drug therapy ; Longevity/drug effects ; Neoplasms/drug therapy ; Phytotherapy ; Plants, Medicinal/chemistry ; Propolis/pharmacology ; p21-Activated Kinases/antagonists & inhibitors
Chemical Substances	Antineoplastic Agents, Phytogenic ; Propolis (9009-62-5) ; p21-Activated Kinases (EC 2.7.11.1) ; Curcumin (IT942ZTH98)
Language	English
Publishing date	2014-05
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	639136-9
ISSN	1099-1573 ; 0951-418X
ISSN (online)	1099-1573
ISSN	0951-418X
DOI	10.1002/ptr.5054
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