Publications by authors named "Ryuichi Sawa"

113 Publications

The Potential Application of Commercially Available Active Video Games to Cardiac Rehabilitation: Scoping Review.

JMIR Serious Games 2022 Mar 18;10(1):e31974. Epub 2022 Mar 18.

Department of Physical Therapy, Faculty of Health Science, Juntendo University, Tokyo, Japan.

Background: Commercially available active video games (AVGs) have recently been used for rehabilitation in some specific patient populations but rarely in those with cardiovascular disease (CVD). Commercially available AVGs are designed to increase motivation for continuous play, which could be applicable to the long-term cardiac rehabilitation process.

Objective: The objective of this scoping review was to assess the effectiveness of AVG-induced physical exercise, safety management, and patient adherence by applying commercially available AVGs to cardiac rehabilitation.

Methods: Four databases (CINAHL, MEDLINE, PubMed, and SPORTDiscus) were searched for all years up to August 12, 2020. Articles were retained if they were written in English, included patients with CVD who were aged 18 years or older, and used AVGs as part of a physical exercise program. The included studies were then evaluated from the viewpoints of effectiveness as physical exercise, safety, and adherence management.

Results: Among 120 nonduplicate articles reviewed, 5 (4.2%) were eligible for inclusion, of which 3 (2.5%) were reported by the same research group. The AVG consoles used were Xbox Kinect and Nintendo Wii, and sports-related programs were adopted for the intervention. No adverse cardiac events occurred in the identified studies, and dropout rates tended to be low.

Conclusions: AVGs appear to be safe and feasible for promoting an active lifestyle in patients with CVD. However, the effectiveness of AVGs alone as a therapeutic exercise to improve physical function may be limited.
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http://dx.doi.org/10.2196/31974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8976248PMC
March 2022

Rediscovery of 4-Trehalosamine as a Biologically Stable, Mass-Producible, and Chemically Modifiable Trehalose Analog.

Adv Biol (Weinh) 2022 Mar 17:e2101309. Epub 2022 Mar 17.

Institute of Microbial Chemistry (BIKAKEN), 3-14-23, Kamiosaki, Shinagawa-ku, Tokyo, 141-0021, Japan.

Nonreducing disaccharide trehalose is used as a stabilizer and humectant in various products and is a potential medicinal drug, showing curative effects on the animal models of various diseases. However, its use is limited as it is hydrolyzed by trehalase, a widely expressed enzyme in multiple organisms. Several trehalose analogs are prepared, including a microbial metabolite 4-trehalosamine, and their high biological stability is confirmed. For further analysis, 4-trehalosamine is selected as it shows high producibility. Compared with trehalose, 4-trehalosamine exhibits better or comparable protective activities and a high buffer capacity around the neutral pH. Another advantage of 4-trehalosamine is its chemical modifiability: simple reactions produce its various derivatives. Labeled probes and detergents are synthesized in one-pot reactions to exemplify the feasibility of their production, and their utility is confirmed for their respective applications. The labeled probes are used for mycobacterial staining. Although the derivative detergents can be effectively used in membrane protein research, long-chain detergents show 1000-3000-fold stronger autophagy-inducing activity in cultured cells than trehalose and are expected to become a drug lead and research reagent. These results indicate that 4-trehalosamine is a useful trehalose substitute for various purposes and a material to produce new useful derivative substances.
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http://dx.doi.org/10.1002/adbi.202101309DOI Listing
March 2022

Association between Abnormal Gait Patterns and an Elevated Degree of Pain after Daily Walking: A Preliminary Study.

Int J Environ Res Public Health 2022 03 1;19(5). Epub 2022 Mar 1.

Department of Community Health Sciences, Kobe University Graduate School of Health Sciences, 7-10-2, Tomogaoka, Suma-ku, Kobe 654-0142, Japan.

This study aimed to investigate whether abnormal gait patterns are associated with experiencing an elevated degree of pain after daily walking. In this preliminary, cross-sectional study, 223 community-dwelling older adults were assessed for pain experienced after daily walking using a simple question that involved asking the subject about their past experiences of an elevated degree of pain after walking for 400 m or more. Gait patterns were assessed using the Comprehensive Gait Assessment using InerTial Sensor score (C-GAITS score), derived from the data measured by Inertial sensors attached to the lower trunk and heel when subjects walked along a 15 m walkway at a self-selected preferred speed. The score was the sum of 10 gait parameter scores. The lower scores indicated more and worse abnormal gait patterns. In total, 24 older adults (10.8%) reported that they experienced pain after daily walking. According to the multiple logistic regression analyses, older adults with a lower total C-GAITS score had a significantly greater probability of having past experiences of pain after walking (odds ratio = 1.11, 95% confidence interval = 1.03-1.20). The findings of this study suggest that more and worse abnormal gait patterns among older adults in a clinical walking test are associated with an elevated degree of pain after daily walking.
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http://dx.doi.org/10.3390/ijerph19052842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8910192PMC
March 2022

Environmental hazards as risk factors for trips and slips at home among Japanese older people: A pilot study toward the development of a self-assessment tool for the home environment.

Geriatr Gerontol Int 2022 Apr 1;22(4):305-310. Epub 2022 Mar 1.

Faculty of Human Sciences, University of Tsukuba, Tokyo, Japan.

Aim: Housing structures differ according to the local culture, climate, and lifestyle, and these unique characteristics usually act as potential hazards for falls, trips, and slips. The purpose of this study was to identify environmental hazards in a Japanese house and their association with falls, trips, and slips among older people.

Methods: A total of 97 older people aged ≥75 years were included in this cross-sectional study. The number of environmental hazards was measured using a 46-item tool designed specifically for this study, and the associations of environmental hazards with falls, trips, and slips were analyzed using univariate and multivariate logistic regressions.

Results: All houses had at least one environmental hazard, and 3-30 environmental hazards were identified. Although the number of environmental hazards was not associated with falls experienced during the past 6 months, a greater number of environmental hazards at home was correlated with the daily experience of trips and slips (odds ratio [OR]: 1.10; 95% confidence interval [CI]: 1.02-1.18). The association remained significant even after adjusting for demographic characteristics and other fall risk factors (OR: 1.11; 95% CI: 1.02-1.21).

Conclusion: We found that Japanese housing structures had unique environmental hazards that might cause trips and slips in older people. Appropriate housing assessments and modifications may help to promote aging-in-place among older people. Geriatr Gerontol Int 2022; 22: 305-310.
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http://dx.doi.org/10.1111/ggi.14365DOI Listing
April 2022

Web Portals for Patients With Chronic Diseases: Scoping Review of the Functional Features and Theoretical Frameworks of Telerehabilitation Platforms.

J Med Internet Res 2022 01 27;24(1):e27759. Epub 2022 Jan 27.

Faculty of Health Science, Juntendo University, Tokyo, Japan.

Background: The COVID-19 pandemic has required an increased need for rehabilitation activities applicable to patients with chronic diseases. Telerehabilitation has several advantages, including reducing clinic visits by patients vulnerable to infectious diseases. Digital platforms are often used to assist rehabilitation services for patients in remote settings. Although web portals for medical use have existed for years, the technology in telerehabilitation remains a novel method.

Objective: This scoping review investigated the functional features and theoretical approaches of web portals developed for telerehabilitation in patients with chronic diseases.

Methods: PubMed and Web of Science were reviewed to identify articles associated with telerehabilitation. Of the 477 nonduplicate articles reviewed, 35 involving 14 portals were retrieved for the scoping review. The functional features, targeted diseases, and theoretical approaches of these portals were studied.

Results: The 14 portals targeted patients with chronic obstructive pulmonary disease, cardiovascular, osteoarthritis, multiple sclerosis, cystic fibrosis diseases, and stroke and breast cancer survivors. Monitoring/data tracking and communication functions were the most common, followed by exercise instructions and diary/self-report features. Several theoretical approaches, behavior change techniques, and motivational techniques were found to be utilized.

Conclusions: The web portals could unify and display multiple types of data and effectively provide various types of information. Asynchronous correspondence was more favorable than synchronous, real-time interactions. Data acquisition often required assistance from other digital tools. Various functions with patient-centered principles, behavior change strategies, and motivational techniques were observed for better support shifting to a healthier lifestyle. These findings suggested that web portals for telerehabilitation not only provided entrance into rehabilitation programs but also reinforced participant-centered treatment, adherence to rehabilitation, and lifestyle changes over time.
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http://dx.doi.org/10.2196/27759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8832270PMC
January 2022

The Relationship between Sarcopenia and Respiratory Muscle Weakness in Community-Dwelling Older Adults.

Int J Environ Res Public Health 2021 12 16;18(24). Epub 2021 Dec 16.

Department of Physical Therapy, Juntendo University, 3-2-12 Hongo, Bunkyo-ku, Ochanomizu Center Building 5F, Tokyo 113-0033, Japan.

An association between respiratory muscle weakness and sarcopenia may provide a clue to the mechanism of sarcopenia development. We aimed to clarify this relationship among community-dwelling older adults. In total, 117 community-dwelling older adults were assessed and classified into 4 groups: robust, respiratory muscle weakness, sarcopenia, and respiratory sarcopenia. The respiratory sarcopenia group (12%) had a significantly higher percentage of males and had lower BMI, skeletal muscle index, skeletal muscle mass, phase angle, and oral function than the robust group (32.5%). All physical functions were significantly lower. The respiratory muscle weakness group (54.7%) had a significantly lower BMI and slower walking speed, compared with the robust group. The sarcopenia group (0.8%) was excluded from the analysis. The percent maximum inspiratory pressure was significantly lower in both the respiratory muscle weakness and respiratory sarcopenia groups, compared with the robust group. Almost all participants with sarcopenia showed respiratory muscle weakness. In addition, approximately 50% had respiratory muscle weakness, even in the absence of systemic sarcopenia, suggesting that respiratory muscle weakness may be the precursor of sarcopenia. The values indicating physical function and skeletal muscle mass in the respiratory muscle weakness group were between those in the robust and the respiratory sarcopenia groups.
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http://dx.doi.org/10.3390/ijerph182413257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8701155PMC
December 2021

Isolation of new derivatives of the 20-membered macrodiolide bispolide from Kitasatospora sp. MG372-hF19.

J Antibiot (Tokyo) 2022 02 6;75(2):77-85. Epub 2021 Dec 6.

Institute of Microbial Chemistry (BIKAKEN), Laboratory of Microbiology, Microbial Chemistry Research Foundation, Tokyo, Japan.

New three macrocyclic diolides, named bispolides C-E (1-3), were isolated from a fermentation broth of the actinomycete strain MG372-hF19, which produces an indole glycoside and leptomycins as we reported previously. The absolute structures of compounds 1-3 were elucidated by NMR and X-ray crystallography. Compounds 1-3 diverge from the known nine bispolides in their different alkylation patterns on the 20-membered macrocyclic diolide skeleton and the side chain in their planar structures. Furthermore, compounds 1-3 exhibited antibacterial activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci and cytotoxic activity against human cancer cell lines. Among them, compound 3 has the most potent biological activities against bacteria and tumor cells. Additionally, using a membrane-potential-sensitive fluorescence probe, we found that compounds 1-3 and elaiophylin have a similar effect on membrane potential in A549 human lung cancer cells.
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http://dx.doi.org/10.1038/s41429-021-00492-5DOI Listing
February 2022

Effects of Telerehabilitation Interventions on Heart Failure Management (2015-2020): Scoping Review.

JMIR Rehabil Assist Technol 2021 Nov 1;8(4):e29714. Epub 2021 Nov 1.

Laboratory for Welfare Technology - Telehealth & Telerehabilitation, Sport Sciences - Performance and Technology, Department of Health Science and Technology, Aalborg University, Aalborg East, Denmark.

Background: Heart failure is one of the world's most frequently diagnosed cardiovascular diseases. An important element of heart failure management is cardiac rehabilitation, the goal of which is to improve patients' recovery, functional capacity, psychosocial well-being, and health-related quality of life. Patients in cardiac rehabilitation may lack sufficient motivation or may feel that the rehabilitation process does not meet their individual needs. One solution to these challenges is the use of telerehabilitation. Although telerehabilitation has been available for several years, it has only recently begun to be utilized in heart failure studies. Especially within the past 5 years, we now have several studies focusing on the effectiveness of telerehabilitation for heart failure management, all with varying results. Based on a review of these studies, this paper offers an assessment of the effectiveness of telerehabilitation as applied to heart failure management.

Objective: The aim of this scoping review was to assess the effects of telerehabilitation in the management of heart failure by systematically reviewing the available scientific literature within the period from January 1, 2015, to December 31, 2020.

Methods: The literature search was carried out using PubMed and EMBASE. After duplicates were removed, 77 articles were screened and 12 articles were subsequently reviewed. The review followed the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses for scoping reviews) guidelines. As measures of the effectiveness of telerehabilitation, the following outcomes were used: patients' quality of life, physical capacity, depression or anxiety, and adherence to the intervention.

Results: A total of 12 articles were included in this review. In reviewing the effects of telerehabilitation for patients with heart failure, it was found that 4 out of 6 randomized controlled trials (RCTs), a single prospective study, and 4 out of 5 reviews reported increased quality of life for patients. For physical capacity, 4 RCTs and 3 systematic reviews revealed increased physical capacity. Depression or depressive symptoms were reported as being reduced in 1 of the 6 RCTs and in 2 of the 5 reviews. Anxiety or anxiety-related symptoms were reported as reduced in only 1 review. High adherence to the telerehabilitation program was reported in 4 RCTs and 4 reviews. It should be mentioned that some of the reviewed articles described the same studies although they employed different outcome measures.

Conclusions: It was found that there is a tendency toward improvement in patients' quality of life and physical capacity when telerehabilitation was used in heart failure management. The outcome measures of depression, anxiety, and adherence to the intervention were found to be positive. Additional research is needed to determine more precise and robust effects of telerehabilitation.
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http://dx.doi.org/10.2196/29714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8593801PMC
November 2021

Micromonosporamide A with Glutamine-Dependent Cytotoxicity from sp. MM609M-173N6: Isolation, Stereochemical Determination, and Synthesis.

Org Lett 2021 10 29;23(20):7981-7985. Epub 2021 Sep 29.

Institute of Microbial Chemistry (BIKAKEN), 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan.

An acyldipeptide, micromonosporamide A, was isolated from the fermentation broth of sp. MM609M-173N6 by bioassay-guided fractionation using a glutamine compensation assay. The planar structure was elucidated on the basis of comprehensive one- and two-dimensional nuclear magnetic resonance and high-resolution mass spectrometry. The relative and absolute configuration of the entire molecule were determined using a combined approach, involving chromatographic analysis by liquid chromatography-mass spectrometry, advanced Marfey's method, and total synthesis. Micromonosporamide A exhibited glutamine-dependent antiproliferative activity.
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http://dx.doi.org/10.1021/acs.orglett.1c02974DOI Listing
October 2021

Quinofuracins F - I, new quinofuracin derivatives produced by Staphylotrichum boninense PF1444.

J Antibiot (Tokyo) 2021 10 29;74(10):758-762. Epub 2021 Jul 29.

Institute of Microbial Chemistry (BIKAKEN), Tokyo, Shinagawa-ku, Japan.

Four new quinofuracins F - I were isolated from the culture broth of Staphylotrichum boninense PF1444. The structures of quinofuracins F - I were elucidated by extensive spectroscopic analysis. These quinofuracins induced tumor suppressor protein p53-dependent cell death in human glioblastoma LNZTA3 cells.
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http://dx.doi.org/10.1038/s41429-021-00452-zDOI Listing
October 2021

The potent protein phosphatase 2A inhibitors aminocytostatins: new derivatives of cytostatin.

J Antibiot (Tokyo) 2021 10 21;74(10):743-751. Epub 2021 Jul 21.

Institute of Microbial Chemistry, Microbial Chemistry Research Foundation (BIKAKEN), Shinagawa-ku, Tokyo, Japan.

Specific inhibitors of protein phosphatase 2A (PP2A) mediate anticancer effects by augmenting the tumor-killing activity of natural killer (NK) cells. In this study, new PP2A inhibitors, aminocytostatins A-E, were isolated from Kitasatospora sp. MJ654-NF4 and structurally characterized. Aminocytostatins are derivatives of cytostatin, which is a specific PP2A inhibitor isolated from the same organism, and aminocytostatins have a characteristic amino group within the lactone moiety. Compared to cytostatin, aminocytostatin A showed a stronger inhibitory activity against PP2A in vitro and augmented the tumor-killing activity of NK cells in vivo. Furthermore, a docking model was generated to demonstrate the favorable activities of aminocytostatin A.
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http://dx.doi.org/10.1038/s41429-021-00455-wDOI Listing
October 2021

Structure-activity relationships of natural quinone vegfrecine analogs with potent activity against VEGFR-1 and -2 tyrosine kinases.

J Antibiot (Tokyo) 2021 10 20;74(10):734-742. Epub 2021 Jul 20.

Institute of Microbial Chemistry (BIKAKEN), Tokyo, Japan.

A series of analogs of vegfrecine, a natural quinone vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor, was synthesized via oxidative amination of 2,5-dihydroxybenzamide with functionalized arylamine followed by ammonolysis and substitution of the quinone ring. The inhibitory activities of the analogs against the VEGFR-1 and -2 tyrosine kinases were assayed in vitro with the aim to identify a compound suitable to treat cancer and inflammatory diseases. Alterations of the functionality of the phenyl group, substitution of the quinone ring, and oxidative cyclization of the 1-carboxamide-2-aminoquinone moiety to form an isoxazole quinone ring were examined. Introduction of halo- and alkyl-substituents at the 5'-position of the phenyl ring resulted in potent inhibition of the VEGFR-1 and -2 tyrosine kinases. In particular, structural modification at C-5' on the phenyl ring was shown to significantly affect the selectivity of the inhibition between the VEGFR-1 and -2 tyrosine kinases. Compound 8, 5'-methyl-vegfrecine, showed superior selectivity toward the VEGFR-2 tyrosine kinase over the VEGFR-1 tyrosine kinase.
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http://dx.doi.org/10.1038/s41429-021-00445-yDOI Listing
October 2021

Saccharobipyrimicin, a new antibiotic from the leaf-litter actinomycete Saccharothrix sp. MM696L-181F4.

J Antibiot (Tokyo) 2021 07 23;74(7):470-473. Epub 2021 Mar 23.

Institute of Microbial Chemistry (BIKAKEN), Shinagawa-ku, Tokyo, Japan.

In the course of screening for new antimicrobial compounds, a new antibiotic substance named saccharobipyrimicin was isolated from the leaf-litter actinomycete Saccharothrix sp. MM696L-181F4. The structure of saccharobipyrimicin was elucidated by various spectral methods, mainly single-crystal X-ray analysis and chemical degradation. It revealed that saccharobipyrimicin contained a 2,2'-bipyridine skeletal structure. Saccharobipyrimicin showed moderate and broad-spectrum antimicrobial activity. Two chemical derivatives of saccharobipyrimicin showed weaker antimicrobial activities than that of saccharobipyrimicin against most test microorganisms except two tolC mutants of Escherichia coli and Neisseria gonorrhoeae.
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http://dx.doi.org/10.1038/s41429-021-00418-1DOI Listing
July 2021

Sealutomicins, new enediyne antibiotics from the deep-sea actinomycete Nonomuraea sp. MM565M-173N2.

J Antibiot (Tokyo) 2021 05 3;74(5):291-299. Epub 2021 Feb 3.

Japan Agency for Marine-Earth Science and Technology (JAMSTEC), 2-15 Natsushima-cho, Yokosuka City, Kanagawa, 237-0061, Japan.

A Nonomuraea sp. strain MM565M-173N2 was isolated from deep-sea sediment off the Sanriku coast, and new antibiotics were evaluated against carbapenem-resistant Enterobacteriaceae (CRE), which is a problematic group of bacteria because of their antimicrobial resistance. From 220 l of fermented broth from strain MM565M-173N2, we isolated four new antibiotics by gel filtration and HPLC, designated as sealutomicins A (1.8 mg), B (1.5 mg), C (0.8 mg), and D (0.8 mg). Their structures were determined from MS, NMR, and CD spectra. Sealutomicin A was found to be a new enediyne antibiotic, while sealutomicins B-D were aromatized products from sealutomicin A. Sealutomicin A showed strong antibacterial activity (MIC 0.05-0.2 μg ml) against CRE.
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http://dx.doi.org/10.1038/s41429-020-00402-1DOI Listing
May 2021

Effects of a wearable device and functional wear on spinal alignment and jump performance.

J Exerc Sci Fit 2021 Apr 10;19(2):91-97. Epub 2020 Oct 10.

Department of Physical Therapy, Faculty of Health Science, Juntendo University, Japan.

Background/objective: To elucidate the effects of walking exercise using a wearable device and functional wear on spinal alignment and jump performance.

Methods: In total, 27 female college soccer players were randomly divided into two groups: trunk solution (TS) and compression garments (CGs). Spinal alignment, jump performance, and electromyography activity during the jump performance of the two groups were measured after a 20-min walking exercise. The values for each group were compared t pre- and post-intervention.

Results: The flexibility of the lower thoracic vertebrae in spinal alignment was increased during extension in the TS group. However, the post-value of the abdominal external oblique muscle during a countermovement jump (CMJ) was significantly lower than its pre-value (p < 0.05). In addition, even though spinal alignment was not affected in the CG group, post-values of the jump height during squat jump and CMJ were significantly higher than their pre-values (p < 0.05). Furthermore, the post-value of the biceps femoris during the countermovement jump with arm was significantly lower than its pre-value (p < 0.05).

Conclusion: Our study suggested that walking exercise using TS may increase the range of motion of the lower thoracic vertebrae in athletes and reduce the muscular activity of the vastus lateralis during CMJ. Additionally, although spinal aliment is not affected, the jump height may increase using CGs.
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http://dx.doi.org/10.1016/j.jesf.2020.10.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736979PMC
April 2021

Metacytofilin has potent anti-malarial activity.

Parasitol Int 2021 Apr 8;81:102267. Epub 2020 Dec 8.

National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan. Electronic address:

Metacytofilin (MCF) was isolated from the fungus Metarhizium sp. TA2759. Although MCF possesses anti-Toxoplasma activity, the effects of this compound against other parasites are unknown. Here, we evaluated the in vitro anti-malarial activity of MCF against the 3D7 strain and the chloroquine-resistant K1 strain of Plasmodium falciparum. The half maximal inhibitory concentrations (IC) of MCF against the 3D7 and K-1 strains following culture for 48 h were 666 nM and 605 nM, respectively. Artemisinin was more potent than MCF against both strains (3D7 IC: 17.4 nM; K-1 IC: 18.3 nM), while chloroquine was ineffective against the chloroquine-resistant strain (3D7 IC: 39.1 nM; K-1 IC: 1.62 μM). MCF affected the ring stage of the parasites, resulting in their death as shown by spots within red blood cells. MCF also inhibited parasite growth following culture for 72 h (3D7 IC, 285 nM). Four optical isomers of cyclo[Leu-Phe]-diketopiperazine derivatives with modified methoxy and/or hydroxyl groups lost anti-malarial activity, suggesting that the spatial positions of the methoxy and hydroxyl groups in MCF play an important role in its anti-malarial effects. Together, these data suggest that MCF may represent a promising lead compound for treatment of drug-resistant malarial parasites.
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http://dx.doi.org/10.1016/j.parint.2020.102267DOI Listing
April 2021

Influence of kinesiophobia with pregnancy-related lumbopelvic pain at late pregnancy on postpartum depressive symptoms.

Phys Ther Res 2020 25;23(1):92-98. Epub 2020 Feb 25.

Department of Public Health, Kobe University Graduate School of Health Sciences, Kobe, Japan.

Objective: To investigate whether kinesiophobia with pregnancy-related lumbopelvic pain at late pregnancy influenced depressive symptoms at 1 month after delivery.

Method: Final participants were 43 pregnant women who experienced pregnancy-related lumbopelvic pain at late pregnancy and completed self-reported questionnaires at late pregnancy and 1 month after delivery. The Tampa Scale for Kinesiophobia was used to evaluate kinesiophobia, and depressive symptoms were assessed using the Self-Rating Depression Scale. We divided participants into two groups (depression and no-depression) using the score of the Self-Rating Depression Scale at 1 month after delivery. Univariate analysis and multiple logistic regression analysis identified kinesiophobia at late pregnancy as an independent predictor of depression at 1 month after delivery.

Results: In univariate analysis, kinesiophobia at late pregnancy was significantly higher in the depression group than in the no-depression group (P= .033). In multiple logistic regression analysis, kinesiophobia at late pregnancy were significantly associated with depression at 1 month after delivery even after adjusting for confounding factors (Odds Ratio, 1.25; 95% Confidence Interval, 1.03-1.52).

Conclusion: Results found that kinesiophobia at late pregnancy negatively influenced depressive symptoms at 1 month after delivery, suggesting that approaches to treat kinesiophobia at late pregnancymight reduce the risk of onset of postpartum depressive symptoms.
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http://dx.doi.org/10.1298/ptr.E9999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344362PMC
February 2020

Human pancreatic cancer cells under nutrient deprivation are vulnerable to redox system inhibition.

J Biol Chem 2020 12 25;295(49):16678-16690. Epub 2020 Sep 25.

Institute of Microbial Chemistry (BIKAKEN), Numazu, Shizuoka, Japan.

Large regions in tumor tissues, particularly pancreatic cancer, are hypoxic and nutrient-deprived because of unregulated cell growth and insufficient vascular supply. Certain cancer cells, such as those inside a tumor, can tolerate these severe conditions and survive for prolonged periods. We hypothesized that small molecular agents, which can preferentially reduce cancer cell survival under nutrient-deprived conditions, could function as anticancer drugs. In this study, we constructed a high-throughput screening system to identify such small molecules and screened chemical libraries and microbial culture extracts. We were able to determine that some small molecular compounds, such as penicillic acid, papyracillic acid, and auranofin, exhibit preferential cytotoxicity to human pancreatic cancer cells under nutrient-deprived compared with nutrient-sufficient conditions. Further analysis revealed that these compounds target to redox systems such as GSH and thioredoxin and induce accumulation of reactive oxygen species in nutrient-deprived cancer cells, potentially contributing to apoptosis under nutrient-deprived conditions. Nutrient-deficient cancer cells are often deficient in GSH; thus, they are susceptible to redox system inhibitors. Targeting redox systems might be an attractive therapeutic strategy under nutrient-deprived conditions of the tumor microenvironment.
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http://dx.doi.org/10.1074/jbc.RA120.013893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864064PMC
December 2020

New chloptosins B and C from an Embleya strain exhibit synergistic activity against methicillin-resistant Staphylococcus aureus when combined with co-producing compound L-156,602.

J Antibiot (Tokyo) 2021 01 14;74(1):80-85. Epub 2020 Aug 14.

Laboratory of Microbiology, Institute of Microbial Chemistry (BIKAKEN), 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo, 141-0021, Japan.

Two new dimeric cyclohexapeptides, chloptosins B and C, were discovered from the culture broth of Embleya sp. MM621-AF10 together with the known compounds chloptosin and L-156,602. The structures of the new chloptosins were determined by spectroscopic studies and advanced Marfey's methods. The stereo structure of the constituent isoleucine was determined by C Marfey's analysis. Chloptosins demonstrated potent antimicrobial activity against Gram-positive bacteria including drug-resistant strains of methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci with MICs of 0.5-2 µg ml. The antimicrobial activities of chloptosins were enhanced by addition of co-producing compound L-156,602, as shown by checkerboard analysis.
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http://dx.doi.org/10.1038/s41429-020-0361-yDOI Listing
January 2021

Collaborative Study to Validate Purity Determination by H Quantitative NMR Spectroscopy by Using Internal Calibration Methodology.

Chem Pharm Bull (Tokyo) 2020 Sep 19;68(9):868-878. Epub 2020 Jun 19.

National Institute of Health Sciences.

NMR spectroscopy has recently been utilized to determine the absolute amounts of organic molecules with metrological traceability since signal intensity is directly proportional to the number of each nucleus in a molecule. The NMR methodology that uses hydrogen nucleus (H) to quantify chemicals is called quantitative H-NMR (H qNMR). The quantitative method using H qNMR for determining the purity or content of chemicals has been adopted into some compendial guidelines and official standards. However, there are still few reports in the literature regarding validation of H qNMR methodology. Here, we coordinated an international collaborative study to validate a H qNMR based on the use of an internal calibration methodology. Thirteen laboratories participated in this study, and the purities of three samples were individually measured using H qNMR method. The three samples were all certified via conventional primary methods of measurement, such as butyl p-hydroxybenzoate Japanese Pharmacopeia (JP) reference standard certified by mass balance; benzoic acid certified reference material (CRM) certified by coulometric titration; fludioxonil CRM certified by a combination of freezing point depression method and H qNMR. For each sample, H qNMR experiments were optimized before quantitative analysis. The results showed that the measured values of each sample were equivalent to the corresponding reference labeled value. Furthermore, assessment of these H qNMR data using the normalized error, E-value, concluded that statistically H qNMR has the competence to obtain the same quantification performance and accuracy as the conventional primary methods of measurement.
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http://dx.doi.org/10.1248/cpb.c20-00336DOI Listing
September 2020

Daily physical activity is associated with increased sonographically measured bone status during lactation.

Womens Health (Lond) 2020 Jan-Dec;16:1745506519900582

Department of Community Health Sciences, Graduate School of Health Sciences, Kobe University, Kobe, Japan.

Objectives: The purpose of this cross-sectional study was to investigate the association between daily physical activity and sonographically measured bone status among women during the lactation period.

Methods: Final participants were 152 women 4 months after childbirth. Bone status of the participants was measured using quantitative ultrasonometry of the calcaneus (speed of sound). Daily physical activity was assessed using the Japanese version of International Physical Activity Questionnaire short version. After getting the International Physical Activity Questionnaire results, we classified participants into three categories (low/moderate/high) according to a protocol. Participants categorized into the low group according to the International Physical Activity Questionnaire were considered to be in the low physical activity group and those categorized into the moderate and high groups were considered to be in the moderate to vigorous physical activity group.

Results: Speed of sound was significantly higher in the moderate to vigorous physical activity group (moderate to vigorous physical activity versus low physical activity, 1533 m/s versus 1523 m/s,  = 0.03). Daily physical activity was significantly associated with speed of sound, even after adjustment for confounding factors and prognosticators ( = 0.195,  = 0.02).

Conclusion: Sonographically measured bone status was significantly higher in women who were physically active than in those who were physically inactive, suggesting that daily physical activity might help to maintain good bone status.
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http://dx.doi.org/10.1177/1745506519900582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6963316PMC
August 2020

A new indole glycoside from Kitasatospora sp. MG372-hF19 carrying a 6-deoxy-α-L-talopyranose moiety.

J Antibiot (Tokyo) 2020 03 18;73(3):167-170. Epub 2019 Nov 18.

Institute of Microbial Chemistry (BIKAKEN), Numazu, 18-24 Miyamoto, Numazu-shi, Shizuoka, 410-0301, Japan.

Small cell lung cancer (SCLC) is a severe malignancy with early and widespread metastasis, and novel therapeutic drugs are needed. To identify cytotoxic natural compounds against SCLC, we screened libraries of microbial fermentation broths using several lung cancer cell lines. We found that the actinomycete strain MG372-hF19 produces a compound that has not been isolated from natural sources but previously chemically synthesized, 6-chloro-1H-indole-3-carboxaldehyde (1), and an entirely new compound, named 6-deoxy-α-L-talopyranose 1-(6-chloro-1H-indole-3-carboxylate) (2), together with leptomycins. The molecular formulas of the compounds were established as CHClNO and CHClNO, respectively, via high-resolution electrospray ionization mass spectrometry, and their structures were determined using detailed NMR. Absolute configurational analysis of the sugar unit of compound 2 revealed that the compound incorporates the rare deoxyhexose 6-deoxy-α-L-talopyranose. Both compounds exhibited weak growth-inhibiting activities against human lung cancer cell lines.
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http://dx.doi.org/10.1038/s41429-019-0258-9DOI Listing
March 2020

Metacytofilin Is a Potent Therapeutic Drug Candidate for Toxoplasmosis.

J Infect Dis 2020 02;221(5):766-774

National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido, Japan.

Background: Toxoplasmosis, a parasitic disease caused by Toxoplasma gondii, is an important cause of miscarriage or adverse fetal effects, including neurological and ocular manifestations in humans. Current anti-Toxoplasma drugs have limited efficacy against toxoplasmosis and also have severe side effects. Therefore, novel efficacious drugs are urgently needed. Here, we identified metacytofilin (MCF) from a fungal Metarhizium species as a potential anti-Toxoplasma compound.

Methods: Anti-Toxoplasma activities of MCF and its derivatives were evaluated in vitro and in vivo using nonpregnant and pregnant mice. To understand the mode of action of MCF, the RNA expression of host and parasite genes was investigated by RNAseq.

Results: In vitro, MCF inhibited the viability of intracellular and extracellular T. gondii. Administering MCF intraperitoneally or orally to mice after infection with T. gondii tachyzoites increased mouse survival compared with the untreated animals. Remarkably, oral administration of MCF to pregnant mice prevented vertical transmission of the parasite. Interestingly, RNA sequencing of T. gondii-infected cells treated with MCF showed that MCF inhibited DNA replication and enhanced RNA degradation in the parasites.

Conclusions: With its potent anti-T. gondii activity, MCF is a strong candidate for future drug development against toxoplasmosis.
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http://dx.doi.org/10.1093/infdis/jiz501DOI Listing
February 2020

Isolation and characterization of antiprotozoal compound-producing Streptomyces species from Mongolian soils.

Parasitol Int 2020 Feb 19;74:101961. Epub 2019 Aug 19.

National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-Cho, Obihiro, Hokkaido 080-8555, Japan. Electronic address:

Natural resources are recognized as important sources of potential drugs for treating various infections, and microorganisms are a rich natural source of diverse compounds. Among the world's microorganisms, actinomycetes, which are abundant in soil and marine, are the well-known producers of a wide range of bioactive secondary metabolites and antibiotics. In the present study, four actinomycetes (samples N25, N6, N18, and N12) were isolated from soil samples in Mongolia. Phylogenetic analysis of these isolates revealed that they share the highest similarity with Streptomyces canus (N25), S. cirratus (N6), S. bacillaris (N18) and S. peucetius (N12), based on 16S rRNA gene sequencing. Crude extracts were obtained from them using ethyl acetate, and the crude fractions were separated by thin layer chromatography. The fractions were then evaluated for their cytotoxicities and their anti-Toxoplasma and antimalarial activities in vitro. The S. canus (N25) crude extract was selected for further chemical characterization based on its antiprotozoal activities. Using liquid chromatography-high resolution mass spectrometry, phenazine-1-carboxylic acid (PCA) was detected and identified in the active fractions of the metabolites from strain N25. We next confirmed that commercially available PCA possesses antiprotozoal activity against T. gondii (IC: 55.5 μg/ml) and Plasmodium falciparum (IC: 6.4 μg/ml) in vitro. The results of this study reveal that soil actinomycetes are potential sources of antiprotozoal compounds, and that PCA merits further investigation as an anti-protozoal agent.
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http://dx.doi.org/10.1016/j.parint.2019.101961DOI Listing
February 2020

Development and validation of Comprehensive Gait Assessment using InerTial Sensor score (C-GAITS score) derived from acceleration and angular velocity data at heel and lower trunk among community-dwelling older adults.

J Neuroeng Rehabil 2019 05 28;16(1):62. Epub 2019 May 28.

Department of Community Health Sciences, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-ku, Kobe, 654-0142, Japan.

Background: Although some gait parameters from inertial sensors have been shown to be associated with important clinical issues, because of controversial results, it remains uncertain which parameters for which axes are clinically valuable. Following the idea that a comprehensive score obtained by summing various gait parameters would sensitively reflect declines in gait performance, we developed a scoring method for community-dwelling older adults, the Comprehensive Gait Assessment using InerTial Sensor score (C-GAITS score). The aim of this study was to examine the internal consistency and the construct validity of this method.

Methods: In this cross-sectional study, the gait performance of 378 community-dwelling older people (mean age = 71.7 ± 4.2 years, 210 women) was assessed using inertial sensors attached to the heel and lower trunk. Participants walked along a 15-m walkway, and accelerations, angular velocity, and walking time were measured. From these data, walking speed, mean stride time, coefficients of variation of stride time and swing time, and autocorrelation coefficients and harmonic ratios of acceleration in vertical, mediolateral, and anteroposterior directions at the lower trunk were calculated. Scoring was performed based on quartile by gender (i.e., scored from 0 to 3) for each of the 10 gait parameters. The C-GAITS score was the sum of these scores (range: 0-30). Lower extremity strength, balance function, fall history, and fear of falling were also assessed.

Results: An exploratory factor analysis revealed that the C-GAITS score yielded four distinct factors explaining 57.1% of the variance. The Cronbach's alpha coefficient was 0.77. A single linear regression analysis showed a significant relationship between total C-GAITS score and walking speed (adjusted R = 0.28). Results from bivariate comparisons using unpaired t-tests showed that the score was significantly related to age (p = 0.002), lower extremity strength (p = 0.007), balance function (p <  0.001), fall history (p = 0.04), and fear of falling (p <  0.001).

Conclusions: Good internal consistency and appropriate construct validity of the C-GAITS score were confirmed among community-dwelling older adults. The score might be useful in clinical settings because of ease of use and interpretation and capability of capturing functional decline.
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http://dx.doi.org/10.1186/s12984-019-0539-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540531PMC
May 2019

Leucinostatin Y: A Peptaibiotic Produced by the Entomoparasitic Fungus Purpureocillium lilacinum 40-H-28.

J Nat Prod 2019 05 24;82(5):1120-1127. Epub 2019 Apr 24.

Institute of Microbial Chemistry (BIKAKEN) , Numazu, 18-24 Miyamoto , Numazu-shi , Shizuoka 410-0301 , Japan.

Leucinostatin Y, a new peptaibiotic, was isolated from the culture broth of the entomoparasitic fungus Purpureocillium lilacinum 40-H-28. The planar structure was elucidated by detailed analysis of its NMR and MS/MS data. The absolute configurations of the amino acids were partially determined by an advanced Marfey's method. The biological activities of leucinostatin Y were assessed using human pancreatic cancer cells, revealing the importance of the C-terminus of leucinostatins for preferential cytotoxicity to cancer cells under glucose-deprived conditions and inhibition of mitochondrial function.
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http://dx.doi.org/10.1021/acs.jnatprod.8b00839DOI Listing
May 2019

Reliability and Validity of the Japanese Version of the Physical Activity Questionnaire for Older Children.

Clin Med Insights Pediatr 2019 19;13:1179556519835833. Epub 2019 Mar 19.

Department of Community Health Sciences, Kobe University Graduate School of Health Sciences, Kobe, Japan.

Objectives: This study aimed to examine the reliability and validity of the Japanese version of the Physical Activity Questionnaire for Older Children (PAQ-C) in Japanese children aged 9 to 12 years.

Methods: A total of 210 children aged between 9 and 12 years participated. Internal consistency and test-retest reliability were evaluated using Cronbach alpha coefficient and intraclass correlation coefficient (ICC), respectively. Validity was evaluated using athletic competence (AC), self-efficacy (SE), body mass index (BMI), body fat percentage (%BF), cardiovascular fitness (CVF), and World Health Organization Health Behavior in School-aged Children (WHO HBSC) physical activity questionnaire.

Results: Internal consistency was acceptable (alpha = 0.80) and test-retest reliability showed excellent agreement (ICC = 0.83). The PAQ-C score was significantly correlated with AC ( = 0.41), SE ( = 0.65), %BF ( = 0.19), and CVF ( = -0.32). The PAQ-C score of the active group classified by the WHO HBSC physical activity questionnaire (mean score ± standard deviation [SD] = 3.03 ± 0.57) was significantly higher than that of the inactive group (mean score ± SD = 2.27 ± 0.63,  < .01).

Conclusions: The PAQ-C had acceptable reliability and validity. The PAQ-C is a useful instrument to evaluate physical activity for Japanese children aged 9 to 12 years.
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http://dx.doi.org/10.1177/1179556519835833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425525PMC
March 2019

Playing football on artificial turf as a risk factor for fifth metatarsal stress fracture: a retrospective cohort study.

BMJ Open 2019 02 20;9(2):e022864. Epub 2019 Feb 20.

Department of Orthopaedics and Sports Medicine, Juntendo University, Tokyo, Japan.

Objective: The fifth metatarsal stress fracture is a common injury among football players. Although several risk factors have been proposed, the association between the playing surface and development of fifth metatarsal stress fractures (MT-5) has not been evaluated. We conducted an epidemiological study using a computer-based survey to investigate the association between the playing surface and development of MT-5.

Methods: This study included 1854 football players, of which 41 experienced MT-5 within the past 24 months. Baseline demographic data and the percentage of time spent playing on artificial turf and clay fields were compared between the non-MT-5 and MT-5 player groups, and the risks for development of MT-5 associated with the playing surfaces were estimated by univariate and multivariate analyses.

Results: There were significant differences in body mass index, years of play, playing categories and playing time on artificial turf between non-MT-5 and MT-5 groups (p<0.05). Generalised estimating equations analyses adjusted for multiple confounders demonstrated that relative to the risk of playing <20% of the time on each surface, the OR (OR: 95% CI) for MT-5 for playing on artificial turf >80% of the time increased (3.44: 1.65 to 7.18), and for playing on a clay field 61%-80% of the time, the OR decreased (0.25: 0.11 to 0.59).

Conclusions: A higher percentage of playing time on an artificial turf was a risk factor for developing MT-5 in football players. This finding could be beneficial for creating strategies to prevent MT-5.
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http://dx.doi.org/10.1136/bmjopen-2018-022864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6398723PMC
February 2019

Flupyranochromene, a novel inhibitor of influenza virus cap-dependent endonuclease, from Penicillium sp. f28743.

J Antibiot (Tokyo) 2019 03 9;72(3):125-133. Epub 2019 Jan 9.

Institute of Microbial Chemistry (BIKAKEN), Shinagawa-ku, Tokyo, Japan.

Influenza virus RNA polymerase has cap-dependent endonuclease activity that produces capped RNA fragments for priming viral mRNA synthesis. This enzymatic activity is essential for viral propagation, but it is not present in any host cellular enzyme, making it an attractive target for the development of anti-influenza drugs. Here, we isolated a novel inhibitor of cap-dependent endonuclease, named flupyranochromene, from the fermentation broth of the fungus Penicillium sp. f28743. Structural analysis revealed that this compound bears a putative pharmacophore that chelates divalent metal ion(s) present in the endonuclease active site in the PA subunit of the polymerase. Consistently, in vitro endonuclease assays showed that flupyranochromene exerts its inhibitory effects by blocking endonucleolytic cleavage by the PA subunit of viral RNA polymerase complex.
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http://dx.doi.org/10.1038/s41429-018-0134-zDOI Listing
March 2019

The Association Between Physical Activity, Including Physical Activity Intensity, and Fear of Falling Differs by Fear Severity in Older Adults Living in the Community.

J Gerontol B Psychol Sci Soc Sci 2020 04;75(5):953-960

Department of Community Health Sciences, Kobe University Graduate School of Health Sciences, Japan.

Objectives: Fear of falling (FoF) is common in older adults. Physical activity decreases as FoF increases. However, this association between physical activity and FoF may vary depending on activity intensity. The current study was performed to explore the associations between FoF and step count, light-intensity physical activity (LPA), and moderate/vigorous-intensity physical activity (MVPA) in community-dwelling older adults.

Methods: This cross-sectional observational study was held at a local community association center, with 242 older adults living independently in the community (mean age: 75.1 ± 5.4 years). FoF was defined using the Falls Efficacy Scale-International and categorized into three levels (low, moderate, and high). Physical activity was measured using a uniaxial accelerometer worn for 7 consecutive days, and by calculating daily step count, LPA, and MVPA, over this period.

Results: Step count and physical activity intensity showed significant linear trends across FoF severity (p < .01, respectively). High FoF decreased step count by approximately 2,000 steps/day. Further, high FoF was significantly associated with short durations of both LPA and MVPA. In addition, moderate FoF was associated with decreased LPA duration, even after adjustment for confounding variables.

Discussion: Physical activity decreased concomitantly with a rise in FoF severity. Moreover, the association between physical activity and FoF differed by physical activity intensity level in community-dwelling older adults. Further studies are needed to investigate the causal relationship between FoF and objective physical activity in this population.
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http://dx.doi.org/10.1093/geronb/gby103DOI Listing
April 2020
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