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  • 1
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    Online Resource
    Non-Achievement of Alanine Aminotransferase Normalization Associated with the Risk of Hepatocellular Carcinoma during Nucleos(t)ide Analogue Therapies: A Multicenter Retrospective Study
    MDPI AG ; 2022
    In:  Journal of Clinical Medicine Vol. 11, No. 9 ( 2022-04-22), p. 2354-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 9 ( 2022-04-22), p. 2354-
    Abstract: Patients with a chronic hepatitis B virus (HBV) infection who are treated with nucleos(t)ide analogues (NAs) are still at risk for hepatocellular carcinoma (HCC), and it has been clinically questioned whether patients with a high risk of HCC can be identified efficiently. We aimed to clarify the risk factors associated with the development of HCC during NA therapies. A total of 611 chronically HBV-infected patients without a history of HCC, who were treated with NAs for more than 6 months (median 72 months), from 2000 to 2021, were included from 16 hospitals in the Tohoku district in Japan. Incidences of HCC occurrence were analyzed with clinical factors, including on-treatment responses. Alanine aminotransferase (ALT) normalization, based on the criteria of three guidelines, was analyzed with other parameters, including the age–male–ALBI–platelets (aMAP) risk score. During the observation period, 48 patients developed HCC, and the cumulative HCC incidence was 10.6% at 10 years. Non-achievement of ALT normalization at 1 year of therapy was mostly associated with HCC development when ALT ≤ 30 U/L was used as the cut-off (cumulative incidence, 19.9% vs. 5.3% at 10 years, p 〈 0.001). The effectiveness of the aMAP risk score at the start of treatment was validated in this cohort. A combination of an aMAP risk score ≥ 50 and non-achievement of ALT normalization could stratify the risk of HCC significantly, and notably, there was no HCC development in 103 patients without these 2 factors. In conclusion, non-achievement of ALT normalization (≤30 U/L) at 1 year might be useful in predicting HCC during NA therapies and, in combination with the aMAP risk score, could stratify the risk more precisely.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm11092354
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662592-1
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  • 2
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    Presence of β-Turn Structure in Recombinant Spider Silk Dissolved in Formic Acid Revealed with NMR
    MDPI AG ; 2022
    In:  Molecules Vol. 27, No. 2 ( 2022-01-14), p. 511-
    Details
    In: Molecules, MDPI AG, Vol. 27, No. 2 ( 2022-01-14), p. 511-
    Abstract: Spider dragline silk is a biopolymer with excellent mechanical properties. The development of recombinant spider silk protein (RSP)-based materials with these properties is desirable. Formic acid (FA) is a spinning solvent for regenerated Bombyx mori silk fiber with excellent mechanical properties. To use FA as a spinning solvent for RSP with the sequence of major ampullate spider silk protein from Araneus diadematus, we determined the conformation of RSP in FA using solution NMR to determine the role of FA as a spinning solvent. We assigned 1H, 13C, and 15N chemical shifts to 32-residue repetitive sequences, including polyAla and Gly-rich regions of RSP. Chemical shift evaluation revealed that RSP is in mainly random coil conformation with partially type II β-turn structure in the Gly-Pro-Gly-X motifs of the Gly-rich region in FA, which was confirmed by the 15N NOE data. In addition, formylation at the Ser OH groups occurred in FA. Furthermore, we evaluated the conformation of the as-cast film of RSP dissolved in FA using solid-state NMR and found that β-sheet structure was predominantly formed.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules27020511
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2008644-1
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  • 3
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    Raman Fingerprints of Rice Nutritional Quality: A Comparison between Japanese Koshihikari and Internationally Renowned Cultivars
    MDPI AG ; 2021
    In:  Foods Vol. 10, No. 12 ( 2021-11-29), p. 2936-
    Details
    In: Foods, MDPI AG, Vol. 10, No. 12 ( 2021-11-29), p. 2936-
    Abstract: Raman spectroscopy was applied to characterize at the molecular scale the nutritional quality of the Japanese Koshihikari rice cultivar in comparison with other renowned rice cultivars including Carnaroli from Italy, Calrose from the USA, Jasmine rice from Thailand, and Basmati from both India and Pakistan. For comparison, two glutinous (mochigome) cultivars were also investigated. Calibrated and validated Raman analytical algorithms allowed quantitative determinations of: (i) amylopectin and amylose concentrations, (ii) fractions of aromatic amino acids, and (iii) protein content and secondary structure. The Raman assessments non-destructively linked the molecular composition of grains to key nutritional parameters and revealed a complex intertwine of chemical properties. The Koshihikari cultivar was rich in proteins (but with low statistical relevance as compared to other investigated cultivars) and aromatic amino acids. However, it also induced a clearly higher glycemic impact as compared to long-grain cultivars from Asian countries. Complementary to genomics and wet-chemistry analyses, Raman spectroscopy makes non-destructively available factual and data-driven information on rice nutritional characteristics, thus providing customers, dietitian nutritionists, and producers with a solid science-consolidated platform.
    Type of Medium: Online Resource
    ISSN: 2304-8158
    URL: Article
    DOI: 10.3390/foods10122936
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2704223-6
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  • 4
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    Effects of Synbiotic Supplementation on Chronic Inflammation and the Gut Microbiota in Obese Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Study
    MDPI AG ; 2021
    In:  Nutrients Vol. 13, No. 2 ( 2021-02-08), p. 558-
    Details
    In: Nutrients, MDPI AG, Vol. 13, No. 2 ( 2021-02-08), p. 558-
    Abstract: The aim of this study was to investigate the effects of 24-week synbiotic supplementation on chronic inflammation and the gut microbiota in obese patients with type 2 diabetes. We randomized 88 obese patients with type 2 diabetes to one of two groups for 24 weeks: control or synbiotic (Lacticaseibacillus paracasei strain Shirota (previously Lactobacillus casei strain Shirota) and Bifidobacterium breve strain Yakult, and galactooligosaccharides). The primary endpoint was the change in interleukin-6 from baseline to 24 weeks. Secondary endpoints were evaluation of the gut microbiota in feces and blood, fecal organic acids, high-sensitivity C-reactive protein, lipopolysaccharide-binding protein, and glycemic control. Synbiotic administration for 24 weeks did not significantly affect changes in interleukin-6 from baseline to 24 weeks (0.35 ± 1.99 vs. −0.24 ± 1.75 pg/mL, respectively). Relative to baseline, however, at 24 weeks after synbiotic administration there were positive changes in the counts of Bifidobacterium and total lactobacilli, the relative abundances of Bifidobacterium species such as Bifidobacterium adolescentis and Bifidobacterium pseudocatenulatum, and the concentrations of acetic and butyric acids in feces. No significant changes in inflammatory markers were found in the synbiotic group compared to the control group. However, synbiotic administration at least partially improved the gut environment in obese patients with type 2 diabetes.
    Type of Medium: Online Resource
    ISSN: 2072-6643
    URL: Article
    DOI: 10.3390/nu13020558
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2518386-2
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  • 5
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    Online Resource
    Association between Vitamin Intake and Chronic Kidney Disease According to a Variant Located Upstream of the PTGS1 Gene: A Cross-Sectional Analysis of Shika Study
    MDPI AG ; 2022
    In:  Nutrients Vol. 14, No. 10 ( 2022-05-16), p. 2082-
    Details
    In: Nutrients, MDPI AG, Vol. 14, No. 10 ( 2022-05-16), p. 2082-
    Abstract: Chronic kidney disease (CKD) patients have been advised to take vitamins; however, the effects have been controversial. The individual differences in developing CKD might involve genetic variants of inflammation, including variant rs883484 located upstream of the prostaglandin-endoperoxide synthase 1 (PTGS1) gene. We aimed to identify whether the 12 dietary vitamin intake interacts with genotypes of the rs883484 on developing CKD. The population-based, cross-sectional study had 684 Japanese participants (≥40 years old). The study used a validated, brief, self-administered diet history questionnaire to estimate the intake of the dietary vitamins. CKD was defined as estimated glomerular filtration 〈 60 mL/min/1.73 m2. The study participants had an average age of 62.1 ± 10.8 years with 15.4% minor homozygotes of rs883484, and 114 subjects had CKD. In the fully adjusted model, the higher intake of vitamins, namely niacin (odds ratio (OR) = 0.74, 95% confidence interval (CI): 0.57–0.96, p = 0.024), α-tocopherol (OR = 0.49, 95% CI: 0.26–0.95, p = 0.034), and vitamin C (OR = 0.97, 95% CI: 0.95–1.00, p = 0.037), was independently associated with lower CKD tendency in the minor homozygotes of rs883484. The results suggested the importance of dietary vitamin intake in the prevention of CKD in middle-aged to older-aged Japanese with minor homozygous of rs883484 gene variant.
    Type of Medium: Online Resource
    ISSN: 2072-6643
    URL: Article
    DOI: 10.3390/nu14102082
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2518386-2
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  • 6
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    Structure–Activity Relationships and Molecular Docking Analysis of Mcl-1 Targeting Renieramycin T Analogues in Patient-derived Lung Cancer Cells
    MDPI AG ; 2020
    In:  Cancers Vol. 12, No. 4 ( 2020-04-03), p. 875-
    Details
    In: Cancers, MDPI AG, Vol. 12, No. 4 ( 2020-04-03), p. 875-
    Abstract: Myeloid cell leukemia 1 (Mcl-1) and B-cell lymphoma 2 (Bcl-2) proteins are promising targets for cancer therapy. Here, we investigated the structure–activity relationships (SARs) and performed molecular docking analysis of renieramycin T (RT) and its analogues and identified the critical functional groups of Mcl-1 targeting. RT have a potent anti-cancer activity against several lung cancer cells and drug-resistant primary cancer cells. RT mediated apoptosis through Mcl-1 suppression and it also reduced the level of Bcl-2 in primary cells. For SAR study, five analogues of RT were synthesized and tested for their anti-cancer and Mcl-1- and Bcl-2-targeting effects. Only two of them (TM-(–)-18 and TM-(–)-4a) exerted anti-cancer activities with the loss of Mcl-1 and partly reduced Bcl-2, while the other analogues had no such effects. Specific cyanide and benzene ring parts of RT’s structure were identified to be critical for its Mcl-1-targeting activity. Computational molecular docking indicated that RT, TM-(–)-18, and TM-(–)-4a bound to Mcl-1 with high affinity, whereas TM-(–)-45, a compound with a benzene ring but no cyanide for comparison, showed the lowest binding affinity. As Mcl-1 helps cancer cells evading apoptosis, these data encourage further development of RT compounds as well as the design of novel drugs for treating Mcl-1-driven cancers.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers12040875
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527080-1
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  • 7
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    Reduction of Superoxide Dismutase 1 Delays Regeneration of Cardiotoxin-Injured Skeletal Muscle in KK/Ta-Ins2Akita Mice with Progressive Diabetic Nephropathy
    MDPI AG ; 2021
    In:  International Journal of Molecular Sciences Vol. 22, No. 11 ( 2021-05-23), p. 5491-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 11 ( 2021-05-23), p. 5491-
    Abstract: Superoxide dismutase (SOD) is a major antioxidant enzyme for superoxide removal, and cytoplasmic SOD (SOD1) is expressed as a predominant isoform in all cells. We previously reported that renal SOD1 deficiency accelerates the progression of diabetic nephropathy (DN) via increasing renal oxidative stress. To evaluate whether the degree of SOD1 expression determines regeneration capacity and sarcopenic phenotypes of skeletal muscles under incipient and advanced DN conditions, we investigated the alterations of SOD1 expression, oxidative stress marker, inflammation, fibrosis, and regeneration capacity in cardiotoxin (CTX)-injured tibialis anterior (TA) muscles of two Akita diabetic mouse models with different susceptibility to DN, DN-resistant C57BL/6-Ins2Akita and DN-prone KK/Ta-Ins2Akita mice. Here, we report that KK/Ta-Ins2Akita mice, but not C57BL/6-Ins2Akita mice, exhibit delayed muscle regeneration after CTX injection, as demonstrated by the finding indicating significantly smaller average cross-sectional areas of regenerating TA muscle myofibers relative to KK/Ta-wild-type mice. Furthermore, we observed markedly reduced SOD1 expression in CTX-injected TA muscles of KK/Ta-Ins2Akita mice, but not C57BL/6-Ins2Akita mice, along with increased inflammatory cell infiltration, prominent fibrosis and superoxide overproduction. Our study provides the first evidence that SOD1 reduction and the following superoxide overproduction delay skeletal muscle regeneration through induction of overt inflammation and fibrosis in a mouse model of progressive DN.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms22115491
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 8
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    Can Homecare Chronic Respiratory Disease Patients with Home Oxygen Treatment (HOT) in Southern Okinawa, Japan Be Evacuated Ahead of the Next Anticipated Tsunami?
    MDPI AG ; 2022
    In:  International Journal of Environmental Research and Public Health Vol. 19, No. 9 ( 2022-05-06), p. 5647-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 19, No. 9 ( 2022-05-06), p. 5647-
    Abstract: An earthquake with a magnitude of 8 or 9 is predicted to occur near the Ryukyu Islands in Japan, for which the Okinawa Prefecture is preparing countermeasures. Evacuating people to a safe shelter within the tsunami arrival time is a crucial countermeasure. This study aims to understand the vulnerabilities of patients with chronic respiratory diseases in southern parts of Okinawa during a tsunami evacuation, thereby calculating evacuation distance of vulnerable patients and creating individual evacuation plans. Data for chronic respiratory patients obtained in July 2021 from the hospitals in Okinawa Prefecture include age, gender, diagnosis, residence, nearest tsunami shelter, oxygen flow at rest and walking, and maximum walking distance for 6 min based on a 6-min walk test. A quantum geographic information system was used for mapping the data. The survival potential of patients with chronic respiratory disease was evaluated by using a tsunami inundation depth of one meter and the distance within which an evacuation can be performed until the first tsunami wave reaches the nearest evacuation shelter. Results revealed a low survival potential for respiratory disease patients under the current tsunami evacuation plan. The study suggests creating an individual evacuation plan for vulnerable patients involving families and medical staff and then conducting a drill for improving the plan.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph19095647
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2175195-X
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  • 9
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    The Role of Polygenic Susceptibility on Air Pollution-Associated Asthma between German and Japanese Elderly Women
    MDPI AG ; 2022
    In:  International Journal of Environmental Research and Public Health Vol. 19, No. 16 ( 2022-08-10), p. 9869-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 19, No. 16 ( 2022-08-10), p. 9869-
    Abstract: Polygenic susceptibility likely influences individual responses to air pollutants and the risk of asthma. We compared the role of polygenic susceptibility on air pollution-associated asthma between German and Japanese women. We investigated women that were enrolled in the German SALIA cohort (n = 771, mean age = 73 years) and the Japanese Shika cohort (n = 847, mean age = 67 years) with known asthma status. Adjusted logistic regression models were used to assess the associations between (1) particulate matter with a median aerodynamic diameter ≤ 2.5μm (PM2.5) and nitrogen dioxide (NO2), (2) polygenic risk scores (PRS), and (3) gene-environment interactions (G × E) with asthma. We found an increased risk of asthma in Japanese women after exposure to low pollutant levels (PM2.5: median = 12.7µg/m3, p-value 〈 0.001, NO2: median = 8.5µg/m3, p-value 〈 0.001) and in German women protective polygenic effects (p-value = 0.008). While we found no significant G × E effects, the direction in both groups was that the PRS increased the effect of PM2.5 and decreased the effect of NO2 on asthma. Our study confirms that exposure to low air pollution levels increases the risk of asthma in Japanese women and indicates polygenic effects in German women; however, there was no evidence of G × E effects. Future genome-wide G × E studies should further explore the role of ethnic-specific polygenic susceptibility to asthma.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph19169869
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2175195-X
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  • 10
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    Favorable Prognosis in Patients with Recovered Pulmonary Hypertension after TAVI: An Analysis of the LAPLACE-TAVI Registry
    MDPI AG ; 2023
    In:  Journal of Clinical Medicine Vol. 12, No. 2 ( 2023-01-16), p. 729-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 12, No. 2 ( 2023-01-16), p. 729-
    Abstract: Pulmonary hypertension (PH) is a common complication of aortic stenosis (AS). Despite the established association between PH and poor outcomes in patients with AS, the prognostic implication of a change in PH after transcatheter aortic valve implantation (TAVI) has been rarely evaluated. This study analyzed a prospective multi-center TAVI registry database involving six Japanese centers and used the transtricuspid pressure gradient (TRPG) obtained by echocardiography to estimate pulmonary artery systolic pressure. The participants (n = 2056) were first divided into two groups by TRPG before TAVI, a PH (−) group (TRPG 〈 30 mmHg) (n = 1407, 61.9%) and a PH (+) group (TRPG ≥ 30 mmHg) (n = 649, 28.6%). Next, by TRPG after (4.1 ± 5.3 days) TAVI, the PH (+) group was further subdivided into two groups, Recovered PH (TRPG 〈 30 mmHg, n = 253) and Persistent PH (TRPG after TAVI ≥ 30 mmHg, n = 396). The median follow-up duration was 1.8 years. The primary and secondary endpoints were the composite and each of cardiovascular (CV) death and heart failure hospitalization, respectively. Unadjusted Kaplan-Meier estimates with log-rank comparisons showed significantly higher cumulative incidences of primary and secondary endpoints in the Persistent PH group compared to other groups. Moreover, adjusted multivariate Cox-proportional hazard analyses showed that a decreased (−10 mmHg) TRPG after TAVI was linearly associated with a reduced risk of the primary endpoint (hazard ratio (HR): 0.76, 95% confidence interval (CI): 0.64–0.90, p = 0.0020). The findings in the present study indicate that the recovery of PH may partly contributes to the prognostic benefit of TAVI procedure in patients with AS and elevated pulmonary artery systolic pressure.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm12020729
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662592-1
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