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  • 1
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    Online Resource
    Long-Term Prognosis of Patients with Myocardial Infarction Type 1 and Type 2 with and without Involvement of Coronary Vasospasm
    MDPI AG ; 2020
    In:  Journal of Clinical Medicine Vol. 9, No. 6 ( 2020-06-02), p. 1686-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 9, No. 6 ( 2020-06-02), p. 1686-
    Abstract: While prognoses in relation to myocardial infarction (MI) type have been elucidated in past reports, the results were not consistent, perhaps due to occurrence of Type 2 MI with CVS and its mortality. The Japanese registry of acute Myocardial Infarction diagnosed by Universal Definition (J-MINUET) is a prospective multicenter registry in Japan. In contrast to thromboembolic event-related Type 1 myocardial infarction (MI), clinical features of Type 2 MI, including coronary vasospasm (CVS), are varied due to the heterogeneous nature of its development. To elucidate the MI type-related all-cause mortality, 2989 consecutive patients with AMI were stratified as Type 1 MI, Type 2 MI with CVS, and Type 2 MI with non-CVS. Most patients (n = 2834; 94.8%) were classified as Type 1 MI and 155 patients (5.2%) were classified as Type 2 MI. Of the Type 2 MI patients, 87 (56% of Type 2 MI) were diagnosed as MI with CVS. Although the 3-year mortality was comparable between Type 1 and Type 2 MI patients, significant differences were observed between Type 2 MI with CVS and with non-CVS (3.4% and 22.1%, p 〈 0.001). Among Japanese patients with AMI, mortality rates between Type 1 MI and Type 2 MI are comparable, but further stratification of Type 2 MI (with or without CVS) may be useful in predicting the prognosis of patients with Type 2 MI.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm9061686
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2662592-1
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  • 2
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    Species Distribution of Candidemia and Their Susceptibility in a Single Japanese University Hospital: Prior Micafungin Use Affects the Appearance of Candida parapsilosis and Elevation of Micafungin MICs in Non-parapsilosis Candida Species
    MDPI AG ; 2021
    In:  Journal of Fungi Vol. 7, No. 8 ( 2021-07-23), p. 596-
    Details
    In: Journal of Fungi, MDPI AG, Vol. 7, No. 8 ( 2021-07-23), p. 596-
    Abstract: Introduction: Micafungin is a recommended echinocandin antifungal agent for candidemia treatment and prophylaxis. However, overuse of echinocandin antifungals may cause resistance. There is currently no information available regarding the low susceptibility associated with using micafungin. This study investigated the effect of micafungin use on changes in the detected Candida species and low susceptibility. Methods: We conducted a retrospective survey and included records of Candida spp. detected in blood cultures from January 2010 to December 2018 in our hospital. Survey items included clinical outcomes at 30 days after positive cultures, patient characteristics, and drug prescription status. Patient background information included gender, previous hospitalization, stay in the intensive care unit, comorbidities, and history of surgery (within 90 days before candidemia onset) and drug exposure. Species detected and their minimum inhibitory concentrations (MICs) and amount of antifungal prescriptions by department were investigated. Risk factors for detecting C. parapsilosis and for low susceptibility to micafungin were evaluated using multivariate analysis. Results: A total of 153 Candida clinical blood isolates were collected and C. albicans was the most prevalent species, followed by C. parapsilosis and C. glabrata. In the analysis by department, antifungal use and non-albicans Candida species were most frequently detected in the hematology department. Multivariate analysis showed that prior micafungin use increased the risk of C. parapsilosis (odds ratio (OR) 4.22; 95% confidence interval (CI) 1.39–12.79; p = 0.011). MIC90 of micafungin on C. glabrata and C. parapsilosis was 1.0 μg/mL. Prior micafungin use was clarified as a risk factor resulting in MIC 〉 0.06 μg/mL for micafungin in non-parapsilosis Candida species (OR 13.2; 95% CI 3.23–54.2; p 〈 0.01). Conclusion: Prior micafungin use increased the risk of C. parapsilosis and the MIC 〉 0.06 μg/mL of micafungin in non-parapsilosis Candida species. Since there are only a few antifungal options, further antifungal stewardship considering azole antifungal agents use is required.
    Type of Medium: Online Resource
    ISSN: 2309-608X
    URL: Article
    DOI: 10.3390/jof7080596
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2784229-0
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  • 3
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    Anticancer Effects of Fucoxanthin in a PDX Model of Advanced Stage Pancreatic Cancer with Alteration of Several Multifunctional Molecules
    MDPI AG ; 2023
    In:  Onco Vol. 3, No. 4 ( 2023-09-24), p. 217-236
    Details
    In: Onco, MDPI AG, Vol. 3, No. 4 ( 2023-09-24), p. 217-236
    Abstract: Pancreatic cancer (PC) is one of the most fatal cancers, and there is an urgent need to develop new anticancer agents with fewer side effects for the treatment of this condition. A patient-derived xenograft (PDX) mouse model transplanted with cancer tissue from patients is widely accepted as the best preclinical model for evaluating the anticancer potential of drug candidates. Fucoxanthin (Fx) is a highly polar carotenoid contained in edible marine brown algae and possesses anticancer activity. However, there is a lack of data on the effects of Fx in PDX models. We investigated the anticancer effects of Fx in PDX mice transplanted with cancer tissues derived from a patient with PC (PC-PDX) using comprehensive protein expression assay. Fx administration (0.3%Fx diet) ad libitum for 27 days significantly abrogated tumor development (0.4-fold) and induced tumor differentiation in PC-PDX mice, as compared to those in the control mice. Fx significantly upregulated the expression of non-glycanated DCN (2.4-fold), tended to increase the expressions of p-p38(Thr180/Tyr182) (1.6-fold) and pJNK(Thr183/Tyr185) (1.8-fold), significantly downregulated IGFBP2 (0.6-fold) and EpCAM (0.7-fold), and tended to decrease LCN2 (0.6-fold) levels in the tumors of the PC-PDX mice, as compared to those in the control mice. Some of the protein expression patterns were consistent with the in vitro experiments. That is, treatment of fucoxanthinol (FxOH), a prime metabolite derived from dietary Fx, enhanced non-glycanated DCN, p-p38(Thr180/Tyr182), and pJNK(Thr183/Tyr185) levels in human PC PANC-1 and BxPC-3 cells.These results suggested that Fx exerts anticancer and differentiation effects in a PC-PDX mice through alterations of some multifunctional molecules.
    Type of Medium: Online Resource
    ISSN: 2673-7523
    URL: Article
    DOI: 10.3390/onco3040016
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 3136452-4
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  • 4
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    Synthesis of Deuterium-Labeled Vitamin D Metabolites as Internal Standards for LC-MS Analysis
    MDPI AG ; 2022
    In:  Molecules Vol. 27, No. 8 ( 2022-04-09), p. 2427-
    Details
    In: Molecules, MDPI AG, Vol. 27, No. 8 ( 2022-04-09), p. 2427-
    Abstract: Blood levels of the vitamin D3 (D3) metabolites 25-hydroxyvitamin D3 (25(OH)D3), 24R,25-dihydroxyvitamin D3, and 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) are recognized indicators for the diagnosis of bone metabolism-related diseases, D3 deficiency-related diseases, and hypercalcemia, and are generally measured by liquid-chromatography tandem mass spectrometry (LC-MS/MS) using an isotope dilution method. However, other D3 metabolites, such as 20-hydroxyvitamin D3 and lactone D3, also show interesting biological activities and stable isotope-labeled derivatives are required for LC-MS/MS analysis of their concentrations in serum. Here, we describe a versatile synthesis of deuterium-labeled D3 metabolites using A-ring synthons containing three deuterium atoms. Deuterium-labeled 25(OH)D3 (2), 25(OH)D3-23,26-lactone (6), and 1,25(OH)2D3-23,26-lactone (7) were synthesized, and successfully applied as internal standards for the measurement of these compounds in pooled human serum. This is the first quantification of 1,25(OH)2D3-23,26-lactone (7) in human serum.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules27082427
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2008644-1
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  • 5
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    Development and Application of SONIC Divertor Simulation Code to Power Exhaust Design of Japanese DEMO Divertor
    MDPI AG ; 2022
    In:  Processes Vol. 10, No. 5 ( 2022-04-28), p. 872-
    Details
    In: Processes, MDPI AG, Vol. 10, No. 5 ( 2022-04-28), p. 872-
    Abstract: An integrated divertor simulation code, SONIC, has been developed in order to predict a self-consistent transport solution of the plasma, neutral and impurities in the scrape-off layer (SOL) and divertor. SONIC code has contributed to determining the divertor design and power handling scenarios for the Japanese (JA) fusion demonstration (DEMO) reactor. Radiative cooling scenario of Ar impurity seeding and the divertor performance have been demonstrated to evaluate the power exhaust scenarios with Psep = 230–290 MW. The simulation identified the decay length of the total parallel heat flux profile as being broader than the electron one, because of the ion convective transport from the outer divertor to the upstream SOL, produced by the plasma flow reversal. The flow reversal also reduced the impurity retention in the outer divertor, which may produce the partial detachment. Divertor operation margin of key power exhaust parameters to satisfy the peak qtarget ≤ 10 MWm−2 was determined in the low nesep of 2 − 3 × 1019 m−3 under severe conditions such as reducing radiation loss fraction, i.e., f*raddiv = (Pradsol + Praddiv)/Psep and diffusion coefficients (χ and D). The divertor geometry and reference parameters (f*raddiv ~ 0.8, χ = 1 m2s−1, D = 0.3 m2s−1) were consistent with the low nesep operation of the JA DEMO concepts. For either severe assumption of f*raddiv ~ 0.7 or χ and D to their half values, higher nesep operation was required. In addition, recent investigations of physics models (temperature-gradient force on impurity, photon transport, neutral–neutral collision) under the DEMO relevant SOL and divertor condition are presented.
    Type of Medium: Online Resource
    ISSN: 2227-9717
    URL: Article
    DOI: 10.3390/pr10050872
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2720994-5
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  • 6
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    Differential Metabolic Stability of 4α,25- and 4β,25-Dihydroxyvitamin D3 and Identification of Their Metabolites
    MDPI AG ; 2023
    In:  Biomolecules Vol. 13, No. 7 ( 2023-06-24), p. 1036-
    Details
    In: Biomolecules, MDPI AG, Vol. 13, No. 7 ( 2023-06-24), p. 1036-
    Abstract: Vitamin D3 (1) is metabolized by various cytochrome P450 (CYP) enzymes, resulting in the formation of diverse metabolites. Among them, 4α,25-dihydroxyvitamin D3 (6a) and 4β,25-dihydroxyvitamin D3 (6b) are both produced from 25-hydroxyvitamin D3 (2) by CYP3A4. However, 6b is detectable in serum, whereas 6a is not. We hypothesized that the reason for this is a difference in the susceptibility of 6a and 6b to CYP24A1-mediated metabolism. Here, we synthesized 6a and 6b, and confirmed that 6b has greater metabolic stability than 6a. We also identified 4α,24R,25- and 4β,24R,25-trihydroxyvitamin D3 (16a and 16b) as metabolites of 6a and 6b, respectively, by HPLC comparison with synthesized authentic samples. Docking studies suggest that the β-hydroxy group at C4 contributes to the greater metabolic stability of 6b by blocking a crucial hydrogen-bonding interaction between the C25 hydroxy group and Leu325 of CYP24A1.
    Type of Medium: Online Resource
    ISSN: 2218-273X
    URL: Article
    DOI: 10.3390/biom13071036
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2701262-1
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  • 7
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    Online Resource
    Subjective Happiness and Sleep in University Students with High Myopia
    MDPI AG ; 2020
    In:  Psych Vol. 2, No. 4 ( 2020-11-18), p. 279-286
    Details
    In: Psych, MDPI AG, Vol. 2, No. 4 ( 2020-11-18), p. 279-286
    Abstract: Purpose: Recent investigations described a host of disadvantageous myopia comorbidities including decreased QOL, depression, and sleep problems. The present study evaluated mental status and habitual sleep in young subjects with myopia based on the reported association between myopic error and psychiatric profiles. Methods: This cross-sectional study surveyed 153 university students using a questionnaire containing the Pittsburgh Sleep Quality Index (PSQI), Subjective Happiness Scale (SHS), short morningness/eveningness questionnaire, and Hospital Anxiety and Depression Scale (HADS). Results: Participants were classified as having high myopia (n = 44), mild myopia (n = 86), or no myopia (n = 23). The SHS and HADS scores in this cohort were significantly worse in the high myopia group than in the other two groups (p 〈 0.05, t-test). PSQI values were not significantly different among the three groups. Regression analysis correlated myopic error with poor SHS (p = 0.003), eveningness chronotype (p = 0.032), late wake-up time (p = 0.024), and late bedtime (p = 0.019). Conclusions: University students with myopia tended to be unhappy, have an eveningness chronotype, wake up late, and go to bed late compared to less myopic subjects. Optimal correction might, therefore, be beneficial to myopic students in addition to preventing progression to high myopia in early childhood to potentially avoid related negative effects on mental health and sleep habits in adolescence.
    Type of Medium: Online Resource
    ISSN: 2624-8611
    URL: Article
    DOI: 10.3390/psych2040021
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2962864-7
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  • 8
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    Somatostatin Receptor 2 Expression Profiles and Their Correlation with the Efficacy of Somatostatin Analogues in Gastrointestinal Neuroendocrine Tumors
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 3 ( 2022-02-02), p. 775-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 3 ( 2022-02-02), p. 775-
    Abstract: Somatostatin analogues (SSAs) are widely used to treat gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Somatostatin receptor 2 (SSTR2) immunoreactivity serves as a predictive marker of the therapeutic efficacy of SSAs in pancreatic NETs. However, SSTR2 expression profiles in tumor cells and their association with the therapeutic efficacy of SSAs remains virtually unknown in gastrointestinal NETs (GI-NETs). Therefore, we evaluated the association between SSTR2 immunoreactivity and embryological origin and proliferative activity in 132 resected surgical tissues of GI-NETs. The correlation between SSAs’ therapeutic efficacy and SSTR2 immunoreactivity was evaluated in 14 GI-NETs treated with SSAs. SSTR2 immunoreactivity was evaluated using Volante scores, immunoreactive scores, and digital image analysis (DIA). SSTR2 immunoreactivity was significantly negatively and positively correlated with the Ki-67 labeling index in foregut and hindgut NETs, respectively. In the normal mucosa, neuroendocrine cells in the rectum had significantly lower positive rates of SSTR2 than those in the stomach and duodenum. SSTR2 expression profiles in GI-NETs could differ by primary sites, while the difference of those between foregut and hindgut NETs might be derived from the SSTR2 status of normal neuroendocrine cell counterparts. In addition, DIA could provide a good alternative for predicting response to SSAs in evaluating SSTR2 immunoreactivity of GI-NETs.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14030775
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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  • 9
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    Secondary Adrenal Insufficiency Due to Isolated ACTH Deficiency Induced by Pembrolizumab: A Report of Two Cases of Uterine Endometrial Cancer
    MDPI AG ; 2023
    In:  Reports Vol. 6, No. 2 ( 2023-04-17), p. 18-
    Details
    In: Reports, MDPI AG, Vol. 6, No. 2 ( 2023-04-17), p. 18-
    Abstract: Immune checkpoint inhibitors (ICIs) enhance antitumoral immune mechanisms and are used to treat various types of solid tumors including those that are microsatellite instability (MSI)-high. Uterine endometrial cancer is one of the most frequent tumor types that shows MSI-high, and, consequently, opportunities to use ICIs for endometrial cancer treatment are increasing. While using ICIs, it is important to monitor and manage various immune-related adverse events (irAEs). Here, we report two cases of secondary adrenal insufficiency during treatment of endometrial cancer with pembrolizumab. Both cases showed appetite loss and general fatigue after the 6th or 12th cycle of pembrolizumab. They were admitted to our hospital because of remarkable hyponatremia. Both cases showed no adrenocorticotropic hormone (ACTH) or cortisol response to CRH loading tests. Other pituitary hormone levels were normal, and MRI revealed no sign of hypophysitis in either patient. They were diagnosed with secondary adrenal insufficiency due to isolated ACTH deficiency and recovered soon after the administration of hydrocortisone and hydration. Thus, we should be aware of irAEs with the use of ICIs. In particular, adrenocortical insufficiency is sometimes lethal without appropriate treatment. Because the clinical symptoms are fatigue, appetite loss, and nausea, patients might be misjudged to have symptoms related to cancer. Checking serum morning cortisol before ICIs use and monitoring serum sodium levels could provide clues to diagnose secondary adrenal insufficiency.
    Type of Medium: Online Resource
    ISSN: 2571-841X
    URL: Article
    DOI: 10.3390/reports6020018
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2963537-8
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  • 10
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    Synthesis of C2-Alkoxy-Substituted 19-Nor Vitamin D3 Derivatives: Stereoselectivity and Biological Activity
    MDPI AG ; 2022
    In:  Biomolecules Vol. 12, No. 1 ( 2022-01-04), p. 69-
    Details
    In: Biomolecules, MDPI AG, Vol. 12, No. 1 ( 2022-01-04), p. 69-
    Abstract: The active form of vitamin D3 (D3), 1a,25-dihydroxyvitamn D3 (1,25D3), plays a central role in calcium and bone metabolism. Many structure–activity relationship (SAR) studies of D3 have been conducted, with the aim of separating the biological activities of 1,25D3 or reducing its side effects, such as hypercalcemia, and SAR studies have shown that the hypercalcemic activity of C2-substituted derivatives and 19-nor type derivatives is significantly suppressed. In the present paper, we describe the synthesis of 19-nor type 1,25D3 derivatives with alkoxy groups at C2, by means of the Julia–Kocienski type coupling reaction between a C2 symmetrical A ring ketone and a CD ring synthon. The effect of C2 substituents on the stereoselectivity of the coupling reaction was evaluated. The biological activities of the synthesized derivatives were evaluated in an HL-60 cell-based assay. The a-methoxy-substituted C2α-7a was found to show potent cell-differentiating activity, with an ED50 value of 0.38 nM, being 26-fold more potent than 1,25D3.
    Type of Medium: Online Resource
    ISSN: 2218-273X
    URL: Article
    DOI: 10.3390/biom12010069
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2701262-1
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