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  • 1
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    Online Resource
    Characterization of Ginkgo biloba Leaf Flavonoids as Neuroexocytosis Regulators
    MDPI AG ; 2020
    In:  Molecules Vol. 25, No. 8 ( 2020-04-17), p. 1829-
    Details
    In: Molecules, MDPI AG, Vol. 25, No. 8 ( 2020-04-17), p. 1829-
    Abstract: Ginkgo biloba leaf (GBL) is known as a potential source of bioactive flavonoids, such as quercetin, arresting the neuronal soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-zippering. Here, the GBL flavonoids were isolated in two different manners and then examined for their bioactivity, physicochemical stability, and biocompatibility. The majority of flavonoids in the non-hydrolyzed and acidolyzed isolates, termed non-hydrolyzed isolate (NI) and acidolyzed isolate (AI) hereafter, were rich in flavonol glycosides and aglycones, respectively. Glycosidic/aglyconic quercetin and kaempferol were abundant in both NI and AI, whereas a little of apigenin, luteolin, and isorhamnetin were found in AI. NI was more thermostable in all pH ranges than quercetin, kaempferol, and AI. NI and AI both inhibited neurotransmitter release from differentiated neuronal PC-12 cells. NI and AI showed 1/2–1/3 lower EC50/CC50 values than quercetin and kaempferol. The NI and AI exhibited no toxicity assessed by the tests on chorioallantoic membranes of hen’s eggs, removing toxicological concerns of irritation potential. Moreover, GBL isolates, particularly AI, showed antioxidant and anti-inflammatory activities in the use below the CC50 levels. Taken together, these results suggest that GBL isolates that are rich in antioxidant flavonoids are effective anti-neuroexocytotic agents with high stability and low toxicity.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules25081829
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2008644-1
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  • 2
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    Can Optic Nerve Sheath Images on a Thin-Slice Brain Computed Tomography Reconstruction Predict the Neurological Outcomes in Cardiac Arrest Survivors?
    MDPI AG ; 2022
    In:  Journal of Clinical Medicine Vol. 11, No. 13 ( 2022-06-26), p. 3677-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 13 ( 2022-06-26), p. 3677-
    Abstract: We analyzed the prognostic performance of optic nerve sheath diameter (ONSD) on thin-slice (0.6 mm) brain computed tomography (CT) reconstruction images as compared to routine-slice (4 mm) images. We conducted a retrospective analysis of brain CT images taken within 2 h after cardiac arrest. The maximal ONSD (mONSD) and optic nerve sheath area (ONSA) were measured on thin-slice images, and the routine ONSD (rONSD) and gray-to-white matter ratio (GWR) were measured on routine-slice images. We analyzed their area under the receiver operator characteristic curve (AUC) and the cutoff values for predicting a poor 6-month neurological outcome (a cerebral performance category score of 3–5). Of the 159 patients analyzed, 113 patients had a poor outcome. There was no significant difference in rONSD between the outcome groups (p = 0.116). Compared to rONSD, mONSD (AUC 0.62, 95% CI: 0.54–0.70) and the ONSA (AUC 0.63, 95% CI: 0.55–0.70) showed better prognostic performance and had higher sensitivities to determine a poor outcome (mONSD, 20.4% [95% CI, 13.4–29.0]; ONSA, 16.8% [95% CI, 10.4–25.0] ; rONSD, 7.1% [95% CI, 3.1–13.5]), with specificity of 95.7% (95% CI, 85.2–99.5). A combined cutoff value obtained by both the mONSD and GWR improved the sensitivity (31.0% [95% CI, 22.6–40.4] ) of determining a poor outcome, while maintaining a high specificity. In conclusion, rONSD was clinically irrelevant, but the mONSD had an increased sensitivity in cutoff having acceptable specificity. Combination of the mONSD and GWR had an improved prognostic performance in these patients.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm11133677
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662592-1
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  • 3
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    Prognostic Significance of CHIP and RIPK3 in Non-Small Cell Lung Cancer
    MDPI AG ; 2020
    In:  Cancers Vol. 12, No. 6 ( 2020-06-08), p. 1496-
    Details
    In: Cancers, MDPI AG, Vol. 12, No. 6 ( 2020-06-08), p. 1496-
    Abstract: RIPK3 is a key regulator of necroptosis, which plays a double-edged sword role in tumor progression. CHIP is an E3 ubiquitin ligase that regulates necroptosis by degrading RIPK3. Here, we investigated the prognostic value of RIPK3 and CHIP expression in 404 patients with non-small cell lung cancer (NSCLC). Expressions of CHIP and RIPK3 showed opposite correlations with survival. CHIP expression was associated with the longer overall survival (OS), whereas RIPK3 expression was associated with the shorter OS. RIPK3 positivity showed marginal association with shorter OS and disease-free survival (DFS) in adjuvant radiotherapy recipients but not in non-recipients, suggesting that necroptosis may induce radioresistance. In multivariate analysis, CHIP expression was associated with longer OS. Compared with other patients, CHIP(−)/RIPK3(+) patients had shorter OS and DFS. In summary, in patients with NSCLC, the expression of CHIP was an independent favorable prognostic factor while that of RIPK3 was an adverse prognostic factor.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers12061496
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527080-1
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  • 4
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    Development and Validation of an Enzyme-Linked Immunosorbent Assay-Based Protocol for Evaluation of Respiratory Syncytial Virus Vaccines
    MDPI AG ; 2024
    In:  Viruses Vol. 16, No. 6 ( 2024-06-12), p. 952-
    Details
    In: Viruses, MDPI AG, Vol. 16, No. 6 ( 2024-06-12), p. 952-
    Abstract: Recently, respiratory syncytial virus (RSV) vaccines based on the prefusion F (pre-F) antigen were approved in the United States. We aimed to develop an enzyme-linked immunosorbent assay (ELISA)-based protocol for the practical and large-scale evaluation of RSV vaccines. Two modified pre-F proteins (DS-Cav1 and SC-TM) were produced by genetic recombination and replication using an adenoviral vector. The protocol was established by optimizing the concentrations of the coating antigen (pre-F proteins), secondary antibodies, and blocking buffer. To validate the protocol, we examined its accuracy, precision, and specificity using serum samples from 150 participants across various age groups and the standard serum provided by the National Institute of Health. In the linear correlation analysis, coating concentrations of 5 and 2.5 μg/mL of DS-Cav1 and SC-TM showed high coefficients of determination (r 〉 0.90), respectively. Concentrations of secondary antibodies (alkaline phosphatase-conjugated anti-human immunoglobulin G, diluted 1:2000) and blocking reagents (5% skim milk/PBS-T) were optimized to minimize non-specific reactions. High accuracy was observed for DS-Cav1 (r = 0.90) and SC-TM (r = 0.86). Further, both antigens showed high precision (coefficient of variation 〈 15%). Inhibition ELISA revealed cross-reactivity of antibodies against DS-Cav1 and SC-TM, but not with the attachment (G) protein.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    URL: Article
    DOI: 10.3390/v16060952
    Language: English
    Publisher: MDPI AG
    Publication Date: 2024
    detail.hit.zdb_id: 2516098-9
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  • 5
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    Substituted Syndecan-2-Derived Mimetic Peptides Show Improved Antitumor Activity over the Parent Syndecan-2-Derived Peptide
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 11 ( 2022-05-24), p. 5888-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 11 ( 2022-05-24), p. 5888-
    Abstract: We previously showed that a synthetic peptide (S2-P) corresponding to a portion of the human syndecan-2 (SDC2) sequence can bind to the pro-domain of matrix metalloproteinase-7 (MMP-7) to inhibit colon cancer activities. Since S2-P had a relatively weak binding affinity for the MMP-7 pro-domain, we herein modified the amino acid sequence of S2-P to improve the anticancer potential. On the basis of the interaction structure of S2-P and MMP-7, four peptides were generated by replacing amino acids near Tyr 51, which is critical for the interaction. The SDC2-mimetic peptides harboring an Ala-to-Asp substitution at the C-terminal side of Tyr 51 (S2-D) or with an Ala-to-Phe substitution at the N-terminal side of Tyr 51 and an Ala-to-Asp substitution at the C-terminal side of Tyr 51 (S2-FE) showed improved interaction affinities for the MMP-7 pro-domain. Compared to S2-P, S2-FE was better able to inhibit the SDC2–MMP-7 interaction, the cell surface localization of MMP-7, the gelatin degradation activity of MMP-7, and the cancer activities (cell migration, invasion, and colony-forming activity) of human HCT116 colon cancer cells in vitro. In vivo, S2-FE inhibited the primary tumor growth and lung metastasis of CT26 mouse colon cancer cells in a xenograft mouse model. Together, these data suggest that S2-FE could be useful therapeutic anticancer peptides for colon cancer.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms23115888
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 6
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    The Psychometric Characteristic of the Taekwondo Electronic Protector Cognition Scale: The Application of the Rasch Model
    MDPI AG ; 2020
    In:  International Journal of Environmental Research and Public Health Vol. 17, No. 10 ( 2020-05-23), p. 3684-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 17, No. 10 ( 2020-05-23), p. 3684-
    Abstract: This research was to investigate the psychometric characteristics of the electronic protector cognition scale by the infit and outfit of taekwondo athletes. Participants were 216 athletes (male = 109; female = 117) from 19 countries competed at the 19th Taekwondo World Championships. The electronic protector cognition scale consisting of 24-item with four subscales was utilized. The electronic protector cognition scale used a five-point Likert grading with 1 (not at all) to 5 (very likely). Analysis using IBM SPSS STATISTICS version 23 (IBM SPSS, Inc., Chicago, IL, USA) was conducted for the 226 data sets collected. WINSTEPS 3.74 (Linacre, 2015) was used for calculating subject reliability, item goodness-of-fit, scale propriety, and item level of difficulty, in order to apply the item response theory to the psychometric characteristics of electronic protectors. The research results showed that it was suitable for subject infit/outfit in taekwondo electronic protector cognition scale as 1.00~1.01 and the input/output of taekwondo electronic protector cognition scale as 1.00~1.01. Secondly, five-point scales were reviewed to be suitable for scale propriety, resulting from stage index judgment. Thirdly, 8 items showed problems in item goodness-of-fit. Finally, scale propriety was reported to be suitable considering the ability distribution of taekwondo players and the level of scale difficulty.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph17103684
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2175195-X
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  • 7
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    Predictive Value of 18F-FDG PET/CT Using Machine Learning for Pathological Response to Neoadjuvant Concurrent Chemoradiotherapy in Patients with Stage III Non-Small Cell Lung Cancer
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 8 ( 2022-04-14), p. 1987-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 8 ( 2022-04-14), p. 1987-
    Abstract: We investigated predictions from 18F-FDG PET/CT using machine learning (ML) to assess the neoadjuvant CCRT response of patients with stage III non-small cell lung cancer (NSCLC) and compared them with predictions from conventional PET parameters and from physicians. A retrospective study was conducted of 430 patients. They underwent 18F-FDG PET/CT before initial treatment and after neoadjuvant CCRT followed by curative surgery. We analyzed texture features from segmented tumors and reviewed the pathologic response. The ML model employed a random forest and was used to classify the binary outcome of the pathological complete response (pCR). The predictive accuracy of the ML model for the pCR was 93.4%. The accuracy of predicting pCR using the conventional PET parameters was up to 70.9%, and the accuracy of the physicians’ assessment was 80.5%. The accuracy of the prediction from the ML model was significantly higher than those derived from conventional PET parameters and provided by physicians (p 〈 0.05). The ML model is useful for predicting pCR after neoadjuvant CCRT, which showed a higher predictive accuracy than those achieved from conventional PET parameters and from physicians.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14081987
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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  • 8
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    Metabolomic Profiles Predict Diabetes Remission after Bariatric Surgery
    MDPI AG ; 2020
    In:  Journal of Clinical Medicine Vol. 9, No. 12 ( 2020-12-01), p. 3897-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 9, No. 12 ( 2020-12-01), p. 3897-
    Abstract: Background: Amino acid metabolites (AAMs) have been linked to glucose homeostasis and type 2 diabetes (T2D). We investigated whether (1) baseline AAMs predict T2D remission 12 months after bariatric surgery and (2) whether AAMs are superior for predicting T2D remission postoperatively compared with existing prediction models. Methods: Among 24 participants undergoing bariatric surgery, 16 diabetes-related AAMs were quantified at baseline and postoperative 3 and 12 months. Existing prediction models included the ABCD, DiaRem, and IMS models. Results: Baseline L-dihydroxyphenylalanine (L-DOPA) (areas under receiver operating characteristic curves (AUROC), 0.92; 95% confidence interval (CI), 0.75 to 1.00) and 3-hydroxyanthranilic acid (3-HAA) (AUROC, 0.85; 95% CI, 0.67 to 1.00) better predicted T2D remission 12 months postoperatively than the ABCD model (AUROC, 0.81; 95% CI, 0.54 to 1.00), which presented the highest AUROC value among the three models. The superior prognostic performance of L-DOPA (AUROC at 3 months, 0.97; 95% CI, 0.91 to 1.00) and 3-HAA (AUROC at 3 months, 0.86; 95% CI, 0.63 to 1.00) continued until 3 months postoperatively. Conclusions: The AAM profile predicts T2D remission after bariatric surgery more effectively than the existing prediction models.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm9123897
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2662592-1
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  • 9
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    Investigation of Prognostic Factors for Intense Pulsed Light Treatment with a Vascular Filter in Patients with Moderate or Severe Meibomian Gland Dysfunction
    MDPI AG ; 2022
    In:  Journal of Clinical Medicine Vol. 11, No. 16 ( 2022-08-12), p. 4724-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 16 ( 2022-08-12), p. 4724-
    Abstract: We aimed to investigate the prognostic factors for, and treatment efficacy of, intense pulsed light (IPL) treatment with a vascular filter in patients with moderate or severe meibomian gland dysfunction (MGD). In this retrospective observational study, 58 moderate or severe MGD patients who underwent IPL treatment with a vascular filter were enrolled. IPL treatment was administered to the upper and lower eyelids four times at two-week intervals. At baseline, and four weeks after IPL, we evaluated the matrix metalloproteinase (MMP)-9 expression levels, tear break-up times (TBUT), ocular surface staining scores, lid margin telangiectasias, and meibomian gland characteristics. The subjective symptoms and adverse effects were reviewed and recorded. Regression analyses were performed to explore the prognostic factors affecting clinical outcomes. IPL treatment using a vascular filter led to improvements in the TBUT, ocular surface staining score, meibomian gland grade, meibum quality and consistency, lid margin telangiectasia, and symptom score (all p 〈 0.001). Furthermore, the positivity rate (90.2% to 70.6%, p = 0.013) and expression levels (1.92 ± 1.18 to 1.24 ± 1.18, p 〈 0.001) of tear MMP-9 improved after the IPL treatment. In multivariate logistic regression analysis, a young age (odds ratio = 0.867, p = 0.007) and a toothpaste-like consistency in the upper lid (odds ratio = 8.449, p = 0.046) were associated with improvements in the meibomian gland grade. No adverse effects were detected. IPL with a vascular filter is a safe and effective treatment for moderate and severe MGD. Age and the meibum consistency in the upper lid are important prognostic factors.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm11164724
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662592-1
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  • 10
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    Safety, Tolerability, and Serum/Tear Pharmacokinetics of Human Recombinant Epidermal Growth Factor Eyedrops in Healthy Subjects
    MDPI AG ; 2022
    In:  Pharmaceuticals Vol. 15, No. 11 ( 2022-10-24), p. 1312-
    Details
    In: Pharmaceuticals, MDPI AG, Vol. 15, No. 11 ( 2022-10-24), p. 1312-
    Abstract: The purpose of this study was to evaluate the safety, tolerability, and pharmacokinetics (PKs) of rhEGF eyedrops after the administration of single and multiple doses in healthy subjects. A phase 1, randomized, double-blind, placebo-controlled, and single-ascending dose (SAD) and multiple-ascending dose (MAD) study were conducted in three dose groups (10, 50, and 100 μg/mL). The subjects randomly received rhEGF eyedrops or the placebo in a 3:1 ratio. Serial blood and tear samples for PK analysis were collected up to 36 h and 180 h post-dose in SAD and MAD studies, respectively. In addition, the serum and tear EGF concentrations were measured. Immunogenicity evaluations were conducted using serum anti-EGF antibody levels. A total of 50 subjects were enrolled and 48 subjects completed the study. Adverse drug reactions were mild and transient. There were no serious adverse events in this study. The tear EGF concentrations rapidly increased and returned to baseline after 4 h without any serum EGF level change after the administration of rhEGF eyedrops. rhEGF eyedrops were safe and well-tolerated in healthy subjects in a dose range of 10–100 μg/mL, indicating suitability for further studies in patients with corneal injury.
    Type of Medium: Online Resource
    ISSN: 1424-8247
    URL: Article
    DOI: 10.3390/ph15111312
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2193542-7
    SSG: 15,3
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