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  • 1
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    Online Resource
    Sphere-Forming Culture for Expanding Genetically Distinct Patient-Derived Glioma Stem Cells by Cellular Growth Rate Screening
    MDPI AG ; 2020
    In:  Cancers Vol. 12, No. 3 ( 2020-02-27), p. 549-
    Details
    In: Cancers, MDPI AG, Vol. 12, No. 3 ( 2020-02-27), p. 549-
    Abstract: Diffusely infiltrating gliomas (DIGs) are difficult to completely resect and are associated with a high rate of tumor relapse and progression from low- to high-grade glioma. In particular, optimized short-term culture-enriching patient-derived glioma stem cells (GSCs) are essential for customizing the therapeutic strategy based on clinically feasible in vitro drug screening for a wide range of DIGs, owing to the high inter-tumoral heterogeneity. Herein, we constructed a novel high-throughput culture condition screening platform called ‘GFSCAN’, which evaluated the cellular growth rates of GSCs for each DIG sample in 132 serum-free combinations, using 13 previously reported growth factors closely associated with glioma aggressiveness. In total, 72 patient-derived GSCs with available genomic profiles were tested in GFSCAN to explore the association between cellular growth rates in specific growth factor combinations and genomic/molecular backgrounds, including isocitrate dehydrogenase 1 (IDH1) mutation, chromosome arm 1p and 19q co-deletion, ATRX chromatin remodeler alteration, and transcriptional subtype. GSCs were clustered according to the dependency on epidermal growth factor and basic fibroblast growth factor (E & F), and isocitrate dehydrogenase 1 (IDH1) wild-type GSCs showed higher E & F dependencies than IDH1 mutant GSCs. More importantly, we elucidated optimal combinations for IDH1 mutant glioblastoma and lower grade glioma GSCs with low dependencies on E & F, which could be an aid in clinical decision-making for these DIGs. Thus, we demonstrated the utility of GFSCAN in personalizing in vitro cultivation to nominate personalized therapeutic options, in a clinically relevant time frame, for individual DIG patients, where standard clinical options have been exhausted.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers12030549
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527080-1
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  • 2
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    Dietary Collagen Hydrolysates Retard Estrogen Deficiency-Induced Bone Loss through Blocking Osteoclastic Activation and Enhancing Osteoblastic Matrix Mineralization
    MDPI AG ; 2022
    In:  Biomedicines Vol. 10, No. 6 ( 2022-06-10), p. 1382-
    Details
    In: Biomedicines, MDPI AG, Vol. 10, No. 6 ( 2022-06-10), p. 1382-
    Abstract: Osteoporosis manifest in postmenopausal women is an osteolytic disease characterized by bone loss, leading to increased susceptibility to bone fractures and frailty. The use of complementary therapies to alleviate postmenopausal osteoporosis is fairly widespread among women. The current study examined that Pangasius hypophthalmus fish skin collagen hydrolysates (fsCH) inhibited ovariectomy (OVX)-induced bone loss by conducting inter-comparative experiments for anti-osteoporotic activity among 206–618 mg/kg fsCH, 2 mg/kg isoflavone, 15 mg/kg glycine–proline–hydroxyproline (GPH) tripeptide, and calcium lactate. Surgical estrogen loss of mice for 8 weeks reduced serum 17β-estradiol levels with uterus atrophy, which was ameliorated by orally administering fsCH or isoflavone to mice. Similar to isoflavone, fsCH containing GPH-enhanced bone mineral density reduced levels of cathepsin K and proton-handling proteins, and elevated collagen 1 level in OVX bones. The treatment with fsCH and isoflavone enhanced the serum levels of collagen synthesis-related procollagen type 1 carboxy/amino-terminal propeptides reduced by OVX, whereas serum levels of osteocalcin and alkaline phosphatase, as well as collagen breakdown-related carboxy/amino-terminal telopeptides of type 1 collagen were reduced in OVX mice treated with fsCH, isoflavone, and calcium lactate. The trabecular bones were newly formed in OVX bones treated with isoflavone and fsCH, but not with calcium lactate. However, a low-dose combination of fsCH and calcium lactate had a beneficial synergy effect on postmenopausal osteoporosis. Furthermore, similar to isoflavone, 15–70 μg/mL fsCH, with its constituents of GPH and dipeptides of glycine–proline and proline–hydroxyproline, enhanced osteogenesis through stimulating differentiation, matrix mineralization, and calcium deposition of MC3T3-E1 osteoblasts. Accordingly, the presence of fsCH may encumber estrogen deficiency-induced bone loss through enhancing osteoclastogenic differentiation and matrix collagen synthesis. Therefore, fsCH may be a natural compound retarding postmenopausal osteoporosis and pathological osteoresorptive disorders.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    URL: Article
    DOI: 10.3390/biomedicines10061382
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2720867-9
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  • 3
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    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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  • 4
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    Proposed Modification of Staging for Distal Cholangiocarcinoma Based on the Lymph Node Ratio Using Korean Multicenter Database
    MDPI AG ; 2020
    In:  Cancers Vol. 12, No. 3 ( 2020-03-24), p. 762-
    Details
    In: Cancers, MDPI AG, Vol. 12, No. 3 ( 2020-03-24), p. 762-
    Abstract: The 8th American Joint Committee on Cancer (AJCC) staging system for distal cholangiocarcinoma (DCC) included a positive lymph node count (PLNC), but a comparison of the prognostic predictive power of PLNC and lymph node ratio (LNR) is still under debate. This study aimed to compare various staging models made by combining the abovementioned factors, identify the model with the best predictive power, and propose a modified staging system. We retrospectively reviewed 251 patients who underwent surgery for DCC at four centers. To determine the superiority of various staging models for predicting overall OSR, Akaike information criterion (AIC), Bayesian information criterion (BIC), AIC correction (AICc), and Harrell’s C-statistic were calculated. In multivariate analysis, age (p = 0.003), total lymph node count (p = 0.033), and revised T(LNR)M staging (p 〈 0.001) were identified as independent factors for overall survival rate. The predictive performance of revised T (LNR) M staging (AIC: 1288.925, BIC: 1303.377, AICc: 1291.52, and Harrell’s C statics: 0.667) was superior to other staging system. A modified staging system consisting of revised T category and LNR predicted better overall survival of DCC than AJCC 7th and AJCC 8th editions. In the future, external validation of the proposed new system using a larger cohort will be required.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers12030762
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
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  • 5
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    Real-World Treatment Selection Factors and 7-Year Clinical Outcomes between Percutaneous Coronary Intervention and Coronary Artery Bypass Graft Surgery in Left Main Disease
    MDPI AG ; 2022
    In:  Journal of Clinical Medicine Vol. 11, No. 3 ( 2022-01-19), p. 503-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 3 ( 2022-01-19), p. 503-
    Abstract: Background: The decision-making factors and long-term clinical outcomes between PCI and CABG in left main (LM) disease are still not well defined in the real world. Methods: We evaluated consecutive patients (n = 230) with LM disease either treated by PCI (n = 118) or CABG (n = 112). The primary endpoint was major adverse cardiovascular events (MACE), defined as a composite of cardiac death, spontaneous myocardial infarction (MI), stroke, and target vessel revascularization (TVR) for 7 years. Results: In the multivariate-adjusted analysis, the presence of intermediate EuroSCORE II and high SYNTAX scores predisposed to CABG. Isolated LM disease was associated with receiving PCI. The PCI group had a similar rate of MACE (HRadj 0.97, 95% CI [0.48–1.94], p = 0.92) and a lower tendency of hard MACE (HRadj 0.49, 95% CI [0.22–1.07] , p = 0.07) compared to the CABG group, mainly due to the balance between a higher rate of TVR (HRadj 9.71, p = 0.02) and a lower rate of stroke (HRadj 0.22, p = 0.09) with the PCI group than in the CABG group. Conclusions: The decision making of treatment strategy was made based on clinical and angiographic factors. The selected patients who received PCI showed similar MACE and trend of a lower rate of composite hard endpoints despite multivariate adjustment.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm11030503
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662592-1
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  • 6
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    Comparison of 7-Year, Real-World Clinical Outcomes between Drug-Coated Balloon Angioplasty versus Drug-Eluting Stent Implantation in Patients with Drug-Eluting Stent In-Stent Restenosis
    MDPI AG ; 2023
    In:  Journal of Clinical Medicine Vol. 12, No. 13 ( 2023-06-24), p. 4246-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 12, No. 13 ( 2023-06-24), p. 4246-
    Abstract: There are no data available comparing the real-world, long-term clinical outcomes of drug-eluting balloon (DEB) angioplasty and drug-eluting stent (DES) implantation in DES in-stent restenosis (ISR) lesions. We aimed to compare the real-world, long-term data available between DEBs and DESs in DES-ISR lesions. We analyzed consecutive DES-ISR lesions (225 lesions from 205 patients; male: 66.3%; mean age: 62.4 years) treated with either DEB or DES. The primary endpoint was target lesion revascularization (TLR), and the primary safety endpoint was the lesion-oriented composite outcome (LOCO). The LOCO is composed of cardiac death, myocardial infarction, and target lesion thrombosis during follow-up. During the 7-year follow-up period, TLR did not differ significantly between the DEB (n = 108) and the DES groups (n = 117) (HR: 1.07; 95% CI: 0.59–1.93, p = 0.83). The LOCO was significantly lower in the DEB group compared to the DES group (HR: 0.40; 95% CI: 0.16–0.98, p = 0.04), which was mainly driven by the lower levels of myocardial infarction (HR: 0.24; 95% CI: 0.06–0.94, p = 0.04) and the absence of target lesion thrombosis in the DEB group (vs. DES group 6%, p = 0.02). Additionally, cardiac death was found to be similar between the DEB and DES groups (HR: 0.56; 95% CI: 0.18–1.75, p = 0.32). DEB angioplasty showed favorable safety with a similar efficacy to that of DES implantation in DES-ISR lesions during the long-term follow-up period.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm12134246
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
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  • 7
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    ABO Blood Type Is Associated with Thrombotic Risk in Patients with Nonvalvular Atrial Fibrillation
    MDPI AG ; 2022
    In:  Journal of Clinical Medicine Vol. 11, No. 11 ( 2022-05-29), p. 3064-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 11 ( 2022-05-29), p. 3064-
    Abstract: Blood type is reportedly correlated with the occurrence of cardiovascular diseases, presumably because of its effect on thrombogenicity. However, the relationship between blood type and thrombotic complications in atrial fibrillation (AF) remains unclear. This retrospective study analyzed the blood types of 1170 AF patients (mean age, 70 years; 58% men) who were followed up for up to 4 years. Patients with greater than mild mitral stenosis or prosthetic valves were excluded. The cohort included 305 (26%) type O, 413 (35%) type A, 333 (28%) type B, and 119 (10%) type AB patients. The primary endpoint of major adverse cerebrovascular events (MACE) occurred in 52 (4.4%) patients. When longitudinal outcomes were plotted, AB blood type patients had worse prognosis than non-AB blood type patients (p = 0.039), particularly type O blood patients (p = 0.049). Multivariate Cox regression analysis revealed that AB blood type was associated with higher MACE rates (adjusted hazard ratio, 2.01; 95% confidence interval, 1.01–4.00; p = 0.048) than non-AB blood types independent of anticoagulation therapy duration or CHA2DS2-VASc score. These indicate that AF patients with AB blood type are at an increased risk of MACE compared to those with non-AB blood type independent of the duration of anticoagulation or the CHA2DS2-VASc score.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm11113064
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
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  • 8
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    Prediction of African Swine Fever Virus Inhibitors by Molecular Docking-Driven Machine Learning Models
    MDPI AG ; 2021
    In:  Molecules Vol. 26, No. 12 ( 2021-06-11), p. 3592-
    Details
    In: Molecules, MDPI AG, Vol. 26, No. 12 ( 2021-06-11), p. 3592-
    Abstract: African swine fever virus (ASFV) causes a highly contagious and severe hemorrhagic viral disease with high mortality in domestic pigs of all ages. Although the virus is harmless to humans, the ongoing ASFV epidemic could have severe economic consequences for global food security. Recent studies have found a few antiviral agents that can inhibit ASFV infections. However, currently, there are no vaccines or antiviral drugs. Hence, there is an urgent need to identify new drugs to treat ASFV. Based on the structural information data on the targets of ASFV, we used molecular docking and machine learning models to identify novel antiviral agents. We confirmed that compounds with high affinity present in the region of interest belonged to subsets in the chemical space using principal component analysis and k-means clustering in molecular docking studies of FDA-approved drugs. These methods predicted pentagastrin as a potential antiviral drug against ASFVs. Finally, it was also observed that the compound had an inhibitory effect on AsfvPolX activity. Results from the present study suggest that molecular docking and machine learning models can play an important role in identifying potential antiviral drugs against ASFVs.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules26123592
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
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  • 9
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    Spontaneous Osteogenic Differentiation of Human Mesenchymal Stem Cells by Tuna-Bone-Derived Hydroxyapatite Composites with Green Tea Polyphenol-Reduced Graphene Oxide
    MDPI AG ; 2023
    In:  Cells Vol. 12, No. 11 ( 2023-05-23), p. 1448-
    Details
    In: Cells, MDPI AG, Vol. 12, No. 11 ( 2023-05-23), p. 1448-
    Abstract: In recent years, bone tissue engineering (BTE) has made significant progress in promoting the direct and functional connection between bone and graft, including osseointegration and osteoconduction, to facilitate the healing of damaged bone tissues. Herein, we introduce a new, environmentally friendly, and cost-effective method for synthesizing reduced graphene oxide (rGO) and hydroxyapatite (HAp). The method uses epigallocatechin-3-O-gallate (EGCG) as a reducing agent to synthesize rGO (E-rGO), and HAp powder is obtained from Atlantic bluefin tuna (Thunnus thynnus). The physicochemical analysis indicated that the E-rGO/HAp composites had exceptional properties for use as BTE scaffolds, as well as high purity. Moreover, we discovered that E-rGO/HAp composites facilitated not only the proliferation, but also early and late osteogenic differentiation of human mesenchymal stem cells (hMSCs). Our work suggests that E-rGO/HAp composites may play a significant role in promoting the spontaneous osteogenic differentiation of hMSCs, and we envision that E-rGO/HAp composites could serve as promising candidates for BTE scaffolds, stem-cell differentiation stimulators, and implantable device components because of their biocompatible and bioactive properties. Overall, we suggest a new approach for developing cost-effective and environmentally friendly E-rGO/HAp composite materials for BTE application.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells12111448
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2661518-6
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  • 10
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    Swept-Source OCT Angiography Features in Patients after Macular Hole Surgery
    MDPI AG ; 2022
    In:  Journal of Personalized Medicine Vol. 12, No. 9 ( 2022-09-13), p. 1493-
    Details
    In: Journal of Personalized Medicine, MDPI AG, Vol. 12, No. 9 ( 2022-09-13), p. 1493-
    Abstract: This study aimed to compare findings of optical coherence tomography (OCT) angiography (OCTA) between eyes with nearly recovered and partially recovered outer retina after full-thickness macular hole (FTMH) surgery and to identify OCTA findings associated with visual acuity. We retrospectively reviewed 30 patients who underwent surgery for idiopathic FTMH. Swept-source OCT (SS-OCT) and OCTA were performed preoperatively and at three and six months postoperatively. Subgroups were divided according to the integrity of the external limiting membranes and ellipsoid zones postoperatively. Correlations of best-corrected visual acuity six months postoperatively with SS-OCT and OCTA measurements were analyzed. There was no difference in preoperative retinal or choroidal vascular index on OCTA between the nearly and partially recovered groups. Six months postoperatively, the choriocapillaris flow-void area was significantly higher in the partially recovered group than in the fellow eye. The nearly recovered group showed better choroidal vascular flow, and vision at six months postoperatively correlated with the ratio of the operated eye’s choriocapillaris flow-void area to the fellow eye. Sufficient choriocapillaris flow on OCTA is associated with better outer retinal recovery and visual outcomes after macular hole surgery.
    Type of Medium: Online Resource
    ISSN: 2075-4426
    URL: Article
    DOI: 10.3390/jpm12091493
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662248-8
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