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  • 1
    Online Resource
    Online Resource
    Clinical Impact of Atypical Chest Pain and Diabetes Mellitus in Patients with Acute Myocardial Infarction from Prospective KAMIR-NIH Registry
    MDPI AG ; 2020
    In:  Journal of Clinical Medicine Vol. 9, No. 2 ( 2020-02-12), p. 505-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 9, No. 2 ( 2020-02-12), p. 505-
    Abstract: Atypical chest pain and diabetic autonomic neuropathy attract less clinical attention, leading to underdiagnosis and delayed treatment. To evaluate the long-term clinical impact of atypical chest pain and diabetes mellitus (DM), we categorized 11,159 patients with acute myocardial infarction (AMI) from the Korea AMI-National Institutes of Health between November 2011 and December 2015 into four groups (atypical DM, atypical non-DM, typical DM, and typical non-DM). The primary endpoint was defined as patient-oriented composite endpoint (POCE) at 2 years including all-cause death, any myocardial infarction (MI), and any revascularization. Patients with atypical chest pain showed higher 2-year mortality than those with typical chest pain in both DM (29.5% vs. 11.4%, p 〈 0.0001) and non-DM (20.4% vs. 6.3%, p 〈 0.0001) groups. The atypical DM group had the highest risks of POCE (hazard ratio (HR) 1.76, 95% confidence interval (CI) 1.48–2.10), all-cause death (HR 2.23, 95% CI 1.80–2.76) and any MI (HR 2.34, 95% CI 1.51–3.64) in the adjusted model. In conclusion, atypical chest pain was significantly associated with mortality in patients with AMI. Among four groups, the atypical DM group showed the worst clinical outcomes at 2 years. Application of rapid rule in/out AMI protocols would be beneficial to improve clinical outcomes.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm9020505
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2662592-1
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  • 2
    Online Resource
    Online Resource
    Persistent Resistant Hypertension Has Worse Renal Outcomes in Chronic Kidney Disease than that Resolved in Two Years: Results from the KNOW-CKD Study
    MDPI AG ; 2021
    In:  Journal of Clinical Medicine Vol. 10, No. 17 ( 2021-09-03), p. 3998-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 10, No. 17 ( 2021-09-03), p. 3998-
    Abstract: Apparent treatment-resistant hypertension (ATRH) is closely related to chronic kidney disease (CKD); however, the long-term outcomes and the effects of improvement in ATRH in patients with CKD are not well understood. We evaluated the relationship between the persistence of ATRH and the progression of CKD. This cohort study enrolled 1921 patients with CKD. ATRH was defined as blood pressure above 140/90 mmHg and intake of three different types of antihypertensive agents, including diuretics, or intake of four or more different types of antihypertensive agents, regardless of blood pressure. We defined ATRH subgroups according to the ATRH status at the index year and two years later. The prevalence of ATRH at baseline was 14.0%. The presence of ATRH at both time points was an independent risk factor for end-point renal outcome (HR, 1.41; 95% CI, 1.04–1.92; p = 0.027). On the other hand, the presence of ATRH at any one of the time points was not statistically significant. In conclusion, persistent ATRH is more important for the prognosis of renal disease than the initial ATRH status. Continuous follow-up and appropriate treatment are important to improve the renal outcomes.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm10173998
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662592-1
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  • 3
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    Online Resource
    Di (Isoquinolin-1-Yl) Sulfane (DIQS) Inhibits Melaninogenesis by Modulating PKA/CREB and MAPK Signaling Pathways
    MDPI AG ; 2021
    In:  Cosmetics Vol. 8, No. 4 ( 2021-11-05), p. 104-
    Details
    In: Cosmetics, MDPI AG, Vol. 8, No. 4 ( 2021-11-05), p. 104-
    Abstract: The novel synthetic compound Di (isoquinolin-1-yl) sulfane (DIQS) was identified by zebrafish larva screening during the development of an agent to inhibit abnormal hyperpigmentation. In this study, we investigated the inhibitory effect of DIQS on melanogenesis and its underlying mechanism. DIQS inhibited melanin production and tyrosinase activity in B16F10 cells stimulated with α-melanocyte-stimulating hormone (α-MSH), as well as zebrafish embryos and reconstituted human skin tissue containing melanocytes. DIQS decreased the mRNA and protein expression of microphthalmia-associated transcription factor (MITF) and tyrosinase at a concentration of 10 μM. DIQS also inhibited the phosphorylation of cAMP response element-binding protein (CREB) and p-p38 and p-JNK stimulated by α-MSH. These results suggest that DIQS attenuates hyperpigmentation via inhibition of the cAMP/PKA/CREB/MITF/tyrosinase axis and MAPK pathways. Liquid chromatography–tandem mass spectrometry analysis revealed that DIQS blocked the conversion of tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA) in zebrafish embryos. Finally, we confirmed that DIQS was non-toxic in reconstituted human tissues such as the epidermis, used to test skin sensitization, and the cornea, used to test eye irritation. In summary, the results of this study suggest the potential of DIQS as a small-molecule agent for skin-whitening cosmetics and the treatment of hyperpigmentation disorders without biological toxicity.
    Type of Medium: Online Resource
    ISSN: 2079-9284
    URL: Article
    DOI: 10.3390/cosmetics8040104
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2720868-0
    SSG: 15,3
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  • 4
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    Online Resource
    Neurochemical Effects of 4-(2Chloro-4-Fluorobenzyl)-3-(2-Thienyl)-1,2,4-Oxadiazol-5(4H)-One in the Pentylenetetrazole (PTZ)-Induced Epileptic Seizure Zebrafish Model
    MDPI AG ; 2021
    In:  International Journal of Molecular Sciences Vol. 22, No. 3 ( 2021-01-28), p. 1285-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 3 ( 2021-01-28), p. 1285-
    Abstract: Epilepsy is one of the most common neurological disorders, and it is characterized by spontaneous seizures. In a previous study, we identified 4-(2-chloro-4-fluorobenzyl)-3-(2-thienyl)-1,2,4-oxadiazol-5(4H)-one (GM-90432) as a novel anti-epileptic agent in chemically- or genetically-induced epileptic zebrafish and mouse models. In this study, we investigated the anti-epileptic effects of GM-90432 through neurochemical profiling-based approach to understand the neuroprotective mechanism in a pentylenetetrazole (PTZ)-induced epileptic seizure zebrafish model. GM-90432 effectively improved PTZ-induced epileptic behaviors via upregulation of 5-hydroxytryptamine, 17-β-estradiol, dihydrotestosterone, progesterone, 5α -dihydroprogesterone, and allopregnanolone levels, and downregulation of normetanephrine, gamma-aminobutyric acid, and cortisol levels in brain tissue. GM-90432 also had a protective effect against PTZ-induced oxidative stress and zebrafish death, suggesting that it exhibits biphasic neuroprotective effects via scavenging of reactive oxygen species and anti-epileptic activities in a zebrafish model. In conclusion, our results suggest that neurochemical profiling study could be used to better understand of anti-epileptic mechanism of GM-90432, potentially leading to new drug discovery and development of anti-seizure agents.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms22031285
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 5
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    Evaluation of the Antiviral Efficacy of Subcutaneous Nafamostat Formulated with Glycyrrhizic Acid against SARS-CoV-2 in a Murine Model
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 11 ( 2023-05-31), p. 9579-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 11 ( 2023-05-31), p. 9579-
    Abstract: The ongoing COVID-19 pandemic highlights the urgent need for effective antiviral agents and vaccines. Drug repositioning, which involves modifying existing drugs, offers a promising approach for expediting the development of novel therapeutics. In this study, we developed a new drug, MDB-MDB-601a-NM, by modifying the existing drug nafamostat (NM) with the incorporation of glycyrrhizic acid (GA). We assessed the pharmacokinetic profiles of MDB-601a-NM and nafamostat in Sprague-Dawley rats, revealing rapid clearance of nafamostat and sustained drug concentration of MDB-601a-NM after subcutaneous administration. Single-dose toxicity studies showed potential toxicity and persistent swelling at the injection site with high-dose administration of MDB-601a-NM. Furthermore, we evaluated the efficacy of MDB-601a-NM in protecting against SARS-CoV-2 infection using the K18 hACE-2 transgenic mouse model. Mice treated with 60 mg/kg and 100 mg/kg of MDB-601a-NM exhibited improved protectivity in terms of weight loss and survival rates compared to the nafamostat-treated group. Histopathological analysis revealed dose-dependent improvements in histopathological changes and enhanced inhibitory efficacy in MDB-601a-NM-treated groups. Notably, no viral replication was detected in the brain tissue when mice were treated with 60 mg/kg and 100 mg/kg of MDB-601a-NM. Our developed MDB-601a-NM, a modified Nafamostat with glycyrrhizic acid, shows improved protectivity against SARS-CoV-2 infection. Its sustained drug concentration after subcutaneous administration and dose-dependent improvements makes it a promising therapeutic option.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms24119579
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 6
    Online Resource
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    Analysis of the Efficacy of Universal Screening of Coronavirus Disease with Antigen-Detecting Rapid Diagnostic Tests at Point-or-Care Settings and Sharing the Experience of Admission Protocol—A Pilot Study
    MDPI AG ; 2022
    In:  Journal of Personalized Medicine Vol. 12, No. 2 ( 2022-02-20), p. 319-
    Details
    In: Journal of Personalized Medicine, MDPI AG, Vol. 12, No. 2 ( 2022-02-20), p. 319-
    Abstract: Aims: To introduce the admission protocol of a COVID-19 specialized hospital outlined by the government, including the assessment of reverse transcription polymerase chain reaction (RT-PCR), low dose chest computed tomography (CT) and antigen-detecting rapid diagnostic test (Ag-RDT) for patient screening. Materials and Methods: This was a retrospective cohort study of 646 patients who were admitted between December 2020, and February 2021, during the third wave of COVID-19 in Korea. Ag-RDT and RT-PCR were routinely performed on all patients who required admission, and low-dose chest CT was performed on high-risk patients with associated symptoms. Any patients with high-risk COVID-19 infection according to the Ag-RDT test were quarantined alone in a negative pressured room, and those with low-risk COVID-19 infection remained in the preemptive quarantine room with or without negative pressure. The diagnostic values of the Ag-RDT test and associated cycle threshold (Ct) values of the RT-PCR test were subsequently evaluated. Results: In terms of the diagnostic value, the Ag-RDT for COVID-19 had a sensitivity of 68.3%, specificity of 99.5%, positive predictive value (PPV) of 90.3%, and negative predictive value (NPV) of 97.9%. For the 355 symptomatic patients with low-dose chest CT, the diagnostic values of combined evaluations had a sensitivity of 90.2%, specificity of 99.0%, PPV of 86.1%, and NPV of 99.3%. The cut-off Ct value for positive Ag-RDT was ≤25.67 for the N gene (sensitivity: 89.3%, specificity: 100%), which was regarded as a high viable virus in cell culture. There were no patients or medical staff who had COVID-19 in the hospital. Conclusion: Appropriate patient care was possible by definitive triage of the area, according to the symptoms and using diagnostic tests. Screening protocols, including the Ag-RDT test and low-dose chest CT, could be helpful in emergency point-of-care settings.
    Type of Medium: Online Resource
    ISSN: 2075-4426
    URL: Article
    DOI: 10.3390/jpm12020319
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662248-8
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  • 7
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    Online Resource
    Emerging Albumin-Binding Anticancer Drugs for Tumor-Targeted Drug Delivery: Current Understandings and Clinical Translation
    MDPI AG ; 2022
    In:  Pharmaceutics Vol. 14, No. 4 ( 2022-03-28), p. 728-
    Details
    In: Pharmaceutics, MDPI AG, Vol. 14, No. 4 ( 2022-03-28), p. 728-
    Abstract: Albumin has shown remarkable promise as a natural drug carrier by improving pharmacokinetic (PK) profiles of anticancer drugs for tumor-targeted delivery. The exogenous or endogenous albumin enhances the circulatory half-lives of anticancer drugs and passively target the tumors by the enhanced permeability and retention (EPR) effect. Thus, the albumin-based drug delivery leads to a potent antitumor efficacy in various preclinical models, and several candidates have been evaluated clinically. The most successful example is Abraxane, an exogenous human serum albumin (HSA)-bound paclitaxel formulation approved by the FDA and used to treat locally advanced or metastatic tumors. However, additional clinical translation of exogenous albumin formulations has not been approved to date because of their unexpectedly low delivery efficiency, which can increase the risk of systemic toxicity. To overcome these limitations, several prodrugs binding endogenous albumin covalently have been investigated owing to distinct advantages for a safe and more effective drug delivery. In this review, we give account of the different albumin-based drug delivery systems, from laboratory investigations to clinical applications, and their potential challenges, and the outlook for clinical translation is discussed. In addition, recent advances and progress of albumin-binding drugs to move more closely to the clinical settings are outlined.
    Type of Medium: Online Resource
    ISSN: 1999-4923
    URL: Article
    DOI: 10.3390/pharmaceutics14040728
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527217-2
    SSG: 15,3
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  • 8
    Online Resource
    Online Resource
    Occult Macular Dysfunction Syndrome: Identification of Multiple Pathologies in a Clinical Spectrum of Macular Dysfunction with Normal Fundus in East Asian Patients: EAOMD Report No. 5
    MDPI AG ; 2023
    In:  Genes Vol. 14, No. 10 ( 2023-09-26), p. 1869-
    Details
    In: Genes, MDPI AG, Vol. 14, No. 10 ( 2023-09-26), p. 1869-
    Abstract: Occult macular dystrophy (OMD) is the most prevalent form of macular dystrophy in East Asia. Beyond RP1L1, causative genes and mechanisms remain largely uncharacterised. This study aimed to delineate the clinical and genetic characteristics of OMD syndrome (OMDS). Patients clinically diagnosed with OMDS in Japan, South Korea, and China were enrolled. The inclusion criteria were as follows: (1) macular dysfunction and (2) normal fundus appearance. Comprehensive clinical evaluation and genetic assessment were performed to identify the disease-causing variants. Clinical parameters were compared among the genotype groups. Seventy-two patients with OMDS from fifty families were included. The causative genes were RP1L1 in forty-seven patients from thirty families (30/50, 60.0%), CRX in two patients from one family (1/50, 2.0%), GUCY2D in two patients from two families (2/50, 4.0%), and no genes were identified in twenty-one patients from seventeen families (17/50, 34.0%). Different severities were observed in terms of disease onset and the prognosis of visual acuity reduction. This multicentre large cohort study furthers our understanding of the phenotypic and genotypic spectra of patients with macular dystrophy and normal fundus. Evidently, OMDS encompasses multiple Mendelian retinal disorders, each representing unique pathologies that dictate their respective severity and prognostic patterns.
    Type of Medium: Online Resource
    ISSN: 2073-4425
    URL: Article
    DOI: 10.3390/genes14101869
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527218-4
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  • 9
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    Online Resource
    Development of a New Nomogram Including Neutrophil-to-Lymphocyte Ratio to Predict Survival in Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization
    MDPI AG ; 2019
    In:  Cancers Vol. 11, No. 4 ( 2019-04-10), p. 509-
    Details
    In: Cancers, MDPI AG, Vol. 11, No. 4 ( 2019-04-10), p. 509-
    Abstract: The neutrophil-to-lymphocyte ratio (NLR) has recently been reported to predict the prognosis of hepatocellular carcinoma (HCC). We explored whether NLR predicted the survival of patients with HCC undergoing transarterial chemoembolization (TACE), and developed a predictive model. In total, 1697 patients with HCC undergoing TACE as first-line therapy at two university hospitals were enrolled (derivation set n = 921, internal validation set n = 395, external validation set n = 381). The tumor size, tumor number, AFP level, vascular invasion, Child–Pugh score, objective response after TACE, and NLR, selected as predictors of overall survival (OS) via multivariate Cox’s regression model, were incorporated into a 14-point risk prediction model (SNAVCORN score). The time-dependent areas under the receiver-operating characteristic curves for OS at 1, 3, and 5 years predicted by the SNAVCORN score were 0.812, 0.734, and 0.700 in the derivation set. Patients were stratified into three risk groups by SNAVCORN score (low, 0–4; intermediate, 5–9; high, 10–14). Compared with the low-risk group, the intermediate-risk (HR 3.10, p 〈 0.001) and high-risk (HR 7.37, p 〈 0.001) groups exhibited significantly greater mortality. The prognostic performance of the SNAVCORN score including NLR in patients with HCC treated with TACE was remarkable, much better than those of the conventional scores. The SNAVCORN score will guide future HCC treatment decisions.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers11040509
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2527080-1
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  • 10
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    Efficacy and Safety of Dual-Drug-Eluting Stents for de Novo Coronary Lesions in South Korea—The Effect Trial
    MDPI AG ; 2020
    In:  Journal of Clinical Medicine Vol. 10, No. 1 ( 2020-12-27), p. 69-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 10, No. 1 ( 2020-12-27), p. 69-
    Abstract: Background: Drug-eluting stents (DESs) are commonly used in percutaneous coronary intervention (PCI) procedures; however, complications including in-stent restenosis and stent thrombosis are significant challenges. The dual-DES is a stent that elutes two drugs to target various stages of the restenosis reaction. This study investigated the safety and efficacy of dual-DES in clinical practice. Methods: This study included 375 patients who underwent PCI with Cilotax™ or DXR™ dual-DESs at one of 13 centers in South Korea. The primary endpoint was target lesion failure (TLF) within 1 year. The secondary endpoints were cardiac death, myocardial infarction (MI), target lesion revascularization (TLR), and stent thrombosis. Results: The rates of TLF in dual-DESs (3.7%) were comparable to those reported in conventional DES. In addition, the DXR™ group had a significantly lower rate of TLF than the Cilotax™ group. In multivariate analysis, the DXR™ group had a lower risk of TLF (adjusted hazard ratio (HR) 0.30, 95% CI 0.09–0.92, p = 0.036) and MI (adjusted HR 0.16, 95% CI 0.03–0.82, p = 0.027) than the Cilotax™ group. Conclusion: Dual-DESs had similar clinical outcomes regarding efficacy and safety as conventional DES. Among the dual-DES, the DXR™ stent as a new generation dual-DES had more favorable clinical outcomes than the Cilotax™ stent.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm10010069
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2662592-1
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