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  • 1
    Online Resource
    Online Resource
    Detailed Molecular Interactions of Favipiravir with SARS-CoV-2, SARS-CoV, MERS-CoV, and Influenza Virus Polymerases In Silico
    MDPI AG ; 2020
    In:  Microorganisms Vol. 8, No. 10 ( 2020-10-20), p. 1610-
    Details
    In: Microorganisms, MDPI AG, Vol. 8, No. 10 ( 2020-10-20), p. 1610-
    Abstract: Favipiravir was initially developed as an antiviral drug against influenza and is currently used in clinical trials against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (COVID-19). This agent is presumably involved in RNA chain termination during influenza virus replication, although the molecular interactions underlying its potential impact on the coronaviruses including SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV) remain unclear. We performed in silico studies to elucidate detailed molecular interactions between favipiravir and the SARS-CoV-2, SARS-CoV, MERS-CoV, and influenza virus RNA-dependent RNA polymerases (RdRp). As a result, no interactions between favipiravir ribofuranosyl-5′-triphosphate (F-RTP), the active form of favipiravir, and the active sites of RdRps (PB1 proteins) from influenza A (H1N1)pdm09 virus were found, yet the agent bound to the tunnel of the replication genome of PB1 protein leading to the inhibition of replicated RNA passage. In contrast, F-RTP bound to the active sites of coronavirus RdRp in the presence of the agent and RdRp. Further, the agent bound to the replicated RNA terminus in the presence of agent, magnesium ions, nucleotide triphosphate, and RdRp proteins. These results suggest that favipiravir exhibits distinct mechanisms of action against influenza virus and various coronaviruses.
    Type of Medium: Online Resource
    ISSN: 2076-2607
    URL: Article
    DOI: 10.3390/microorganisms8101610
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2720891-6
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  • 2
    Online Resource
    Online Resource
    Substrate Dependence in Aqueous Diels-Alder Reactions of Cyclohexadiene Derivatives with 1,4-Benzoquinone
    MDPI AG ; 2005
    In:  Molecules Vol. 10, No. 1 ( 2005-01-31), p. 244-250
    Details
    In: Molecules, MDPI AG, Vol. 10, No. 1 ( 2005-01-31), p. 244-250
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/10010244
    Language: English
    Publisher: MDPI AG
    Publication Date: 2005
    detail.hit.zdb_id: 2008644-1
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  • 3
    Online Resource
    Online Resource
    Biocompatibility Evaluation of Carbon Nanohorns in Bone Tissues
    MDPI AG ; 2023
    In:  Nanomaterials Vol. 13, No. 2 ( 2023-01-05), p. 244-
    Details
    In: Nanomaterials, MDPI AG, Vol. 13, No. 2 ( 2023-01-05), p. 244-
    Abstract: With the advent of nanotechnology, the use of nanoparticles as drug delivery system (DDS) has attracted great interest. We aimed to apply carbon nanohorns (CNHs) as DDS in the development of new treatments for bone diseases. We evaluated the in vitro and in vivo cellular responses of CNHs in bone-related cells compared with carbon blacks (CBs), which are similar in particle size but differ in surface and structural morphologies. Although in vitro experiments revealed that both CNHs and CBs were incorporated into the lysosomes of RAW264-induced osteoclast-like cells (OCs) and MC3T3-E1 osteoblast-like cells (OBs), no severe cytotoxicity was observed. CNHs reduced the tartrate-resistant acid phosphatase activity and expression of the differentiation marker genes in OCs at noncytotoxic concentrations, whereas the alkaline phosphatase activity and differentiation of OBs increased. Under calcification of OBs, CNHs increased the number of calcified nodules and were intra- and extracellularly incorporated into calcified vesicles to form crystal nuclei. The in vivo experiments showed significant promotion of bone regeneration in the CNH group alone, with localized CNHs being found in the bone matrix and lacunae. The suppression of OCs and promotion of OBs suggested that CNHs may be effective against bone diseases and could be applied as DDS.
    Type of Medium: Online Resource
    ISSN: 2079-4991
    URL: Article
    DOI: 10.3390/nano13020244
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662255-5
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  • 4
    Online Resource
    Online Resource
    Risk Factors for Early Mortality in Older Patients with Traumatic Cervical Spine Injuries—A Multicenter Retrospective Study of 1512 Cases
    MDPI AG ; 2023
    In:  Journal of Clinical Medicine Vol. 12, No. 2 ( 2023-01-16), p. 708-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 12, No. 2 ( 2023-01-16), p. 708-
    Abstract: For older patients with decreased reserve function, traumatic cervical spine injuries frequently lead to early mortality. However, the prognostic factors for early mortality remain unclear. This study included patients aged ≥65 years and hospitalized for treatment of traumatic cervical spine injuries in 78 hospitals between 2010 and 2020. Early mortality was defined as death within 90 days after injury. We evaluated the relationship between early mortality and the following factors: age, sex, body mass index, history of drinking and smoking, injury mechanisms, presence of a cervical spine fracture and dislocation, cervical ossification of the posterior longitudinal ligament, diffuse idiopathic skeletal hyperostosis, American Spinal Injury Association Impairment Scale, concomitant injury, pre-existing comorbidities, steroid administration, and treatment plan. Overall, 1512 patients (mean age, 75.8 ± 6.9 years) were included in the study. The early mortality rate was 4.0%. Multivariate analysis identified older age (OR = 1.1, p 〈 0.001), male sex (OR = 3.7, p = 0.009), cervical spine fracture (OR = 4.2, p 〈 0.001), complete motor paralysis (OR = 8.4, p 〈 0.001), and chronic kidney disease (OR = 5.3, p 〈 0.001) as risk factors for early mortality. Older age, male sex, cervical spine fracture, complete motor paralysis, and chronic kidney disease are prognostic factors for early mortality in older patients with traumatic cervical spine injuries.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm12020708
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662592-1
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  • 5
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    Online Resource
    Inflammatory and Hypercoagulable Biomarkers and Clinical Outcomes in COVID-19 Patients
    MDPI AG ; 2021
    In:  Journal of Clinical Medicine Vol. 10, No. 14 ( 2021-07-13), p. 3086-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 10, No. 14 ( 2021-07-13), p. 3086-
    Abstract: Systemic inflammation and hypercoagulopathy are known pathophysiological processes of coronavirus disease 2019 (COVID-19), particularly in patients with known cardiovascular disease or its risk factors (CVD). However, whether a cumulative assessment of these biomarkers at admission could contribute to the prediction of in-hospital outcomes remains unknown. The CLAVIS-COVID registry was a Japanese nationwide retrospective multicenter observational study, supported by the Japanese Circulation Society. Consecutive hospitalized patients with pre-existing CVD and COVID-19 were enrolled. Patients were stratified by the tertiles of CRP and D-dimer values at the time of admission. Multivariable Cox proportional hazard models were constructed. In 461 patients (65.5% male; median age, 70.0), the median baseline CRP and D-dimer was 58.3 (interquartile range, 18.2–116.0) mg/L and 1.5 (interquartile range, 0.8–3.0) mg/L, respectively. Overall, the in-hospital mortality rate was 16.5%, and the rates steadily increased in concordance with both CRP (5.0%, 15.0%, and 28.2%, respectively p 〈 0.001) and D-dimer values (6.8%, 19.6%, and 22.5%, respectively p = 0.001). Patients with the lowest tertiles of both biomarkers (CRP, 29.0 mg/L; D-dimer, 1.00 mg/L) were at extremely low risk of in-hospital mortality (0% until day 50, and 1.4% overall). Conversely, the elevation of both CRP and D-dimer levels was a significant predictor of in-hospital mortality (Hazard ratio, 2.97; 95% confidence interval, 1.57–5.60). A similar trend was observed when the biomarker threshold was set at a clinically relevant threshold. In conclusion, the combination of these abnormalities may provide a framework for rapid risk estimation for in-hospital COVID-19 patients with CVD.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm10143086
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662592-1
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  • 6
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    Delirium Risk Score in Elderly Patients with Cervical Spinal Cord Injury and/or Cervical Fracture
    MDPI AG ; 2023
    In:  Journal of Clinical Medicine Vol. 12, No. 6 ( 2023-03-20), p. 2387-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 12, No. 6 ( 2023-03-20), p. 2387-
    Abstract: The number of elderly patients with cervical trauma is increasing. Such patients are considered to be at high risk for delirium, which is an acute neuropsychological disorder that reduces the patient’s capacity to interact with their environment due to impairments in cognition. This study aimed to establish a risk score that predicts delirium in elderly patients with cervical SCI and/or cervical fracture regardless of treatment type. This retrospective cohort study included 1512 patients aged ≥65 years with cervical SCI and/or cervical fracture. The risk factors for delirium according to treatment type (surgical or conservative) were calculated using multivariate logistic regression. A delirium risk score was established as the simple arithmetic sum of points assigned to variables that were significant in the multivariate analyses. Based on the statistical results, the delirium risk score was defined using six factors: old age (≥80 years), hypoalbuminemia, cervical fracture, major organ injury, dependence on pre-injury mobility, and comorbid diabetes. The score’s area under the curve for the prediction of delirium was 0.66 (p 〈 0.001). Although the current scoring system must be validated with an independent dataset, the system remains beneficial because it can be used after screening examinations upon hospitalization and before deciding the treatment strategy.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm12062387
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662592-1
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  • 7
    Online Resource
    Online Resource
    Effects of Dementia on Outcomes after Cervical Spine Injuries in Elderly Patients: Evaluation of 1512 Cases in a Nationwide Multicenter Study in Japan
    MDPI AG ; 2023
    In:  Journal of Clinical Medicine Vol. 12, No. 5 ( 2023-02-27), p. 1867-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 12, No. 5 ( 2023-02-27), p. 1867-
    Abstract: We aimed to retrospectively investigate the demographic characteristics and short-term outcomes of traumatic cervical spine injuries in patients with dementia. We enrolled 1512 patients aged ≥ 65 years with traumatic cervical injuries registered in a multicenter study database. Patients were divided into two groups according to the presence of dementia, and 95 patients (6.3%) had dementia. Univariate analysis revealed that the dementia group comprised patients who were older and predominantly female and had lower body mass index, higher modified 5-item frailty index (mFI-5), lower pre-injury activities of daily living (ADLs), and a larger number of comorbidities than patients without dementia. Furthermore, 61 patient pairs were selected through propensity score matching with adjustments for age, sex, pre-injury ADLs, American Spinal Injury Association Impairment Scale score at the time of injury, and the administration of surgical treatment. In the univariate analysis of the matched groups, patients with dementia had significantly lower ADLs at 6 months and a higher incidence of dysphagia up to 6 months than patients without dementia. Kaplan–Meier analysis revealed that patients with dementia had a higher mortality than those without dementia until the last follow-up. Dementia was associated with poor ADLs and higher mortality rates after traumatic cervical spine injuries in elderly patients.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm12051867
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662592-1
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  • 8
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    Plasma Membrane Ca2+–ATPase in Rat and Human Odontoblasts Mediates Dentin Mineralization
    MDPI AG ; 2021
    In:  Biomolecules Vol. 11, No. 7 ( 2021-07-10), p. 1010-
    Details
    In: Biomolecules, MDPI AG, Vol. 11, No. 7 ( 2021-07-10), p. 1010-
    Abstract: Intracellular Ca2+ signaling engendered by Ca2+ influx and mobilization in odontoblasts is critical for dentinogenesis induced by multiple stimuli at the dentin surface. Increased Ca2+ is exported by the Na+–Ca2+ exchanger (NCX) and plasma membrane Ca2+–ATPase (PMCA) to maintain Ca2+ homeostasis. We previously demonstrated a functional coupling between Ca2+ extrusion by NCX and its influx through transient receptor potential channels in odontoblasts. Although the presence of PMCA in odontoblasts has been previously described, steady-state levels of mRNA-encoding PMCA subtypes, pharmacological properties, and other cellular functions remain unclear. Thus, we investigated PMCA mRNA levels and their contribution to mineralization under physiological conditions. We also examined the role of PMCA in the Ca2+ extrusion pathway during hypotonic and alkaline stimulation-induced increases in intracellular free Ca2+ concentration ([Ca2+]i). We performed RT-PCR and mineralization assays in human odontoblasts. [Ca2+] i was measured using fura-2 fluorescence measurements in odontoblasts isolated from newborn Wistar rat incisor teeth and human odontoblasts. We detected mRNA encoding PMCA1–4 in human odontoblasts. The application of hypotonic or alkaline solutions transiently increased [Ca2+]i in odontoblasts in both rat and human odontoblasts. The Ca2+ extrusion efficiency during the hypotonic or alkaline solution-induced [Ca2+] i increase was decreased by PMCA inhibitors in both cell types. Alizarin red and von Kossa staining showed that PMCA inhibition suppressed mineralization. In addition, alkaline stimulation (not hypotonic stimulation) to human odontoblasts upregulated the mRNA levels of dentin matrix protein-1 (DMP-1) and dentin sialophosphoprotein (DSPP). The PMCA inhibitor did not affect DMP-1 or DSPP mRNA levels at pH 7.4–8.8 and under isotonic and hypotonic conditions, respectively. We also observed PMCA1 immunoreactivity using immunofluorescence analysis. These findings indicate that PMCA participates in maintaining [Ca2+]i homeostasis in odontoblasts by Ca2+ extrusion following [Ca2+] i elevation. In addition, PMCA participates in dentinogenesis by transporting Ca2+ to the mineralizing front (which is independent of non-collagenous dentin matrix protein secretion) under physiological and pathological conditions following mechanical stimulation by hydrodynamic force inside dentinal tubules, or direct alkaline stimulation by the application of high-pH dental materials.
    Type of Medium: Online Resource
    ISSN: 2218-273X
    URL: Article
    DOI: 10.3390/biom11071010
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2701262-1
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  • 9
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    Online Resource
    Simple Methods for Evaluating Acid Permeation and Biofilm Formation Behaviors on Polysiloxane Films
    MDPI AG ; 2022
    In:  Materials Vol. 15, No. 6 ( 2022-03-19), p. 2272-
    Details
    In: Materials, MDPI AG, Vol. 15, No. 6 ( 2022-03-19), p. 2272-
    Abstract: The sulfuric acid permeation and biofilm formation behaviors of polysiloxane films have been investigated, and simple methods for evaluating the sulfuric acid permeation and biofilm formation behaviors have been proposed in this paper. The polysiloxane films used in these experiments were practically impermeable to the aqueous sulfuric acid solution, and the amount of biofilm formation varied depending on the composition of the films. Further, the amount of sulfuric acid permeation can be estimated by measuring the polarization curves of polysiloxane films with different thicknesses formed on iron electrodes. By measuring the adhesion work of pure water and simulated biofilm droplets on polysiloxane films of different compositions, we can estimate the resistance of biofilm formation on the polysiloxane films.
    Type of Medium: Online Resource
    ISSN: 1996-1944
    URL: Article
    DOI: 10.3390/ma15062272
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2487261-1
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  • 10
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    Mutated KIT Tyrosine Kinase as a Novel Molecular Target in Acute Myeloid Leukemia
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 9 ( 2022-04-23), p. 4694-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 9 ( 2022-04-23), p. 4694-
    Abstract: KIT is a type-III receptor tyrosine kinase that contributes to cell signaling in various cells. Since KIT is activated by overexpression or mutation and plays an important role in the development of some cancers, such as gastrointestinal stromal tumors and mast cell disease, molecular therapies targeting KIT mutations are being developed. In acute myeloid leukemia (AML), genome profiling via next-generation sequencing has shown that several genes that are mutated in patients with AML impact patients’ prognosis. Moreover, it was suggested that precision-medicine-based treatment using genomic data will improve treatment outcomes for AML patients. This paper presents (1) previous studies regarding the role of KIT mutations in AML, (2) the data in AML with KIT mutations from the HM-SCREEN-Japan-01 study, a genome profiling study for patients newly diagnosed with AML who are unsuitable for the standard first-line treatment (unfit) or have relapsed/refractory AML, and (3) new therapies targeting KIT mutations, such as tyrosine kinase inhibitors and heat shock protein 90 inhibitors. In this era when genome profiling via next-generation sequencing is becoming more common, KIT mutations are attractive novel molecular targets in AML.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms23094694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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