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  • 1
    Online Resource
    Online Resource
    Endometriosis Might Be Inversely Associated with Developing Chronic Kidney Disease: A Population-Based Cohort Study in Taiwan
    MDPI AG ; 2016
    In:  International Journal of Molecular Sciences Vol. 17, No. 7 ( 2016-07-07), p. 1079-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 17, No. 7 ( 2016-07-07), p. 1079-
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms17071079
    Language: English
    Publisher: MDPI AG
    Publication Date: 2016
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 2
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    Online Resource
    Biodistribution of Intra-Arterial and Intravenous Delivery of Human Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles in a Rat Model to Guide Delivery Strategies for Diabetes Therapies
    MDPI AG ; 2022
    In:  Pharmaceuticals Vol. 15, No. 5 ( 2022-05-12), p. 595-
    Details
    In: Pharmaceuticals, MDPI AG, Vol. 15, No. 5 ( 2022-05-12), p. 595-
    Abstract: Umbilical cord mesenchymal stem cell-derived extracellular vesicles (UC-MSC-EVs) have become an emerging strategy for treating various autoimmune and metabolic disorders, particularly diabetes. Delivery of UC-MSC-EVs is essential to ensure optimal efficacy of UC-MSC-EVs. To develop safe and superior EVs-based delivery strategies, we explored nuclear techniques including positron emission tomography (PET) to evaluate the delivery of UC-MSC-EVs in vivo. In this study, human UC-MSC-EVs were first successfully tagged with I-124 to permit PET determination. Intravenous (I.V.) and intra-arterial (I.A.) administration routes of [124I]I-UC-MSC-EVs were compared and evaluated by in vivo PET-CT imaging and ex vivo biodistribution in a non-diabetic Lewis (LEW) rat model. For I.A. administration, [124I] I-UC-MSC-EVs were directly infused into the pancreatic parenchyma via the celiac artery. PET imaging revealed that the predominant uptake occurred in the liver for both injection routes, and further imaging characterized clearance patterns of [124I]I-UC-MSC-EVs. For biodistribution, the uptake (%ID/gram) in the spleen was significantly higher for I.V. administration compared to I.A. administration (1.95 ± 0.03 and 0.43 ± 0.07, respectively). Importantly, the pancreas displayed similar uptake levels between the two modalities (0.20 ± 0.06 for I.V. and 0.24 ± 0.03 for I.A.). Therefore, our initial data revealed that both routes had similar delivery efficiency for [124I] I-UC-MSC-EVs except in the spleen and liver, considering that higher spleen uptake could enhance immunomodulatory application of UC-MSC-EVs. These findings could guide the development of safe and efficacious delivery strategies for UC-MSC-EVs in diabetes therapies, in which a minimally invasive I.V. approach would serve as a better delivery strategy. Further confirmation studies are ongoing.
    Type of Medium: Online Resource
    ISSN: 1424-8247
    URL: Article
    DOI: 10.3390/ph15050595
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2193542-7
    SSG: 15,3
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  • 3
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    Online Resource
    High-Throughput Chemical Screening and Structure-Based Models to Predict hERG Inhibition
    MDPI AG ; 2022
    In:  Biology Vol. 11, No. 2 ( 2022-01-28), p. 209-
    Details
    In: Biology, MDPI AG, Vol. 11, No. 2 ( 2022-01-28), p. 209-
    Abstract: Chemical inhibition of the human ether-a -go-go-related gene (hERG) potassium channel leads to a prolonged QT interval that can contribute to severe cardiotoxicity. The adverse effects of hERG inhibition are one of the principal causes of drug attrition in clinical and pre-clinical development. Preliminary studies have demonstrated that a wide range of environmental chemicals and toxicants may also inhibit the hERG channel and contribute to the pathophysiology of cardiovascular (CV) diseases. As part of the US federal Tox21 program, the National Center for Advancing Translational Science (NCATS) applied a quantitative high throughput screening (qHTS) approach to screen the Tox21 library of 10,000 compounds (~7871 unique chemicals) at 14 concentrations in triplicate to identify chemicals perturbing hERG activity in the U2OS cell line thallium flux assay platform. The qHTS cell-based thallium influx assay provided a robust and reliable dataset to evaluate the ability of thousands of drugs and environmental chemicals to inhibit hERG channel protein, and the use of chemical structure-based clustering and chemotype enrichment analysis facilitated the identification of molecular features that are likely responsible for the observed hERG activity. We employed several machine-learning approaches to develop QSAR prediction models for the assessment of hERG liabilities for drug-like and environmental chemicals. The training set was compiled by integrating hERG bioactivity data from the ChEMBL database with the Tox21 qHTS thallium flux assay data. The best results were obtained with the random forest method (~92.6% balanced accuracy). The data and scripts used to generate hERG prediction models are provided in an open-access format as key in vitro and in silico tools that can be applied in a translational toxicology pipeline for drug development and environmental chemical screening.
    Type of Medium: Online Resource
    ISSN: 2079-7737
    URL: Article
    DOI: 10.3390/biology11020209
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2661517-4
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  • 4
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    Online Resource
    Reactivity of a Carene-Derived Hydroxynitrate in Mixed Organic/Aqueous Matrices: Applying Synthetic Chemistry to Product Identification and Mechanistic Implications
    MDPI AG ; 2021
    In:  Atmosphere Vol. 12, No. 12 ( 2021-12-03), p. 1617-
    Details
    In: Atmosphere, MDPI AG, Vol. 12, No. 12 ( 2021-12-03), p. 1617-
    Abstract: β-hydroxynitrates (HN) are a major class of products formed during OH and NO3 initiated oxidation of terpenes. Their production contributes significantly to secondary organic aerosol (SOA) formation and NOx sequestration. However, studying the condensed phase reactions of this important class of molecules has been hindered by the lack of commercially available authentic standards. The goal of this work was to examine the influence of water concentration and solvent identity on product yields of a tertiary HN derived from 3-carene prepared in house. To assess the role of water on conversion chemistry, bulk-phase reactions were conducted in DMSO-d6, a non-nucleophilic solvent, with a gradient of water concentrations, and analyzed with 1H NMR. Product identifications were made by comparison with authentic standards prepared in house. Four major products were identified, including an unexpected diol produced from carbocation rearrangement, diol diastereomers, and trans-3-carene oxide, with varying yields as a function of water concentration. Product yields were also measured in two protic, nucleophilic solvents, MeOD-d4 and EtOD-d6. Finally, reactions with added chloride formed alkyl chloride products in yields approaching 30%. These results are among the first to highlight the complexities of nucleophilic reactions of hydroxynitrates in bulk, mixed aqueous/organic media and to identify new, unexpected products.
    Type of Medium: Online Resource
    ISSN: 2073-4433
    URL: Article
    DOI: 10.3390/atmos12121617
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2605928-9
    SSG: 23
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  • 5
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    Online Resource
    Workplace Assessment Scale: Pilot Validation Study
    MDPI AG ; 2022
    In:  International Journal of Environmental Research and Public Health Vol. 19, No. 19 ( 2022-09-29), p. 12408-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 19, No. 19 ( 2022-09-29), p. 12408-
    Abstract: First responders, such as police officers, paramedics, and firefighters are at an increased risk of experiencing negative mental health outcomes compared to the general population. This predisposition can partially be attributed to common occupational stressors, which may provoke strong feelings of betrayal and humiliation. The Workplace Assessment Scale (WAS) was developed as there is currently no appropriate measure to assess such feelings in the first responder population. Initial development of the WAS included a Betrayal Subscale and the Humiliation Subscale, each comprised of 5 Likert scale questions which ask participants to report the frequency at which they experience specific feelings associated with their workplace. This pilot validation study was conducted to determine if there is preliminary evidence to support a large-scale validation study. To determine this, we assessed the internal structure and the convergent, concurrent, and predictive validity of the WAS. Based on 21/22 (95%) participant responses, a factor analysis did not support the two-factor model we anticipated, with only one factor and seven items retained from the original version of the scale. However, the internal consistency of the remaining items was strong. The validity analysis found moderate convergent validity and weak predictive validity based on correlations between the WAS and other psychometric scales. Minimal concurrent validity was noted. Additional research is needed for further analysis and validation of the WAS.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph191912408
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2175195-X
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  • 6
    Online Resource
    Online Resource
    Prediction of Incontinence after Robot-Assisted Radical Prostatectomy: Development and Validation of a 24-Month Incontinence Nomogram
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 7 ( 2022-03-24), p. 1644-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 7 ( 2022-03-24), p. 1644-
    Abstract: Incontinence after robot-assisted radical prostatectomy (RARP) is feared by most patients with prostate cancer. Many risk factors for incontinence after RARP are known, but a paucity of data integrates them. Prospectively acquired data from 680 men who underwent RARP January 2008–December 2015 and met inclusion/exclusion criteria were queried retrospectively and then divided into model development (80%) and validation (20%) cohorts. The UCLA-PCI-Short Form-v2 Urinary Function questionnaire was used to categorize perfect continence (0 pads), social continence (1–2 pads), or incontinence (≥3 pads). The observed incontinence rates were 26% at 6 months, 7% at 12 months, and 3% at 24 months. Logistic regression was used for model development, with variables identified using a backward selection process. Variables found predictive included age, race, body mass index, and preoperative erectile function. Internal validation and calibration were performed using standard bootstrap methodology. Calibration plots and receiver operating curves were used to evaluate model performance. The initial model had 6-, 12-, and 24-month areas under the curves (AUCs) of 0.64, 0.66, and 0.80, respectively. The recalibrated model had 6-, 12-, and 24-month AUCs of 0.52, 0.52, and 0.76, respectively. The final model was superior to any single clinical variable for predicting the risk of incontinence after RARP.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14071644
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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  • 7
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    Online Resource
    Studies of Nickel/Samarium-Doped Ceria for Catalytic Partial Oxidation of Methane and Effect of Oxygen Vacancy
    MDPI AG ; 2021
    In:  Catalysts Vol. 11, No. 6 ( 2021-06-14), p. 731-
    Details
    In: Catalysts, MDPI AG, Vol. 11, No. 6 ( 2021-06-14), p. 731-
    Abstract: We investigated the performance of nickel/samarium-doped ceria (Ni/SDC) nanocatalysts on the catalytic partial oxidation of methane (CPOM). Studies of temperature-programmed surface reaction and reduction reveal that catalytic activity is determined by a synergistic effect produced by Ni metals and metal-support interaction. Catalytic activity was more dependent on the Ni content below 600 °C, while there is not much difference for all catalysts at high temperatures. The catalyst exhibiting high activities toward syngas production (i.e., a CH4 conversion 〉 90% at 700 °C) requires a medium Ni-SDC interaction with an Sm/Ce ratio of about 1/9 to 2/8. This is accounted for by optimum oxygen vacancies and adequate ion diffusivity in the SDCs which, as reported, also display the highest ion conductivity for fuel cell applications.
    Type of Medium: Online Resource
    ISSN: 2073-4344
    URL: Article
    DOI: 10.3390/catal11060731
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662126-5
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  • 8
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    Online Resource
    Real Time Breath Analysis Using Portable Gas Chromatography for Adult Asthma Phenotypes
    MDPI AG ; 2021
    In:  Metabolites Vol. 11, No. 5 ( 2021-04-23), p. 265-
    Details
    In: Metabolites, MDPI AG, Vol. 11, No. 5 ( 2021-04-23), p. 265-
    Abstract: Asthma is heterogeneous but accessible biomarkers to distinguish relevant phenotypes remain lacking, particularly in non-Type 2 (T2)-high asthma. Moreover, common clinical characteristics in both T2-high and T2-low asthma (e.g., atopy, obesity, inhaled steroid use) may confound interpretation of putative biomarkers and of underlying biology. This study aimed to identify volatile organic compounds (VOCs) in exhaled breath that distinguish not only asthmatic and non-asthmatic subjects, but also atopic non-asthmatic controls and also by variables that reflect clinical differences among asthmatic adults. A total of 73 participants (30 asthma, eight atopic non-asthma, and 35 non-asthma/non-atopic subjects) were recruited for this pilot study. A total of 79 breath samples were analyzed in real-time using an automated portable gas chromatography (GC) device developed in-house. GC-mass spectrometry was also used to identify the VOCs in breath. Machine learning, linear discriminant analysis, and principal component analysis were used to identify the biomarkers. Our results show that the portable GC was able to complete breath analysis in 30 min. A set of nine biomarkers distinguished asthma and non-asthma/non-atopic subjects, while sets of two and of four biomarkers, respectively, further distinguished asthmatic from atopic controls, and between atopic and non-atopic controls. Additional unique biomarkers were identified that discriminate subjects by blood eosinophil levels, obese status, inhaled corticosteroid treatment, and also acute upper respiratory illnesses within asthmatic groups. Our work demonstrates that breath VOC profiling can be a clinically accessible tool for asthma diagnosis and phenotyping. A portable GC system is a viable option for rapid assessment in asthma.
    Type of Medium: Online Resource
    ISSN: 2218-1989
    URL: Article
    DOI: 10.3390/metabo11050265
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662251-8
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  • 9
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    Online Resource
    Reduced Steroid Metabolites Identify Infection-Prone Children in Two Independent Pre-Birth Cohorts
    MDPI AG ; 2022
    In:  Metabolites Vol. 12, No. 11 ( 2022-11-13), p. 1108-
    Details
    In: Metabolites, MDPI AG, Vol. 12, No. 11 ( 2022-11-13), p. 1108-
    Abstract: Recurrent respiratory infections are a leading cause of morbidity and mortality in early life, but there is no broadly accepted means to identify infection-prone children during this highly vulnerable period. In this study, we investigated associations between steroid metabolites and incident respiratory infections in two pre-birth cohorts to identify novel metabolomic signatures of early infection proneness. Children from the Vitamin D Antenatal Asthma Reduction Trial and the Copenhagen Prospective Studies on Asthma in Childhood were included, and profiling was performed on plasma samples collected at ages 1 and 6 years. Both cohorts recorded incidence of lower respiratory infections, upper respiratory infections, ear infections, and colds. Poisson regression analysis assessed the associations between 18 steroid metabolites and the total number of respiratory infections that occurred in offspring during follow-up. We found that steroid metabolites across androgenic, corticosteroid, pregnenolone, and progestin classes were reduced in children that suffered more infections, and these patterns persisted at age 6 years, generally reflecting consistency in direction of effect and significance. Our analysis suggested steroid metabolite measurement may be useful in screening for infection proneness during this critical developmental period. Future studies should clinically evaluate their potential utility as a clinical screening tool.
    Type of Medium: Online Resource
    ISSN: 2218-1989
    URL: Article
    DOI: 10.3390/metabo12111108
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662251-8
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  • 10
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    Online Resource
    Alantolactone Suppresses Proliferation and the Inflammatory Response in Human HaCaT Keratinocytes and Ameliorates Imiquimod-Induced Skin Lesions in a Psoriasis-Like Mouse Model
    MDPI AG ; 2021
    In:  Life Vol. 11, No. 7 ( 2021-06-25), p. 616-
    Details
    In: Life, MDPI AG, Vol. 11, No. 7 ( 2021-06-25), p. 616-
    Abstract: Psoriasis is an immune-mediated inflammatory disease that affects 2% to 3% of the world population. Alantolactone, a sesquiterpene lactone, was isolated from Inula helenium and Radix inulae and has several biological effects, including antifungal, anthelmintic, antimicrobial, anti-inflammatory, antitrypanosomal, and anticancer properties. This study aimed to evaluate the antipsoriatic potential of alantolactone in vitro and in vivo and to explore its underlying mechanisms. These results showed that alantolactone significantly attenuated IL-17A, IL-22, oncostatin M, IL-1α, and TNF-α (M5) cytokine-induced hyperproliferation in HaCaT keratinocytes. Moreover, M5 cytokines significantly upregulated the mRNA levels of TNF-α, IL-6, IL-1β, and IL-8. However, alantolactone attenuated the upregulation of these inflammatory cytokines. In addition, alantolactone was found to inhibit STAT3 phosphorylation and NF-κB p65 nuclear translocation in HaCaT keratinocytes. Furthermore, alantolactone treatment in mice significantly alleviated the severity of skin lesions (erythema, scaling and epidermal thickness, and inflammatory cell infiltration) and decreased the mRNA expression of inflammatory cytokines (e.g., TNF-α, IL-6, IL-1β, IL-8, IL-17A, and IL-23) in an IMQ-induced-like mouse model. Therefore, our new findings revealed that alantolactone alleviates psoriatic skin lesions by inhibiting inflammation, making it an attractive candidate for future development as an antipsoriatic agent.
    Type of Medium: Online Resource
    ISSN: 2075-1729
    URL: Article
    DOI: 10.3390/life11070616
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662250-6
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