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  • 1
    Online Resource
    Online Resource
    Limited Clinical and Diagnostic Utility of Circulating Tumor DNA Detection in Patients with Early-Stage Well-Differentiated Thyroid Cancer: Comparison with Benign Thyroid Nodules and Healthy Individuals
    MDPI AG ; 2021
    In:  Healthcare Vol. 9, No. 4 ( 2021-04-01), p. 386-
    Details
    In: Healthcare, MDPI AG, Vol. 9, No. 4 ( 2021-04-01), p. 386-
    Abstract: Limited data are available on the diagnostic utility of circulating tumor DNA (ctDNA) in early-stage thyroid cancers for BRAF, KRAS, NRAS, and TERT promoter mutations, which are known detectable markers for thyroid cancers. Here, we analyzed the above driver mutations in ctDNA and matched neoplastic tissues from patients with early-stage thyroid cancers in order to investigate diagnostic utility of circulating markers in distinguishing from other mimicking thyroid lesions and healthy individuals. In total, 73 matched neoplastic tissue and plasma samples [thyroid cancers (n = 62), benign thyroid disorders (n = 8), and parathyroid lesions (n = 3)] and 54 plasma samples from healthy individuals (as controls) were analyzed for BRAF, KRAS, NRAS, and TERT promoter mutations using peptide nucleic acid clamp real-time PCR. Although only one patient with an indeterminate lesion on thyroid cytology showed KRAS mutation (codon 146) in the preoperative plasma, that KRAS mutation was not identified in the stage I papillary thyroid carcinoma tissue. In the remaining 72 plasma samples, no other mutations were identified in BRAF, NRAS, and TERT promoter genes. The concordance rates of mutational results between the plasma and tumor tissue or metastatic lymph node were very low. One (1.9%) of the 54 healthy individuals harbored a KRAS mutation in the plasma samples. The ctDNA results did not represent the mutational profile of primary or metastatic thyroid cancers, warranting a caution for interpretation. The clinical utility of BRAF, KRAS, NRAS, and TERT promoter mutation analysis on ctDNA appears to be limited to early-stage thyroid cancers.
    Type of Medium: Online Resource
    ISSN: 2227-9032
    URL: Article
    DOI: 10.3390/healthcare9040386
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2721009-1
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  • 2
    Online Resource
    Online Resource
    Feasibility of a 12 Week Physical Intervention to Prevent Cognitive Decline and Disability in the At-Risk Elderly Population in Korea
    MDPI AG ; 2020
    In:  Journal of Clinical Medicine Vol. 9, No. 10 ( 2020-09-28), p. 3135-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 9, No. 10 ( 2020-09-28), p. 3135-
    Abstract: There is a need for measures that can prevent the onset of dementia in the rapidly aging population. Reportedly, sustained physical exercise can prevent cognitive decline and disability. This study aimed to assess the feasibility of a 12-week physical exercise intervention (PEI) for delay of cognitive decline and disability in the at-risk elderly population in Korea. Twenty-six participants (aged 67.9 ± 3.6 years, 84.6% female) at risk of dementia were assigned to facility-based PEI (n = 15) or home-based PEI (n = 11). The PEI program consisted of muscle strength training, aerobic exercise, balance, and stretching using portable aids. Feasibility was assessed by retention and adherence rates. Physical fitness/cognitive function were compared before and after the PEI. Retention and adherence rates were 86.7% and 88.3%, respectively, for facility-based PEI and 81.8% and 62.3% for home-based PEI. No intervention-related adverse events were reported. Leg strength/endurance and cardiopulmonary endurance were improved in both groups: 30 s sit-to-stand test (facility-based, p = 0.002; home-based, p = 0.002) and 2 -min stationary march (facility-based, p = 0.001; home-based, p = 0.022). Cognitive function was improved only after facility-based PEI (Alzheimer’s Disease Assessment Scale-cognitive total score, p = 0.009; story memory test on Literacy Independent Cognitive Assessment, p = 0.026). We found that, whereas our PEI is feasible, the home-based program needs supplementation to improve adherence.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm9103135
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2662592-1
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  • 3
    Online Resource
    Online Resource
    Constituents of Gastrodia elata and Their Neuroprotective Effects in HT22 Hippocampal Neuronal, R28 Retinal Cells, and BV2 Microglial Cells
    MDPI AG ; 2020
    In:  Plants Vol. 9, No. 8 ( 2020-08-18), p. 1051-
    Details
    In: Plants, MDPI AG, Vol. 9, No. 8 ( 2020-08-18), p. 1051-
    Abstract: Gastrodia elata is widely used in traditional medicine and contains various types of metabolites with pharmacological activity. In the course of searching for neuroprotective molecules associated with the potential of G. elata in the treatment of neurodegenerative disorders, two new phenolic compounds (1 and 2) and a new tripeptide (3), together with 16 known compounds (4–19), were isolated from the rhizomes of G. elata. The structures of the compounds were determined by the interpretation of spectroscopic data, including nuclear magnetic resonance and mass spectrometry data. All obtained compounds were assessed for their ability to protect neuronal cells against neurotoxicity and neuroinflammation. Of these, 4 and 5 were found to possess moderate activities in HT22 hippocampal neuronal cells, whereas 2, 6, and 7 showed weak activities in R28 retinal cells. Additionally, compound 9 showed moderate inhibitory activity on lipopolysaccharide-induced nitric oxide production in BV2 microglial cells.
    Type of Medium: Online Resource
    ISSN: 2223-7747
    URL: Article
    DOI: 10.3390/plants9081051
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2704341-1
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  • 4
    Online Resource
    Online Resource
    Development of a Human Estrogen Receptor Dimerization Assay for the Estrogenic Endocrine-Disrupting Chemicals Using Bioluminescence Resonance Energy Transfer
    MDPI AG ; 2021
    In:  International Journal of Environmental Research and Public Health Vol. 18, No. 16 ( 2021-08-23), p. 8875-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 18, No. 16 ( 2021-08-23), p. 8875-
    Abstract: Endocrine-disrupting chemicals (EDCs) are found in food and various other substances, including pesticides and plastics. EDCs are easily absorbed into the body and have the ability to mimic or block hormone function. The radioligand binding assay based on the estrogen receptors binding affinity is widely used to detect estrogenic EDCs but is limited to radioactive substances and requires specific conditions. As an alternative, we developed a human cell-based dimerization assay for detecting EDC-mediated ER-alpha (ERα) dimerization using bioluminescence resonance energy transfer (BRET). The resultant novel BRET-based on the ERα dimerization assay was used to identify the binding affinity of 17β-estradiol (E2), 17α-estradiol, corticosterone, diethylhexyl phthalate, bisphenol A, and 4-nonylphenol with ERα by measuring the corresponding BRET signals. Consequently, the BRET signals from five chemicals except corticosterone showed a dose-dependent sigmoidal curve for ERα, and these chemicals were suggested as positive chemicals for ERα. In contrast, corticosterone, which induced a BRET signal comparable to that of the vehicle control, was suggested as a negative chemical for ERα. Therefore, these results were consistent with the results of the existing binding assay for ERα and suggested that a novel BRET system can provide information about EDCs-mediated dimerization to ERα.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph18168875
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2175195-X
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  • 5
    Online Resource
    Online Resource
    A Novel Propofol Dosing Regimen for Pediatric Sedation during Radiologic Tests
    MDPI AG ; 2022
    In:  Journal of Clinical Medicine Vol. 11, No. 17 ( 2022-08-29), p. 5076-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 17 ( 2022-08-29), p. 5076-
    Abstract: The dose of propofol for pediatric sedation during radiologic tests has been proposed as an equation of 0.75 + 0.14 × age (months) + 45.82 × body surface area (m2) based on results in a previous study. We compared this equation and the conventional dosing strategy for sedation in children undergoing radiologic tests. An amount of 180 children scheduled for magnetic resonance imaging (MRI) were randomized to experimental and control groups. The initial induction dose of propofol calculated using the equation was administered in the experimental group. In the control group, children received 1 mg/kg of the initial induction dose of propofol. Then, 0.5 mg/kg of the additional dose was followed to induce sedation in both groups. When awake or moving, a rescue injection of 0.5 mg/kg propofol was given. The total induction dose was more significant in the experimental group. The number of injections for induction in the experimental group was lesser. The dose and number of rescue injections in the experimental group were significantly less. The equation for the induction dose of propofol in a previous study could achieve quick induction of sedation and prevent a rescue injection during sedation. However, caution is needed when using the equation.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm11175076
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662592-1
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  • 6
    Online Resource
    Online Resource
    Lipid/Clay-Based Solid Dispersion Formulation for Improving the Oral Bioavailability of Curcumin
    MDPI AG ; 2022
    In:  Pharmaceutics Vol. 14, No. 11 ( 2022-10-24), p. 2269-
    Details
    In: Pharmaceutics, MDPI AG, Vol. 14, No. 11 ( 2022-10-24), p. 2269-
    Abstract: This study was conducted to develop a lipid/clay-based solid dispersion (LSD) formulation to enhance the dissolution and oral bioavailability of poorly soluble curcumin. Krill oil and aminoclay were used as a lipid and a stabilizer, respectively, and LSD formulations of curcumin were prepared by an antisolvent precipitation method combined with freeze-drying process. Based on the dissolution profiles, the optimal composition of LSD was determined at the weight ratio of curcumin: krill oil: aminoclay of 1:5:5 in the presence of 0.5% of D-α-tocopherol polyethylene glycol succinate. The structural and morphological characteristics of the LSD formulation were determined using X-ray powder diffraction, differential scanning calorimetry, and scanning electron microscopy. Crystalline curcumin was changed to an amorphous form in the LSD formulation. At the pH of acidic to neutral, the LSD formulation showed almost complete drug dissolution ( 〉 90%) within 1 h, while pure curcumin exhibited minimal dissolution of less than 10%. Furthermore, the LSD formulation had significantly improved oral absorption of curcumin in rats, where Cmax and AUC of curcumin were 13- and 23-fold higher for the LSD formulation than for the pure drug. Taken together, these findings suggest that the krill oil-based solid dispersion formulation of curcumin effectively improves the dissolution and oral bioavailability of curcumin.
    Type of Medium: Online Resource
    ISSN: 1999-4923
    URL: Article
    DOI: 10.3390/pharmaceutics14112269
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527217-2
    SSG: 15,3
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  • 7
    Online Resource
    Online Resource
    PSEN1 p.Thr116Ile Variant in Two Korean Families with Young Onset Alzheimer’s Disease
    MDPI AG ; 2018
    In:  International Journal of Molecular Sciences Vol. 19, No. 9 ( 2018-09-02), p. 2604-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 19, No. 9 ( 2018-09-02), p. 2604-
    Abstract: An in depth study of PSEN1 mutation p.Thr116Ile (c.335C 〉 T) is presented from two Korean families with autosomal dominant inheritance. Clinical manifestation of our patients included memory loss, attention deficits, visuospatial dysfunction, agnosia, aphasia, apraxia, and personality changes, which occurred in their 30s. PSEN1 Thr116Ile was initially discovered in an Italian patient and two French families with early onset Alzheimer’s disease (EOAD) with similar age of onset. To verify the possible pathogenic mechanisms of mutation, in silico predictions and 3D modeling were performed. Structure predictions revealed significant aberrations in first hydrophilic loop (HL-I loop). The hydrophobic isoleucine could alter the loop orientation through increased hydrophobic contacts with the surrounding amino acids. Mutation could destroy a possible hydrogen bond between tyrosine 115 and threonine 116, which may affect the loop conformation. HL-I was confirmed as a conservative region of PSEN1, which may be critical in PSEN1 functions. An additional pathogenic mutation, PSEN1 Thr116Asn, was also found for the same residue, where the patient presented young onset AD (YOND). Other mutations in HL-I loop, such as Tyr115His and Glu120Asp, were described in patients with YOND, supporting the critical role of HL-I loop in PSEN1 activity.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms19092604
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 8
    Online Resource
    Online Resource
    Clinical and Neuroimaging Features in Charcot–Marie–Tooth Patients with GNB4 Mutations
    MDPI AG ; 2021
    In:  Life Vol. 11, No. 6 ( 2021-05-28), p. 494-
    Details
    In: Life, MDPI AG, Vol. 11, No. 6 ( 2021-05-28), p. 494-
    Abstract: Charcot–Marie–Tooth disease (CMT) is the most common inherited peripheral neuropathy. Mutations in the GNB4 gene cause dominant intermediate CMT type F (CMTDIF). The aim of this study is to investigate phenotypic heterogeneities and characteristics of CMT patients with GNB4 mutations. We enrolled 1143 Korean CMT families and excluded 344 families with a PMP22 duplication. We further analyzed the 799 remaining families to find their GNB4 mutations using whole-exome sequencing (WES). We identified two mutations (p.Gly77Arg and p.Lys89Glu) in three families, among which a heterozygous p.Gly77Arg mutation was novel. In addition, a significant uncertain variant (p.Thr177Asn) was observed in one family. The frequency of the GNB4 mutation in the Korean population is 0.38% in PMP22 duplication-negative families. All three families showed de novo mutation. Electrophysiological findings regarding the p.Lys89Glu mutation showed that the motor nerve conduction velocity (MNCV) of the median nerve was markedly reduced, indicating demyelinating neuropathy, and sural nerve biopsy revealed severe loss of myelinated axons with onion bulb formation. Lower extremity Magnetic Resonance Imaging (MRI) demonstrated relatively more severe intramuscular fat infiltrations in demyelinating type (p.Lys89Glu mutation) patients compared to intermediate type (p.Gly77Arg mutation) patients. The anterolateral and superficial posterior compartment muscles of the distal calf were preferentially affected in demyelinating type patients. Therefore, it seems that the investigated GNB4 mutations do cause not only the known intermediate type but also demyelinating-type neuropathy. We first presented three Korean families with GNB4 mutations and found phenotypic heterogeneities of both intermediate and demyelinating neuropathy. We suggest that those findings are useful for the differential diagnosis of CMT patients with unknown GNB4 variants.
    Type of Medium: Online Resource
    ISSN: 2075-1729
    URL: Article
    DOI: 10.3390/life11060494
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662250-6
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  • 9
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    Online Resource
    Association between Dietary Protein Intake, Regular Exercise, and Low Back Pain among Middle-Aged and Older Korean Adults without Osteoarthritis of the Lumbar Spine
    MDPI AG ; 2022
    In:  Journal of Clinical Medicine Vol. 11, No. 5 ( 2022-02-24), p. 1220-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 5 ( 2022-02-24), p. 1220-
    Abstract: This study aimed to evaluate the effect of dietary protein intake and regular exercise on low back pain (LBP) using data from the Korea National Health and Nutrition Examination Survey. A total of 2367 middle-aged and older adults (≥50 years) who underwent dual-energy X-ray absorptiometry and plain radiography of the lumbar spine were included. LBP was defined using a questionnaire to determine the presence of LBP lasting more than 30 days in the preceding three months. Twenty-four-hour dietary recall data were used to estimate protein intake, and regular exercise was assessed using the International Physical Activity Questionnaire. Multivariable logistic regression analysis revealed that men who did not perform regular exercise had a high probability of LBP (odds ratio [OR] 2.34; 95% confidence interval [CI] 1.24–4.44). Low protein intake ( 〈 0.8 g/kg/day) was associated with high odds for LBP in women (OR 1.83; 95% CI 1.12–2.99). Low protein intake and lack of regular exercise were also associated with a higher probability of LBP in women (OR 2.91; 95% CI 1.48–5.72). We recommend that women over 50 years of age consume the recommended daily amount of protein to prevent LBP and engage in regular exercise.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm11051220
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
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  • 10
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    Interleukin-22 Induces the Infiltration of Visceral Fat Tissue by a Discrete Subset of Duffy Antigen Receptor for Chemokine-Positive M2-Like Macrophages in Response to a High Fat Diet
    MDPI AG ; 2019
    In:  Cells Vol. 8, No. 12 ( 2019-12-06), p. 1587-
    Details
    In: Cells, MDPI AG, Vol. 8, No. 12 ( 2019-12-06), p. 1587-
    Abstract: Interleukin-22 (IL-22) is a cytokine with important functions in host defense and inflammatory responses and has recently been suggested to play a role in immune-inflammatory system in the context of obesity and its metabolic consequences. The specific cellular targets and mechanisms of IL-22-mediated obesity are largely unknown however. We here identified a previously unknown subset of monocyte-derived Duffy antigen receptors for chemokines (DARC)+ macrophages in epididymal fat adipose tissue and found that they are preferentially recruited into the crown-like structures of adipose tissue in the mouse upon high fat diet-induced obesity. Importantly, DARC+ macrophages highly express the IL-22 receptor (IL-22Ra1). Exposure to recombinant IL-22 shifts macrophages to an alternative M2 polarization pathway and augments DARC expression via a STAT5b signaling axis. STAT5b directly binds to the DARC promoter and a STAT5 inhibitor abrogates the IL-22-mediated induction of DARC. These M2-like DARC+ subpopulations of monocytes/macrophages were elevated in obese db/db mice compared to WT lean mice. Furthermore, subsets of CD14+ and/or CD16+ monocytes/macrophages within human peripheral blood mononuclear cell populations express DARC and the prevalence of these subsets is enhanced by IL-22 stimuli. This suggested that IL-22 is a critical cytokine that promotes the infiltration of adipose tissue macrophages, that regulate inflammatory processes. Taken together, our present findings provide important insights into the molecular mechanism by which IL-22 signal modulates DARC expression in M2-like macrophages.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells8121587
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2661518-6
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