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1.
Viruses ; 12(7)2020 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-32605105

RESUMO

In this study, we investigated the role of microRNA-99a (miR-99a) in hepatitis C virus (HCV) replication and lipogenesis in hepatocytes. Cell-culture-derived HCV (HCVcc) infection caused down-regulation of miR-99a in Huh-7 cells, and the relative levels of miR-99a were significantly lower in the sera of the HCV-infected patients than in those of healthy controls. Transfection of miR-99a-5p mimics resulted in a decrease in the intracellular and secreted HCV RNA levels. It also caused a decreased mammalian target of rapamycin (mTOR) protein level and phosphorylation of its downstream targets in HCV-replicating cells. Sterol regulatory element binding protein (SREBP)-1c expression and intracellular lipid accumulation decreased when either miR-99a-5p mimics or si-mTOR was transfected in oleic acid-treated Huh-7 cells. Overexpression of mTOR rescued HCV RNA replication and lipid droplet accumulation in miR-99a-5p mimics-transfected HCV replicon cells. Our data demonstrated that miR-99a ameliorates intracellular lipid accumulation by regulating mTOR/SREBP-1c and causes inefficient replication and packaging of intracellular HCV.

2.
Endocrinol Metab (Seoul) ; 35(2): 272-287, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32615711

RESUMO

Growth hormone (GH) deficiency is caused by congenital or acquired causes and occurs in childhood or adulthood. GH replacement therapy brings benefits to body composition, exercise capacity, skeletal health, cardiovascular outcomes, and quality of life. Before initiating GH replacement, GH deficiency should be confirmed through proper stimulation tests, and in cases with proven genetic causes or structural lesions, repeated GH stimulation testing is not necessary. The dosing regimen of GH replacement therapy should be individualized, with the goal of minimizing side effects and maximizing clinical improvements. The Korean Endocrine Society and the Korean Society of Pediatric Endocrinology have developed a position statement on the diagnosis and treatment of GH deficiency. This position statement is based on a systematic review of evidence and expert opinions.

3.
Intern Med J ; 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32618101

RESUMO

OBJECTIVE: Cardiac dysfunction is a common sequela in patients with sepsis and multi-organ dysfunction. Echocardiography is commonly used in the investigation of circulatory failure. We aimed to evaluate the prognostic value of echocardiographic parameters in patients with septic shock. METHODS: This study was a retrospective trial. We included patients who were admitted to ICU with septic shock. The patients' echocardiograms, clinical data, and outcomes were obtained from their medical records. Associations between echo-cardiogram variables and mortality were assessed using logistic regression, controlled for age, sex, BMI, and the interval between the ICU admission and echocardiogram. The utility of statistically significant echocardiogram variables to predict mortality were assessed using receiver operating characteristic (ROC) curves. RESULTS: The outcomes presented that Tricuspid Annular Plane Systolic Excursion(TAPSE) was statistically significantly associated with both ICU (p = 0.02) and 90-day (p = 0.001) mortality. From the ROC curves, TAPSE emerged a significant and moderate predictor for 90-day (area under curve (AUC) = 0.69, 95% CI = 0.565-0.814) and in-ICU mortality (AUC = 0.762, 95% CI = 0.652-0.871). The optimal cut-off for TAPSE was 2.1 cm for both 90-day mortality (sensitivity of 80% and specificity and 58%) and in-ICU mortality (sensitivity of 69% and specificity of 77%). CONCLUSION: TAPSE was associated with increased mortality in those with sepsis and suspicion of cardiac dysfunction. This is a hypothesis generating paper that an association may be present and requires significant more work with expansion to the entire population base. This article is protected by copyright. All rights reserved.

4.
Viruses ; 12(6)2020 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-32599836

RESUMO

Atypical porcine pestivirus (APPV), currently classified as pestivirus K, causes congenital tremor (CT) type A-II in piglets. Eighteen APPV strains were identified from 2297 South Korean wild boars captured in 2019. Phylogenetic analysis of the structural protein E2 and nonstructural proteins NS3 and Npro classified the APPV viruses, including reference strains, into Clades I, II and III. Clade I was divided into four subclades; however, the strains belonging to the four subclades differed slightly, depending on the tree analysis, the NS3, E2, and Npro genes. The maximum-likelihood method was assigned to South Korean wild boar APPV strains to various subclades within the three trees: subclades I.1 and I.2 in the E2 tree, subclade I.1 in the Npro tree, and subclades I.1 and I.4 in the NS3 ML tree. In conclusion, APPV among South Korean wild boars belonging to Clade I may be circulating at a higher level than among the South Korean domestic pig populations.

5.
Am J Kidney Dis ; 2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32628990

RESUMO

RATIONALE & OBJECTIVE: Maintenance hemodialysis (MHD) patients are a population highly vulnerable to infection with SARS-CoV-2. The current study was designed to evaluate the prevalence of SARS-CoV-2 infection based on both nucleic acid testing (NAT) and antibody testing in Chinese MHD patients. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: From Dec 1, 2019 to Mar 31, 2020, 1027 MHD patients in five large hemodialysis centers in Wuhan, China were enrolled. Patients were screened by blood tests, chest computed tomography, NAT and antibody tests for SARS-CoV-2. EXPOSURE: NAT and antibody tests for SARS-CoV-2. OUTCOMES: Morbidity, clinical features, laboratory and radiologic findings. ANALYTICAL: Approach Differences between groups were examined by Student's t-test or Mann-Whitney U test, comparing those not infected to those infected and comparing those with infection detected by NAT to with positive serology tests and negative NAT. RESULTS: Of the 1027 MHD patients, 99 cases have been identified as SARS-CoV-2 infection, equivalent to a prevalence of 9.6%. In the 99 cases, 52 (53%) patients were diagnosed with SARS-CoV-2 infection by positive NAT; 47 (48%) patients were identified by positive IgG or IgM antibodies against SARS-CoV-2 with negative NAT. The spectrum of antibody profiles in these 47 patients showed IgM antibodies in 5 (11%), IgG antibodies in 35 (75%), and both positive IgM and IgG antibodies in 7 (15%). 51% of the infected patients were asymptomatic during the epidemic. Patients with hypertensive kidney disease were more often identified with infection by SARS-CoV-2 infection and they tended to be more symptomatic than other patient groups. LIMITATIONS: Possibility of false positives and false negatives for both NAT and antibody testing; possible lack of generalizability to other dialysis populations. CONCLUSIONS: Half of the SARS-CoV-2 infections in MHD patients were subclinical and unidentified by universal chest CT and selective NAT. Serologic testing may help to evaluate the overall prevalence and understand the diversity of clinical course among MHD patients infected with SARS-CoV-2.

6.
Aging (Albany NY) ; 122020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32632040

RESUMO

Recent studies have confirmed that both cancer-associated bone marrow mesenchymal stem cells (BM-MSCs, MSCs) and glioma stem-like cells (GSCs) contribute to malignant progression of gliomas through their mutual interactions within the tumor microenvironment. However, the exact ways and relevant mechanisms involved in the actions of GSCs and MSCs within the glioma microenvironment are not fully understood. Using a dual-color fluorescence tracing model, our studies revealed that GSCs are able to spontaneously fuse with MSCs, yielding GSC/MSC fusion cells, which exhibited markedly enhanced proliferation and invasiveness. MiR-146b-5p was downregulated in the GSC/MSC fusion cells, and its overexpression suppressed proliferation, migration and invasion by the fusion cells. SMARCA5, which is highly expressed in high-grade gliomas, was a direct downstream target of miR-146b-5p in the GSC/MSC fusion cells. miR-146b-5p inhibited SMARCA5 expression and inactivated a TGF-ß pathway, thereby decreasing GSC/MSC fusion cell proliferation, migration and invasion. Collectively, these findings demonstrate that miR-146b-5p suppresses the malignant phenotype of GSC/MSC fusion cells in the glioma microenvironment by targeting a SMARCA5-regulated TGF-ß pathway.

7.
Exp Cell Res ; : 112137, 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32534061

RESUMO

PI3K/AKT is one of the key pathways that regulate cell behaviors including apoptosis, proliferation, and differentiation. Although previous studies have demonstrated that this pathway is a crucial regulator of osteoblasts, the role of PI3K/AKT in fracture healing remains unclear. It is well known that the Wnt/ß-catenin pathway plays an essential role in bone regeneration. However, whether there exists crosstalk between Wnt/ß-catenin and PI3K/AKT in regulating osteoblasts and bone repair has not been reported. To address these issues, we establish a stabilized fracture model in mice and show that PI3K inhibitor LY294002 substantially inhibits the bone healing process, suggesting that PI3K/AKT promotes fracture repair. More importantly, we report that PI3K/AKT increases phosphorylation of GSK-3ß at Ser9 and phosphorylation of ß-catenin at Ser552 in fracture callus and murine osteoblastic MC3T3-E1 cells, both of which lead to ß-catenin stabilization, nuclear translocation, as well as ß-catenin-mediated TCF-dependent transcription, suggesting that ß-catenin is activated downstream of PI3K/AKT. Furthermore, we show that ICG001, the inhibitor of ß-catenin transcriptional activity, attenuates PI3K/AKT-induced osteoblast proliferation, differentiation, and mineralization, indicating that the PI3K/AKT/ß-catenin axis is functional in regulating osteoblasts. Notably, the PI3K/AKT pathway is also activated by Wnt3a and is involved in Wnt3a-induced osteoblast proliferation and differentiation. Hence, our results reveal the existence of a Wnt/PI3K/AKT/ß-catenin signaling nexus in osteoblasts, highlighting complex crosstalk between PI3K/AKT and Wnt/ß-catenin pathways that are critically implicated in fracture healing.

8.
J Pathol ; : e5474, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32476131

RESUMO

Advances in tissue clearing and microscopy make it possible to study human diseases in three dimensions (3D). High-grade tumor budding is known to be associated with poor prognosis in various cancers; however, little is known about the 3D architecture of TB. Using tissue clearing, we analyzed the 3D structure of tumor budding and E-cadherin expression in 31 extrahepatic cholangiocarcinomas. A total of 31 thick slabs (up to 5 mm) were harvested from surgically resected tumor tissue, including 27 hilar and 4 distal cholangiocarcinomas. Twenty-eight cases were adenocarcinoma, and three were undifferentiated carcinoma. After clearing, the tissues were immunolabeled with antibodies to cytokeratin 19 and to E-cadherin, and then visualized using light-sheet and confocal laser scanning microscopy. Tumor budding was evaluated in hematoxylin and eosin-stained sections (2D) using standard pathological criteria. Of the 31 cancers, 13 showed low-grade tumor budding and 18 showed high-grade tumor budding. First, 3D analysis revealed that the neoplastic cells in tumor buds of adenocarcinoma were typically not individual islands of cells, but rather tips of attenuated protrusions connected to the main tumor. Second, adenocarcinomas with low-grade tumor budding were composed predominantly of tubules that only focally form cords at the periphery. By contrast, adenocarcinomas with high-grade tumor budding predominantly formed cords in both centers and peripheries of the tumors. Third, adenocarcinoma with low-grade tumor budding was characterized by a few short protrusions with few branches, whereas adenocarcinoma with high-grade tumor budding was characterized by longer protrusions with more branching. Finally, immunolabeling of E-cadherin was stronger in the center of the adenocarcinoma but decreased at the tips of protrusions. E-cadherin loss was more extensive in the protrusions of high-grade tumor budding than in the protrusions of low-grade tumor budding. Our findings suggest that tumor buds as seen in 2D are, in fact, cross-sections of attenuated but contiguous protrusions extending from the main tumor. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

9.
Lab Chip ; 20(13): 2394-2402, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32510532

RESUMO

Understanding the complex fluid flow in the alveoli is of great significance for studying the transport and deposition of fine particles in the deep lung. In this study, we developed an experimental platform to study detailed acinar flow through precisely controlling the flow parameters in a single microfluidic alveolar chip with rhythmic wall expansion. Numerical modelling was also carried out to study the flow parametrically. Detailed alveolar flow patterns at different generations were measured and compared with numerical simulation results. In spite of the low Re number, the alveolar flow is very complex and different flow patterns coexist in the alveolar tree. Stagnation saddle points in the alveolar flows were experimentally observed for the first time, suggesting the existence of complex chaotic flows in the alveoli which confirms the numerical predictions. This study provides valuable data for understanding the alveolar flow and the transport of micro- and nanoparticles in alveolar cells.

10.
Theranostics ; 10(13): 5943-5956, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32483429

RESUMO

ACT001, which is derived from an ancient anti-inflammatory drug, has been shown to cross the blood-brain barrier in preclinical studies and has demonstrated anti-glioblastoma (GBM) activity in clinical trials. However, its pharmacological potential for anti-GBM immune response modulation remains unclear. The chemical structure of ACT001 indicates that it may bind to STAT3 and thus modulate antitumor immune response. Methods: Bioinformatics and immunohistochemistry (IHC) were used to assess STAT3 and PD-L1 expression in gliomas. Western blotting, RT-PCR and immunofluorescence were used to detect PD-L1 and p-STAT3 expression in glioma cells exposed to ACT001. Chromatin immunoprecipitation, an ACT001-Biotin probe, and a dual-luciferase reporter assay were used to detect direct modulation. The in vivo efficacy of ACT001 was evaluated in GL261 murine glioma model. Survival analyses were conducted using the log-rank (Mantel-Cox) test. Results: Bioinformatic analysis of 1,837 samples from 4 public glioma datasets showed that STAT3 mRNA expression was correlated with the degree of malignancy and therapeutic resistance and that STAT3 mRNA expression was related to immunosuppression, leukocyte infiltration, and PD-L1 expression. IHC staining of 53 tissue samples confirmed that relatively high phosphorylated STAT3 and PD-L1 protein expression was associated with a relatively advanced World Health Organization (WHO) glioma grade. Next, we confirmed that ACT001 treatment reduced PD-L1 expression and STAT3 phosphorylation. An ACT001-biotin probe was used to verify that ACT001 bound to STAT3. We also demonstrated that STAT3 bound to the PD-L1 promoter. The inhibition of PD-L1 expression and STAT3 phosphorylation by ACT001 could be rescued by STAT3 overexpression. Additionally, ACT001 inhibited GBM growth and decreased PD-L1 expression in vivo. The expression of the M2 markers CD206 and CD163 was decreased, while that of the antitumor immune markers iNOS and IFNγ was increased by ACT001 in vivo. Conclusion: Our results demonstrate that STAT3 plays a key role in immunosuppression of glioma and is inhibited by ACT001. ACT001 inhibits PD-L1 transcription and modulates anti-tumor immune response in glioma bearing mice. These findings will help us to understand the mechanism of ACT001 in GBM therapy.

11.
J Enzyme Inhib Med Chem ; 35(1): 1403-1413, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32588683

RESUMO

Tubulin polymerisation inhibitors that target colchicine binding site were powerful anticancer agents. Although along the years many colchicine binding site inhibitors (CBSIs) have been reported, few piperidine derivatives were identified as CBSIs. In this regard, we focussed efforts on the piperidine as a promising chemotype to develop potent CBSIs. Herein, novel piperidine derivatives were synthesised and evaluated for their antiproliferative activities. Among them, compound 17a displayed powerful anticancer activity with the IC50 value of 0.81 µM against PC3 cells, which was significantly better than 5-fluorouracil. It could inhibit tubulin polymerisation binding at the colchicine site and inhibit the tumour growth in vitro and in vivo. Further biological studies depicted that 17a suppressed the colony formation, induced apoptosis, and inhibited epithelial-mesenchymal transition against PC3 cells. These results revealed that compound 17a is a promising colchicine binding site inhibitor for the treatment of cancer and it is worthy of further exploitation.

12.
Cancer Sci ; 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32589305

RESUMO

Transgenic green fluorescent protein (GFP) gene mice are widely used. And for the unique advantages of immunodeficient animals in the field of oncology research, we aim to establish a nude mouse inbred strain, which stably expresses EGFP (enhanced-GFP) for the use of transplanted tumor microenvironment (TME) research. Female C57BL/6-Tg(CAG-EGFP) mice were backcrossed with male BALB/c nude mice for eleven generations. The genotype and phenotype of novel inbred strain Foxn1nu .B6-Tg(CAG-EGFP) were identified by biochemical loci detection, skin transplantation and flow cytometry. PCR and fluorescence spectrophotometry were performed to evaluate the relative expression of EGFP in different parts of the brain. Red fluorescence protein (RFP) gene was stably transfected into human glioma stem cells (GSCs) SU3, and then were transplanted intracerebrally or ectopic into Foxn1nu .B6-Tg(CAG-EGFP) mice. Cells co-expression of EGFP and RFP in transplanted tissues were further analyzed with Live Cell Imaging System and FISH. The inbred strain Foxn1nu .B6-Tg(CAG-EGFP) shows different levels of EGFP expression in brain tissue. The hematological and immune cells of the inbred strain mice were close to nude mice. EGFP was stably expressed in multiple sites of Foxn1nu .B6-Tg(CAG-EGFP) mice including brain tissue. With the dual-fluorescence tracing transplanted tumor model, we found that SU3 induced host cells malignant transformation in TME, and tumor/host cells fusion. In conclusion, EGFP is differentially and widely expressed in brain tissue of Foxn1nu .B6-Tg(CAG-EGFP), which is an ideal model for TME investigation. With Foxn1nu .B6-Tg(CAG-EGFP) mice, our research demonstrated that host cells malignant transformation and tumor/host cells fusion play an important role in tumor progression.

13.
Orthop Surg ; 12(3): 931-937, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32495510

RESUMO

OBJECTIVES: Occipitocervical fusion (OCF) is an effective treatment for instability of occipitocervical junction (OCJ). The occipital condyle screw serves as a novel surgical technique for occipitocervical fixation. However, the intraoperative procedures for the occipital condyle screw technique have relied on surgeons' experience, so the pool of surgeons who are able to perform this surgery safely is limited. The present study aims to evaluate the feasibility and safety of the occipital condyle screw technique using human cadavers and to provide image anatomy for clinical application basis. METHODS: The scientific study comprised 10 fresh-frozen cadaveric specimens from the anatomy department of Qingdao University. Placement of the occipital condyle screws (3.5 mm diameter and 20.0 mm length) was performed in the 10 fresh-frozen cadaveric specimens with intact occipitocervical junctions, respectively. Occipitocervical CT was performed for all specimens and the DICOM data was obtained. Occipitocervical CT three-dimensional (3D) reconstruction was performed for the cadavers. Morphometric analysis was performed on the bilateral occipitocervical junction of 10 cadaveric specimens based on the 3D reconstruction CT images. Detailed morphometric measurements of the 20 occipital condyles screws were conducted including the average length of the screw trajectory, inside and upper tilting angles of screws, distance to the hypoglossal canal, and to the medial wall of occipital condyle. RESULTS: Placement of the occipital condyle screws into the 20 occipital condyles of the 10 cadaveric specimens was performed successfully and the trajectory of implantation was satisfactory according to 3D CT reconstruction images, respectively. There was no obvious injury to the spinal cord, nerve root, and vertebral artery. The length of the bilateral screw trajectory was, respectively, 20.96 ± 0.91 mm (left) and 20.59 ± 0.77 mm (right) (t = 1.306, P > 0.05). The upper tilting angle of bilateral screws was, respectively, 11.24° ± 0.74° (left) and 11.11° ± 0.64° (right) (t = 0.681, P > 0.05). The inside tilting angle of bilateral screws was, respectively, 31.00° ± 1.32° (left) and 30.85° ± 1.27° (right) (t = 0.307, P > 0.05). The screw's distance to the bilateral hypoglossal canal was, respectively, 4.84 ± 0.54 mm (left) and 4.70 ± 0.54 mm (right) (t = 0.685, P > 0.05). The screw's distance to the medial wall of the bilateral occipital condyle was, respectively, 5.13 ± 0.77 mm (left) and 5.04 ± 0.71 mm (right) (t = 0.384, P > 0.05). CONCLUSION: The occipital condyle screw technique can serve as a feasible and safe treatment for instability of the occipitocervical junction with meticulous preoperative planning of the screw entry point and direction based on individual differences. Morphometric trajectory analysis is also an effective way to evaluate the surgical procedure.

14.
J Orthop Surg Res ; 15(1): 229, 2020 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-32571371

RESUMO

OBJECTIVE: Chondrosarcoma is the second most common primary bone sarcoma; however, unlike other tumors, the biopsy cannot easily make a definite diagnosis or predict the histological grade. This meta-analysis was performed to evaluate the utility of 18F-FDG PET and PET/CT to differentiate chondrosarcoma from benign cartilaginous lesions and to predict the histopathological grade of chondrosarcoma. MATERIAL AND METHODS: A comprehensive search was performed in three electronic databases including Medline/PubMed, the Cochrane Library and Embase to retrieve diagnostic studies evaluating the role of 18F-FDG PET or PET/CT for appraising the status of chondrosarcoma. Reference lists of related articles were also scrutinized manually. Useful data were extracted to calculate the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), the summary receiver operating characteristic curve (sROC), and the area under the curve (AUC) of 18F-FDG PET or PET/CT in diagnosing chondrosarcoma, and pooled weighted mean differences (WMD) of maximum standardized uptake value (SUVmax) between different entities of cartilaginous neoplasms by using Stata 19.0. RESULTS: A total of twelve studies provided sufficient data for the quantitative analysis. For the diagnosis of chondrosarcoma, the pooled sensitivity, specificity, and DOR of 18F-FDG PET were 0.84 (95% confidence interval [CI] 0.46 to 0.97), 0.82 (95% CI 0.55 to 0.94), and 24.244 (95% CI 1.985 to 96.148), respectively while those of 18F-FDG PET/CT were 0.94 (95% CI 0.86 to 0.97), 0.89 (95% CI 0.82 to 0.93), and 112.999 (95% CI 41.341 to 308.866), respectively. The pooled WMD of SUVmax were - 0.89 (95% CI -1.67 to -0.10) between benign cartilaginous lesions and grade 1 (G1) chondrosarcoma, -1.94 (95% CI -2.76 to -1.12) between G1 and grade 2 (G2) chondrosarcoma, and - 2.37 (95% CI -5.79 to 1.05) between G2 and grade 3 (G3) chondrosarcoma. CONCLUSIONS: In a word, 18F-FDG PET/CT revealed excellent accuracy in the diagnosis of chondrosarcoma and might assist in clinical decision-making. Meanwhile, although SUVmax alone showed restricted ability to differentiate benign cartilaginous lesions and G1 chondrosarcoma, as well as between G2 and G3 chondrosarcoma, it can identify intermediate/high-grade chondrosarcoma from low-grade ones. LEVEL OF EVIDENCE: Level I evidence, a summary of meta-analysis.

15.
Korean J Intern Med ; 2020 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-32506867

RESUMO

Background/Aims: Thyroid hormones are involved in wide range of glucose metabolism functions. Overt thyroid dysfunctions are related to altered glucose homeostasis. However, it is not conclusive as to whether subtle changes in thyroid hormones within normal ranges can induce alterations in glucose homeostasis. The aim of this study was to evaluate the association between thyroid hormone and glucose homeostasis parameters in subjects without overt thyroid dysfunction based on nationwide population data. Methods: In the Sixth Korea National Health and Nutrition Examination Survey 2015 (n = 7,380), data were collected from subjects with insulin and thyroid function measurements who were older than 19-years-old. After the exclusion of 5,837 subjects, a total of 1,543 patients were included in the analysis. Subjects were categorized into the quartiles of the free thyroxine (FT4). Fasting glucose, insulin, homeostatic model assessment of insulin resistance and hemoglobin A1c (HbA1c) levels were considered to be glucose homeostasis parameters. Results: Subjects with the highest FT4 quartile showed significantly lower fasting insulin and HbA1c levels. A significant inverse correlation FT4 and HbA1c levels was observed (ß = -0.261, p = 0.025). In the logistic regression analysis, the highest quartile of FT4 was demonstrated to lower the risk of HbA1c to a greater degree than the median by approximately 40%, after adjusting for confounders, compared to the lowest quartile (p = 0.028). Conclusions: We demonstrated subjects with a lower FT4 quartile exhibited high risk of HbA1c levels above the median value in a representative Korean population. Subjects with the lowest FT4 quartile should be cautiously managed in terms of altered glucose homeostasis.

17.
Eur J Med Chem ; 201: 112510, 2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-32592915

RESUMO

ß-Lactam, commonly referred as azetidin-2-one, is a multifunctional building block for synthesizing ß-amino ketones, γ-amino alcohols, and other compounds. Besides its well known antibiotic activity, this ring system exhibits a wide range of activities, attracting the attention of researchers. However, the structurally diverse ß-lactam analogues as anticancer agents and their different molecular targets are poorly discussed. The purpose of this review is 3-fold: (1) to explore the molecular hybridization approach to design ß-lactams hybrids as anticancer agents; (2) the structure activity relationship of the most active anticancer ß-lactams and (3) to summarize their antitumor mechanisms.

18.
Environ Pollut ; 265(Pt A): 114564, 2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32505937

RESUMO

In remediation of dense non-aqueous phase liquids (DNAPLs), colloidal biliquid aphrons (CBLAs) could be added to produce a lower density nonaqueous phase which mitigate downward migration of DNAPL to non-polluted aquifers. There is still a big gap in the application of CBLAs in the remediation of actual polluted sites, especially the absence of relevant studies on its transport behavior in the sites, and its structural model has not been fully verified. These two factors could affect the effectiveness of CBLAs in the underground environment and its effect on density control. In this study, we prepared CBLAs with different surfactants and verified the structural model of CBLA based on their particle size distributions and demulsification performance. We studied the effects of particle concentrations, injection velocities, and porous media size on the migration of CBLA using the breakthrough curves and distribution profiles along the column. Experimental results indicated that surface elasticity of CBLAs was inversely proportional to the concentration of the anionic surfactant sodium dodecyl sulphate (SDS), which led to easier demulsification of CBLA with the increase in SDS concentration. This observation was in agreement with the verified structural model of the CBLA which constitute both internal nonionic and external anionic surfactants. Furthermore, CBLA deposition is mainly caused by interception and is not suitable for application in fine media. Low concentration of CBLA and high injection flow rate help CBLA to form a remediation area with a certain radius. This study solved the problem of DNAPLs in contaminated groundwater from the perspective of density regulation, and made contributions towards the development of combined remediation approaches using CBLAs.

19.
Psychiatry Res ; 290: 113165, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32559564

RESUMO

The aim of this study was to develop a screening questionnaire to distinguish high-risk individuals associated with game overuse from casual internet users. Reliability, validity, and diagnostic ability were evaluated for the newly developed Game Overuse Screening Questionnaire (GOS-Q). Preliminary items were assessed by 50 addiction experts online and 30 questions were selected. A total of 158 subjects recruited from six community centers for internet addiction participated in this study. Finally, 150 people were used in the analysis after excluding eight non-respondents. GOS-Q, Young's internet addiction scale, and Korean scale for internet addiction were used to assess concurrent validity. Internal consistency and item-total correlations were favorable (α= 0.96, r= 0.47-0.82). Test-retest reliability was moderate in size (r= 0.74). GOS-Q showed superior concurrent validity, and the highest correlation with Y-Scale (r= 0.77). The construct validity was marginally supported by a six-factor model using exploratory factor analysis. The area under the Receiver Operating Characteristic curve was 0.945. The high-risk addiction group was effectively characterized by a cut-off point of 38.5, with a sensitivity of 0.87 and a specificity of 0.88. Overall, the current study supports the use of GOS-Q as a reliable screening tool in a variety of settings.

20.
Artigo em Inglês | MEDLINE | ID: mdl-32560522

RESUMO

Women experience more stress in middle age than in other life stages, and health in middle age is vital, because it influences the quality of life in old age. In this study, the effects of a forest therapy program on physiological changes in 53 middle-aged women (divided into two groups) who lived in the city were examined. One group participated in a three-day program in the forest, followed by three days in the city; the other group participated in a three-day program in the city, followed by three days in the forest. Forest experiments were conducted in a "healing forest," and urban experiments were conducted near a university campus. Blood tests were performed to evaluate the physiological effects of forest therapy. Differences in serotonin levels and vitamin D levels were verified before and after the forest (experimental group) and urban (control group) programs through paired t-tests. Statistically significant increases in serotonin levels were noted for participants in the forest program; vitamin D levels also increased, but not by statistically significant values. The findings of this study verify that forest therapy programs promote health among middle-aged women, and may prevent disease and improve quality of life.

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