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1.
Korean J Physiol Pharmacol ; 28(3): 209-217, 2024 05 01.
Article in English | MEDLINE | ID: mdl-38682169

ABSTRACT

In addition to cellular damage, ischemia-reperfusion (IR) injury induces substantial damage to the mitochondria and endoplasmic reticulum. In this study, we sought to determine whether impaired mitochondrial function owing to IR could be restored by transplanting mitochondria into the heart under ex vivo IR states. Additionally, we aimed to provide preliminary results to inform therapeutic options for ischemic heart disease (IHD). Healthy mitochondria isolated from autologous gluteus maximus muscle were transplanted into the hearts of Sprague-Dawley rats damaged by IR using the Langendorff system, and the heart rate and oxygen consumption capacity of the mitochondria were measured to confirm whether heart function was restored. In addition, relative expression levels were measured to identify the genes related to IR injury. Mitochondrial oxygen consumption capacity was found to be lower in the IR group than in the group that underwent mitochondrial transplantation after IR injury (p < 0.05), and the control group showed a tendency toward increased oxygen consumption capacity compared with the IR group. Among the genes related to fatty acid metabolism, Cpt1b (p < 0.05) and Fads1 (p < 0.01) showed significant expression in the following order: IR group, IR + transplantation group, and control group. These results suggest that mitochondrial transplantation protects the heart from IR damage and may be feasible as a therapeutic option for IHD.

2.
Front Public Health ; 12: 1326457, 2024.
Article in English | MEDLINE | ID: mdl-38481836

ABSTRACT

Objectives: Injury prevention can be achieved through various interventions, but it faces challenges due to its comprehensive nature and susceptibility to external environmental factors, making it difficult to detect risk signals. Moreover, the reliance on standardized systems leads to the construction and statistical analysis of numerous injury surveillance data, resulting in significant temporal delays before being utilized in policy formulation. This study was conducted to quickly identify substantive injury risk problems by employing text mining analysis on national emergency response data, which have been underutilized so far. Methods: With emerging issue and topic analyses, commonly used in science and technology, we detected problematic situations and signs by deriving injury keywords and analyzing time-series changes. Results: In total, 65 injury keywords were identified, categorized into hazardous, noteworthy, and diffusion accidents. Semantic network analysis on hazardous accident terms refined the injury risk issues. Conclusion: An increased risk of winter epidemic fractures due to extreme weather, self-harm due to depression (especially drug overdose and self-mutilation), and falls was observed in older adults. Thus, establishing effective injury prevention strategies through inter-ministerial and interagency cooperation is necessary.


Subject(s)
Data Mining , Seasons , Time Factors
3.
Article in English | MEDLINE | ID: mdl-38083125

ABSTRACT

Vertebral Compression Fracture (VCF) is one of the common fractures, especially for elderlies. As it affects postural deformation that may cause secondary disorders in the respiratory or digestive system if not treated in time, diagnosis of VCF is crucial. Using deep learning model based detection technology in diagnosis can reduce the workload of healthcare workers and misdiagnosis. Hence in this work, we propose ALiGN, a compression fracture detection model in the lumbar vertebra based on a deep convolutional neural network (CNN). Specifically, we take the location of each vertebral body into account via a feature pyramid network with an attention mechanism. Our proposed model outperforms the earlier works with a sensitivity 0.9729, specificity 0.9914, and mAP 0.7882.


Subject(s)
Fractures, Compression , Spinal Fractures , Humans , Spinal Fractures/diagnostic imaging , Spinal Fractures/complications , Fractures, Compression/diagnostic imaging , Fractures, Compression/complications , Lumbar Vertebrae/diagnostic imaging
4.
Org Lett ; 25(49): 8932-8936, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-38049370

ABSTRACT

A copper-catalyzed chemo- and stereoselective method for the synthesis of (E)-2-silyl-1,3-butadienes from a broad range of allenols using mild Si-B reagents is reported in this study. Our protocol required a short reaction time at ambient temperature to produce the desired dienes in high yields. Synthetic applications are highlighted by the one-pot synthesis of tetrasubstituted arylsilanes from allenols as well as the further functionalization of C-Si bonds.

5.
Int J Mol Sci ; 24(21)2023 Nov 06.
Article in English | MEDLINE | ID: mdl-37959001

ABSTRACT

Cannabidiol (CBD), a major non-psychoactive component of the cannabis plant, has shown therapeutic potential in Alzheimer's disease (AD). In this study, we identified potential CBD targets associated with AD using a drug-target binding affinity prediction model and generated CBD analogs using a genetic algorithm combined with a molecular docking system. As a result, we identified six targets associated with AD: Endothelial NOS (ENOS), Myeloperoxidase (MPO), Apolipoprotein E (APOE), Amyloid-beta precursor protein (APP), Disintegrin and metalloproteinase domain-containing protein 10 (ADAM10), and Presenilin-1 (PSEN1). Furthermore, we generated CBD analogs for each target that optimize for all desired drug-likeness properties and physicochemical property filters, resulting in improved pIC50 values and docking scores compared to CBD. Molecular dynamics (MD) simulations were applied to analyze each target's CBD and highest-scoring CBD analogs. The MD simulations revealed that the complexes of ENOS, MPO, and ADAM10 with CBD exhibited high conformational stability, and the APP and PSEN1 complexes with CBD analogs demonstrated even higher conformational stability and lower interaction energy compared to APP and PSEN1 complexes with CBD. These findings demonstrated the capable binding of the six identified targets with CBD and the enhanced binding stability achieved with the developed CBD analogs for each target.


Subject(s)
Alzheimer Disease , Cannabidiol , Humans , Alzheimer Disease/metabolism , Cannabidiol/pharmacology , Cannabidiol/therapeutic use , Molecular Docking Simulation , Amyloid beta-Protein Precursor/metabolism , Molecular Dynamics Simulation
6.
Int J Bioprint ; 9(5): 765, 2023.
Article in English | MEDLINE | ID: mdl-37555082

ABSTRACT

Hydrogels have the potential to play a crucial role in bioelectronics, as they share many properties with human tissues. However, to effectively bridge the gap between electronics and biological systems, hydrogels must possess multiple functionalities, including toughness, stretchability, self-healing ability, three-dimensional (3D) printability, and electrical conductivity. Fabricating such tough and self-healing materials has been reported, but it still remains a challenge to fulfill all of those features, and in particular, 3D printing of hydrogel is in the early stage of the research. In this paper, we present a 3D printable, tough, and self-healing multi-functional hydrogel in one platform made from a blend of poly(vinyl alcohol) (PVA), tannic acid (TA), and poly(acrylic acid) (PAA) hydrogel ink (PVA/TA/PAA hydrogel ink). Based on a reversible hydrogen-bond (H-bond)-based double network, the developed 3D printable hydrogel ink showed excellent printability via shear-thinning behavior, allowing high printing resolution (~100 µm) and successful fabrication of 3D-printed structure by layer-by-layer printing. Moreover, the PVA/TA/PAA hydrogel ink exhibited high toughness (tensile loading of up to ~45.6 kPa), stretchability (elongation of approximately 650%), tissue-like Young's modulus (~15 kPa), and self-healing ability within 5 min. Furthermore, carbon nanotube (CNT) fillers were successfully added to enhance the electrical conductivity of the hydrogel. We confirmed the practicality of the hydrogel inks for bioelectronics by demonstrating biocompatibility, tissue adhesiveness, and strain sensing ability through PVA/TA/PAA/CNT hydrogel ink.

7.
Food Res Int ; 164: 112133, 2023 02.
Article in English | MEDLINE | ID: mdl-36737888

ABSTRACT

Parkinson's disease (PD) is a neurodegenerative disorder that is characterized by dopaminergic neuronal damage. In this study, three tea extracts from Hadong, Korea, were evaluated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity damage model (C57BL/6 mice) for their therapeutic effects against PD: green tea (GT), semi-fermented tea (SFT), and fermented tea (FT). Theaflavin content in the teas increased but catechin content decreased with the degree of fermentation. In addition, SFT showed the highest theanine and γ-aminobutyric acid contents. SFT at a concentration of 25 µg/mL showed the highest activity in the 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay among all samples. Furthermore, the 2,2'-azino-bis 3-ethylbenzothiazoline-6-sulfonic acid radical scavenging activity of 25 µg/mL SFT was higher than that of l-ascorbic acid. Fermented tea suppressed the expression of inflammatory cytokines, such as interleukin-6, tumor necrosis factor-alpha, inducible nitric oxide synthase, cyclooxygenase-2, and macrophage-1, as well as inhibited overexpression of apoptotic signals, including p-53, cleaved caspase-3, and poly (ADP-ribose) polymerase-1. Moreover, GT, SFT, and FT regulated the MPTP-induced oxidative stress-related factors, including superoxide dismutase, glutathione-S-transferase, and nicotinamide adenine dinucleotide phosphate oxidase 4. Fermented tea also alleviated MPTP-induced behavioral impairment and dopaminergic neuronal damage and reduced α-synuclein levels. These results indicate that fermented tea is effective for the treatment of neuro-inflammatory, neuro-apoptotic, and neuro-oxidative disorders.


Subject(s)
Neuroprotective Agents , Parkinson Disease , Animals , Mice , Parkinson Disease/drug therapy , Parkinson Disease/metabolism , Antioxidants/pharmacology , Antioxidants/therapeutic use , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/therapeutic use , Mice, Inbred C57BL , Inflammation/drug therapy , Tea
8.
Int J Biol Macromol ; 226: 90-101, 2023 Jan 31.
Article in English | MEDLINE | ID: mdl-36502788

ABSTRACT

We evaluated the neuroprotective effect of L-theanine in Parkinson's disease and the underlying mechanism focusing on WNT/ß-catenin signaling mediated by the MAPK pathway. We treated MPTP-induced SH-SY5Y cells with various concentrations of L-theanine (50, 100, 200, and 500 µg/mL), and we also treated Parkinson's model mice with L-theanine. L-theanine treatment effectively reduced the immunohistochemical hallmarks of Parkinson's disease, particularly Lewy bodies and α-synuclein, and increased the number of tyrosine hydroxylase-positive cells. L-theanine also improved the motor dysfunction in MPTP-induced Parkinson's disease model mice as measured by the rotarod test. The levels of several pro-inflammatory mediators that are overexpressed in Parkinson's disease, namely TNF-α, IL-6, COX-2, and MAC-1, were reduced following L-theanine treatment, and the levels of the pro-apoptotic proteins Bcl-2, caspase-3, p53, and PARP-1 were significantly reduced. L-theanine regulated the oxidative stress-related factors SOD-1, GST, and NOX-4 by targeting several proteins related to WNT/ß-catenin signaling, i.e., ß-catenin, WNT-3a, WNT-5a, TCF1/TCF7, and LEF1, via the MAPK pathway (p-JNK, p-ERK, and p-p38). Our results indicate that L-theanine is neuroprotective and has anti-inflammatory effects that could be beneficial for treating Parkinson's disease.


Subject(s)
Neuroblastoma , Neuroprotective Agents , Parkinson Disease , Mice , Humans , Animals , Parkinson Disease/drug therapy , Parkinson Disease/metabolism , beta Catenin/metabolism , Wnt Signaling Pathway , Neuroprotective Agents/pharmacology , Mice, Inbred C57BL
9.
Article in English | MEDLINE | ID: mdl-36498144

ABSTRACT

Coronavirus disease 2019 (COVID-19) led to the loss of lives and had serious social and economic effects. Countries implemented various quarantine policies to reduce the effects. The countries were divided into low- and high-risk groups based on the differences in quarantine policies and their levels of infection. Quarantine policies that significantly contributed to risk reduction were determined by analyzing 11 quarantine indicators for reducing the spread of COVID-19. The cross-tabulation and Chi-square tests were used to compare the quarantine policies by the groups. Multivariate logistic regression was used to determine the useful quarantine policies implemented by the low-risk group to verify quarantine policies for minimizing the negative effects. The analysis showed that the low- and medium-risk groups showed significant differences for 9 of the 11 indicators, and 4 of these differentiated the low- from the medium-risk group. Countries with strict quarantine policies related to workplace closure and staying at home were more likely to be included in the low-risk group. These policies had a significant impact in the low-risk countries and could contribute to reducing the spread and effects of COVID-19 in countries included in the high-risk group.


Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , COVID-19/prevention & control , SARS-CoV-2 , Quarantine , Government
10.
Diagnostics (Basel) ; 12(9)2022 Sep 18.
Article in English | MEDLINE | ID: mdl-36140656

ABSTRACT

Body composition, including sarcopenia, adipose tissue, and myosteatosis, is associated with unfavorable clinical outcomes in patients with coronavirus disease (COVID-19). However, few studies have identified the impact of body composition, including pre-existing risk factors, on COVID-19 mortality. Therefore, this study aimed to evaluate the effect of body composition, including pre-existing risk factors, on mortality in hospitalized patients with COVID-19. This two-center retrospective study included 127 hospitalized patients with COVID-19 who underwent unenhanced chest computed tomography (CT) between February and April 2020. Using the cross-sectional CT images at the L2 vertebra level, we analyzed the body composition, including skeletal muscle mass, visceral to subcutaneous adipose tissue ratio (VSR), and muscle density using the Hounsfield unit (HU). Of 127 patients with COVID-19, 16 (12.6%) died. Compared with survivors, non-survivors had low muscle density (41.9 vs. 32.2 HU, p < 0.001) and high proportion of myosteatosis (4.5 vs. 62.5%, p < 0.001). Cox regression analyses revealed diabetes (hazard ratio [HR], 3.587), myosteatosis (HR, 3.667), and a high fibrosis-4 index (HR, 1.213) as significant risk factors for mortality in patients with COVID-19. Myosteatosis was associated with mortality in hospitalized patients with COVID-19, independent of pre-existing prognostic factors.

11.
IEEE J Biomed Health Inform ; 26(8): 4270-4280, 2022 08.
Article in English | MEDLINE | ID: mdl-35511839

ABSTRACT

Electronic health record (EHR) data are sparse and irregular as they are recorded at irregular time intervals, and different clinical variables are measured at each observation point. In this work, to handle irregular multivariate time-series data, we consider the human knowledge of the aspects to be measured and time to measure them in different situations, known as multi-view features, which are indirectly represented in the data. We propose a scheme to realize multi-view features integration learning via a self-attention mechanism. Specifically, we devise a novel multi-integration attention module (MIAM) to extract complex information that is inherent in irregular time-series data. We explicitly learn the relationships among the observed values, missing indicators, and time interval between the consecutive observations in a simultaneous manner. In addition, we build an attention-based decoder as a missing value imputer that helps empower the representation learning of the interrelations among multi-view observations for the prediction task this decoder operates only in the training phase so that the final model is implemented in an imputation-free manner. We validated the effectiveness of our method over the public MIMIC-III and PhysioNet challenge 2012 datasets by comparing with and outperforming the state-of-the-art methods in three downstream tasks i.e., prediction of the in-hospital mortality, prediction of the length of stay, and phenotyping. Moreover, we conduct a layer-wise relevance propagation (LRP) analysis based on case studies to highlight the explainability of the trained model.


Subject(s)
Electronic Health Records , Humans
12.
Bioelectrochemistry ; 145: 108102, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35338862

ABSTRACT

CO2 can be a next generation feedstock for electricity-driven bioproduction due to its abundance and availability. Microbial electrosynthesis (MES), a promising technique for CO2 electroconversion, provides an attractive route for the production of valuable products from CO2, but issues surrounding efficiency and reasonable productivity should be resolved. Improving the anode performance for water oxidation under neutral pH is one of the most important aspects to advance current MES. Here, we introduce cobalt-phosphate (Co-Pi) assisted water oxidation at the counter electrode (i.e., anode) to upgrade the MES performance at pH 7.0. We show that CO2 can be converted by photochemoautotrophic bacterium, Rhodobacter sphaeroides into organic acids and carotenoids in the MES reactor. Planktonic cells of R. sphareroides in the Co-Pi anode equipped MES reactor was ca. 1.5-fold higher than in the control condition (w/o Co-Pi). The faradaic efficiency of the Co-Pi anode equipped MES reactor was remarkably higher (58.3%) than that of the bare anode (27.8%). While the system can improve the CO2 electroconversion nonetheless there are some further optimizations are necessary.


Subject(s)
Rhodobacter sphaeroides , Carbon Dioxide , Cobalt , Electrodes , Phosphates , Water
13.
Colloids Surf B Biointerfaces ; 210: 112244, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34896691

ABSTRACT

We investigated the immunomodulatory and anti-inflammatory efficacy of hederagenin coating on maghemite (γ-Fe2O3) nanoparticles (HM) in atopic dermatitis (AD), as well as the physical and optical properties of maghemite nanoparticles (MP) using SEM, XRD spectroscopy, UV-vis spectra, Raman spectra, and FTIR spectroscopy. Dose-dependent treatment with HM (10, 50, 100, 200 µg/mL) inhibited the expression of Interleukin-2 (IL-2) and Tumor necrosis factor- α (TNF-α) in inflammatory induced HaCaT and Jurkat cells with inflammation caused by TNF/IFN-γ and PMA/A23187. AD model was induced by performing topical application of 2,4-dinitrochlorobenzene (DNCB) and dermatophagoides farinae extract (DFE) for a 31-day period on 8-week-old BALB/c mice. The HM treatments efficiently diminished the AD-like cutaneous lesion induced by DNCB-DFE sensitization in mice. Compared to the AD-only groups, HM treatment considerably attenuated mast cell infiltration and lowered epidermal, and dermal thickness of mice ears skin. In addition, HM treatment prominently alleviated the enlarged size and weight of lymph nodes. Furthermore, HM treatment resulted in a notable reduction in the mRNA expression of Th1 cytokines (TNF-α and IFN-γ), Th2 cytokines (IL-4 and IL-6), Th17 (IL-17), and TSLP. Our data showed that HM provides better AD attenuation compared to MP. Additionally, HM had synergistic effect and act as anti-inflammatory and immunomodulatory agent. Thus, HM shows great potential in AD medication and as a substitution of non-steroid-based medication.


Subject(s)
Dermatitis, Atopic , Nanoparticles , Animals , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Cytokines/genetics , Dermatitis, Atopic/chemically induced , Dermatitis, Atopic/drug therapy , Ferric Compounds , Mice , Mice, Inbred BALB C , Oleanolic Acid/analogs & derivatives , Skin
14.
Diagnostics (Basel) ; 11(6)2021 Jun 09.
Article in English | MEDLINE | ID: mdl-34207587

ABSTRACT

Adipose tissue and skeletal muscle is associated with non-alcoholic fatty liver disease (NAFLD). This study evaluates the association between body composition and histologic severity in patients with NAFLD. Using the cross-sectional CT images at the level of L3 vertebra and the histologic findings of 178 patients with biopsy-proven NAFLD, we analyzed the correlation of the histologic findings to the skeletal muscle index (SMI), subcutaneous adipose tissue index (SATI), and visceral adipose tissue index (VATI), which is defined as the body composition area (cm2) by height squared (m2). The clinical and laboratory features with body composition were analyzed to determine the risk factors for advanced fibrosis. The VATI significantly increased in severe non-alcoholic steatohepatitis (NASH) or advanced fibrosis. In addition, the VATI was correlated with the NAFLD activity score (NAS) and the fibrosis stage. In multivariate analyses, age (odds ratio (OR), 1.09; 95% confidence interval (CI), 1.02-1.19; p = 0.025), severe NASH (OR, 8.66; 95% CI, 2.13-46.40; p = 0.005), and visceral adiposity (OR, 6.77; 95% CI, 1.81-29.90; p = 0.007) were independently associated with advanced fibrosis in patients with NAFLD. Visceral adiposity is correlated with the histologic severity of NAFLD, which is independently associated with advanced fibrosis.

15.
J Cereb Blood Flow Metab ; 40(10): 2115-2131, 2020 10.
Article in English | MEDLINE | ID: mdl-31744388

ABSTRACT

Vascular dysfunction is correlated to the incidence and severity of Alzheimer's disease. In a mouse model of Alzheimer's disease (APP/PS1) using in vivo, time-lapse, multiphoton microscopy, we found that occlusions of the microvasculature alter amyloid-beta (Aß) plaques. We used several models of vascular injury that varied in severity. Femtosecond laser-induced occlusions in single capillaries generated a transient increase in small, cell-sized, Aß deposits visualized with methoxy-X04, a label of fibrillar Aß. After occlusions of penetrating arterioles, some plaques changed morphology, while others disappeared, and some new plaques appeared within a week after the lesion. Antibody labeling of Aß revealed a transient increase in non-fibrillar Aß one day after the occlusion that coincided with the disappearance of methoxy-X04-labeled plaques. Four days after the lesion, anti-Aß labeling decreased and only remained in patches unlabeled by methoxy-X04 near microglia. Histology in two additional models, sparse embolic occlusions from intracarotid injections of beads and infarction from photothrombosis, demonstrated increased labeling intensity in plaques after injury. These results suggest that microvascular lesions can alter the deposition and clearance of Aß and confirm that Aß plaques are dynamic structures, complicating the interpretation of plaque burden as a marker of Alzheimer's disease progression.


Subject(s)
Alzheimer Disease/pathology , Microvessels/pathology , Plaque, Amyloid/pathology , Amyloid beta-Peptides/metabolism , Animals , Arterioles/diagnostic imaging , Female , Immunohistochemistry , Intracranial Thrombosis/pathology , Male , Mice , Mice, Transgenic , Microglia/pathology , Microscopy, Fluorescence, Multiphoton , Stilbenes , Stroke/pathology
16.
Health Hum Rights ; 21(2): 97-107, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31885440

ABSTRACT

This paper examines how issues related to abortion have historically been influenced by population control policies in South Korea and how the contemporary reproductive justice movement in South Korea has contributed to social change. On April 11, 2019, South Korea's Constitutional Court ruled that the ban on abortion was unconstitutional. As a result, South Korea's legislature must revise the 66-year-old anti-abortion law by December 31, 2020. This historic decision was closely related to the advocacy of a number of feminist groups, doctors' organizations, disability rights groups, youth activists, and religious groups in South Korea, who collectively formed the Joint Action for Reproductive Justice (Joint Action) in 2017. This paper describes the activism and actions of Joint Action as a key part of reproductive justice movements in Korea. Joint Action was initiated by an organization for women with disabilities, and once formed, they worked collectively to frame abortion as a social justice issue that goes beyond the pro-choice versus pro-life binary. By focusing on the composition, strategies, and main agenda of Joint Action, this paper analyzes how Joint Action influenced the Constitutional Court's 2019 decision to decriminalize abortion in South Korea and how the court established that it is the government's responsibility to ensure every individual's reproductive health and rights.


Subject(s)
Abortion, Legal/legislation & jurisprudence , Public Policy , Reproductive Rights/legislation & jurisprudence , Social Justice , Women's Rights/legislation & jurisprudence , Female , Feminism , Government , Humans , Republic of Korea , Social Change
17.
Psychol Health ; 34(5): 626-643, 2019 05.
Article in English | MEDLINE | ID: mdl-30669877

ABSTRACT

OBJECTIVE: This meta-analysis tested the relation between forgiveness of others and physical health (PH) with age, gender, race, education level, employment status, sample type, research design, type of PH variables, and publication status as the potential moderators. DESIGN: Eligible studies had participants with or without physical or mental health problems and had quantitative data on forgiveness of others and PH. The random-effects model was used to aggregate Fisher's z effect sizes, which were converted back to correlation coefficients. MAIN OUTCOME MEASURES: State forgiveness (forgiving an offense or offender) measures, trait forgiveness (a disposition to forgive) measures and physical health measures were included in the meta-analysis. RESULTS: A hundred and twenty-eight studies (N = 58,531) were retrieved, in which the mean effect sizes showed a significant positive relationship between forgiveness of others and PH (r = 0.14, p < 0.001, 95% CI [0.11, 0.17]). Further, no moderators showed a significant relation between forgiveness of others and PH. CONCLUSIONS: The positive relation between forgiveness of others and PH was not affected by potential moderators. Because the results are correlational, more forgiveness interventions may be needed to examine the causal effect of the relation between forgiveness of others and PH.


Subject(s)
Forgiveness , Health Status , Interpersonal Relations , Humans
18.
PLoS One ; 10(11): e0142326, 2015.
Article in English | MEDLINE | ID: mdl-26605916

ABSTRACT

BACKGROUND: Rapid diagnosis for time-sensitive illnesses such as stroke, cardiac arrest, and septic shock is essential for successful treatment. Much attention has therefore focused on new strategies for rapid and objective diagnosis, such as Point-of-Care Tests (PoCT) for blood biomarkers. Here we use a biomimicry-based approach to demonstrate a new diagnostic platform, based on enzymes tethered to nanoparticles (NPs). As proof of principle, we use oriented immobilization of pyruvate kinase (PK) and luciferase (Luc) on silica NPs to achieve rapid and sensitive detection of neuron-specific enolase (NSE), a clinically relevant biomarker for multiple diseases ranging from acute brain injuries to lung cancer. We hypothesize that an approach capitalizing on the speed and catalytic nature of enzymatic reactions would enable fast and sensitive biomarker detection, suitable for PoCT devices. METHODS AND FINDINGS: We performed in-vitro, animal model, and human subject studies. First, the efficiency of coupled enzyme activities when tethered to NPs versus when in solution was tested, demonstrating a highly sensitive and rapid detection of physiological and pathological concentrations of NSE. Next, in rat stroke models the enzyme-based assay was able in minutes to show a statistically significant increase in NSE levels in samples taken 1 hour before and 0, 1, 3 and 6 hours after occlusion of the distal middle cerebral artery. Finally, using the tethered enzyme assay for detection of NSE in samples from 20 geriatric human patients, we show that our data match well (r = 0.815) with the current gold standard for biomarker detection, ELISA-with a major difference being that we achieve detection in 10 minutes as opposed to the several hours required for traditional ELISA. CONCLUSIONS: Oriented enzyme immobilization conferred more efficient coupled activity, and thus higher assay sensitivity, than non-tethered enzymes. Together, our findings provide proof of concept for using oriented immobilization of active enzymes on NPs as the basis for a highly rapid and sensitive biomarker detection platform. This addresses a key challenge in developing a PoCT platform for time sensitive and difficult to diagnose pathologies.


Subject(s)
Aging/blood , Biological Assay/standards , Enzymes, Immobilized/chemistry , Infarction, Middle Cerebral Artery/blood , Phosphopyruvate Hydratase/blood , Stroke/blood , Animals , Biomarkers/blood , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Enzymes, Immobilized/genetics , Enzymes, Immobilized/metabolism , Female , Genes, Reporter , Humans , Infarction, Middle Cerebral Artery/diagnosis , Infarction, Middle Cerebral Artery/physiopathology , Luciferases/chemistry , Luciferases/genetics , Luciferases/metabolism , Male , Nanoparticles/chemistry , Point-of-Care Systems , Pyruvate Kinase/chemistry , Pyruvate Kinase/genetics , Pyruvate Kinase/metabolism , Rats , Rats, Sprague-Dawley , Recombinant Fusion Proteins/chemistry , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Silicon Dioxide/chemistry , Stroke/diagnosis , Stroke/physiopathology , Time Factors
19.
Molecules ; 20(9): 17393-404, 2015 Sep 18.
Article in English | MEDLINE | ID: mdl-26393568

ABSTRACT

This study compared the ability of nine culinary plant extracts containing a wide array of phytochemicals to inhibit fructose uptake and then explored the involvement of intestinal fructose transporters and phytochemicals for selected samples. The chemical signature was characterized by high performance liquid chromatography with mass spectrometry. Inhibition of [(14)C]-fructose uptake was tested by using human intestinal Caco-2 cells. Then, the relative contribution of the two apical-facing intestinal fructose transporters, GLUT2 and GLUT5, and the signature components for fructose uptake inhibition was confirmed in naive, phloretin-treated and forskolin-treated Caco-2 cells. HPLC/MS analysis of the chemical signature revealed that guava leaf contained quercetin and catechin, and turmeric contained curcumin, bisdemethoxycurcumin and dimethoxycurcumin. Similar inhibition of fructose uptake (by ~50%) was observed with guava leaf and turmeric in Caco-2 cells, but with a higher contribution of GLUT2 for turmeric and that of GLUT5 for guava leaf. The data suggested that, in turmeric, demethoxycurcumin specifically contributed to GLUT2-mediated fructose uptake inhibition, and curcumin did the same to GLUT5-mediated fructose uptake inhibition, but GLUT2 inhibition was more potent. By contrast, in guava leaf, catechin specifically contributed to GLUT5-mediated fructose uptake inhibition, and quercetin affected both GLUT5- and GLUT2-mediated fructose uptake inhibition, resulting in the higher contribution of GLUT5. These results suggest that demethoxycurcumin is an important contributor to GLUT2-mediated fructose uptake inhibition for turmeric extract, and catechin is the same to GLUT5-mediated fructose uptake inhibition for guava leaf extract. Quercetin, curcumin and bisdemethoxycurcumin contributed to both GLUT5- and GLUT2-mediated fructose uptake inhibition, but the contribution to GLUT5 inhibition was higher than the contribution to GLUT2 inhibition.


Subject(s)
Curcuma/chemistry , Fructose/metabolism , Phytochemicals/pharmacology , Plant Extracts/analysis , Psidium/chemistry , Caco-2 Cells , Curcumin/analogs & derivatives , Curcumin/pharmacology , Diarylheptanoids , Gene Expression Regulation, Enzymologic/drug effects , Glucose Transporter Type 2/metabolism , Glucose Transporter Type 5/metabolism , Humans , Phytochemicals/chemistry , Plant Extracts/pharmacology , Quercetin/pharmacology
20.
Nanotoxicology ; 9(6): 802-11, 2015.
Article in English | MEDLINE | ID: mdl-25395166

ABSTRACT

While many in vivo and in vitro toxicology studies of multi-walled carbon nanotubes (MWCNTs) have already indicated that exposure to MWCNTs can potentially induce health effects in humans, the actual health effects of MWCNTs among exposed workers are not yet known. Moreover, the levels of exposure and internal doses of MWCNTs are becoming more and more important for estimating the health effects resulting from exposure to MWCNTs. However, information on biomonitoring and exposure to MWCNTs remains limited. Therefore, the authors conducted a health surveillance study in a workplace that manufactures MWCNTs, including assessment of the personal and area exposure levels to MWCNTs, a walk-through evaluation of the manufacturing process, and collection of blood and exhaled breath condensates (EBCs) from the MWCNT manufacturing and office workers. In addition, a pulmonary function test was also conducted on the MWCNT manufacturing workers (9) and office workers (4). The worker exposure to elemental carbon was found to be 6.2-9.3 µg/m(3) in the personal samplings and 5.5-7.3 µg/m(3) in the area samplings. Notwithstanding, the workers exhibited a normal range of hematology and blood biochemistry values and normal lung function parameters. When analyzing the EBCs, the malondialdehyde (MDA), 4-hydroxy-2-hexenal (4-HHE) and n-hexanal levels in the MWCNT manufacturing workers were significantly higher than those in the office workers. The MDA and n-hexanal levels were also significantly correlated with the blood molybdenum concentration, suggesting MDA, n-hexanal and molybdenum as useful biomarkers of MWCNT exposure.


Subject(s)
Health Status Indicators , Inhalation Exposure , Nanotubes, Carbon/toxicity , Occupational Exposure , Occupational Health , Workplace/organization & administration , Adult , Biomarkers/analysis , Female , Humans , Inhalation Exposure/adverse effects , Inhalation Exposure/analysis , Male , Occupational Exposure/adverse effects , Occupational Exposure/analysis , Occupational Health/standards , Respiratory Function Tests , Workplace/standards
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